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  • drug2916: Placebo
    • Placebo (543) Hydroxychloroquine (100) Standard of Care (41) Azithromycin (38) Tocilizumab (37) Questionnaire (33) Placebo oral tablet (31) Convalescent Plasma (28) Remdesivir (28) Standard of care (26) Favipiravir (23) No intervention (23) Convalescent plasma (22) Ivermectin (22) Placebos (17) Nitazoxanide (15) Survey (15) placebo (15) Enoxaparin (14) Methylprednisolone (14) Vitamin C (14) Control (13) Colchicine (12) Hydroxychloroquine Sulfate (12) Blood sample (11) Lopinavir/ritonavir (10) Questionnaires (10) Ruxolitinib (10) Saline (10) blood sample (10) Anakinra (9) Dexamethasone (9) Losartan (9) Standard care (9) Usual Care (9) Vitamin D (9) no intervention (9) Camostat Mesilate (8) Nasopharyngeal swab (8) Questionnaire Administration (8) Zinc (8) Baricitinib (7) Chloroquine (7) Oseltamivir (7) Saliva collection (7) Standard treatment (7) questionnaire (7) survey (7) Blood sampling (6) Clazakizumab (6) DAS181 (6) LY3819253 (6) Normal Saline (6) Normal saline (6) Prednisone (6) Vitamin D3 (6) blood sampling (6) convalescent plasma (6) Ad26.COV2.S (5) Best Practice (5) COVID-19 Convalescent Plasma (5) COVID-19 convalescent plasma (5) Cyclosporine (5) Doxycycline (5) Hydroxychloroquine (HCQ) (5) Lopinavir / Ritonavir (5) Lung ultrasound (5) Mepolizumab (5) Midazolam (5) Online Survey (5) Quality-of-Life Assessment (5) Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (5) Rivaroxaban (5) Sarilumab (5) Standard Medical Treatment (5) Standard of Care (SOC) (5) UC-MSCs (5) hydroxychloroquine (5) questionnaire assesment (5) AZD1222 (4) Acalabrutinib (4) Alirocumab (4) Ascorbic Acid (4) Aspirin (4) Association atezolizumab + BDB001 + RT (4) BCG Vaccine (4) Blood draw (4) COVID-19 (4) Cholecalciferol (4) Colchicine Tablets (4) Dapagliflozin (4) Data collection (4) Evolocumab (4) Famotidine (4) Gam-COVID-Vac (4) HCQ (4) Hydrocortisone (4) Interferon Beta-1A (4) Interferon beta-1a (4) Lopinavir/Ritonavir (4) Matching placebo (4) Mavrilimumab (4) Melatonin (4) Methotrexate (4) Nitric Oxide (4) Nivolumab (4) Observational (4) Online questionnaire (4) Online survey (4) Ontamalimab (4) Opaganib (4) Oxygen (4) Peginterferon beta-1a (4) Placebo Administration (4) Povidone-Iodine (4) Presatovir (4) Prone position (4) Prone positioning (4) RLS-0071 (4) Reslizumab (4) Ribavirin (4) Rifampin (4) Rosuvastatin (4) SARS-CoV-2 (4) Standard Care (4) Telemedicine (4) Telerehabilitation (4) Usual care (4) Yoga (4) anti-SARS-CoV-2 convalescent plasma (4) standard care (4) 3D Telemedicine (3) ACE inhibitor (3) AG0302-COVID19 (3) Abatacept (3) Allopurinol (3) Anti-SARS-CoV2 Serology (3) Apremilast (3) BAY1817080 (3) BCG vaccine (3) BI 764198 (3) BI 894999 (3) BNT162b1 (3) BNT162b2 (3) Best Supportive Care (3) Biospecimen Collection (3) COVID-19 RT-PCR (3) COViage (3) Chloroquine or Hydroxychloroquine (3) Chloroquine phosphate (3) Clinical data (3) Clopidogrel (3) Cognitive Behavioral Therapy (3) Control group (3) DWRX2003 (3) ECG (3) EIDD-2801 (3) Echocardiography (3) Eltrombopag (3) Exercise (3) Heparin (3) Interferon Beta-1B (3) Interview (3) Itraconazole (3) LY3832479 (3) Lenzilumab (3) Mesenchymal Stromal Cells (3) Mesenchymal stromal cells (3) Mindfulness (3) Nafamostat Mesilate (3) Naltrexone (3) Nitric Oxide Gas (3) No Intervention (3) No intervention, observational study (3) Observation (3) Pentoxifylline (3) Phase 2 (3) Placebo oral capsule (3) Plasma (3) Probiotic (3) Prone Positioning (3) Prospective study with two measurement points investigating the impact of viral mitigation protocols on mental health (3) REGN10933+REGN10987 combination therapy (3) RT-PCR (3) Ravulizumab (3) Relamorelin (3) Remestemcel-L (3) SARS-CoV-2 convalescent plasma (3) Saline Placebo (3) Sargramostim (3) Selinexor (3) Serological test (3) Siltuximab (3) SnPP Protoporphyrin plus Sunlight exposure (3) Standard of care (SOC) (3) Supportive Care (3) Survey Administration (3) Suspension of heat killed (autoclaved) Mycobacterium w (3) Telmisartan (3) VPM1002 (3) Verinurad (3) Vitamin Super B-Complex (3) blood donation SMS (3) exhaled breath sampling (3) observational (3) placebo for risankizumab (3) risankizumab IV (3) risankizumab SC (3) self-administered questionnaire (3) standard of care (3) standard therapy (3) 0.9% Saline (2) 100 mg/mL Virazole (2) 2D Telemedicine (2) 50 mg/mL Virazole (2) AG0301-COVID19 (2) ARB (2) ATI-450 (2) AZD5718 (2) Abidol hydrochloride (2) Acalabrutinib Treatment A (2) Acalabrutinib Treatment B (2) Acalabrutinib Treatment C (2) Aeonose (2) Aerobic Exercise Training (2) Allocetra-OTS (2) Ampion (2) Angiotensin 1-7 (2) Angiotensin II (2) Angiotensin converting enzyme inhibitor (2) Antibiotics (2) Arbidol (2) Assessment of behavioral response to emotional stimulation (2) Assessment of work-related stress (2) Association atezolizumab + BDB001+ RT (2) Atorvastatin (2) Attention Placebo (2) Ayurveda (2) Azithromycin Tablets (2) BCG-Denmark (2) BI 474121 (2) BIIB091 (2) Bacille Calmette-Guérin (BCG) (2) Baloxavir Marboxil (2) Baricitinib Oral Tablet (2) Bemiparin (2) Bevacizumab Injection (2) Bicalutamide 150 Mg Oral Tablet (2) Biological data (2) Biological sample collection (2) Blood samples (2) Blood test (2) Blood tests (2) Breath Biopsy face masks with removable filters and fitted PVA strip (2) Brequinar (2) Brief cognitive intervention (2) Bucillamine (2) CELLECTRA® 2000 (2) CFTR Modulators (2) COVID Convalescent Plasma (2) COVID-19 Serology (2) COVID-19 Therapeutic Biologics - Spike-GM-CSF Protein Lactated Ringer's Injection (2) COVID-19 pandemic (2) COVID-19 patients (2) CT-P59 (2) CT-Scan (2) CYT107 (2) Cabotegravir Tablets (2) Camostat Mesylate (2) Canakinumab (2) Candin (2) Cannabidiol (2) Carboplatin (2) Cardiac and electrodermal recordings (2) ChAdOx1 MERS (2) ChAdOx1 nCoV-19 (2) Chemotherapy (2) Chloroquine Sulfate (2) Chloroquine or hydroxychloroquine (2) Clinical Examination (2) Clinical assessment (2) Convalescent COVID 19 Plasma (2) Convalescent Plasma (CP) (2) Convalescent Plasma (anti-SARS-CoV-2 plasma) (2) Convalescent Plasma Transfusion (2) Conventional treatment (2) Corticosteroid (2) Daclatasvir (2) Data Collection (2) Data record (2) Deferoxamine (2) Dexamethasone injection (2) Diagnostic test (2) Disulfiram (2) Dornase Alfa Inhalation Solution [Pulmozyme] (2) Duvelisib (2) EC-18 (2) EDP1815 (2) EXO 1 inhalation (2) EXO 2 inhalation (2) Early-Dexamethasone (2) Ebselen (2) Eculizumab (2) Electronic questionnaire (2) Enhanced Usual Care (2) Enoxaparin 40 Mg/0.4 mL Injectable Solution (2) Ensifentrine (2) Exebacase (2) Exercise program (2) Exercise training (2) Exposure (2) Expressive writing (2) Famotidine 20 MG (2) Favipiravir Placebo (2) Fiberoptic Endoscopic Evaluation of Swallowing (2) Fisetin (2) Flow cytometric analysis (2) Fluoxetine (2) Follow up (2) Functional Assessment of Cancer Therapy - Spiritual Well-Being Scale (2) GLPG3970 (2) GLS-5300 (2) GSK3640254 (2) Guduchi Ghan Vati (2) HB-adMSCs (2) HFNC (2) Hepatitis A vaccine (2) High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule (2) Home exercise (2) Human immunoglobulin (2) Hydroxychloroquine + azithromycin (2) Hydroxychloroquine - Weekly Dosing (2) Hydroxychloroquine 200 Mg Oral Tablet (2) Hydroxychloroquine Sulfate 200 MG (2) Hydroxychloroquine Sulfate 200 MG [Plaquenil] (2) Hydroxychloroquine Sulfate Loading Dose (2) Hydroxychloroquine Sulfate Regular dose (2) Hydroxychloroquine Sulfate Tablets (2) Hydroxychloroquine and Azithromycin (2) Hypothermia (2) ICU treatment (2) IMU-838 (2) INO-4800 (2) IVIG (2) Ibrutinib (2) Icosapent ethyl (2) Inactivated SARS-CoV-2 Vaccine (Vero cell) (2) Infliximab (2) Interferon beta-1b (2) Interleukin-7 (2) Iodine Complex (2) Ivermectin Oral Product (2) Ivermectin Pill (2) Ivermectin and Doxycycline (2) Ixazomib (2) KB109 + Self Supportive Care (SSC) (2) Ketogenic diet (2) L-ascorbic acid (2) Lanadelumab (2) Leflunomide (2) Leronlimab (700mg) (2) Lopinavir-Ritonavir (2) Low Dose Radiation Therapy (2) Low Dose Radiotherapy (2) Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule (2) Low molecular weight heparin (2) M5049 (2) MEDI3506 (2) MSC (2) MagPro X100 Stimulator, B70 Fluid-Cooled Coil (2) Matched Placebo (2) Meaning Centered Psychotherapy for Latinos (2) Meaning Centered Psychotherapy for Latinos for Waitlist Control Patients (2) Meditation (1 x 20-minute guided audio training) (2) Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule (2) Meplazumab for Injection (2) Metformin (2) Methylprednisolone Sodium Succinate (2) Mindfulness Based Intervention (2) Mobocertinib (2) Molnupiravir (2) Moxifloxacin (2) N-Acetyl cysteine (2) N-acetylcysteine (2) NORS (Nitric Oxide Releasing Solution) (2) Nasal swab (2) Nasopharyngeal swabs (2) Neuromuscular Blocking Agents (2) Niclosamide (2) Niclosamide Oral Tablet (2) Nigella Sativa / Black Cumin (2) Nitrogen gas (2) Observational study (2) Olokizumab 64 mg (2) Other (2) PLACEBO (2) PLX-PAD (2) PUL-042 Inhalation Solution (2) Paracetamol (2) Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances (2) Peginterferon Lambda-1A (2) Pembrolizumab (2) Peripheral blood draw (2) Phase 1 (2) Phone call (2) Physiotherapy (2) Placebo Comparator (2) Placebo capsules (2) Placebo inhalation (2) Placebo on a 0- and 28-day schedule (2) Postcard (2) Povidone-Iodine Nasal Spray and Gargle (2) Pozelimab (2) Practice details (2) Prazosin (2) Pre-assessment questionnaire (2) Psychoeducation (2) Pulmozyme (2) RECOP unit patient (2) RLF-100 (aviptadil) (2) RO6889450 (2) RTB101 (2) Rabeprazole (2) Radiation therapy (2) Radiotherapy (2) Recombinant new coronavirus vaccine (CHO cell) low-dose group (2) Recombinant new coronavirus vaccine (CHO cells) high-dose group (2) Recombinant new coronavirus vaccine (CHO cells) placebo group (2) Remdesivir placebo (2) Rifampicin (2) Rilpivirine Tablets (2) Risankizumab (2) Rituximab (2) Routine care for COVID-19 patients (2) Ruxolitinib Oral Tablet (2) SAB-185 (2) SARS-CoV-2 diagnostic rapid test (2) SARS-CoV-2 rS/Matrix-M1 Adjuvant (2) SARS-Cov2 testing (2) SEL-212A (2) SEL-212B (2) SOC + Placebo (2) Saline solution (2) Saliva sample collection (2) Sample collection (2) Sampling (2) Self Supportive Care (SSC) Alone (2) Seraph 100 (2) Serology test for COVID-19 (2) Serum testing (2) Sevoflurane (2) Simple cognitive task intervention (2) Simvastatin (2) Single Dose of Hydroxychloroquine (2) Sirolimus (2) SivoMixx (200 billion) (2) Spirometry (2) Standard Therapy (2) Standard of Care (SoC) (2) Standard of care treatment (2) Stellate Ganglion Block (2) T3011 (2) TD-0903 (2) Taking blood samples (capillary and venous), saliva sampling and nasopharyngeal sampling. (2) Telehealth (2) Telisotuzumab vedotin (2) Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg (2) Tezepelumab (2) Therapeutic Plasma Exchange (2) Therapeutic anticoagulation (2) Throat swab (2) Thymalfasin (2) Tildrakizumab (2) Tocilizumab (TCZ) (2) Tocilizumab Injection (2) Tofacitinib (2) Tofacitinib 10 mg (2) Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit (2) Two doses of low dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 (2) Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 (2) Two doses of placebo at the schedule of day 0,28 (2) Unfractionated heparin (2) Virtual Reality (2) Volatile Organic Compounds analysis (2) Volitional help sheet (2) Vonoprazan (2) basic treatment (2) blood draw (2) blood samples (2) blood test (2) mRNA-1273 (2) nasopharyngeal swab (2) other (2) oxygen therapy (2) pregnant women with laboratory-confirmed 2019-n-CoV (2) prone position (2) retrospective analysis (2) rhTPO (2) serology (2) survey work (2) tabelecleucel (2) tocilizumab (2) unfractionated Heparin (2) venous ultrasound (2) vv-ECMO + cytokine adsorption (Cytosorb adsorber) (2) vv-ECMO only (no cytokine adsorption) (2) "Calm" is a mindfulness meditation mobile app (1) "Vernonia amygdalina" (1) (Standard of Care) SoC (1) - Synthetic anti-malarial drugs (1) 0.075% Cetylpyridinium Chloride (1) 0.12% Chlorhexidine Gluconate (1) 0.12% Chlorhexidine Gluconate Mouth Rinse (1) 0.12% Chlorhexidine oral/nasal rinse (1) 0.5% Povidone Iodine (1) 0.5% Povidone/Iodine oral/nasal rinse (1) 0.9% Normal Saline (1) 0.9% Sodium Chloride (Placebo) (1) 0.9% Sodium-chloride (1) 0.9% saline (1) 0.9% sodium chloride (normal saline) (1) 0.9%NaCl (1) 0.9%sodium chloride (1) 1% Hydrogen Peroxide (1) 1% w/v Povidone-iodide (1) 1. Characterize the immune response after infection with SARS-CoV-2 (1) 1.5-2% w/v Hydrogen Peroxide (1) 10% Povidone-iodine nasal decolonization swab plus 0.12% CHG oral rinse (1) 11C-ER176 (1) 12 weeks of bicycle exercise (1) 12-page health warning leaflet (1) 12-week FMS Intervention (1) 14C-lazertinib (1) 150 ppm Nitric Oxide delivered through LungFit Delivery System (1) 18F-DX600 PET/CT (1) 18F-Florbetaben (1) 18F-GP1 PET CT (1) 18F-MK-6240 (1) 18F-αvβ6-BP (1) 1: ILT101 (1) 1: Naproxen (1) 1: Prone positioning (1) 1: Usual practice (1) 1: discontinuation of RAS blocker therapy (1) 1D (1) 20 Mg Prednisone for 14 days (1) 20 mg MitoQ (1) 2019-nCoV IgG/IgM Rapid Test Cassette (1) 2019-nCoV PCR (1) 21% Ethanol plus essential oils (1) 25-OH cholecalciferol (1) 2: No instruction regarding positioning (1) 2: Placebo Comparator (1) 2: Standard of care (1) 2: Usual practice + SYMBICORT RAPIHALER (1) 2: continuation of RAS blocker therapy (1) 3 Wishes Project (1) 30 Gy over 3 weeks (1) 300 mg of omega3-FA (1) 35 ml blood, 5 tubes LITHIUM HEPARINATE at each time (cured Patients) (1) 35 ml blood, 5 tubes LITHIUM HEPARINATE at each time (hospitalized Patients ) (1) 38 questions questionnaire (1) 38-questions questionnaire (1) 3D (1) 40-Steps-test (1) 40mg of MitoQ (1) 40ml blood sample (1) 4Plants/Azythromycin (1) 5-ALA-Phosphate + SFC (5-ALA + SFC) (1) 50 Gy Radiation Therapy (1) 55 Gy Radiation Therapy (1) 5Fluorouracil (1) 6 minute walk test (1) 60 Gy Radiation Therapy (1) 68Ga-DX600 PET/CT (1) 7-day exposure therapy via self-developed app according to (Haberkamp et al., submitted) (1) 80 ppm Nitric Oxide delivered through LungFit Delivery System (1) A $10 Survey Incentive (1) A $20 Survey Incentive (1) A short video intervention (1) A vignette intervention (1) AAZ Covid-19 rapid test (1) ABC/3TC (1) ABPM (1) ABTL0812 (1) ABX464 (1) ACE Inhibitors and Calcium Channel Blockers (1) ACE inhibitor, angiotensin receptor blocker (1) ACEI (1) ACEI/ARB (1) ACEIs (1) ACT-1014-6470 (1) ACT-20-CM (1) ACT-20-MSC (1) ACT-541478 10 mg (1) ACT-541478 100 mg (1) ACT-541478 1000 mg (1) ACT-541478 30 mg (1) ACT-541478 300 mg (1) ACT-541478 dose E1 (1) ACT-541478 high or low dose (or placebo) (1) ADAM Sensor (1) ADCT-301 (1) ADM03820 (1) AI model (1) AIRVO (1) AK119 (1) ALLOCETRA-OTS (1) ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS (1) ALX148 (1) ALZT-OP1 (cromolyn and ibuprofen) ALZT-OP1a (cromolyn) and ALZT-OP1b (ibuprofen) (1) AMA Acknowledgement Drug Pricing (1) AMY-101 (1) AN69-Oxiris (1) AN69-Standard (1) APL-9 (1) APPS (1) ARALAST NP (1) ARBIDOL 100 MG KAPSUL (1) ARBOX (1) ARBs and/or ACE inhibitors (1) ARCT-021 Dose 1 (1) ARCT-021 Dose 2 (1) ARCT-021 Dose 3 (1) ARCT-021 Dose 4 (1) ARCT-021 Dose Regimen 1 (1) ARCT-021 Dose Regimen 2 (1) ARDSNet (1) ARFC mask (1) ARGX-117 (1) ARGX-117 + rHuPH20 (1) ASC09/ritonavir group (1) ASC09F+Oseltamivir (1) ASP0367 (1) ASP2390 (1) ASP7317 (1) ASP8374 (1) ASSIST (1) ASTX660 (1) AT-001 (1) AT-527 (1) ATAFENOVIR 200 MG KAPSUL (1) ATI-1777 (1) ATYR1923 1 mg/kg (1) ATYR1923 3 mg/kg (1) AUDIT score interpretation sheet adapted from the Department of Health of Hong Kong (1) AUP1602-C (1) AV-COVID-19 (1) AVIGAN (1) AVIGAN 200 MG Film Tablets (1) AVIGAN 200 mg FT (1) AVIGAN 200 mg Film Tablets (1) AVM0703 (1) AVP 4 (1) AVP I (1) AVP II (1) AWARD advice (1) AWARD plus COVID-specific advice (1) AZD1390 (1) AZD1656 (1) AZD2693 (1) AZD7442 (1) AZD8154 Monodose DPI presented in capsules (1) AZD8154 Placebo Monodose DPI presented in capsules (1) AZD8154 nebuliser (1) AZD9567 (1) AZD9833 Oral Solution (1) AZD9833 film-coated tablet A Dose 1 (1) AZD9833 film-coated tablet A Dose 2 (1) AZD9833 film-coated tablet B Dose 1 (1) AZD9833 film-coated tablet B Dose 2 (1) AZD9977 (1) Abdominal ultrasound (1) Abidol Hydrochloride combined with Interferon atomization (1) Abiraterone Acetate (1) Abivertinib (1) Absolute Pro LL stent (1) Acacia Senegal (1) Acalabrutinib Treatment D (1) Acceptability questionnaire (1) Access to training facility (1) Accuchek Inform II platform (1) Acetazolamide + supplemental oxygen + PAP therapy (1) Acetylsalicylic acid (1) Acknowledgement Racial Injustice AMA (1) Acthar Gel (1) Actigraph (1) Active COVID-19 disease (1) Active Choice (1) Active Comparator (1) Active Comparator: Control (1) Active Control (1) Active PBMT/sMF (1) Active control condition (1) Active control:Healthy Living (1) Active nudge text feedback (1) Activity (1) Activity plan to break up sitting time (1) Acyclovir (1) Ad26.ZEBOV (1) Ad5-nCoV (1) Ad5FGF-4 (1) Adalimumab (1) Additional and minimal collection of products of the human body carried out during a sample for standard of care (1) Additional biological samples (1) Adenosine (1) Adenovirus Type-5 Vectored COVID-19 Vaccine (1) AdimrSC-2f (1) Administration of Equine immunoglobulin anti SARS-CoV-2 (1) Admission to ICU for COVID-19 (1) Adsorbed COVID-19 (inactivated) Vaccine (1) Aerobic training (1) Aerolized Hydroxychloroquine Sulfate (1) Aerosol Box (1) Aerosol-reducing Mask (1) Aerosolized 13 cis retinoic acid (1) Aerosolized 13 cis retinoic acid plus Inhalation administration by nebulization captopril 25mg (1) Aerosolized All trans retinoic acid (1) Aerosolized All-Trans Retinoic acid plus oral Tamoxifen (1) Aerosolized Isotretinoin plus Tamoxifen (1) African American Sender Acknowledgement (1) African American Sender in Informational Videos. (1) After COVID-19 Pandemic (1) AirGo Respiratory Monitor (1) Airwave Oscillometry (1) Airway pressure release ventilation (1) Albendazole (1) Albuterol - Control (1) Albuterol - Experimental (1) Alcohol (1) Alcohol brief intervention (1) Alexa Amazon (1) Alferon LDO (1) Algorithm-based recommendation (1) Alisporivir (1) AlloStim (1) Allogeneic NK transfer (1) Allogeneic and expanded adipose tissue-derived mesenchymal stromal cells (1) Allogenic pooled olfactory mucosa-derived mesenchymal stem cells (1) Almitrine (1) Alprazolam 1mg XR (1) Alteplase 100 MG [Activase] (1) Alteplase 50 MG [Activase] (1) Alternating face-to-face medical visits and video medical consultations (1) Aluminum adjuvant (1) Aluminum hydroxide (1) Aluminum hydroxide adjuvant (Alhydrogel®) (1) Alvelestat (1) Ambrisentan (1) Amiodarone (1) Amlodipine (1) Amlodipine 2.5 mg/indapamide 1.25 mg (1) Amoxicillin-clavulanate (1) An auto-questionnaire comprising three psychometric scales (1) Anakinra +/- Ruxolitinib (stages 2b/3) (1) Anakinra 100Mg/0.67Ml Inj Syringe (1) Anakinra 149 MG/ML Prefilled Syringe [Kineret] (1) Anakinra Prefilled Syringe (1) Anakinra alone (stages 2b/3) (1) Anakinra and Ruxolitinib (Advanced stage 3) (1) Anakinra and Ruxolitinib (overcome stage 3) (1) Anakinra and Zinc (1) Anakinra plus oSOC (1) Analogs, Prostaglandin E1 (1) Analysis of cytokine response, innate and adaptive immune response, complement activation, and serum neurofilaments as a marker of neurological damage. (1) Anatomic Pulmonary Resection (1) Anger message (1) Angiography (1) Angiography scanner (1) Angiotensin II Receptor Blockers (1) Angiotensin Receptor Blockers (1) Angiotensin receptor blocker (1) Angiotensin-(1-7) (1) Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) (1) Anluohuaxian (1) Anthocyanins (1) Anti SARS-CoV 2 Convalescent Plasma in critical COVID-19 patients (1) Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients (1) Anti- SARS-CoV-2 Plasma (1) Anti-COVID-19 human immunoglobulin (1) Anti-Human Thymocyte Immunoglobulin, Rabbit (1) Anti-SARS-CoV-2 Human Convalescent Plasma (1) Anti-SARS-CoV-2 IgT seropositivity (1) Anti-SARS-CoV-2 convalescent plasma (1) Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) (1) Anti-SARS-CoV-2 immunoglobulin (1) Anti-SARS-CoV2 serological controls and serum neutralization (1) Anti-Sars-CoV-2 Convalescent Plasma (1) Anti-coronavirus antibodies (immunoglobulins) obtained with DFPP form convalescent patients (1) Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients (1) Antibody Test (1) Antibody test (SARS-CoV2) (1) Antibody testing (1) Antibody titration (1) Antibody-Rich Plasma from COVID-19 recovered patients (1) Anticoagulant Therapy (1) Anticoagulation Agents (Edoxaban and/or high dose LMWH) (1) Antihemophilic Factor (Recombinant) (1) Antihypertensive Agents (1) Antioxidation Therapy (1) Antithrombotic Therapy (anticoagulant and/or antiplatelet) before admission for Covid19 (1) Antroquinonol (1) Anxiety Reduction Training (1) Any drug used to treat Covid-19 (1) Apilimod Dimesylate Capsule (1) Apixaban (1) Apixaban 2.5 MG (1) Apixaban 5MG (1) Apo-Hydroxychloroquine (1) Appeals (1) Appendectomy (1) Apple Watch Series 5 (1) Application of tele-rehabilitation (1) Apramycin injection (1) Aprepitant injectable emulsion (1) Aprotinin (1) Arbidol Hydrochloride Granules (1) Argatroban (1) Arm exercise electrocardiographic stress test (1) Artemesia annua (1) ArtemiC (1) Artemisia Annua Leaf (1) Artemisinin / Artesunate (1) Arterial Blood Gas test (ABG) (1) Artesunate (1) Artesunate-amodiaquine (1) Ascorbic Acid and Zinc Gluconate (1) Aspirin 100mg (1) Aspirin 75mg (1) Aspirin 81 mg (1) Assembled mask (1) Assessing antibody responses, neutralizing capacity and memory B-cell function (1) Assessing impact of COVID19 (1) Assessment of Dietary Changes in Adults in the Quarantine (1) Assessment of cardiovascular diseases and cardiovascular risk factors (1) Assessment of lung mechanics and heart-lung interactions (1) Assessment of postnatal depression using the the Edinburgh questionnaire between 4 and 6 weeks after delivery (1) Assessment of ventilator-associated pneumonia criteria (1) Assigned Strategies: Active Choice (1) Assigned Strategies: Enhanced Active Choice (1) Assigned Strategies: Opt-in (1) Association of diltiazem and niclosamide (1) Asthma controller therapies (incl. prednisone/prednisolone) (1) Asthma reliever therapies (1) AstroStem-V (1) Asunercept (1) Asynchronies detection (1) Asynchronous self-directed digital training (1) Atazanavir (1) Atazanavir and Dexamethasone (1) Atezolizumab (1) Atomoxetine hydrochloride (1) Atorvastatin 20 Mg Oral Tablet (1) Atorvastatin 20mg (1) Atorvastatin 40mg (1) Atovaquone/Azithromycin (1) Attention Bias Modification (ABM) (1) Attention Control Group (1) Attention Control Intervention 4 (1) Attention Training Program (1) Attention control (1) Audit and Feedback (1) Auditory Evoked Potentials (AEP) (1) Augmentin (ES)-600 (1) Auricular neuromodulation (1) Auricular percutaneous neurostimulation (1) Auscul-X (1) Auto-questionnaires (patients co infected HIV Sras-CoV-2) (1) Autologous Adipose MSC's (1) Autologous Bone Graft (1) Autologous Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC) (1) Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells (1) Automated oxygen administration - FreeO2 (1) Auxora (1) Avdoralimab (1) Aviptadil 67μg (1) Aviptadil by intravenous infusion + standard of care (1) Awake Prone Positioning (1) Awake Proning (1) Awake prone positioning (1) Awake proning (1) Ayurvedic Kadha (1) Azacitidine (1) Azinc (1) Azithromycin (Azithro) (1) Azithromycin 250 MG (1) Azithromycin 250 MG Oral Capsule (1) Azithromycin 500 milligram (mg) oral Tablet (1) Azithromycin 500Mg Oral Tablet (1) Azithromycin Capsule (1) Azithromycin and hydroxychloroquine (1) Azithromycin with amoxicillin/clavulanate (1) Açaí palm berry extract - natural product (1) BACMUNE (MV130) (1) BAN2401 (1) BAT (1) BAT + Calcifediol (1) BAT2020 (1) BAX 888 (1) BAY1211163 Dose 1 (1) BAY1211163 Dose 2 (1) BAY1211163 Dose 3 (1) BAY1211163 Dose 4 (1) BAY1211163 Dose 5 (1) BAY1237592 (1) BAY2328065 LSF (1) BAY2328065 tablet (1) BBV152A - Phase I (1) BBV152A - Phase II (1) BBV152B - Phase I (1) BBV152B - Phase II (1) BBV152C - Phase I (1) BCG (1) BCG GROUP (1) BCG vaccine (Freeze-dried) (1) BDB-001 Injection (1) BGB DXP593 (1) BGB-DXP593 (1) BI 1015550 (1) BI 1358894 (1) BI 1569912 (1) BI 425809 (1) BI 706321 (1) BI 730357 (1) BIIB107 (1) BIIB133 (Dapirolizumab pegol) (1) BIKTARVY Tablets (BIK) (1) BIO 300 Oral Suspension (1) BIO101 (1) BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM (1) BIOVITALS (1) BLAfit® (1) BLD-2660 (1) BLZ945 (1) BM-Allo.MSC (1) BM-MSCs (1) BMS program (1) BMS-986253 (1) BMS-986256 (1) BMS-986259 (1) BMS-986322 (1) BMS-986322 Placebo (1) BMS-986337 (1) BMS-986337 Placebo (1) BNT162a1 (1) BNT162b3 (1) BNT162c2 (1) BRII-196 (1) BRII-198 (1) BTL-TML-COVID (1) BVA-100 (1) BVRS-GamVac (1) BVRS-GamVac-Combi (1) Bacillus Calmette-Guerin (BCG) (1) Back Side of the Moon (1) Background questionnaire (1) Bactek-R (1) Bacterial species isolated (1) Balance exercise (1) Bamlanivimab (1) Bardoxolone methyl (1) Bariatric procedures (1) Bariatric surgery (1) Baricitinib (janus kinase inhibitor) (1) Baricitinib 4 MG Oral Tablet (1) Baricitinib or Anakinra (1) Barrier box (1) Base therapy (1) Baseline and during hospitalization blood samples (1) Baseline blood sample (1) Baseline message (1) Basic Body Awareness Therapy (1) Basic Go NAPSACC (1) Beck Depression Inventory (BDI) (1) Bedside lung ultrasound (1) Behavioral Activation SSI (1) Behavioral Activation in real-life (1) Behavioral activation, evidence-based sleep strategies including sleep restriction, exposure-based strategies, promotion of physical activity and recuperating activities, psychoeducational material (1) Behavioral: OCAT (1) Behavioral: OCAT-sham (1) Behaviour Change Technique Intervention to Improve Quality of Life (1) Bemiparin sodium (1) Bemotrizinol (1) Benlysta (1) Berberine (1) Bereavement Virtual Support Group (1) Berzosertib (1) Best Available Therapy (1) Best Available Therapy (BAT) (1) Best Message + Augmented Message or Implementation Strategy (1) Best Message Alone (1) Best Standard of Care (1) Best Standard of Care + CARDIO (1) Best available care (1) Best available treatment (1) Best standard of care (1) Best supportive care" which includes antivirals /antibiotics/ hydroxychloroquine; oxygen therapy (1) Bevacizumab (1) Bimekizumab (1) BioMedomics COVID-19 IgM-IgG Rapid Test (1) Biocollection (1) Biocontainment Device For Aerosol Generating Procedures (Biobox) (1) Biological (1) Biological Sample Collection (1) Biological collection (patients co infected HIV Sras-CoV-2) (1) Biological collection with nasopharyngeal samples, saliva, blood, stool and urine (1) Biological sample and clinical data collection (1) Biological samples specific to research (1) Biological sampling (1) Biological test (1) Biological/Vaccine: Angiotensin peptide (1-7) derived plasma (1) Biological/Vaccine: Recombinant new coronavirus vaccine (CHO cell) low-dose group (1) Biological/Vaccine: Recombinant new coronavirus vaccine (CHO cells) high-dose group (1) Biological/Vaccine: Recombinant new coronavirus vaccine (CHO cells) placebo group (1) Biological: COVID-19 convalescent plasma (1) Biological: mRNA-1273: 100 mcg (1) Biological: mRNA-1273: 50 mcg (1) Biological: oral polio vaccine (1) Biomarker (TropT, Myoglobin, CK, CK-MB, LDH, D-dimer, CRP, PCT) (1) Biomarkers expression (1) Biosensor (1) Biosensors (1) Biospecimen collection (1) Bivalirudin Injection (1) Bleomycin and Vincristine (BV) (1) Blink and Masseter Inhibitory Reflex (1) Blood Collection (1) Blood D-dimer assay (1) Blood Draw (1) Blood Sample (1) Blood Test (1) Blood Transfusion (1) Blood analysis (1) Blood and derivatives. (1) Blood collection (1) Blood collection on admission and longitudinally (1) Blood collection on their first consultation and 10 to 14 days later (1) Blood donation from convalescent donor (1) Blood for anti-drug antibody (ADA) (1) Blood for pharmacokinetic samples (1) Blood for research purposes (1) Blood group determination (1) Blood plasma (1) Blood sample and data record (1) Blood sample collection (1) Blood sample for serological test (1) Blood sample for serology to measure past infection with SARS-CoV-2 (1) Blood sample for whole genome sequencing (1) Blood samples (collection of 5 mL of blood in a dry tube) (1) Blood samples collection (1) Blood test for IgG antibodies against SARS-CoV-2 (1) Blood tests sputum, nasal lavage and brushing (1) Bloodwork (1) Body Project (BP) (1) Bolus placebo (1) Bolus vitamin D3 (1) Bone Marrow Harvest (1) Bone conduction headphones (1) Bovine Lactoferrin (1) Bovine Lipid Extract Surfactant (1) Brain Health Education (BHE) (1) Brain MRI (1) Brain MRI scan (1) Brainstem Responses Assessment Sedation Score (BRASS) (1) Brazilian Green Propolis Extract (EPP-AF) (1) Breastfeeding (1) Breastfeeding Support Provided to Mothers Through WhatsApp Messaging Application (1) Breastfeeding self-efficacy (BSE) (1) Breath Biopsy (1) Breath Biopsy Analysis (1) Breath Test & Cheek Swab (1) Breath biopsy sampling using the ReCIVA Breath Sampler (1) Breath sample (1) Breath test (1) Breathing exercise, intensive spirometry use, supported cough, progressive mobilisation and ambulation (1) Brensocatib 10 mg (1) Brensocatib 25 mg (1) Brexanolone (1) Bridge therapy (1) Brief Behavioral Activation Treatment (1) Brief Behavioral Activation with Mental Imagery (1) Brief Psychiatric Rating Scale (1) Brief Skills for Safer Living (1) Brief cognitive behavioral therapy (1) Brief educational video (1) Brief informational infographic (1) Bromhexine 8 MG (1) Bromhexine Hydrochloride (1) Bromhexine Hydrochloride Tablets (1) Bromhexine Oral Tablet and/or hydroxychloroquine tablet (1) Bromhexine and Spironolactone (1) Broncho-Vaxom® (1) Bronchoalveolar Lavage (BAL) (1) Budesonide (1) Budesonide Nasal (1) Budesonide dry powder inhaler (1) Buprenorphine Sublingual Product (1) Burnout (1) Buspirone + PAP therapy (1) Butterfly (1) Butterfly iQ (1) C-reactive protein (1) C21 (1) C2Rx (1) C3+ Holter Monitor (1) CAG length <22 (1) CAG length >=22 (1) CALY-002 (1) CAM2038 (1) CAP-1002 Allogeneic Cardiosphere-Derived Cells (1) CAPABLE Transitions (1) CAStem (1) CBD Isolate (1) CBT-OSA (1) CCP (1) CCTP (1) CD24 Extracellular Domain-IgG1 Fc Domain Recombinant Fusion Protein CD24Fc (1) CD24Fc (1) CD55 (1) CDC training (1) CDX-0159 (1) CELLECTRA™ 2000 (1) CERC-002 (1) CETA Short Session (CSS) (1) CFZ533 (1) CGB-S-100 (1) CH505TF gp120 (1) CHAMindWell (1) CHEST CT SCAN (1) CHLORPROMAZINE (CPZ) (1) CHMI (1) CHX0.12+CPC0.05 oral rinse (PerioAidActive Control) (1) CICI - Feasibility trial study group (1) CIG Axial (1) CIG Tilted (1) CK0802 (1) CLBS119 (1) CLIA of IgG and IgM against SARS-Cov-2 (1) CME (active control) (1) CMR with T1 and T2 mapping (1) CNM-ZnAg (1) CNS magnetic resonance imaging (MRI) imaging (1) COM-COVID anonimous survey (1) COMPASS (1) CONTROL GROUP (1) CONVALESCENT PLASMA (1) COPAN swabbing and blood sample collection (1) COSH Self-help smoking cessation booklet (1) COVI-AMG (1) COVI-GUARD (1) COVI-VAC (1) COVICU (1) COVID 19 Convalescent Plasma (1) COVID 19 Diagnostic Test (1) COVID 19 Self-Questionnaire (1) COVID 19 diagnostic test by PCR (1) COVID 19 impact (1) COVID 19 serology (1) COVID WHELD (1) COVID Watch (1) COVID positive via testing (1) COVID visitation restrictions (1) COVID-19 Androgen Sensitivity Test (CoVAST) (1) COVID-19 Antibody testing (1) COVID-19 Antigen/Antibody Rapid Testing, mobile device image capture and telemedicine support (1) COVID-19 Breastfeeding Support (1) COVID-19 Convalescent Plasma (CCP) (1) COVID-19 Convalscent Plasma (1) COVID-19 Diagnostic and Assessment Tests (1) COVID-19 FACILITY (1) COVID-19 IgG / IgM rapid test (whole blood, serum, plasma) (1) COVID-19 IgG/IgM Rapid Test Cassette test (Healgen Scientific, Houston, Texas, USA) (1) COVID-19 PCR (1) COVID-19 PCR Swab (1) COVID-19 PCR and Serology (1) COVID-19 PCR and serology testing (1) COVID-19 Pandemic (1) COVID-19 Pneumonia (1) COVID-19 Specific T Cell derived exosomes (CSTC-Exo) (1) COVID-19 Swab (1) COVID-19 and Intensive Care (1) COVID-19 antibodies testing (1) COVID-19 antibody point of care test kit (1) COVID-19 barrier box (1) COVID-19 convalescent hyperimmune plasma (1) COVID-19 convalescent plasma (CCP) plus standard of care (SOC) (1) COVID-19 diagnostic PCR (1) COVID-19 diagnostic test (1) COVID-19 e-package: Psychological wellbeing for healthcare workers (1) COVID-19 experience surveys (1) COVID-19 exposure (1) COVID-19 infection (1) COVID-19 infection status (1) COVID-19 positive via testing (1) COVID-19 related health warning leaflet (1) COVID-19 standard care (1) COVID-19 survey (1) COVID-19 swap test PCR (1) COVID-19 test, polymerase chain reaction for SARS-CoV-2 (1) COVID-19 treatment (1) COVID-19 treatments (1) COVID-19+ observational (1) COVID-VIRO® test (1) COVID-surgRES questionaire (1) COVID19 (1) COVID19 convalescent plasma infusion (1) COVID19 vaccine (1) COVIDSeq Test (1) COVSurf Drug Delivery System (1) CPAP (1) CPAP treatment (1) CPI-006 (1) CRESTOR® (1) CRI management (1) CSL324 (1) CT of the chest (1) CT score (1) CT-P59/Placebo (1) CT-V (1) CT-imaging (1) CT-scan (1) CT-scan with minimal invasive autopsy (1) CTUS examination (1) CUROSURF® (poractant alfa) (1) CVL-865 High dose (1) CVL-865 low dose (1) CVnCoV (Dose level confirmed in Part 1) (1) CVnCoV 6 μg (1) CVnCoV 8 μg (1) CVnCoV 8 μg (4 μg double dose) (1) CVnCoV Vaccine (1) CYNK-001 (1) CYP 450 Substrates (1) CYP-001 (1) Cabotegravir 200 mg/mL (1) Cabotegravir 400 mg/mL (1) Cabotegravir Injectable Suspension (CAB LA) (1) Cabotegravir extended release suspension for injection (long-acting) (1) Cabotegravir sodium (Oral Lead In) (1) Caffeine 200 mg (1) Calcium Channel Blockers (1) Calm Meditation App (1) Cambridge Validated Viral Detection Method (1) Camidanlumab Tesirine (1) Camostat (1) Canakinumab 150 MG/ML [Ilaris] (1) Canakinumab Injection 300mg (1) Canakinumab Injection 600mg (1) Candesartan (1) Canine odor detection of Volatile Organic Compounds (1) Cannabidiol, pharmaceutically produced with < 5 ppm THC (1) Cannabidivarin (1) Cannabis, Medical (1) Capillary Collection & Testing (1) Capillary and salivary sampling (1) Caption AI (1) Cardiac Magnetic resonance imaging (1) Cardiac rehabilitation (1) Cardiac surgery (1) Cardiopulmonary resuscitation (1) Cardiorespiratory Exercise (1) Caring Contacts (1) Carotid Artery Reactivity Testing (1) Carrageenan nasal and throat spray (1) Carrimycin (1) Case fatality rate (1) Cash transfer (1) Ceftaroline (1) Ceftriaxone (1) Cell therapy protocol 1 (1) Cell therapy protocol 2 (1) Cellectra 2000 Electroporation (1) Cellular response (1) Cemdisiran (1) Cenicriviroc (1) Cenicriviroc (CVC) (1) Cenobamate (1) Centricyte 1000 (1) Centrum Adult (under 50) multivitamin (1) Ceralasertib (1) Cerebral compliance and hemodynamics monitoring (1) Cerebrospinal fluid sampling, meningeal and brain parenchyma biopsies (1) Certified cloth face mask plus preventive information (1) ChAd155-RG (1) ChAdOx1 nCoV-19 (Abs 260) (1) ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost (1) ChAdOx1 nCoV-19 (qPCR) (1) ChAdOx1 nCoV-19 0.5mL boost (1) ChAdOx1 nCoV-19 0.5mL prime plus boost (1) ChAdOx1 nCoV-19 full boost (1) ChAdOx1 nCoV-19 half boost (1) ChAdOx1 nCoV-19 single dose (1) ChAdOx1 nCoV-19 two dose (1) ChAdOx1-HPV (1) ChAdox1 n-CoV-19 (Abs 260) vaccine low dose (1) Change in knowledge, motivation, skills, resources (1) Change in preference to surgery under COVID-19 pandemic. (1) Chat-based instant messaging support (1) Chat-based support (1) Chest MRI (1) Chest computed tomography (CT) (1) Chest physiotherapy using a non-invasive oscillating device (1) Chinese Herbal Medicine (1) Chinese medicine treatment (1) Chiropractic care (more than one visit) (1) Chiropractic care (one visit) (1) Chlorhexidine Gluconate (1) Chloroquine Diphosphate (1) Chloroquine Phosphate Tablets (1) Chloroquine analog (GNS651) (1) Chloroquine diphosphate (1) Chlorpromazine (1) Choice of Assignment: Active Choice (1) Choice of Assignment: Enhanced Active Choice (1) Choice of Assignment: Opt-in (1) Choices and judgements (1) Chronic Hypersensitivity Pneumonitis Health Related Quality of Life Survey Instrument (1) ChulaCov19 mRNA vaccine (1) Ciclesonide (1) Ciclesonide Inhalation Aerosol (1) Ciclesonide Metered Dose Inhaler [Alvesco] (1) Cimetidine (1) Cisplatin (1) Clarithromycin (1) Clazakizumab 12.5 mg (1) Clazakizumab 25 mg (1) Clevudine (1) Clinical diagnosis of COVID-19 by a health care professional (1) Clinical examination (1) Clinical interview (1) Clinical, functional and radiological lung involvement evolution (1) Clinical, laboratory and imaging characteristics of pneumonia (1) Clinolipid (1) CloSYS mouthwash (1) Clofazimine (1) Clopidogrel 75mg (1) Closed-loop control of oxygen supplementation by O2matic (1) Cloth Face Mask (1) Clungene rapid test cassette (1) Co-created intervention (1) Co-formulated Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) (1) Co-mestring (co-coping) (1) CoYoT1 Care (1) Coala Heart Monitor (1) Cod liver oil (1) Cognitive Behavioural Group Therapy for Perinatal Anxiety (1) Cognitive Behavioural Therapy for Insomnia (1) Cognitive Behavioural Therapy with Mindfulness classes (1) Cognitive Stimulation (1) Cognitive Training (1) Cognitive and behavioral intervention. (1) Cognitive behavioral therapy (CBT) (1) Cognitive testing (1) Cohort (1) Colchicine 0.5 MG (1) Colchicine 1 MG Oral Tablet (1) Colchicine Pill (1) Colchicine plus symptomatic treatment (paracetamol) (1) ColdZyme® mouth spray (1) Coldamaris lozenges (1) Colgate Peroxyl mouthwash (1) Colgate Total mouthwash (1) Colgate periogard mouthwash (1) Collagen-Polyvinylpyrrolidone (1) Collection of Biological Samples (1) Collection of blood samples in order to create a biocollection (1) Collection of breath sample (1) Collection of odour samples (1) Collection of samples (1) Collection of tears and saliva. (1) Colorectal resection (1) Colorectal resections (1) Combination (1) Combination of Lopinavir /Ritonavir and Interferon beta-1b (1) Combination of oral polio vaccine and NA-831 (1) Combined ART/hydroxychloroquine (1) Combined use of a respiratory broad panel multiplex PCR and procalcitonin (1) Commercial membrane for Extracorporeal Blood Purification Therapy (EBPT) (1) Common Elements Toolbox (1) Common Elements Toolbox- Adult version (COMET-A) (1) Communication (1) Communication type (1) Community Referral as appropriate (1) Community based combination HIV prevention package (1) Community identity recruitment (1) Community interest message (1) Community-driven messages to promote COVID-19 testing (1) Comparable Placebo (1) Comparable Placebo of Oral Polio Vaccine and Placebo of drug (1) Comparable Placebo of drug (1) Comparator (1) Comparator full face mask 1 (1) Comparator full face mask 2 (1) Comparator full face mask 3 (1) Compassion focused intervention (1) Complement dosage (1) Complete thrombophilic profile testing by multiplex PCR (1) Completion of post telemedicine encounter survey (1) Completion of pre-pandemic survey (1) Completion of survey after peak of pandemic (1) Complex diagnostic panel (1) Comprehensive treatment (1) Computed Tomography (CT) (1) Computer Based Response Training Weight Loss Intervention (1) Computer task questionnaires (1) Computerized Talking Touchscreen (1) Conestat alfa (1) Conexiones (1) Confinement and Communication During the COVID-19 Pandemic (1) Conjunctival swab and nasopharyngeal swab (1) Connected devices measurements (1) Connor-Davidson Resilience Scale 10 items (CD-RISC 10) (1) Contain COVID Anxiety SSI (1) Continuation of ACEi/ARB (1) Continuation of ARB/ACEI (1) Continuation of anti-TNF treatment (1) Continuous Positive Airway Pressure (1) Continuous renal replacement therapy (1) Continuous vital sign monitoring - Isansys Patient Status Engine (1) Control (albumin 5%) (1) Control (standard clinical practice) (1) Control Blend (1) Control Group (pharmacotherapy and/or psychotherapy, n=10) (1) Control Intervention (1) Control Period (1) Control arm (1) Control for aerosol generating procedures (1) Control message (1) Control patients (1) Control swab (1) Control-EDI (1) ConvP (1) Convalescent Immune Plasma (1) Convalescent Plasma 1 Unit (1) Convalescent Plasma 2 Units (1) Convalescent Plasma as Therapy for Covid-19 patients (1) Convalescent Plasma from COVID-19 donors (1) Convalescent Plasma of patients with COVID-19 (1) Convalescent SARS COVID-19 plasma (1) Convalescent Serum (1) Convalescent anti-SARS-CoV-2 MBT Plasma (1) Convalescent anti-SARS-CoV-2 plasma (1) Convalescent plasma (CP) (1) Convalescent plasma transfusion (1) Convalesscent Plasma (1) Conventional N95 respirator (1) Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) (1) Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granules (1) Conventional oxygen therapy (1) Conventional physical therapy (1) Conventional therapy first (1) Cooking Training (1) Coping strategies video (1) Cord Tissue Mesenchymal Stromal Cells (1) Cordio App (1) Core Warming (1) Corn oil (placebo) (1) CoronaCideTM COVID-19 IgM/IgG Rapid Test and Premier Biotech COVID-19 IgM/IgG Rapid Test (1) CoronaVac (1) Coronary artery calcium score and cardiac computed tomographic angiography (1) Coronavirus Disease 2019 (1) Corticosteroid injection (1) Corticosteroids and Derivatives (1) Cosentyx (1) Cospherunate/Azythromycine (1) Cospherunate/Phytomedicine/Azythromycien (1) Cost-Benefit Frame (1) Counseling Services Alone (1) Counter Attitudinal Therapy (1) Couples' Intervention (1) CovX (1) Covax-19™ (1) Covid ICU containment measures (1) Covid-19 + patients (1) Covid-19 Antibody testing (IgG and IgM) (1) Covid-19 Rapid Test Kit (RAPG-COV-019) (1) Covid-19 Standard of Care (1) Covid-19 presto test (1) Covid-19 swab PCR test (1) Covid19 (1) Covidfree@home (1) Covigenix VAX-001 (1) Covigenix VAX-001 placebo (1) Crest Pro-Health Multi-Protection mouthwash (1) Crisis intervention therapy (1) Crisis management coaching (1) Crizanlizumab (1) Cross Sectional study using scientifically validated psychometric Scales (1) Cross-sectional observational study (1) Cross-sectional study examining the impact of information sources to obtain information about COVID-19 on depression and anxiety symptoms (1) Cross-sectional study investigating the association of NPIs with mental health (1) Curently used therapy for COVID-19 non-critical patients (1) Current care per UCLA treating physicians (1) Customized questionnaire (1) Cyclosporin A (1) CytoSorb (1) CytoSorb 300 mL device (1) CytoSorb-Therapy (1) Cytochrome P450 (CYP) Substrates (1) Cytokine Adsorption (1) Cytokines dosage (1) Cytokines measurement (1) D-1553 (1) D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester (1) D-dimer,CBC.ESR,CRP, (1) DAS181 COVID-19 (1) DAS181 OL (1) DASS-21 instrument (depression and anxiety) (1) DAXI for injection Dose HIGH DOSE (1) DAXI for injection dose LOW DOSE (1) DAXI for injection dose MEDIUM DOSE (1) DB-001 (1) DFV890 (1) DIG Axial (1) DIG Tilted (1) DPPFit (1) DUR-928 (1) DWJ1248 (1) Dabigatran etexilate (1) Dabigatran etexilate + BI 1323495 (1) Daclatasvir 120 mg (1) Daclatasvir 60 mg (1) Daily Coping Toolkit (1) Daily Monitoring (1) Daily Vitamin D3 (1) Daily placebo (1) Danoprevir+Ritonavir (1) Dapagliflozin 10 MG (1) Dapagliflozin 10 mg (1) Darunavir and Cobicistat (1) Darunavir/Cobicistat (1) Darvadstrocel (1) Data Collection: Clinical Care Assessments (1) Data collection and clinical testing of subjects (1) Data collection and rhinopharyngeal swab (1) Data collection from blood draw (1) Data collection from lumbar puncture (1) Data collection from medical files (1) Data collection up to 1 year (1) Data monitoring for 48h within the first 12 hours of admission for COVID-19 (1) Data registry (1) Data research, database analysis (1) Ddrops® products, 50,000 IU, Oral (1) Decidual Stromal Cells (DSC) (1) Decitabine (1) Deep Breathing training (1) Deep Venous Disease Diagnostic (1) Defibrotide (1) Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days (1) Defibrotide Injection (1) Degarelix (1) Delayed diagnostics Anyplex TMII RV16 Detection (1) Delivery of iStride™ device gait treatment using telemedicine (1) DeltaRex-G (1) Dental pulp mesenchymal stem cells (1) Depression, Anxiety and Stress Scale (1) Descartes 30 (1) Description of groups caracteristics (1) Desferal 500 MG Injection (1) Desidustat (1) Detection of anti-COVID-19 antibody level (1) Determination of physical activity, quality of life, stress levels of isolated people at home with the danger of coronavirus. (1) Device used to record voice for screening (1) Dexamethasone (high dose) (1) Dexamethasone 2 MG/ML (1) Dexamethasone and Hydroxychloroquine (1) Dexcom G6 (1) Dexmedetomidine Injectable Product (1) Dexmethylphenidate (1) DiaNose (1) Diabetes type 2 (1) Diagnosis of SARS-Cov2 by RT-PCR and : IgG, Ig M serologies in the amniotoc fluid, the blood cord and the placenta (1) Diagnostic Laboratory Biomarker Analysis (1) Diagnostic Test: serology test for COVID-19 (1) Diagnostic examination for venous thromboembolism (1) Diagnostic mammography (1) Diagnostic test Covid-19 (1) Diagnostic test for SARS-Cov2 for patients and health staff (1) Diagnostic test for detection of SARS-CoV-2 (1) Dialectical Behavioral Therapy (DBT) Skills (1) Dialyzable Leukocyte Extract (1) Diet tracking and survey (1) Dietary Intervention (1) Dietary Supplement containing resistant starch (1) Dietary advice (1) Dietary advice and advice on timing (1) Dietary counselling on Food Groups according to IYC Feeding practices, WHO (1) Dietary intake, body composition, lifestyle, and CVD risk factors (1) Dietary program (1) Differences in triage (1) Difficulties lived by disabled children's parents in the period of COVID-19 pandemic (1) Diffusing capacity of carbon monoxide (1) DigiVis visual acuity app (1) Digital Health Literacy Intervention (1) Digital Health Online Platform (1) Digital cardiac Counseling (1) Digital intervention (1) Digital oximeter monitoring (1) Digoxin (1) Digoxin 0.25 mg (1) Diphenhydramine (1) Dipyridamole (1) Dipyridamole 100 Milligram(mg) (1) Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care (1) Direct Antigen Tests for COVID-19 (1) Direct laryngoscope (1) Direct laryngoscopy (1) DirectCAM (1) Discontinuation of ACEi/ARB (1) Discontinuation of ARB/ACEI (1) Discontinuation of anti-TNF treatment (1) Discussion Board for Social Support +Basic Feedback (1) Discussion Board for Social Support+Personalized Feedback (1) Disease-modifying antirheumatic drugs (DMARDs) (1) Distilled water (1) Docetaxel (1) Dociparastat sodium (1) Doctella telehealth monitoring (1) Doctor Spot (1) Dolutegravir (1) Doppler Echo (1) Dornase Alfa (1) Dornase Alfa Inhalation Solution (1) Dose Finding Phase (MTD) (1) Dose of Tinzaparin or Dalteparin (1) Dose of tinzaparin or dalteparin (1) Double-Blind NT-I7 (1) Double-Blind Placebo (1) Double-Trunk Mask (1) Doxycyclin (1) Doxycycline Hcl (1) Drug COVID19-0001-USR (1) Drug Isotretinoin (13 cis retinoic acid ) capsules+standard treatment (1) Drug: GS-5734 - 1.00 mg/kg (1) Drug: GS-5734 - 2.00 mg/kg (1) Drug: Isotretinoin plus Tamoxifen (1) Drug: Isotretinoin(Aerosolized 13 cis retinoic acid) (1) Drug: Isotretinoin(Aerosolized 13 cis retinoic acid) plus Aerosolized Itraconazole (1) Drug: NA-831 (1) Drug: NA-831 - 0.10 mg/kg (1) Drug: NA-831 - 0.20 mg/kg (1) Drug: Standard treatment Standard treatment (1) Drugs and supportive care (1) Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) (1) Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg) (1) DuACT (1) Duo Venous Stent System (1) Duodenal biopsy (1) Dupilumab (SAR231893/REGN668) (1) Duplex ultrasound and Computed Tomography Angiography (1) During COVID-19 Pandemic (1) Durvalumab (1) Dutasteride (1) Duty Frame (1) DynamX Bioadaptor (1) Dynamic 3D bone motion capture (1) Dysphagia Handicap Index (DHI) (1) E-cigarette ad exposure (1) ECCO2R (1) ECG from handheld device (1) ECG-Holter (1) ECMO Implantation (1) EEG (1) EG-HPCP-03a (1) EG-HPCP-03a Placebo (1) EHR-based Clinician Jumpstart (1) EIT-Group (1) ELISA (1) ELISA and Rapid test to detect antibodies against COVID-19 (1) ELIZA, Extraction of nucleic acid ,Determination of viral genome by using PCR, Quantitative real-time PCR to assess viral load ,Immunohistochemistry analysis of EMB. (1) ELMO PROJECT AT COVID-19: PROOF OF CONCEPT AND USABILITY (1) ELMO PROJECT AT COVID-19: STUDY IN HUMANS (1) EMDR (1) EMPOWER (1) ENT exam (1) EP (1) EPDS (Edinburgh Postnatal Depression Scale) (1) EPIC risk score display (1) EQ001 (1) EQ001 Placebo (1) ESOGER (1) ESPRIMO (1) ESPRIT™ BTK Device (1) EU-approved RoActemra (1) EUROIMMUN assay (1) EXN407 (1) EarSats Pulse Oximeter Probe (1) Early Aggressive Therapy or Traditional Therapy (1) Early rehabilitation (1) EasyCov POC (1) Echo-Doppler (1) Economic benefit message (1) Economic freedom message (1) Edinburgh Postnatal Depression Scale (EDPS) (1) Edoxaban Tablets (1) Education (1) Education sessions (1) Educational Program on Air Pollution as a Health Risk Reduction Strategy (1) Educational meetings and visual prompts (1) Educational outreach (1) Effects of a 2-week DASH/SRD intervention vs. control diet on HFpEF functional cardiovascular risk factors (1) Effortful Control Camp (1) Eicosapentaenoic acid gastro-resistant capsules (1) Ejaculated semen sample (1) Elaborative Reminiscence (ER) (1) Elagolix (1) Elective Cancer Surgery (1) Electric pad for human external pain therapy (1) Electrical Impedance Tomography (EIT) (1) Electrical Impedance tomography (1) Electrocardiogram, telemetry, echocardiogram, laboratory values (1) Electrocardiogram, transthoracic echocardiography and clinico-biological parameters in routine care (1) Electroencephalogram with EKG lead (1) Electronic Health Record Review (1) Electronic Survey questionnaire (1) Electronic survey (1) Electrotherapy group (1) Elisa-test for IgM and IgG to SARS-CoV-2 (1) Emapalumab (1) Embarrassment message (1) Emergency Laparotomy (1) Emergency Ventilator Splitter (1) Emergency surgery (1) Emotion Regulation Training via Telehealth (1) Emotion- and Relationship-Focused Therapeutic Interview (1) Emotional Freedom Technique (1) Emotional Support Plan (1) Emphasis of Academic Researchers Involvement (1) Emphasis of Government Involvement (1) Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet (1) Emtricitabine/tenofovir (1) Emtricitabine/tenofovir disoproxil (1) Enbrel (1) End tidal breath sample (1) Endoscopic intervention (1) Endoscopic management according to standard of care (1) Endoscopic procedure (1) Endothelial damage and angiogenic biomarkers (1) Endothermal Ablation (ETA) (1) Enduring Happiness and Continued Self-Enhancement (ENHANCE) for COVID-19 (1) Enhanced Chronic Disease Self-management program (1) Enhanced Go NAPSACC (1) Enhanced Milieu Teaching (1) Enhanced hygiene measures (1) Enhanced linkage (1) Enhanced supervised fitness training (1) Enoxaparin 1 mg/kg (1) Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml (1) Enoxaparin Higher Dose (1) Enoxaparin Prefilled Syringe [Lovenox] (1) Enoxaparin Prophylactic Dose (1) Enoxaparin sodium (1) Enoxaparin/Lovenox Intermediate Dose (1) Enriched Survey Feedback (1) Ensifentrine Dose 1 (1) Environmental Decontamination (1) Environmental exposure and clinical features (1) Enzalutamide (1) Enzalutamide Pill (1) EpiVacCorona (EpiVacCorona vaccine based on peptide antigens for the prevention of COVID-19) (1) Equipment with smartwatch throughout hospital stay on the general ward (1) Ergoferon (1) Eritoran (1) Erlotinib (1) Escin (1) Esflurbiprofen hydrogel patch 165 mg (EFHP) (1) Esomeprazole 20mg (1) Esophageal temperature monitoring probe (1) Essential Oil Blend (1) Essential oils (1) Estradiol patch (1) Estrogen Therapy (1) Ethanol with Asprin (1) Etoposide (1) Etoposide (ET) (1) Evaluate HACOR score effectivity in this patients (1) Evaluation of changes in the diagnostic-therapeutic pathway for patients affected by pancreatic cancer (1) Evaluation of clinical, instrumental and laboratory diagnostics tests (1) Evaluation of the epidemiological characteristics of coronavirus infection (SARS-CoV-2) (1) Examinations for the research: (1) Examine the impact of COVID-19 during pregnancy (1) Exercise Group (1) Exercise Intervention (1) Exercise Testing and Training (1) Exercise Training Only (1) Exercise and Cognitive Training (1) Exercise booklet (1) Exercise brochure (1) Exercise capacity (1) Exercise physiology (1) Exercise training group (1) Experiences in Close Relationship Scale questionnaire (ECR-S) (1) Experimental 1 (1) Experimental 2 (1) Experimental Group (1) Experimental drug (1) Experimental: PIVOT with MI (1) Experimental: Questionnaire without precaution information (1) Experts consensus (1) Expiratory training device (1) Exposed to the novel coronavirus disease 2019 (1) Exposure (not intervention) - SARS-CoV-2 infection (1) Exposure Therapy (1) Exposure to the Dutch measures due to the Covid-19 pandemic. (1) Exposure to the SARS-CoV-2 (1) Exposure to the SARS-CoV-2 and its consequences (1) Exposure: Covid-19 infection (1) Expression of receptors and activating proteases (1) Extended Vision IOL (1) Extended sampling and procedures (1) Extra blood sample (1) Extracorporeal Membrane Oxygenation (1) Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter (1) Extracorporeal left hemicolectomy anastomosis (1) Extracorporeal membrane oxygenation (1) Extravascular Lung Water Index (1) Eye Movement Desensitisation and Reprocessing Recent traumatic Event Protocol (1) EyeQue Insight (1) F-652 (1) F-FMISO PET/CT Scan (1) FAVICOVIR 200 mg Film Tablet (1) FAVIR 200 MG FT (1) FAVIRA 200 MG Film Tablet (1) FBT (1) FBT+Variety (1) FEIBA (1) FFP (1) FFP2 (1) FITSTART+ PBI (1) FLOW intervention (1) FLT3 Ligand (CDX-301) (1) FMD (1) FNC dummy tablet+Standard of Care (1) FNC+Standard of Care (1) FSD201 (1) FT516 (1) FTC/TAF (1) FTX-6058 oral capsule(s) - Two dosing periods (1) FTX-6058 oral capsule(s) / Midazolam Syrup (1) FTX-6058/placebo oral capsule(s) (1) FX06 (1) Face mask sampling (1) Face-to-face medical visits (1) Face-to-face training (1) Facial fractures reduction or osteosynthesis (1) Facial mask (1) Family Nurture Intervention (FNI) (1) FamilyChildCare (provisional name of app) (1) Farmalarm (1) Favipiravir (3200 mg + 1200 mg) (1) Favipiravir (3200 mg + 1200 mg) combined with Azithromycin (1) Favipiravir (3200 mg + 1200 mg) combined with Hydroxychloroquine (1) Favipiravir (3600 mg + 1600 mg) (1) Favipiravir + Currently used therapy (1) Favipiravir + Standard of Care (1) Favipiravir Combined With Tocilizumab (1) Favipiravir and Hydroxychloroquine (1) Favipiravir plus Nitazoxanide (1) Favipiravir tablets (1) Fecal Microbiota Therapy (FMT) (1) Feeling Good Digital App (1) Fenofibrate (1) Fiberoptic Bronchoscopy (FOB) (1) Fibreoptic Endoscopic Evaluation of Swallowing (FEES) (1) Fibrin generation markers assays (1) Fidaxomicin (1) File Scanning (1) File scanning (1) Filgotinib (1) FilmArray PCR on respiratory samples (1) FilmArray Pneumonia (1) Filtration Test (1) Fingerstick (1) Fingolimod 0.5 mg (1) Fit test (1) Five-days oseltamivir (1) Fixed Anchoring Strategy (1) Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration (PH FDC SC) (1) Fixed-duration Hydrocortisone (1) Fixed-duration higher dose Hydrocortisone (1) Flexitouch Plus with Cellular Connectivity (FT-CC) (1) Flotetuzumab (1) Flow controlled ventilation (Evone-ventilator) (1) Flow cytometry (1) Flu shot (1) FluBlok (1) Flucelvax (1) Flurbiprofen 100 mg (1) Fluvirin (1) Fluvoxamine (1) Fluzone High Dose (1) Flywheel exercise (1) Focus Group Interviews (1) Focused/Targeted Message (1) Folfirinox (1) Folic Acid (1) Follow up calls (1) Follow-up at 14 days (1) Follow-up of patients with COVID-19 (1) Follow-up visit (1) Fondapariniux (1) Fondaparinux (1) Food Ads (1) Forced expiratory technique and induced sputum (1) Formulation without Active Drug (1) Fosfomycin disodium (1) Fostamatinib (1) Fourth Trimester Mobile Tool (1) Freestyle Libre 14 day CGM system (1) Fremanezumab-Vfrm (1) Froben 100 mg comprimidos revestidos (1) Fruquintinib (1) Full Spectrum CBD Oil (1) Functional MRI (1) Furosemide Injection Solution for subcutaneous administration (80 mg) (1) Furosemide Injection, USP (1) Fuzheng Huayu Tablet (1) GAD-7 (7-item Generalized Anxiety Disorder) (1) GAD-7 (General Anxiety Disorder) scale (1) GAD-7 General anxiety disorder scale (1) GAMUNEX-C (1) GC4419 (1) GC5131 (1) GENUS device (Active Settings) (1) GENUS device (Sham Settings) (1) GLA-SE adjuvant (1) GLPG3667 (1) GLS-1027 (1) GLS-1200 (1) GM-CSF (1) GNX102 (1) GO2 PEEP MOUTHPIECE (1) GPs reports of potential patient safety incidents, non-COVID-19 related (1) GRAd-COV2 (1) GSK2982772 (1) GSK3494245 (1) GSK3640254 200 mg (1) GSK3640254 Oral tablet (1) GSK3739937 (1) GSK3858279 (1) GSK3882347 (1) GSK3915393 Capsules (1) GSK3915393 Solution for Infusion (1) GSK3923868 (1) GX-19 (1) Gait Retraining (1) Galidesivir (1) Gam-COVID-Vac Lyo (1) Gamification (1) Ganovo+ritonavir+/-Interferon nebulization (1) Garadacimab, Factor XIIa Antagonist Monoclonal Antibody (1) Gargle/Mouthwash (1) Gas exchange measurement (1) Gas exchanges at different PEEP (1) Gastrointestinal endoscopy (1) General Communication Message (1) General Parenting Advice (1) General Public cohort (1) General health education (1) General health through IM Apps (1) Generalized Anxiety Disorder-7 (GAD 7) (1) Generalized Anxiety Disorder-7 (GAD-7) (1) Generic Response Training Control Intervention (1) Gepotidacin (1) Gimsilumab (1) Global Longitudinal Strain (1) Glucose tablets (1) Gluten (1) Glycaemic levels (1) Glycine (1) Goal Management Training (GMT) (1) Goal-Oriented Attentional Self-Regulation (GOALS) (1) Graded exercise test (1) Graded exposure therapy (1) Group 1 (1) Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed (1) Group 2: control group with enoxaparin 40mg/d (1) Group A HCQ (1) Group A: oropharygeal spray and immunostimulant (1) Group B Control (1) Group B: Placebo oropharyngeal spray + Active principle immunostimulant (1) Group C:Active principle oropharyngeal spray + Placebo taken PO (1) Group CBT (1) Group D:Placebo oropharyngeal spray + Placebo taken PO (1) Group Exercise Classes (1) Group Lifestyle Balance (1) Group Lifestyle Balance™ (1) Group Social ABCs (1) Group1 (1) Growth Hormone (1) Growth Mindset (1) Growth Mindset SSI (1) Guanfacine hydrochloride (SPD503) (1) Guided online support program (1) Guilt message (1) HADS (1) HADS questionnaire (1) HB-adMSC (1) HCQ & AZ (1) HCQ & AZ vs HCQ+SIR (1) HCQ+AZT (1) HFB30132A (1) HFNO (1) HIIT (intervention) (1) HIT-exercise (1) HLCM051 (1) HLX70 (1) HLX71 (1) HOME-CoV rule implementation (1) HOPE intervention (1) HPV vaccine, Gardasil 9 (1) HaRTC (1) Halo Oral Spray (1) Halo Placebo (1) Hand sanitizer and hand washing (1) Haptic stimulation (1) Health Care Worker Survey (1) Health Enhancement Program (1) Health Promotion Program with cartoon education for Children with Asthma (1) Health Questionnaire (1) Health supplements (1) Health warning leaflet (1) Health-related quality of life (1) Healthy Minds Program Foundations Training (1) Healthy Weight Program (HW) (1) Healthy lifestyle advise (1) Heated Vest (1) Helmet CPAP (1) Helmet Continuous Positive Airway Pressure (CPAP) (1) Helmet non-invasive ventilation (1) Helmet non-invasive ventilation (NIV) (1) Hemanext One (1) Hemodynamics changes at different PEEP (1) Hemopurifier (1) Heparin - Prophylactic dosage (1) Heparin - Therapeutic dosage (1) Heparin Infusion (1) Heparin SC (1) Heparin sodium (1) Hesperidin and Diosmin mixture (1) Hidroxicloroquina (1) Hidroxicloroquine (1) High Dose of KBP-COVID-19 (1) High Flow Nasal Oxygen (HFNO) (1) High Intensity Interval Training group (1) High Intensity Resistance (HIT-RT) and Endurance exercise (HIIT) (1) High Oxalate Diet (1) High PEEP with end inspiratory pause (1) High PEEP without end inspiratory pause (1) High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule (1) High dose Interferon-beta 1a (1) High dose radiation 100 cGy (1) High flow nasal cannula (1) High flow nasal cannula HFNC (1) High nitrite/NDMA meals (1) High-Concentration Essential Oil (1) High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma (1) High-Titer COVID-19 Convalescent Plasma (HT-CCP) (1) High-flow nasal cannula (1) High-intensity training (1) High-titer Convalescent COVID-19 Plasma (CCP1) (1) Higher-dose (1) Home Health Agency Care (1) Home Pulse Oximetry Monitoring (1) Home Sleep Apnea Testing or In-hospital Polysomnography (1) Home exercise program (1) Home sample collection of concerning mole with physician supervision (1) Home visiting (1) Home-based exercise (1) Home-use Test and Follow-up Questionnaire (1) Honey (1) Hormones (1) Hospital admission (1) Hospital anxiety and depression scale (1) Hospital: DD-CA (1) Hospital: Usual Care (UC) (1) Hospitalized Patients for COVID-19 Infection (1) Huaier Granule (1) Human Amniotic Fluid (1) Human Biological samples (1) Human Coach first, then Virtual Assistant (1) Human Cord Tissue Mesenchymal Stromal Cells (hCT-MSCs) (1) Human biological samples (1) Human milk donors (1) Human umbilical cord derived CD362 enriched MSCs (1) Human umbilical cord mesenchymal stem cells + best supportive care (1) Humanistic Care (1) Humor/Salience (1) Hydrogen Oxygen Generator with Nebulizer (1) Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03 (1) Hydroxychloroquin with Azithromycin (1) Hydroxychloroquine (placebo) (1) Hydroxychloroquine + Azithromycin (1) Hydroxychloroquine + Metabolic cofactor supplementation (1) Hydroxychloroquine + Sorbitol (1) Hydroxychloroquine + azithromycin + / - tocilizumab (1) Hydroxychloroquine + lopinavir/ritonavir (1) Hydroxychloroquine + placebo (1) Hydroxychloroquine , Sofosbuvir, daclatasvir (1) Hydroxychloroquine - Daily Dosing (1) Hydroxychloroquine - Daily dosing (1) Hydroxychloroquine Only Product in Oral Dose Form (1) Hydroxychloroquine Oral Product (1) Hydroxychloroquine Pill (1) Hydroxychloroquine Pre-Exposure Prophylaxis (1) Hydroxychloroquine SAR321068 (1) Hydroxychloroquine Sulfate (HCQ) (1) Hydroxychloroquine Sulfate + Azithromycin (1) Hydroxychloroquine Sulfate + Azythromycin (1) Hydroxychloroquine Sulfate 200 milligram (mg) Tab (1) Hydroxychloroquine Sulfate 400 mg twice a day (1) Hydroxychloroquine Sulfate 600 mg once a day (1) Hydroxychloroquine Sulfate 600 mg twice a day (1) Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets (1) Hydroxychloroquine and azithromycin treatment (1) Hydroxychloroquine and azithromycin treatment arm. (1) Hydroxychloroquine as post exposure prophylaxis (1) Hydroxychloroquine combined with Azithromycin (1) Hydroxychloroquine in combination of Azithromycin (1) Hydroxychloroquine plus Nitazoxanide (1) Hydroxychloroquine plus standard preventive measures (1) Hydroxychloroquine sulfate (1) Hydroxychloroquine sulfate &Azithromycin (1) Hydroxychloroquine, Azithromycin (1) Hydroxychloroquine, Clindamycin (1) Hydroxychloroquine, Clindamycin, Primaquine - high dose. (1) Hydroxychloroquine, Clindamycin, Primaquine - low dose. (1) Hydroxychloroquine, Doxycycline (1) Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) (1) Hydroxychloroquine/Azithromycine (1) Hydroxychloroquine/Chloroquine (1) Hydroxycloroquine and Azythromycine (1) Hyperbaric Chamber (1) Hyperbaric Oxygen (1) Hyperbaric Oxygen Therapy (1) Hyperbaric Oxygen Therapy (HBOT) (1) Hyperbaric oxygen (1) Hyperbaric oxygen therapy (1) Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device) (1) Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) (1) Hyperimmune plasma (1) Hyperpolarized Xenon-129 MRI of the lungs (1) Hypertension (1) Hypocaloric, low carbohydrate diet (1) Hypocaloric, moderate low fat diet (1) Hypofractionated intensity modulated radiotherapy (1) Hypothermia Via Cooling Machine- Arctic Sun 5000 (1) IC14 (1) IC14, a monoclonal antibody against CD14 (1) ICU Recovery + Physical Therapy (1) ID NOW vs. Accula (1) IER-R (posttraumatic stress) (1) IGV-001 Cell Immunotherapy (1) IIBR-100 high-dose (prime) (1) IIBR-100 low-dose (prime-boost) (1) IIBR-100 medium dose (prime) (1) IIBR-100, low dose (prime) (1) IIEF-5 questionnaire (1) IMM-101 (1) IN01 vaccine (1) INB03 (1) INC424 / Ruxolitinib (1) INM005 (1) INO-4700 (1) INOpulse (1) IO-202 Dose Escalation (1) IO-202 Dose Expansion (1) ION-827359 (1) IP-10 in CDS protocol (1) IPSS questionnaire (1) ISIS 721744 (1) IV Deployment Of cSVF In Sterile Normal Saline IV Solution (1) IV Dexamethasone (1) IVERMECTIN (IVER P®) arm will receive IVM 600 µg / kg once daily plus standard care. CONTROL arm will receive standard care. (1) IW-3718 (1) Ibudilast (1) Ibuprofen (1) Icatibant (1) Icosapent ethyl (IPE) (1) Identification by PCR of the SARS-COV-2 virus in samples taken from the fetus (1) IgG (1) IgG SARS CoV 2 antibodies (1) IgG SARS CoV2 (1) IgG antibodies immunoassay (1) IgG test (1) IgIV (1) IgM and IgG diagnostic kits to SARS-CoV-2 (1) Iloprost (1) Imaging (1) Imaging by thoracic scanner (1) Imaging of the lungs (1) Imatinib (1) Imatinib Mesylate (1) Imatinib tablets (1) Imetelstat (1) Immune response study (1) Immunfluorescence (1) Immunofluorescence Imaging (1) Immunofree tablets and Reginmune capsule (1) Immunoglobulin (1) Immunoglobulin of cured patients (1) Immunoglubulins (1) Immunological profiling (1) Immunosuppressive (1) Immunosuppressive Agents (1) Impact Event Score (1) Impact of COVID-19 questionnaire (1) Impact of Event Scale-Revised (1) Implementation Facilitation (IF) (1) In-Person Default (1) In-person in clinic follow-up visit (1) In-person instruction (1) Inactivated SARS CoV 2 vaccine (Vero cell). Wuhan (1) Inactivated SARS-CoV-2 vaccine (Vero cell) (1) Inactivated convalescent plasma (1) IncobotulinumtoxinA 100 UNT Injection [Xeomin] (1) Increasing Willingness and Uptake of COVID-19 Testing and Vaccination (1) Independent Living Program for Affordable Housing. (1) Individualised Ayurveda (1) Individualized-Chinese herbal medicine (1) Indomethacin (1) Infant Mental Health-Home Visiting (1) Infectious Disease and Cardiology Clinical Consultations (1) Inflammatory cytokines and chemokines profiles of patients with dexmedetomidine administration (1) Influenza vaccination at different time points (1) Information (1) Information and referral condition (1) Information leaflet (1) Information-only intervention (1) Informational videos and social media campaigns encouraging cancer screening. (1) Informed consent (1) Infrared Energy and Dietary Supplement (1) Infusion IV of Mesenchymal Stem cells (1) Infusion of 10 mg/kg Infliximab (1) Infusion of 5 mg/kg Infliximab (1) Infusion placebo (1) Inhaled Hypertonic ibuprofen (1) Inhaled ILOPROST (1) Inhaled Supplemental Oxygen (1) Inhaled beclomethasone (1) Inhaled budesonide (1) Inhaled budesonide and formoterol (1) Inhaled nitric oxide (iNO) (1) Inhaled nitric oxide gas (1) Inhaled placebo (1) Inhaled sedation (1) Injection and infusion of LV-SMENP-DC vaccine and antigen-specific CTLs (1) Injection into olfactory cleft (1) Inspiratory Muscle Training (1) Inspiratory training device (1) Insulin (1) Insulin icodec (1) Insulin regimen (1) Interactive workshops LiPAT intervention group (1) Interferon alfa (1) Interferon-Alpha2B (1) Interferon-Beta (1) Interferon-ß-1a (1) Interferon-β 1a (1) Interferon-β1a (1) Interleukin 6 (IL6) Antagonist (1) Interleukin 6 (IL6) Antagonist and corticosteroids (1) Interleukin assessment in semen (1) Interleukin-1 receptor antagonist (1) Interleukin-6 Gene-174C detection (1) Intermediate dose thromboprophylaxis (1) Intermittent prone positioning instructions (1) Internet Cognitive Behavioral Therapy plus CHAMindWell (1) Internet-based Cognitive Behavioral Therapy (1) Internet-based guided self-help based on CBT principles (1) Internet-based self-help (1) Internet-based self-help after 3 weeks (1) Internet-connected computer tablet (1) Internet-delivered cognitive behavior therapy (ICBT) for dysfunctional worry related to the Covid-19 pandemic (1) Interpersonal Therapy (1) Intervention App (1) Intervention for COVID-19 preventive protocols (1) Intervention for TECC Model (1) Intervention group CoronaCope (1) Intervention group_rehabilitation program (1) Intervention program (1) Intervention, TBN (1) Intervention-EDI and health coaching (1) Interview by psychologists (1) Interviews only. (1) Intra-articular corticosteroid injection (1) Intracorporeal left hemicolectomy anastomosis (1) Intralipid (1) Intramuscular Vaccine (1) Intranasal heparin sodium (porcine) (1) Intraosseous access (1) Intravenous Immune Globulin (1) Intravenous Immunoglobulin (1) Intravenous Infusions of Stem Cells (1) Intravenous access (1) Intravenous drug (1) Intravenous saline injection (Placebo) (1) Intravenous sedation (1) Intubation Box (1) Invasive mechanical ventilation (1) Invasive mechanical ventilation using the Unisabana-Herons Ventilator during 24 hours (1) Investigation of smell and taste disorders (1) Investigation of the prevalence of test positivity (1) Investigational Product - ViraCide (1) Ion Mobility Spectrometry (IMS) (1) Iota carrageenan nasal spray and Ivermectin oral drops (used as buccal drops) (1) Iota-Carrageenan (1) Isoflurane Inhalant Product (1) Isoniazid, Rifampicin, Pyrazinamide and Ethambutol (1) Isoprinosine (1) Isoquercetin (IQC-950AN) (1) Isotonic saline (1) Isotonic saline 0.9% (1) Isotretinoin Only Product in Oral Dose Form (1) Isotretinoin(Aerosolized 13 cis retinoic acid) +standard treatment (1) Itolizumab IV infusion (1) Ivermectin (IVM) (1) Ivermectin + Doxycycline (1) Ivermectin + Doxycycline + Placebo (1) Ivermectin + Placebo (1) Ivermectin 3mg Tab (1) Ivermectin 5 MG/ML oral solution, Aspirin 250 mg tablets (1) Ivermectin 5 MG/ML oral solution, Dexamethasone 4-mg injection, Enoxaparin injection. Inpatient treatment with mechanical ventilation in ICU. (1) Ivermectin 5 mg/mL oral solution, Dexamethasone 4-mg injection, Aspirin 250 mg tablets (1) Ivermectin 6 MG Oral Tablet (2 tablets) (1) Ivermectin Injectable Solution (1) Ivermectin Tablets (1) Ivermectin and Doxycyline (1) Ivermectin nasal (1) Ivermectin oral (1) Ivermectin plus Nitazoxanide (1) Ivermectin wth chloroquine (1) Ixazomib Placebo (1) JNJ-53718678 (1) JNJ-53718678 125 mg (1) JNJ-53718678 2.5 mg/kg (1) JNJ-53718678 250 mg (1) JNJ-53718678 3 mg/kg (1) JNJ-53718678 4.5 mg/kg (1) JNJ-66525433 (1) JS016 (anti-SARS-CoV-2 monoclonal antibody) (1) Janus Kinase Inhibitor (ruxolitinib) (1) KELEA Excellerated Water (1) KIR phenotype evaluation (1) KOH 10 % (1) Kaletra and beta interferon (1) Kamada Anti-SARS-CoV-2 (1) Kaplan Meier analysis (1) Ketamine (1) Ketamine Hydrochloride (1) Ketamine Injectable Product (1) Ketogenic diet with phytoextracts (1) Ketotifen 1 MG (1) Kevzara sc (1) Knowledge, Attitude, Practice, Awareness, Preference (1) Kundalini Yoga and Anxiety Reduction Training (1) L-Citrulline (1) L-citrulline (1) LAMP (1) LAU-7b (1) LB1148 (1) LDAEP (1) LEAF-4L6715 (1) LIIT.CI ACT (1) LIIT.CI CFT (1) LIVE (1) LMWH (1) LNP023 (1) LRX712 (1) LSALT peptide (1) LY3127804 (1) LY3473329 (1) LYMPHOCYTE MONOCYTE RATIO (1) Lab workup (on admission and regularly during follow up). (1) Laboratory Analyses (1) Laboratory Biomarker Analysis (1) Laboratory test positive for SARS-CoV-2 virus (1) Laboratory tests (1) Lactobaciltus rhamnosus GG (1) Lactobaciltus rhamnosus GG Placebo (1) Lactoferrin (1) Lactoferrin (Apolactoferrin) (1) Lambda 180 mcg S.C (1) Lasix® (1) Late dexamethazone (1) Late-Dexamethasone (1) Lateral Position (left and right lateral decubitus) (1) Lazertinib (1) Leadership Training (1) Learning running subcuticular sutures on the Gamified Educational Network (1) Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5. (1) Lenoxin® (1) Let It Out (LIO)-C (1) Leukapheresis (1) Levamisole (1) Levamisole Pill + Budesonide+Formoterol inhaler (1) Levamisole and Isoprinosine (1) Levamisole and isoprinosine (1) Levilimab (1) Lianhua Qingwen (1) Liberase Enzyme (Roche) (1) Licensed seasonal influenza vaccine (1) Licorice extract (1) Lidocaine 2% (1) Life2000® Ventilator (1) LifeSignals Biosensor 1AX* (1) Lifelight® Data Collect Blood Pressure Group (1) Lifelight® Data Collect Oxygen Saturation Group (1) Lifestyle App (1) Lifestyle change promotion program (1) Lifestyle intervention (1) Lifestyle medicine (1) Lift (1) Limbix Spark (1) Linagliptin (1) Linagliptin 5 MG (1) Linagliptin tablet (1) Liquid Alpha1-Proteinase Inhibitor (Human) (1) Liquid Model (1) Liquid Peanut Extract (1) Listerine Mouthwash Product (1) Live Long Walk Strong rehabilitation program (1) Liver function tests ,serum ferritin and PCR for COVID-19 . (1) Liver injury (1) Local Bone Autograft (1) Local standard of care (1) Lock-down and social distancing (1) Lopinavir (1) Lopinavir / Ritonavir plus Ribavirin (1) Lopinavir / ritonavir tablets combined with Xiyanping injection (1) Lopinavir / ritonavir, alpha-interferon nebulization,Abidor Hydrochloride (1) Lopinavir 200 MG / Ritonavir 50 MG [Kaletra] (1) Lopinavir 200Mg/Ritonavir 50Mg FT Reference (1) Lopinavir 200Mg/Ritonavir 50Mg FT Test (1) Lopinavir 200Mg/Ritonavir 50Mg Tab (1) Lopinavir and Ritonavir Tablets (1) Lopinavir and ritonavir (1) Lopinavir-Ritonavir Drug Combination (1) Lopinavir/ Ritonavir (1) Lopinavir/ Ritonavir Oral Tablet (1) Lopinavir/ Ritonavir Placebo (1) Lopinavir/Ritonavir + hydoxychloroquine (1) Lopinavir/Ritonavir 200 MG-50 MG Oral Tablet (1) Lopinavir/Ritonavir 400 mg/100 mg (1) Lopinavir/ritonavir treatment (1) Losmapimod oral tablet (1) Loss Frame and Fear Appeals (1) Lovenox 40 MG in 0.4 mL Prefilled Syringe (1) Low Dose (10 mg) Control (1) Low Dose Radiation Therapy (LD-RT) (1) Low Dose of KBP-COVID-19 (1) Low Molecular Weight Heparin (1) Low Oxalate Diet (1) Low PEEP - FiO2 high (1) Low PEEP - FiO2 low (1) Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule (1) Low dose CT (1) Low dose Interferon-beta 1a (1) Low dose Low molecular weight heparin or Placebo (1) Low dose Radiotherapy (1) Low dose radiation 35 cGy (1) Low dose radiation therapy (1) Low dose whole lung radiotherapy for older patients with COVID-19 pneumonitis (1) Low fat "standard care" control breakfast (1) Low flow ECMO driving by CVVH machine (1) Low nitrite/NDMA meals (1) Low or upper respiratory tract sample (1) Low-Carb High-Fat breakfast (1) Low-Carbohydrate Diet (1) Low-Concentration Essential Oil (1) Low-Intensity Psychosocial Interventions through Telemental health (1) Low-dose Chest CT (1) Low-dose radiotherapy (1) Lower-dose prophylactic anticoagulation (1) Lucinactant (1) Lumbar Puncture (1) Lung CT (1) Lung CT scan analysis in COVID-19 patients (1) Lung Cancer Screening Decision Tool (1) Lung Function Test (1) Lung Function tests (1) Lung Low Dose Radiation (1) Lung Ultrasound (1) Lung impedance technique (1) Lung ultrasound use in patients hospitalized with COVID (1) LungFit™ (1) M201-A Injection (1) MAGEC Spine Rod (1) MANAGEMENT OF COVID-19 (1) MAS825 (1) MBCT/MBSR (1) MCC IMS (1) MCN (Methylene blue, vitamin C, N-acetyl cysteine) (1) MEDI7219 (1) MELT-100 (1) MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg (1) MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg (1) MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg (1) MFS (1) MGA012 (1) MGC018 (1) MK-5475 (1) MLS Laser (1) MMR vaccine (1) MPT0B640 (1) MR or M-M-R II ® vaccine (1) MR-Pro-ADM (1) MRI (1) MRI (heart, brain, lungs, kidney) (1) MRI scans (1) MRx-4DP0004 (1) MSB11456 (1) MSC Treatment (1) MSCT (1) MSCs (1) MSCs-derived exosomes (1) MSTT1041A (1) MSTT1041A-matched Placebo (1) MULTI-LINK 8 LL stent (1) MULTI-LINK 8 SV stent (1) MULTI-LINK 8 stent (1) MVA-BN-Filo (1) MVA-HPV (1) MVA-MERS-S_DF1 - High Dose (1) MVA-MERS-S_DF1 - Low Dose (1) MVA-SARS-2-S vaccinations (days 0 & 28) (1) MVC-COV1901 (1) MW33 injection (1) MW33 injection placebo (1) Machine Learning/AI Algorithm (1) Machine learning model (1) Macrolide administered for 3-5 days (1) Macrolide administered for up to 14 days (1) Magnetic Resonance Imaging (1) Magnetic Resonance Imaging (MRI) (1) Magnetic Resonance Spectroscopy (MRS). (1) Maintenance or reduction of immunosuppression (1) MakAir (1) Male Sexual Health Questionnaire (MSHQ) (1) Maltodextrin (1) Mannitol (1) Manremyc (1) Maraviroc (1) Maraviroc + Currently used therapy (1) Maraviroc 300 mg (1) Maraviroc+Favipiravir+CT (1) Marker Therapeutics D2000 Cartridge (D2000) for use with the Spectra Optia® Apheresis System (Optia SPD Protocol) (1) Masimo, LidCO (1) Masked Saline Placebo (1) Maslach Burnout Inventory (MBI) (1) Massive parallel sequencing of host genome (1) Matched Placebo Hydroxychloroquine (1) Matched placebo (1) Matching Placebo (1) Maternal stress (1) Maximal effort test (1) McGrath videolaryngoscope (1) Measles-Mumps-Rubella Vaccine (1) Mechanical Trombectomy (1) Mechanical ventilation with the automated BVM compressor (1) Med-South Weight Loss Intervention (1) Media Intervention (1) Medical Mask (1) Medical Ozone procedure (1) Medical Record Review - Inpatient Treatment (1) Medical records-based recommendation (1) Medical/surgical mask (1) Medically Tailored Meals (1) Medication Review (1) Meditation Therapy (1) Meditation and Anxiety Reduction Training (1) Meditation app usage (1) Mediterranean diet, no caloric restriction (1) Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule (1) Medtronic Interstim II Model 3058 Neurostimulator (1) Mefloquine (1) Mefloquine + azithromycin + / - tocilizumab (1) Melatonin 2mg (1) Melatonin intravenous (1) Melphalan (1) MenACWY (1) MenACWY boost (1) MenACWY single dose (1) MenACWY two dose (1) MenACWY vaccine (1) MenCare+/Bandebereho fathers'/couples' group education (1) Mental Health questionnaire (1) Mental imagery (1) Mepolizumab 100 MG [Nucala] (1) Merimepodib (1) Mesenchymal Stem Cell (1) Mesenchymal Stem Cells derived from Wharton Jelly of Umbilical cords (1) Mesenchymal Stromal Cells infusion (1) Mesenchymal Stromal Stem Cells - KI-MSC-PL-205 (1) Mesenchymal cells (1) Mesenchymal stem cell (1) Mesenchymal stem cell therapy (1) Mesenchymal stem cells (1) Mesenchymal stromal cell-based therapy (1) Message directing subjects to information on COVID-19 vaccine safety and efficacy (1) Messaging (1) MetaNeb® System (1) Metacognitive therapy and work-focused interventions (1) MetfoLiquid GeriaSan® (1) Metformin XR (1) Methotrexate-LDE phase 1 (1) Methotrexate-LDE phase 2 (1) MethylPREDNISolone 80 Mg/mL Injectable Suspension (1) Methylene Blue 5 MG/ML (1) Methylene-Blue Photodisinfection (1) Methylprednisolone Injectable Product (1) Methylprednisolone Injection (1) Metoprolol 100 mg (1) Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) (1) Microcrystalline Cellulose, NF (1) Micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) oral suspension (1) Microscopy of defined brain regions on autopsy specimens (1) Midazolam 5 mg (2.5 mL) (1) Midazolam injection (1) Middle-dose (1) Milk of magnesia (1) MindRhythm Harmony (1) Mindful Self-Compassion (1) Mindfullness based cognitive program (1) Mindfulness + Compassion Intervention (MC) (1) Mindfulness Alone (MO) Intervention (1) Mindfulness Based Cognitive Therapy for Resilience During COVID-19 plus CHAMindWell (1) Mindfulness Meditation (1) Mindfulness Rounds (1) Mindfulness Training (1) Mindfulness based intervention (1) Mindfulness exercises (1) Mindfulness intervention (1) Mindfulness program (1) Mindfulness session(s) (1) Mindfulness training (1) Mindfulness training (MT) Connect (1) Mindfulness-Based Cognitive Therapy (1) Mindfulness-based "STOP touching your face" practice (1) Minimal Attention Control Intervention (1) MinnRAP Peer Support Program (1) Minocycline (1) Mobile Enhanced Prevention Support (1) Mobile Mental Health App - 1 (1) Mobile Mental Health App - 10 (1) Mobile Mental Health App - 2 (1) Mobile Mental Health App - 3 (1) Mobile Mental Health App - 4 (1) Mobile Mental Health App - 5 (1) Mobile Mental Health App - 6 (1) Mobile Mental Health App - 7 (1) Mobile Mental Health App - 8 (1) Mobile Mental Health App - 9 (1) Model Building (1) Model validation (1) Moderate Intensity Aerobic Exercises (1) Moderate-intensity continuous training (1) Modified Bai He Gu Jin Tang (1) Modified Rankin score (1) Molgramostim nebuliser solution (1) Mometasone furoate (1) Monalizumab (1) Monitoring Visit - Baseline (1) Monitoring Visit - Week 4 (1) Monitoring Visit - Week 8 (1) Monitoring for aggravation (1) Monitoring physiological data with the Hexoskin smart shirt (1) Monodose RS01 (1) Montelukast 10 mg (1) Montelukast 10mg (1) Montelukast Oral Granules (1) Montmorrillonite (1) Morning Bright Light Therapy (1) Mother Provides MOM (1) Motivational social support from nurse (1) Motivational social support from nurse with additional support from significant other (1) Moxibustion plus Cupping (1) Moxifloxacin or Levofloxacin (1) Mucodentol (1) Multi Modal Balance Training (1) Multi-tasking Training (1) MultiStem (1) Multicapillary column coupled ion mobility spectrometry (1) Multifrequency Bioimpedance Spectroscopy (1) Multimodal intervention strategy (1) Multiple Doses of Anti-SARS-CoV-2 convalescent plasma (1) Multivitamin (1) Mupirocin (1) Muscle Relaxation Therapy (1) Muscle ultrasound (1) MuscleSound Ultrasound (1) Museum virtual guided tours (1) Music Therapy (1) MySafeRx Inspire Flex (1) MySafeRx Inspire Plus (1) N terminal pro B type natriuretic peptide (NTproBNP), D-Dimer, and serum Tropinin - I (1) N-803 (1) N-95 Respirator (1) N-acetyl cysteine (1) N95 Respirator (1) N95 respirator (1) NA (no intervention) (1) NA-831 (1) NA-831 and Atazanavir (1) NA-831and Dexamethasone (1) NAD+ (1) NBT-NM108 (1) NETosis markers (1) NG Biotech (1) NG test (1) NGM621 (1) NHANES smell and taste tests (1) NICU Acquires MOM (1) NIO® (Intraosseous access) (1) NIVOLUMAB (1) NK Cells (1) NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells (1) NK-1R antagonist (1) NO gas (1) NO intervention planned due to the observational study design - only a diagnostic testing (1) NO intervention planned due to the observational study design only a diagnostic testing (1) NO-Immunosuppressive (1) NOX66 (1) NP-120 (Ifenprodil) (1) NT-I7 (1) NaCl (1) NaCl 0.9% (1) NaCl Solution (1) Nafamostat Mesylate (1) Naltrexone 380 MG (1) Narrative Exposure Therapy (1) Narrative Writing (1) Nasal Brushing (1) Nasal Dexamethasone (1) Nasal Irrigation (1) Nasal Spray (1) Nasal Swab (1) Nasal lavage (1) Naso pharyngeal swab (1) NasoVAX (1) Nasopharyngeal (NP) swab (1) Nasopharyngeal Swab (1) Nasopharyngeal and throat/oropharyngeal swabs analyses by RT-PCR and ddPCR (1) Nasopharyngeal swab and main laboratory (1) Nasopharyngeal, oropharyngeal, or saliva swab (1) Natural Honey (1) Nebulised heparin (1) Nebulised unfractionated heparin (UFH) (1) Nebulized Furosemide (1) Nebulized Platelet Lysate (1) Nebulized Saline (1) Nebulized Sterile Saline (1) Nebulized administration of RLF-100 or Placebo (1) Negative COVID Test Result - Hypothetical Scenario (1) Negative Ion Generator (1) Nemolizumab (1) NestaCell® (1) Neural network diagnosis algorithm (1) Neurocognitive assessment (1) Neuromuscular Electrical Stimulation (1) Neuromuscular evaluation (1) Neutral Aspheric Monofocal IOL (1) Neutral writing control (1) Neutralizing antibodies (1) New QIAstat-Dx fully automatic multiple PCR detection platform (1) New screening strategy (1) Newsfeed function (1) Next generation Sequencing (NGS) analysis (1) Niclosamide suspension (1) Nicotinamide riboside (1) Nicotine 7 mg/ 24h Transdermal Patch - 24 Hour (1) Nicotine patch (1) Nigella sativa (1) Nil intervention (1) Nintedanib (1) Nintedanib 150 MG (1) Nintedanib 150 MG [Ofev] (1) Nitazoxanide 500 MG (1) Nitazoxanide 500Mg Oral Tablet (1) Nitazoxanide Tablets (1) Nitazoxanide and atazanavir/ritonavir (1) Nitazoxanide with ivermectin (1) Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation (1) Nitric Oxide delivered via LungFit™ system (1) Nitric Oxide lozenges, 30 mg (1) Nitric Oxide-Continuous and Sessions (1) Nitric Oxide-Releasing Drug (1) Nitric Oxide-Sessions (1) Nivolumab Injection (1) No Intervention - Observational Study (1) No Messaging (1) No Personal protective equipment (PPE) (1) No Racial Inequality Highlighting (1) No Treatment (1) No intervention (survey study for medical doctors). (1) No intervention - exposure is to COVID-19 (1) No intervention - quality of life measure (1) No intervention / Compare the difference in respiratory rate between H0 and H12 of the initiation of morphine between the control and interventional groups (1) No intervention / Evaluation of the ferritin and glycosylated ferritin by standard approved serological tests (1) No intervention on patients (1) No intervention, observational (1) No intervention, this is an observational study that uses validated questionnaires and qualitative interviews.. (1) No interventions (1) No interventions planned (1) No interverntion (1) No research related technology based social interactions (1) No special intervention (1) Non Extracorporeal Membrane Oxygenation (1) Non Intervention (1) Non applicable (1) Non interventional study (1) Non invasive visual acuity testing (1) Non-ACEI/ARB (1) Non-Anchoring Strategy Control (1) Non-Heated Vest (1) Non-Interventional (1) Non-Mindfulness intervention (1) Non-contact ECG (1) Non-contact MCE system (1) Non-convalescent Plasma (control plasma) (1) Non-convalescent fresh frozen plasma (Standard plasma) (1) Non-enhanced CT scan of the chest (1) Non-food Ads (1) Non-hospitalization procedures (1) Non-interventional (1) Non-interventional study (1) Non-invasive brainstem stimulation (1) Non-invasive cardiac imaging (1) Non-invasive red LLLT treatment to chest of patient. (1) Non-invasive ventilatory support (1) None - NA (1) Norketotifen (1) Normal (9%) Saline (1) Normal Saline 0.9% (1) Normal Saline Infusion + standard of care (1) Normal Saline intranasal (1) Normal saline 0.9% (1) Normal saline solution (NSS), Placebo - Phase 1 (1) Normal saline solution (NSS), Placebo - Phase 2 (1) Normal saline solution (NSS), Placebo, Day 189 - Phase 2 (1) Normal saline solution (NSS), Placebo, Day 21 - Phase 1 (1) Normal saline solution (NSS), Placebo, Day 21 - Phase 2 (1) Norovirus Bivalent (GI.1 / GII.4) Vaccine（high） (1) Norovirus Bivalent (GI.1 / GII.4) Vaccine（low） (1) Norovirus Bivalent (GI.1 / GII.4) Vaccine（middle） (1) Not bravery message (1) Novel laser inferometry test for CORONA virus (1) Ntombi Vimbela! intervention (1) NuSepin® 0.1 mg (1) NuSepin® 0.2 mg (1) Nudge (1) Nursing care to reduce anxiety, fear and loneliness (1) Nutrition (1) Nutrition Consult and Protein Supplementation (1) Nutrition support (1) Nutritional assessment (1) Nutritional counseling (1) Nutritional education (1) Nutritional support system (NSS) (1) Nuvastatic (1) NİCaS (1) OLO-1 Medical Molecular Sieve Oxygen Generator (1) ONC201 (1) OP-101 (1) OPT101 (1) OT Guided Cognitive Interventions (1) Obesity (1) Observation of Virtual Actions (1) Observation of Virtual Actions (step 4) (1) Observation of behavior and COVID-19 infection will be conducted. (1) Observation of patients with known, suspected, or at risk for COVID-19 infection (1) Observation only (1) Observational (registry) (1) Observational Study (1) Observational cohort study on the natural history of hospitalized SARS-COV-2 patients. (1) Observational measurement of biometric data. No change to health care provided. (1) Observational only (1) Observational study only (1) Obtainment of nasopharyngeal, oropharyngeal, buccal, nasal and saliva samples (1) Obvio-19 app (1) Occupational health workers (1) Octagam (1) Octagam 10% (1) Odd/Even birth year intervention groups (1) Office FU (1) Olaparib Oral Tablet [Lynparza] (1) Olfaction testing (1) Olfactometry (1) Olfactory retraining (1) Omega 3/Nigella Sativa Oil (1) Omega 3/Nigella Sativa Oil/Anise seed capsule (1) Omega 3/Nigella Sativa Oil/Deglycyrrhizinated Licorice (1) Omega 3/Nigella Sativa Oil/Indian Costus (1) Omega 3/Nigella Sativa Oil/Quinine pills (1) Omega-3 Fatty Acid Supplement (1) Omeprazole 20mg (1) Omeprazole 40 mg (1) Omnibiotic AAD (1) On-Line Survey (1) On-line exercise and education (1) On-site exercise and education (1) OnabotulinumtoxinA 100 UNT [Botox] (1) One COVID-19 vaccine candidate (TMV-083) administration - High dose (1) Online 1-Day Cognitive Behavioural Therapy (CBT)-Based Workshop (1) Online Intervention Mental Health COVID-19 (1) Online Questionnaire (1) Online Questionnaires (1) Online Survey about Dietary and Lifestyle Habits (1) Online bibliotherapy programme (1) Online cognitive behavioral therapy (CBT) (1) Online educational intervention to enhance cultural competance (1) Online educational intervention to reduce ageism (1) Online instruction (1) Online questionnaire and interviews (1) Online support Group (1) Online training (1) Only Standard Treatment (1) Ophtamesone (1) Ophthalmologic exam (1) Opt-in Recruitment Email (1) Opt-out Recruitment Email (1) Optical Coherence Tomography (OCT) (1) Optical coherence tomography angiography (1) Optimal-Massive Intervention (1) Optimized Management of Covid-19 Positive Kidney Transplant Recipients: Single Center Experience from the Middle East (1) Optional blood completion (1) Optional questionnaire completion (1) Oral (1) Oral 25-Hydroxyvitamin D3 (1) Oral administration of Colchicine plus Herbal Phenolic Monoterpene Fractions (1) Oral fluid swab (1) Oral supplement enriched in antioxidants (1) Oral-B Mouth Sore mouthwash (1) Oropharyngeal Swab (1) Orthopaedic Surgical Procedures (1) Oseltamivir 75mg (1) Osimertinib (1) Others(No intervention) (1) Otilimab (1) Outpatient MRI (1) Oxaloacetate Medical Food/Dietary Supplement (1) Oxidative Stress ELISA Kit (1) Oxycodone and Midazolam (1) Oxycodone, Paroxetine, and Quetiapine (1) Oxygen Hood (1) Oxygen Therapy (1) Oxygen gas (1) Oxygen supply (1) Oxygen-ozone therapy, probiotic supplementation and Standard of care (1) Oxytocin (1) Ozanimod (1) Ozone auto-hemotherapy (1) P2Et (Caesalpinia spinosa extract) (1) PACE-Life (1) PARTNER-MH (1) PCL COV05 - COVID 19 Ag Rapid FIA test (Rapid Antigen Test) (1) PCR for COVID-19 (1) PCR, lung ultrasound (1) PD-1 blocking antibody+standard treatment (1) PDS-08 (1) PEAR-008 (1) PEEP trial (1) PEP flute (1) PET-CT of 18F-FDG (1) PET/CT Scan (1) PF-06650833 (1) PF-06882961 20 mg (1) PF-06882961 20MG (1) PF-06939999 dose escalation (1) PF-06939999 in combination with docetaxel (1) PF-06939999 monotherapy (1) PF-07104091 + palbociclib (1) PF-07104091 + palbociclib + letrozole (1) PF-07104091 monotherapy (1) PF-07304814 (1) PH-combination therapy (1) PH-monotherapy (1) PH94B (1) PHQ-9 (9-item Patient Health Questionnaire) (1) PHQ-9 (Patient Health Questionnaire) Depression Scale (1) PHQ-9 Depression Scale (1) PHR160 Spray (1) PLACEBO GROUP (1) PLN-74809 (1) POOL LAMP (1) POOL RT-PCR (1) PP-MI Intervention (1) PRO questionnaire (1) PRO-SERO-COV (1) PROStep Dashboard (clinicians) (1) PROTECTIVE VENTILATION (1) PRV-015 (1) PSC-04 (1) PSG (1) PSQI (1) PSS (Perceived Stress Scale) (1) PT-PCR test for SARS-CoV-2 (1) PT-Pal (1) PT-X and IMT (1) PTC299 (1) PTSD (1) PWV (1) Pacebo: Calcium citrate (1) Pacel BPC (1) Pacel FDPC (1) Pacing + mindfulness (1) Package Quantity (cigarillos) (1) Paclitaxel (PTX) (1) Pacritinib (1) Palliative care assessment (1) Pamrevlumab (1) Pandemic control measures (1) Paraclinical examination (1) Paramedic Coaching (1) Parent Education (1) Parents and Infants Engaged (1) Part 1 - TL-895 (1) Part 2 - Placebo (1) Part 2 - TL-895 (1) Partially HLA-matched SARS-CoVSTs (1) Partner-assisted intervention (1) Passed infection of SARS-CoV-2 (1) Passive Microwave Radiometry (1) Patch, Nicotine (1) Patch, Placebo (1) Pathogen-specific aAPC (1) Pathways for Parents after Incarceration (1) Patient Characteristics (1) Patient Education (1) Patient Health Questionnaire (PHQ-9) (1) Patient Health Questionnaire-9 (PHQ-9) (1) Patient Navigation Program (1) Patient Status Engine (1) Patient management suffering of coronavirus infection (1) Patient sampling (1) Patient with SAR-CoV-2 infection (1) Patient-centred advice on Telephone Consultation in TB Patients: (1) Patient-only intervention (1) Patients admitted to Intensive Care Unit with SARS-CoV2 (1) Patients received standard of care treatment during hospitalization (1) Patients with the treatment agains COVID19 (1) Pectin (1) Peer Education on Exercise for Recovery (1) Peer Resilience Champion (1) Peginterferon Lambda-1a (1) Peginterferon lambda alfa-1a subcutaneous injection (1) Pegylated Interferon-α2b (1) Pegylated interferon lambda (1) Pembrolizumab (MK-3475) (1) Pemziviptadil (PB1046) (1) Pen injector (1) Penn Microbiome Therapy - 001 (1) Penn Microbiome Therapy - 002 (1) Penn Microbiome Therapy - 003 (1) Percutaneous Coronary Revascularization for STEMI (1) Percutaneous Transluminal Angioplasty (PTA) Device (1) Performance of WHEELS-I in promoting DASH/SRD adoption (1) Performance of the test antigenic and test RT-PCR (1) Performing Virtual Actions (1) Performing of lung ultrasound (1) Performing routine care (clinical and paraclinical tests) (1) Peripheral Blood (1) Peripheral blood sampling (1) Peripheral venous ultrasound (1) Personal Exercise Intervention (1) Personal Protective Testing Booth (1) Personal behaviours (1) Personal freedom message (1) Personal identity recruitment (1) Personal protective equipment (1) Personal protective equipment (PPE) (1) Personal protective equipment from biological hazard (1) Personalized Anchoring Strategy (1) Personalized ambulatory training (1) Personalized health education (1) Phentermine 37.5 Mg (1) Philips Lumify Ultrasound System (1) Phlebotomy (1) Phone Administration of Questionnaires (1) Phone interviews (1) Phone-call screening and management by a medical student/general practitioner tandem (1) Phosphate buffered saline Placebo (1) Photobiomodulation (1) Phsyiotherapy (1) Physical Activities & Activity Booklets (1) Physical Activity (1) Physical Exam (1) Physical Exercises (1) Physical Therapy (1) Physical Therapy Exercise (1) Physical exercise (1) Physician Survey (1) Physiological saline solution (1) Physiological serum (1) Physiology (1) Physiotherapy - Manual Therapy (1) Piclidenoson (1) Pilot a rapid SARS-CoV-2 testing strategy (1) Pioglitazone (1) Pioglitazone 30 mg (1) Pioglitazone 45 mg (1) Pipeline™ Flex Embolization Device with Shield Technology™ (1) Piperacillin-tazobactam (1) Piperacillin/tazobactam (1) Pirfenidone (1) Placebo (0.9% normal saline) (1) Placebo (1 tablet daily during 60 days) + Personal Protective Equipment (PPE) (1) Placebo (Methylcellulose) capsule (1) Placebo (PB0) (1) Placebo (PBO) (1) Placebo (Plasma-Lyte 148) (1) Placebo (carrier control) (1) Placebo (for Zonisamide) (1) Placebo (human albumin 1%) (1) Placebo (sodium chloride bufus, solvent for the preparation of dosage forms for injection 0.9%) (1) Placebo - Phase I (1) Placebo - Starch Powder Soft gels (1) Placebo 0.10 mg + 1.00 mg/kg (1) Placebo 0.20 mg + 2.00 mg/kg (1) Placebo 0.9% NaCl solution (1) Placebo 250 cc 24 hours continuous infusion for 15 days (1) Placebo Atazanavir (1) Placebo Control (1) Placebo Daclatasvir 120 (1) Placebo Daclatasvir 60 mg (1) Placebo EC-18 (1) Placebo Glycerin SLIT (1) Placebo Group (1) Placebo Hydroxychloroquine (1) Placebo Infusion (1) Placebo LSF (1) Placebo Nitazoxanide (1) Placebo Oil (1) Placebo PBMT/sMF (1) Placebo Ribavirin (1) Placebo Saline (1) Placebo Sofosbuvir/Daclatasvir 120 (1) Placebo Sofusbuvir + Daclatasvir 60 mg (1) Placebo Starch (1) Placebo Subcutaneous Solution (1) Placebo Tablet (1) Placebo Vaccine (1) Placebo comparator: DW-NI (1) Placebo comparator: DW-NS (1) Placebo control (non-behavioral infographic) (1) Placebo for Azithromycin (1) Placebo for Hydroxychloroquine (1) Placebo for Risankizumab IV (1) Placebo for Risankizumab SC (1) Placebo for Upadacitinib (1) Placebo injection (1) Placebo intravenous (1) Placebo matching to gepotidacin (1) Placebo mouthwash (water) (1) Placebo nebuliser solution (1) Placebo of FX06 (1) Placebo of Hydroxychloroquine (1) Placebo of LPV/r Tablets (1) Placebo of NICOTINE Transdermal patch (1) Placebo of excipient(s) will be administered (1) Placebo on a 0- and 14-day schedule (1) Placebo oral (1) Placebo oral capsule; From August 2020 'no additional treatment' (1) Placebo pMDI (1) Placebo patch (1) Placebo plus standard preventive measures (1) Placebo solution (1) Placebo tablet (1) Placebo to Match RDV (1) Placebo videos (1) Placebo- 0.10 mg/kg (1) Placebo- 0.20 mg/kg (1) Placebo- 1.00 mg/kg (1) Placebo- 2.00 mg/kg (1) Placebo-LDE phase 2 (1) Placebo/Aluminum Adjuvant of Inactivated SARS-CoV-2 vaccine (1) Placebo/Control (1) Placebo: Emtricitabine/tenofovir disoproxil Placebo (1) Placebo: Hydroxychloroquine (1) Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells (1) Plant Polyphenol (1) Plaquenil 200Mg Tablet (1) Plasma Donation (1) Plasma IgG levels (1) Plasma exchange (1) Plasma expansion with Ringer's Acetate (1) Plasma from COVID-19 convalescent patient (1) Plasma from a volunteer donor (1) Platelet count, platelet, mean platelet volume and platelet distribution Width in COVID-19 (1) Pleth variability index (1) Plethysmography & DLCO (1) Plitidepsin 1.5 mg/day (1) Plitidepsin 2.0 mg/day (1) Plitidepsin 2.5 mg/day (1) Pneumococcal 13 - valent conjugate vaccine (1) Pneumococcal Conjugate Vaccine - formulation 1 (1) Pneumococcal Conjugate Vaccine - formulation 2 (1) Pneumococcal Conjugate Vaccine - formulation 3 (1) Pneumococcal Vaccine Polyvalent (1) Pneumococcal vaccine (1) Point of care ultrasound (1) Point-of-Care Ultrasonography (POCUS) (1) Point-of-care test for SARS-CoV-2 (1) Poly I: Poly C12U (Rintatolimod) (1) Polymorphism of the HSD3B1 (1) Polyoxidonium (1) Positive COVID Test Result - Hypothetical Scenario (1) Positive Emotion Skills Course (1) Positive Minds Strong Bodies Enhanced (1) Positive Peer Journaling (PPJ) (1) Positive feedback (1) Post COVID-19 Functional Satus Scale (1) Post Traumatic Stress Disorder questionnaire (PTSD-8) (1) Post-intensive Care unit syndrome (1) Post-mortem tissue collection (1) Postpartum women under investigation for Coronavirus or diagnosed with COVID-19 (1) Postural Positioning (1) Povidine iodine nasal swabs (1) Povidone-Iodine (PVP-I) (1) Povidone-Iodine 0.4% NI (1) Povidone-Iodine 0.5% (1) Povidone-Iodine 0.5% NI (1) Povidone-Iodine 0.5% NS (1) Povidone-Iodine 0.6% NI (1) Povidone-Iodine 0.6% NS (1) Povidone-Iodine 2% (1) Povidone-Iodine Solution 1.25% w/w [0.125% available iodine] USP (1) Povidone-iodine (1) Powered Air purifying respirator (1) PrEP (1) Prasugrel (1) Prasugrel Hydrochloride 10 MG Oral Tablet (1) Pravastatin (1) Pravastatin 40 mg (1) Pre-operative breast magnetic resonance imaging (1) Prediction Market (1) Predictive factors for clinical response in patients with COVID-19. (1) Predictors adverse evolution (1) Predictors of health care provide (1) Prednisolone (1) Prednisolone 5 mg (1) Prednisone tablet (1) Pregnant women under investigation for Coronavirus or diagnosed with COVID-19 (1) Preload meals that are solid or texture modified and are fortified with protein or not fortified with protein (1) Premier Biotech COVID-19 IgG/IgM Rapid test Cassette (1) Presatovir placebo (1) Prescription Opioid Management App (1) Presence of specific anti-SARS-CoV-2 antibodies (1) Present Tense Talk (PTT) (1) PreserVision AREDS formulation gel tabs (1) PressureWire X (1) Prevalence of COVID-19 (1) Prevenar 7 and Prevenar 13 (1) Preventive information (1) Previfenon® (1) Primary care (1) Primary care professionals reports of potential patient safety incidents, non-COVID-19 related (1) PrimePro (1) Pro BNP , Vitamin D (1) Probiorinse (1) Probiotic and LC-PUFA (1) Probiotics (1) Problem Management Plus (1) Problem-solving and relationship improvement intervention. (1) Progesterone 100 MG (1) Prognostic score (1) Progressive Exercise Training (1) Progressive cycling exercise test to exhaustion (1) Project ECHO (1) Project Health (1) Prolastin (1) Prolectin-M; a (1-6)-alpha-D-Mannopyranose class (1) Prolonged Exposure (PE) (1) Prolonged Proned Positioning (1) Promotion of flour (1) Prone (1) Prone Positioning (PP) (1) Prone decubitus (1) Prone position ventilation (1) Prone positioning (PP) (1) Prophylactic/Intermediate Dose Enoxaparin (1) Propofol (1) Propranolol Hydrochloride (1) Proprietary extract of Nerium oleander (1) Prosocial acts (1) Prospective Chart Review (1) Prospective oberservational registry (1) Prospective observation (1) Prospective study across two time-points examining the impact of viral mitigation protocols on mental health (1) Prospective study with two measurement points investigating the impact of viral mitigation protocols on parental burnout (1) Protocolised mechanical ventilation strategy (1) Proton Therapy (1) Prototype BMS-986165 (1) Prototype swab (1) Provision of flour (1) Proxalutamide (1) Psilocybin (1) Psychiatric counseling (1) Psycho-Social Questionnaire (1) Psycho-education (1) Psychoeducation and Safety (1) Psychoeducational intervention (1) Psychological and Behaviour Change Support (1) Psychological and physical rehabilitation based humanistic care (1) Psychological stress and adaptation at work score (PSAS) (1) Psychological treatment (1) Psychosocial stimulation and healthy eating education (1) Public Health England Gold Standard (1) Public space exposure (1) Pulmonary Function Tests (PFT) (1) Pulmonary Physiotherapy Techniques (1) Pulmonary Rehabilitation (1) Pulmonary Vascular Permeability Index (1) Pulmonary and Motor Rehabilitation (1) Pulmonary function test (1) Pulmonary function testing (1) Pulmonary function tests (1) Pulmonary ultrasound (1) Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) (1) Pulse CO-Oximetry Hemoglobin measurement transcutaneous (1) Pulse Oximeter (1) Pulse oximeter (1) Pulse oximetry (1) Pyridostigmine Bromide (1) Pyronaridine-Artesunate (1) Pyronaridine-artesunate (1) Q-NRG Metobolic Cart Device (1) Q16 testing (1) QFR (1) QMF149 (1) QazCovid-in® - COVID-19 inactivated vaccine (1) QuadraMune(TM) (1) Quadrivalent RIV with 2018-2019 NH H3 strain (1) Quadrivalent RIV with 2018-2019 NH H3 strain and adjuvant (1) Quadrivalent RIV with H3 strain 1 (1) Quadrivalent RIV with H3 strain 1 and adjuvant (1) Quadrivalent RIV with H3 strain 2 (1) Quadrivalent RIV with H3 strain 2 and adjuvant (1) Qualitative Interview (1) Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) (1) Quality Improvement (1) Quality of Life (1) Quality of life assessment (1) Quality of life promotion (1) Quantitative IgG Test (1) Quantitative analysis of SARS-CoV-2 antibodies (1) Quantitative analysis of anti-SARS-CoV-2-antibodies (1) Quantitative and qualitative assessments of mental health (1) Quantra System (1) Quercetin (1) Quercetin Phytosome (1) Quercetin Prophylaxis (1) Quercetin Treatment (1) Questionaire (1) Questionnaire and interview (1) Questionnaire by phone call (1) Questionnaire collection (1) Questionnaire for evaluation of confinement on deviant sexual fantasies (1) Questionnaire forms (1) Questionnaire including validated tools such as Patient Health Questionnaire (PHQ-9), the 7-item Generalised Anxiety Disorder (GAD- 7), the 7-item insomnia severity index (1) Questionnaire with precaution information (1) Questionnaire, phone call (1) Questionnaire, same tools as before, with inclusion of PCL5 questionnaire too. (1) Questionnaire-based observational study (1) Questionnaires for specific phobia (1) Questionnaires on psychological quality of life (1) Questionnaires, spirometry (1) Questionnary (1) Quetiapine (1) Quick Defense (1) Quidel Sofia SARS Antigen FIA (1) Quinquina-Stevia/Azythromycin (1) RAAS inhibitor [continued standard of care] (1) RAPA-501-Allo off-the-shelf Therapy of COVID-19 (1) RAPID-3 (1) RBA-2 (1) RBT-9 (90 mg) (1) RDV (1) RECHARGE (1) REGN10933 + REGN10987 (1) REGN10933+REGN10987 (1) REGN3048 (1) REGN3051 (1) RESP301, a Nitric Oxide generating solution (1) RIA-device (Remote Investigation and Assessment) (1) RISE (1) RO6953958 (1) RO7234292 (RG6042) (1) RPH-104 80 mg (1) RS blend (1) RSV LID/ΔM2-2/1030s (1) RSV Mobile Application (1) RSV vaccine formulation 1 (1) RSV vaccine formulation 2 (1) RSVPreF3 formulation 2 (1) RSVPreF3 formulation 3 (1) RT PCR SARS-CoV-2 (1) RT-PCR Covid-19 (1) RT-PCR SARS-Cov2 (1) RT-PCR and antibody testing (1) RT-qPCR test (1) RTLS data (1) RUC-4 Compound (1) RUTI® vaccine (1) Rabies Vaccine (1) Racial Inequality Highlighted (1) Racial/Ethnic Frame (1) Radiological Detection (1) Radspherin (1) Raman analysis of saliva, characterization of the Raman database and building of the classification model (1) Ramelteon 8mg (1) Ramipril 2.5 MG Oral Capsule (1) Random Donor Plasma (1) Randomized to Delayed Cord Clamping at birth (1) Randomized to Umbilical Cord Milking at birth (1) Ranitidine (1) Rapamycin (1) Rapid Diagnostic Test vs PCR (1) Rapid Onsite COVID-19 Detection (1) Rapid detection test (1) Rapid diagnostics using Anyplex TMII RV16 Detection (1) Rapid molecular test (1) Rarefaction (1) Rayaldee 30Mcg Extended-Release (ER) Capsule (1) Razuprotafib (1) Razuprotafib Subcutaneous Solution (1) ReWalk 6.0 (1) Reading a Book (1) Real cTBS to the vmPFC (1) Real iTBS to the dlPFC (1) Real-time chat-based support through IM Apps (1) Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) (1) Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) plus Aerosolized 13 cis retinoic acid (1) Recombinant Human Interferon α2b Spray (1) Recombinant Interferon Alfa-2b (1) Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) -placebo (1) Recombinant S protein SARS vaccine (1) Recombinant human alkaline phosphatase (1) Recombinant human angiotensin-converting enzyme 2 (rhACE2) (1) Recombinant human interferon α1β (1) Recombinant human plasma gelsolin (Rhu-pGSN) (1) Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) (1) Recombinase aided amplification (RAA) assay (1) Reconsolidation of Traumatic Memories (RTM) (1) Reduced Dose Bevacizumab (1) Reference Treatment- BMS-986165-01 (1) Reference: Favipiravir 200 mg (Avigan) (1) Referral card (1) Regadenoson (1) Regadenoson myocardial perfusion imaging stress test (1) Registery Data Collection (1) Regular Inpatient Medical Care (1) Regular messages through Instant Messaging (IM) (1) Rehabilitation (1) Rehabilitation exercise protocol (1) Reinforcement learning message delivery (1) Relamorelin 10 μg (1) Relation between frailty and clinical outcomes in elderly patients with COVID-19. (1) Relaxation (1) Relaxation Breathing (1) Relaxation Therapy (1) Remain COVID Free SSI (1) Remdesivir (RDV) (1) Remdesivir-HU (1) Remimazolam (1) Remote Caregiver Training (1) Remote Cognitive Behavioral Therapy for Insomnia (1) Remote Intensive Group Behavioral Treatment (IGBT) (1) Remote Photoplethysmography (rPPG) vital sign acquisition (1) Remote Problem Management Plus (1) Remote consultation (1) Remote controlled exercise (1) Remote pulmonary rehabilitation (1) Removal of dead space filter (1) Renin-angiotensin system inhibitors (1) Repeat SARS-CoV-2 IgG antibodies at 45-65 days (1) Replenish protein group (1) Reporting of anosmia, ageusia and other clinical symptoms (1) Repository Corticotropin Injection (1) ResCure™ (1) Resilience Program (1) Resolute Onyx (1) Respiratory Exercise Training (1) Respiratory Mechanics (1) Respiratory Training (1) Respiratory filter in-line placed with the standard mouthpiece (1) Respiratory mechanics measurement (1) Respiratory physiotherapy (1) Respiratory rehabilitation (1) Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening (1) Response and Attention Training (1) Responsive training with no video feedback (1) Responsive training with video feedback (1) Resveratrol (1) Resveratrol Placebo (1) Retrospective case-control analysis (1) Retrospective data collection (1) Reverse transcription polymerase chain reaction (1) Reverse-transcription polymerase chain reaction (RT-PCR) (1) RhACE2 APN01 (1) Riboflavin Placebo (1) Rifaximin Novel Formulation (1) Rilematovir (1) Rilematovir X mg/kg (1) Rilpivirine Injectable Suspension (RPV LA) (1) Rilpivirine extended release suspension for injection (long-acting) (1) Ringer solution (1) Rintatolimod (1) Risankizumab IV (1) Risankizumab SC (1) Risk factors (1) Risk of MERS infection (1) Risk reduction (1) Risperidone (1) Ritonavir (1) Ritonavir+Oseltamivir (1) Ritonavir/lopinavir (1) Rivaroxaban 2.5 MG (1) Rivaroxaban 2.5 Mg Oral Tablet (1) Rivaroxaban placebo tablets (1) RoActemra iv (1) RoActemra sc (1) Robot Assisted Percutaneous Cardiovascular Intervention (1) Robotic therapy (1) Rosuvastatin (Inhibitor arm) (1) Rosuvastatin (Placebo arm) (1) Rosuvastatin + BAY1817080 (1) Rosuvastatin + BI 1323495 (1) Routine Oral Care and Analgesia (1) Routine care (no SARS-CoVSTs) (1) Routine standard of care (1) Rt PCR (1) Ruconest (1) Ruxolitinib 5 MG (1) Ruxolitinib administration (1) Ruxolitinib plus simvastatin (1) SAB-301 (1) SAMBA II (Diagnostic for the Real World) (1) SAR443122 (1) SARILUMAB (1) SARS-CoV (1) SARS-CoV 2 RNA PCR Semen (1) SARS-CoV 2 RNA PCR Urine (1) SARS-CoV-2 Ab (1) SARS-CoV-2 Antibody Analysis (1) SARS-CoV-2 IgG (1) SARS-CoV-2 IgG Antibody Testing Kit (1) SARS-CoV-2 PCR (1) SARS-CoV-2 S1/S2 IgG (1) SARS-CoV-2 Specific T Cells (1) SARS-CoV-2 and/or MIS-C Exposure (1) SARS-CoV-2 antibody based IVIG therapy (1) SARS-CoV-2 antibody immunoassays (1) SARS-CoV-2 antibody test (1) SARS-CoV-2 antibody testing (1) SARS-CoV-2 convalescent plasma treatment (1) SARS-CoV-2 non-immune Plasma (1) SARS-CoV-2 plasma (1) SARS-CoV-2 questionnaire survey (1) SARS-CoV-2 rS - Phase 1 (1) SARS-CoV-2 rS/Matrix M1-Adjuvant (1) SARS-CoV-2 rS/Matrix-M Adjuvant - Day 189 - Phase 2 (1) SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 1 (1) SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 1 (1) SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 2 (1) SARS-CoV-2 rS/Matrix-M Adjuvant, Days 0 and 21 - Phase 2 (1) SARS-CoV-2 rapid diagnostic test (COVID-PRESTO® IgM/IgG, AAZ, Boulogne-Billancourt, France) (1) SARS-CoV-2 research in nasopharyngeal swab, sperm and serologics (1) SARS-CoV-2 serological assessment (IgG) (1) SARS-CoV-2 testing on the Eppendorf Thermal Cycler PCR system using self-collected saliva as the specimen (1) SARS-CoV-2 vaccine (inactivated) (1) SARS-CoV-2 vaccine formulation 1 with adjuvant 1 (1) SARS-CoV-2 vaccine formulation 1 with adjuvant 2 (1) SARS-CoV-2 vaccine formulation 2 with adjuvant 1 (1) SARS-CoV-2 vaccine formulation 2 with adjuvant 2 (1) SARS-CoV-2 vaccine formulation 2 without adjuvant (1) SARS-CoV-2 viral composition (1) SARS-CoV-2-test (1) SARS-CoV2 Autoantibody detection (1) SARS-CoV2 Infection (1) SARS-CoV2 serum antibody testing (1) SARS-Cov-2 infection (1) SARSCoV2 Convalescent Plasma (1) SBI-101 (1) SBRT (1) SCB-2019 (1) SCB-2019 with AS03 adjuvant (1) SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant (1) SCD (1) SCH Intervention (1) SCTA01 (1) SECRET questionnaire (1) SELF-BREATHE (1) SF12, EQ-5D-5L and work status standardized quantitative assessments (1) SHG (1) SHINGRIX (Zoster Vaccine REcombinant, Adjuvanted) (1) SKILLZ-Girl Enhanced football curriculum (1) SLEDD with a L-MOD (1) SMBI digital app (1) SMS message support (1) SMS messages (1) SMS-based support (1) SNDX-6352 (1) SNG001 (1) SNO (1) SOC (1) SOC + IFX-1 (1) SOC + Intravenous Famotidine (1) SOC plus 15mg/kg EB05 IV (1) SOC plus Placebo IV (1) SOC: Temozolomide (1) SPEQ (Specific Psychotic Experiences Questionnaire) - Paranoia and Grandiosity Subscales (1) SPIN-CHAT Program (1) SPIRIT-in person (1) SPIRIT-remote (1) SSE educational intervention (1) ST-2427 (1) STC-19 score (1) STI-5656 (1) STP + COVID-19 Convalescent Plasma (CP) (1) STP + Standard Plasma (SP) (1) Saline Control (1) Saline Nasal Irrigation (1) Saline containing 1% Human serum albumin（solution without UC-MSCs） (1) Saline nasal and throat spray (1) Saline oral/nasal rinse (1) Saline placebo (1) Saline with Baby Shampoo Nasal Irrigation (1) Saline-sodium citrate (SSC) buffer (1) Saliva (1) Saliva Assay (1) Saliva and NPS test (1) Saliva sample (1) Saliva specimen (1) Saliva test kit (1) Saliva-based testing (1) Sample (1) Sample Collection/Performance Evaluation (A) (1) Sample Collection/Performance Evaluation (B) (1) Sampling (EDTA blood, pharyngeal and nose swabs, bronchoalveolar lavage ,urine) (1) Sampling of SARS-CoV-2 RNA from nasopharyngeal swab specimen or saliva collected via Salivette Cortisol (1) Sampling of tissue (1) Sampling salivary (1) Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA] (1) Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA] (1) Sarilumab Prefilled Syringe (1) Sarilumab SAR153191 (1) Sars-Cov-2 serology (1) Sars-Cov2 serology (1) Satisfaction evaluation (1) Savicell's ImmunoBiopsy™ (1) Saxagliptin (1) Scanning Chest X-rays and performing AI algorithms on images (1) Schirmer Test I (1) Screening breast magnetic resonance imaging (1) Screening digital breast tomosynthesis (1) Screening digital mammography (1) Screening test for covid ( RT PCR and CT Chest) (1) Secukinumab 150 MG/ML Subcutaneous Solution [COSENTYX] (1) Sedentary behaviour (1) Self Study (1) Self-Compassion for Chronic Pain Virtual Group Treatment Program (1) Self-Help Therapy (1) Self-System Therapy (1) Self-acupressure (1) Self-administered questionnaires (1) Self-awareness Control (1) Self-focused acts (1) Self-guided exercises (1) Self-help booklet (1) Self-help guided by a lay provider (1) Self-interest message (1) Self-management booklet (SWitCh: Stay well during COVID-19) (1) Self-prone position recommendation (1) Self-questionnary (1) Selitrectinib (BAY2731954) (1) Semen Qualitative Analysis (1) Semi-directive interview (1) Semi-structured telephone questionnaire (1) Senicapoc (1) Sensbiosys (1) Sensitivity Intervention (1) Sensitivity and Couples' Intervention (1) SensiumVitals wearable sensor (1) Sequencing (1) Seraph®-100 Microbind® Affinity Blood Filter (1) Serelogy testing, RT PCR (1) Serial seroconversion measurements in hospital employees during the COVID-19 pandemic (1) Serologic SARS-CoV-2 screening (1) Serologic assays for antibodies to SARS-CoV-2 (1) Serologic immunoassays to SARS-CoV-2 antibodies (1) Serologic testing (1) Serological Assay or IgG for SARS-CoV-2 (1) Serological analyses to be lead on a pre-existing biobank (1) Serological screening for IgG and IgM antibodies against COVID-19 (1) Serological test for COVID-19. (1) Serological testing (1) Serological tests will be applied on patients blood sampling (1) Serology (1) Serology Test (1) Serology for Covid-19 (1) Serology test follow-up (1) Seroprevalence of SARS-CoV-2 infection in patients with HIV infection (1) Serum SARs COV 2 IGg screening in health care workers (1) Serum test (1) Serum tube collection (1) Serum zinc, vitamin d vitamin b12 levels . (1) Setanaxib (1) Severe Acute Respiratory Syndrome CoronaVirus 2 detection (1) Sevoflurane inhalant product (1) Sham Attention Training (1) Sham Device Treatment (1) Sham Stimulation (1) Sham cTBS to the vmPFC (1) Sham iTBS to the dlPFC (1) Sham intervention (1) Sham irradiation (1) Shared Decision Making (1) Shock-dependent hydrocortisone (1) Sildenafil (1) Sildenafil citrate tablets (1) Silymarin (1) Simha Kriya (1) Simple chest tomography (1) Simplified Geriatric Evaluation (1) Simulation Airway Coaching (1) Simulation Intervention (1) Simulation of Repurposed Drugs for COVID-19 (1) Simultaneous EGD and colonoscopy (1) Singing for Lung Health group attendance (1) Single Session Problem-Solving Intervention (1) Single fraction whole lung radiotherapy (1) Single high dose vitamin D (1) Sirolimus 1 MG/ML (1) Sirukumab (1) Sitagliptin (1) Six Minute Walk Test (6MWT) (1) Six-minute walk test (6MWT) (1) Six-month ARV dispensing (1) Skin biopsy (1) Sleep App (1) Sleep Education (1) Sleepio (1) Slef questionnaires fulfilment (1) Small Gift (1) Smartphone application LiPAT (1) Smartphone-based voice and self-reported symptom collection (1) Smokefree Homes (1) Snorkel-based improvised personal protective equipment (1) Social ABCs (1) Social Communication and Emotional Skill Development (SCESD) module (1) Social Distancing Advertisements (1) Social Incentive (1) Social comparison Intervention (1) Social media & news consumption (1) Socialization (1) Sodium Bicarbonate (1) Sodium Chloride 9mg/mL (1) Sodium Nitrite (1) Sodium bicarbonate (1) Sofosbuvir (1) Sofosbuvir + Daclatasvir 120 mg (1) Sofosbuvir 400 MG plus Daclatasvir 200mg (1) Sofosbuvir and Ledipasvir (1) Sofosbuvir plus Ledipasvir (1) Sofosbuvir/Daclatasvir (1) Sofosbuvir/daclatasvir (1) Software Messaging (1) Sofusa DoseConnect (1) Sofusbuvir + Daclastavir 60 mg (1) Solaraze (1) Solcera (1) Soluble Urokinase Plasminogen Activator Receptor (1) Solution-Focused Support Program (1) Sonclot Coagulation and platelet function Analyzer SCP1, Sienco, USA (1) Spartan COVID-19 System (1) Spartan COVID-19 Test (1) Spartan Cube Point-of Care Covid-19 test (1) Spasticity Take Control (1) Specific anti-SARS-CoV-2 antibodies (1) Specimen Collection (1) Spectrila® (1) Spironolactone 100mg (1) Sputum analysis (1) Sputum and blood sampling (1) Sputum collection (1) Sputum sample (1) St. George's Respiratory Questionnaire (SGRQ) (1) Staff Wellbeing Centres (1) Stakeholder of TIP-OA Program (1) Stamaril (live attenuated yellow fever vaccine) (1) Standar medical treatmen (1) Standar of care (1) Standard (specific) therapy for COVID-19 (1) Standard 12-lead ECG, NT-proBNP, echocardiography (1) Standard COVID-19 therapies (1) Standard Care Therapy (1) Standard Dissemination Practice (1) Standard Donor Plasma (1) Standard Dose Bevacizumab (1) Standard Incentive (1) Standard Mask (1) Standard Of Care (SOC) (1) Standard Of Care (SOC) + Placebo (1) Standard Plasma (FFP) (1) Standard Public Health measures (1) Standard SII SBCC (1) Standard Therapy Protocol (STP) (1) Standard Treatment (1) Standard Ventilation Strategy (1) Standard administration of oxygen flow (1) Standard care delivered in the isolation hospitals. (1) Standard care therapy (1) Standard charity resources (1) Standard communication email (1) Standard diagnosis test (1) Standard interface (1) Standard medical care (1) Standard mouthpiece (1) Standard of Care (Intravenous access) (1) Standard of Care (SOC) + ANG-3777 (1) Standard of Care (SOC) and Colchicine+Rosuvastatin (1) Standard of Care (SOC): Radiation Therapy (1) Standard of Care Treatment (1) Standard of Care Triple IS (1) Standard of Care thromboprophylaxis (1) Standard of care (Paracetamol) (1) Standard of care (SOC) plus placebo (1) Standard of care for SARS-CoV-2 infection (1) Standard of care management (1) Standard of care therapies (1) Standard of care therapy (1) Standard of care. (1) Standard oxygen therapy (1) Standard protein group (1) Standard screening strategy (1) Standard smoking cessation therapy for TUD plus Chess-based cognitive treatment (1) Standard supportive care (1) Standard therapeutic protocol (1) Standard therapy (1) Standard therapy for AUD (1) Standard therapy for AUD plus Chess-based cognitive treatment (1) Standard therapy for COVID-19 according to the stablished hospital protocols. (1) Standard therapy for TUD (1) Standard therapy of COVID-19 (1) Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation (1) Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection (1) Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation (1) Standard therapy recommended by the Ministry of Health of the Russian Federation. (1) Standard treatment according to the Clinical protocols (1) Standard treatment for COVID-19 (1) Standard-of-care (1) Standard-of-care treatment (1) Standard-titer Convalescent COVID-19 plasma (CCP2) (1) Standardised questionnaires (1) Standardized crisis management and coping protocol plan toward Coronavirus disease 2019 (COVID-19) (1) Standards of Care (1) Standart Care given during normal examination (1) State-trait anxiety inventory scale (1) Statins (Cardiovascular Agents) (1) Stem Cell Educator-Treated Mononuclear Cells Apheresis (1) Stem Cell Product (1) Step monitoring (1) Stereotactic Radiotherapy (1) Sterile Normal Saline for Intravenous Use (1) Sterile Water for Injection (1) Sterile normal saline (0.9%) (1) Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection (1) Stool collection (1) Stool collection or fecal swab (1) Stools (1) Streptokinase (1) Stress and emotion management (1) Stretching for People with MS: An Illustrated Manual (1) Study A (1) Study Arm (1) Study B (1) Study C (1) Study D (1) Study Group (1) Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2 (1) Subacute rehabilitation (1) Sublingual Methylene blue (1) Suboxone (1) Sudarshan Kriya Yoga (SKY) (1) Sulfonatoporphyrin(TPPS) plus Sunlight exposure. (1) Sulodexide (1) Sumifilam (PTI-125), 100 mg tablet (1) Supera 7.5 OD stent (1) Supine Positioning (1) Supine position (1) Supplement Drink (1) Support treatment (1) Supported Adopted Intervention 1 (1) Supported Adopted Intervention 2 (1) Supported Adopted Intervention 3 (1) Supportive Therapy SSI (1) Supraflex Cruz 60 Micron (1) Suramin (1) Surfactant (1) Surfactant assessment (1) Surge capacity (1) Surgery (1) Surgery: Dynamic Hip Screw, hemiarthroplasty, hip replacement, intramedullary nail (1) Surgical Management (1) Surgical Management + Treatment (1) Surgical Stripping (1) Surgical facial mask (1) Surgical mask (1) Surgical procedures performed under general anesthesia (1) Surveillance card (1) Survey Group (1) Survey administration (1) Survey and Questionnaire (1) Survey to assess Post traumatic stress and anxiety at inclusion and 6 months later (1) Surveys (1) Susceptibility to infection (1) Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors (1) Sustained attention (1) Swallowing evaluation with the EAT-10 and the volume-viscosity swallowing test (V-VST) (1) SyB V-1901 (1) Symptom Survey (1) Symptom and Exposure Surveys (1) Symptomatic drugs (1) Symptomatic treatment (paracetamol or best symptomatic treatment based on doctor recommendations) (1) Symptomatology, Treatment. daily Activities and Anxiety for Cardiovascular patients Survey (STRATA) (1) Symptoms entered into the CovidX application (1) Symptoms questionnare (1) Synchronous large group online workshop (1) Synthetic neutralising antibodies (1) Syringe (1) Systemic indirect endovenous ozone therapy (1) T memory cells and NK cells (1) T-Detect™ SARS-CoV-2 Assay (1) T-cell receptor (TCR) repertoire (1) T3 solution for injection (1) T89 (1) TAK-018 (1) TAK-018 Placebo (1) TAK-671 (1) TAK-671 Placebo (1) TAK-788 (1) TAK-906 Maleate (1) TAK-906 Maleate Placebo (1) TAK-981 (1) TAPE-Software (1) TAVR or SAVR (1) TBD Compound 1 (1) TBD Compound 2 (1) TBD Compound 3 (1) TCC-COVID mHealth solution (1) TCM prescriptions (1) TD-1058 (1) TD-1473 [Tablet A] (1) TD-1473 [Tablet B] (1) TD139 (1) TDCS (1) TDR (1) TEACCH School Transition to Employment and Postsecondary Education (T-STEP) (1) TEAM Wheels (1) TEM-tPA (1) TERA Intervention (1) TERN-101 (1) TGplPTH1-34 in fibrin (1) TJ003234 (1) TLRs activation measurement (1) TMS (1) TNKase (1) TOF protocol (1) TRIIM Treatment (1) TRV027 (1) TXA127 (1) TY027 (1) Table Setting Training (1) Tacrolimus (1) Tafenoquine Oral Tablet (1) Take Control (1) Taking Time (1) Taking biological samples (1) Taking blood samples for analyzing progesterone levels (1) Talabostat Mesylate plus Pembrolizumab (1) Tap water (1) Taste and olfactory function evaluation (1) Taste test (1) Team Intervention (1) Tear Collection (1) Tears swab (1) Technology based social interactions (1) Technology-assisted Index (1) Teduglutide (1) Tele-Pulmonary rehabilitation (1) Tele-Yoga Therapy (1) Tele-delivered psychological intervention (1) Tele-interventions related to diabetes management and mental well-being (1) Tele-medicine platform (1) Tele-yoga therapy (1) TeleCAM (1) Teleconsultation either by phone or by computer consultation (1) Telehealth CBT (1) Telehealth Consultation (1) Telehealth coaching sessions (1) Telehealth monitoring (1) Telehealth phone calls (1) Telemedicine FU (1) Telemedicine follow-up visit (1) Telemedicine to remote outpatient visit in bariatric patient (1) Telephone Coaching (1) Telephone follow-up (1) Telephone interview (1) Telephone survey (1) Telephonic interview during the Italian lockdown. (1) Telephonic medical visit (1) Telerehabilitation-Based (1) Telesimulation (1) Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg (1) Telmisartan 20 mg/amlodipine 2.5 mg . (1) Telmisartan 20 mg/indapamide 1.25 mg (1) Telmisartan 40Mg Oral Tablet (1) Telmisartan 40mg (1) Telmisartan arm will receive 80 mg Telmisartan twice daily plus standard care. (1) Temporarily holding the RAAS inhibitor [intervention] (1) Temsirolimus (1) Ten-days oseltamivir (1) Tenecteplase (1) Tenofovir/ Emtricitabine ( 300 mg / 200 mg daily during 60 days) + Personal Protective Equipment (PPE) (1) Test PCR (1) Test for SARS-CoV-2 (1) Test: Favipiravir 200 mg (LOQULAR) (1) Tested for SARS-CoV-2 (regardless of the result) (1) Testing Sensitivity for SARS-CoV-2 Virus in Symptomatic Individuals (1) Testing for SARS-CoV-2 (1) Testing of SARS-CoV-2 antibodies (1) Testing procedure for Binding antibodies (1) Tests (1) Tetrandrine (1) Text material for psychoeducation and audio for relaxation techniques (1) Text message (1) Tezacaftor/Ivacaftor + Ivacaftor (1) Thalidomide (1) The CRAFT program (adapted due to COVID-19) (1) The DryShield (1) The MBSR program (adapted due to COVID-19) (1) The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care: (1) The PREPARE program (1) The Vie Scope laryngoscope (1) The control group will not receive hydroxychloroquine (1) The demographic, clinical, laboratory, and instrumental data (1) The high-volume evacuator (1) The saliva ejector (1) The standard Macintosh laryngoscope (1) The standard of care (1) The study does not required (1) The usual treatment (1) Therapeutic Anticoagulation (1) Therapeutic Exercise and Education (1) Therapeutic Plasma Exchange (TPE) (1) Therapeutic Plasma exchange (1) Therapeutic plasma exchange (1) Therapeutic plasma exchange (TPE) (1) Therapist Guided E-Therapy (1) Therapist-guided one-session online exposure therapy according to (Öst, 1989) (1) Therapy Intervention (1) There is no intervention (1) There is no intervention in this study (1) Thermography (1) Thiazide or Thiazide-like diuretics (1) This is an online survey with no intervention. (1) Thoracic CT Scan (1) Thorax CT (1) Thoraxic computed tomography (1) Three doses of high-dose recombinant SARS-CoV-2 vaccine (Sf9 Cell) at the schedule of day 0, 14, 28 (1) Three doses of placebo at the schedule of day 0, 14, 28（high-dose group） (1) Threshold IMT device (1) Throat swab and/or nasopharyngeal swab (1) Throat swab sample for measuring current infection with SARS-CoV-2 (1) Thrombin Generation Assay (TGA) (1) Thrombin generation test assay (1) Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) (1) Thromboprophylaxis (1) Thymosin+standard treatment (1) Ticagrelor (1) Tigerase® and best available care (1) Tinzaparin or unfractionated heparin (1) Tirofiban Injection (1) Tislelizumab (1) Tissue plasminogen activator (1) Titanium blood test (1) To assess for development of IgG antibodies against SARS-CoV2 (1) Tociliuzumab (1) Tocilizumab +/- ruxolitinib (stages 2b/3) (1) Tocilizumab 180 MG/ML (1) Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA] (1) Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (1) Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses) (1) Tocilizumab Injection [Actemra] (1) Tocilizumab Prefilled Syringe (1) Tocilizumab and Ruxolitinib (Advanced stage 3) (1) Toffee Full Face Mask (1) Tomeka® (1) Toraymyxin PMX-20R (PMX Cartridge) (1) Toremifene (1) Tracheal intubation and cardiopulmonary resuscitation (1) Tracheal suction (1) Tracheostomy (1) Tracheostomy with aerosol box in COVID-19 positive patients (1) Tracheotomy (1) Tradipitant (1) Traditional Chinese Medicine Prescription (1) Traditional Proning Arm (1) Traditional antirheumatic drugs (1) Training (1) Training and Technical Assistance (1) Training clinicians in basic critical care and the management of severe COVID-19 cases (1) Training for Awareness, Resilience, and Action (TARA) (1) Training load (1) Training of youth, community health assistants and community health workers. (1) Training session adressing information and health literacy (1) Training video on anxiety, fear and loneliness in the COVID-19 environment. (1) Training, Tech. Assistance, Quality Assurance/Improvement (1) Tramadol (1) Tranexamic acid (1) Tranexamic acid tablets (1) Trans Sodium Crocetinate (1) Transcendental meditation (1) Transcranial Electrical Stimulation (1) Transcutaneous Auricular Vagus Nerve Stimulation (1) Transfusion of COVID-19 convalescent plasma (1) Transfusion of SARS-CoV-2 Convalescent Plasma. (1) Transfusion of standard Plasma. (1) Transitional Online Peer Support Group (n=20) (1) Transparent, reusable respirator (1) Transplant patient (1) Transpulmonary pressure measurements (1) Transpulmonary thermodilution (1) Trauma Informed Psychotherapy (1) Trauma Informed Yoga (1) Trauma-informed yoga video recording (1) Treadmill electrocardiographic stress test (1) Treamid (1) Treatment (1) Treatment A (1) Treatment As Usual (1) Treatment B (1) Treatment C (1) Treatment and prophylaxis (1) Treatment as usual (1) Treatment as usual vitamin D (1) Treatment for COVID-19 (1) Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of seven days : (1) Treatment with Dexmedetomidine (1) Tremelimumab (1) Triazavirin (Riamilovir) (1) Trimethoprim Sulfamethoxazole (TMP/SMX) (1) Trimodulin (1) Trivia Training (1) Trust in science message (1) Tuberculin test (1) Two COVID-19 vaccine candidate (TMV-083) administrations - High dose (1) Two COVID-19 vaccine candidate (TMV-083) administrations - Low dose (1) Two dose MenACWY vaccine (1) Two dose MenACWY vaccine min. 4 weeks apart (1) Two doses of commercial scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 (1) Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule (1) Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule (1) Two doses of high dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 (1) Two doses of high-dose recombinant SARS-CoV-2 vaccine (Sf9 Cell) at the schedule of day 0, 28 (1) Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule (1) Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule (1) Two doses of middle-dose recombinant SARS-CoV-2 vaccine (Sf9 Cell) at the schedule of day 0, 28 (1) Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 (1) Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 in elderly (1) Two doses of placebo at the emergency vaccination schedule (1) Two doses of placebo at the routine vaccination schedule (1) Two doses of placebo at the schedule of day 0, 28（high-dose group） (1) Two doses of placebo at the schedule of day 0, 28（middle-dose group） (1) Tympanic Temperature (1) UB-612 (1) UCMSCs (1) UCPVax + Nivolumab (1) ULTRAPROTECTIVE VENTILATION (1) UNI911 INHALATION (1) UNIKINON (Chloroquine phosphate) 200mg tablets (1) UTTR1147A (1) UTTR1147A-matched Placebo (1) UV Light Treatment (1) Ulinastatin (1) Ultimaster Tansei 80 Micron (1) Ultra Brief Online Mindfulness-based Intervention (1) Ultra-Low-dose radiotherapy (1) Ultrasonography (1) Ultrasound lung imaging as part of FAST+ evaluation (1) Ultrasound of the lower limbs (1) Umbilical Cord Lining Stem Cells (ULSC) (1) Umbilical Cord Mesenchymal Stem Cells (1) Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. (1) Umbilical cord Wharton's jelly-derived human (1) Umbilical cord derived mesenchymal stem cells (1) Umifenovir (1) Unavailable COVID Test Result - Hypothetical Scenario (1) Unfractionated Heparin IV (1) Unfractionated heparin SC (1) Unfractionated heparin nebulized (1) Unified Protocol for COVID-19 Parenting Stress (UP-COVID) (1) Uniform random message delivery (1) Universal Screening Arm (1) Unsupervised exercise (1) Unsupervised physical activities (1) Upadacitinib (1) Upadacitinib (ABT-494) (1) Urinary Incontinence (1) Urine Test (1) Urine collection (1) Urine sample (1) Use of Doctorgram Mobile Application (1) Use of Doctorgram Patient Kit (1) Use of Facetime with child and parents during induction (1) Use of Remote Pulse Oximeter (1) Use of mobile application (1) Use of social media during COVID-19 (1) Use of the pinpointIQ solution (physIQ, Inc.) (1) Use of virus (Covid-19) genome sequence report to inform infection prevention control procedures (1) Usual Care Only (1) Usual Care plus Customized Referrals (1) Usual antibiotic treatment (1) Usual care positioning with no instructions (1) V-SARS (1) V/Q SPECT-CT (1) V/Q Vest (1) V590 (1) V591 (1) VC (1) VCPM (1) VESTA respirator (1) VIB4920 (1) VIB7734 (1) VIP4SCI (1) VIR-7831 (1) VITROS Anti-SARS-CoV-2 IgG test (1) VR for psychoeducation and relaxation (1) VRC-FLUNPF0103-00-VP VRC-FLUNPF0103-00-VP (H10ssF-6473) (1) VRC-MALMAB0100-00-AB (1) VRC-SRSDNA015-00-VP (1) VXA-CoV2-1 (1) Vaccine (1) Vaginal fluid Covid-19 PCR test (1) Valbenazine (1) Valproate (1) Valsartan (Diovan) (1) Values Clarification and Attitudes Transformation (VCAT) Workshop (1) Vancomycin (1) Vancomycin with Taper/Pulse (1) Vascular surgery (1) Vehicle (1) Vehicle + Heparin along with best supportive care (1) Vehicle Control (1) VenaSeal™ Closure System (1) Venepuncture (1) Venous Draw & Testing (1) VentaProst (inhaled epoprostenol delivered via a dedicated delivery system) (1) Ventil - a gas flow divider (1) Verapamil (1) Veru-111 (1) VibroLUNG (1) Video (1) Video Chat + Basic Feedback (1) Video Chat +Personalized Feedback (1) Video Dance classes (1) Video Default (1) Video Visit (1) Video about safety and effectiveness of adult seasonal flu vaccination (1) Video based aerobic exercise (1) Video based exercise (1) Video-Based (1) Video-Based intervention (1) Videofluoroscopic Swallowing Study (VFSS) (1) Videofluoroscopy (1) Vie Scope laryngoscopy (1) Vielight RX Plus (1) Views and experiences of health care professionals working in intensive care units during the COVID-19 pandemic (1) Viral Specific T-cells (VSTs) (1) Virtual ACT Workshop for Emotional Eating (1) Virtual Assistant first, then Human Coach (1) Virtual Care and Remote Automated Monitoring (1) Virtual Care at Home (1) Virtual Group Exercise (1) Virtual Group Intervention (1) Virtual Peer Support Platform (1) Virtual Reality Behavioral Activation (1) Virtual Reality Goggles (1) Virtual Reality Pain Neuroscience Education (1) Virtual cOaching in making Informed Choices on Elder Mistreatment Self-Disclosure (VOICES) (1) Virtual reality therapy first (1) Virtual-Care Cognitive Behavioural Therapy (1) Viruxal Oral and Nasal Spray (1) Vit D (1) VitalConnect Vital Sign Patch (1) Vitamin B12 (1) Vitamin C tablets (1) Vitamin D 1000 IU (1) Vitamin D3 or Placebo (1) Vitamin E (1) Vitamins (1) Vitamins and Minerals (1) Viusid and Asbrip (1) VivaDiag™ COVID-19 lgM/IgG Rapid Test (1) ViviGen® Cellular Bone Matrix (1) Voice Symptom Scale (VoiSS) (1) Volunteer of TIP-OA Program (1) Voraxaze (1) Voriconazole Inhalation Powder (1) WALC-R (1) WEB BASED EDUCATION (1) WFI 5% glucose (1) WFI water nebulization (1) WFIT (1) WHO recommendations (waiting condition) (1) WHOQOL-BREF (1) WHOQOL-BREF survey (1) WJ-MSCs (1) WW (1) Wait list time (1) Wait-list control (1) Waiting list (1) Waiting list where participants wait for delayed treatment (1) Waitlist (1) Walk Test (1) Water Without an Elevated Level of KELEA (1) Wearable Activity Trackers, Exercise Prescription and Virtual Care (1) Wearable Medical Device (Empatica E4) (1) Wearing surgical face mask sprayed with hypertonic saline (1) Web + text smoking cessation intervention (1) Web Based Questionnaire (1) Web Based Survey (1) Web application users (1) Web-based REDCap survey (1) Web-based psychosocial peer-to-peer support (1) Web-based self-report questionnaires (1) WebEx Physical Activity Program (1) Weck-cel Swab Collection (1) Weekly Assessment (1) Weight Counseling (1) Weight Loss (1) Wellness (1) Wharton's jelly derived Mesenchymal stem cells. (1) White Sender in Acknowledgement (1) White Sender in Informational Videos (1) Whole Exome Sequencing (1) Whole Genome Analysis (1) Whole exome sequencing (1) Withings ScanWatch (1) Without haptic stimulation (1) Woebot Substance Use Disorder (1) Women receiving extra remembering by healthcare (1) Workshops control group LiPAT (1) Wrist-worn feedback physical activity monitor (1) Written Information (1) Written Summary of Rounds (1) XAV-19 (1) XC221 (1) XCEL-UMC-BETA (1) XIENCE PRIME BTK stent (1) XatJove Anoia Aplication (1) Xiyanping injection (1) Xpert Pro stent (1) YH25448 (1) Yin Hu Qing Wen Granula(low does) (1) YinHu QingWen Decoction (1) YinHu QingWen Decoction(low dose) (1) Yinhu Qingwen Granula (1) Yoga Nidra (1) Yoga group (1) Zanubrutinib (1) Zaritt Burden Interview (1) Zavegepant (BHV-3500) (1) Zilucoplan® (1) Zinc (Placebo) (1) Zinc Citrate (1) Zinc Gluconate (1) Zinc Picolinate (1) Zinc Picolinate Placebo (1) Zinc Sulfate (1) Zinc gluconate (1) Zithromax Oral Product (1) Zofin (1) Zolpidem + PAP therapy (1) Zonisamide (1) [14C]-GSK3640254 intravenous infusion (1) [14C]-GSK3640254 powder (1) [14C]-radiolabelled BI 1358894 (1) [14C]AZD9833 Solution for Infusion, (NMT 22.8 kBq/5mL) (1) [68Ga]Ga-DOTA-(RGD)2 PET/CT (1) [TIMP-2]*[IGFBP-7] (1) a specifically designed self-administered questionnaire (1) a survey (1) acetylsalicylic acid (1) actigraphy (1) acute kidney injury (1) additional blood tubes (1) aerosol box (1) aerosolized DNase (1) after-each-case room disinfection (1) agenT-797 (1) airway management during sedation or general anesthesia (1) all treatment about COVID-2019 (1) allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC) (1) allogeneic mesenchymal stem cell (1) alpha one antitrypsin inhalation (1) alveolar recruitment (1) amlodipine 5 mg/indapamide 2.5 mg (1) amoxicillin/clavulanate (1) anti-CD40 antibody (CDX-1140) (1) anti-SARS-CoV-2 IgY (1) anti-SARS-CoV-2 human convalescent plasma (1) anti-SARS-CoV-2 plasma (1) antidiabetic treatment (1) antithymocyte globulin (rabbit) (1) appendectomy (1) artus Influenza A/B RT-PCR Test (1) assessment of the sequelae after hospitalization for Sars-COV-2 (1) attendance by ambulance crew (1) auscultation by using traditional stethoscope and electronic stethoscope under full PPE (1) autologous adipose-derived stem cells (1) autopsy (1) avdoralimab (1) azithromycin (1) azoximer bromide (1) bacTRL-Spike (1) behavioral lifestyle intervention (1) belatacept (1) bidirectional oxygenation mouthpiece (1) biochemical analysis (1) biological assays in particular on the lipid metabolism (1) biological samples collection (1) biological samples day of delivery (1) biological samples, questionnaires and interviews (1) biopsies of subcutaneous adipose tissue (1) blastocyst-stage embryo transfer (1) blood collection via fingerprick (1) blood sample for seroepidemiological investigation (1) blood sampling for biobank (1) blood test for SARS-COV2 serology (1) blood tests (1) bromelain (1) bronchoscopy examination (1) canakinumab (1) captopril 25mg (1) care as usual (1) care modalities (1) carotid-femoral pulse-wave velocity (1) cellulose-containing placebo capsules (1) cenicriviroc (1) chest radiography (1) chest x-ray (1) chiropractic team (1) chlorine dioxide 3000 ppm (1) chloroquine (1) cholecalciferol 200,000 IU (1) cholecalciferol 50,000 IU (1) chronic pain team (1) cleavage-stage embryo transfer (1) collection of biological samples (1) collection of mucosal lining fluid (1) collection of swabs (1) community health worker support (1) comparison of sample collection methods (1) complication (1) computerized cognitive training (CCT) (1) congenital malformation (1) conjunctival RT PCR (1) conjunctival swab (1) consultation (1) control (1) convalescent plasma application to SARS-CoV-2 infected patients (1) convalescent plasma from recovered COVID 19 donor (1) conventional management of patients (1) conventional oxygen (1) corticosteroid nasal irrigation (1) covid-19 positive pregnant women (1) ctDNA blood sampling (1) current IPAC-UHN PPE (1) daily room disinfection (1) daily syndromic surveillance (1) dapansutrile capsules (1) data record (1) decisions of limitations and stop processing (1) demographic and clinical data obtained from hospital's electronic medical record. (1) diagnostic (1) diagnostic tests for COVID-19 infection (1) dialysis (1) digoxin (1) double gloves (1) draw blood (1) e-Psychotherapy (1) e-ink screen (1) eHealth (1) eHealth +counselling contacts (1) eM2M (1) ePNa-CheXED (1) echocardiogram 2D (1) eculizumab (1) efgartigimod IV (1) efgartigimod PH20 SC (1) electrolytes (1) ensoETM device (1) ensoETM. Esophageal cooling during AF ablation (1) enzalutamide (1) enzalutamide Placebo (1) epidemiological and demographic characteristics (1) evaluation of skin microvascular flow and reactivity (1) everolimus (1) exchange blood transfusion from normal donor (1) exercise brochure (1) exposure (1) fMRI (1) faecal sample collector (1) famotidine (1) favipiravir (1) favipiravir tablets+chloroquine phosphatetablets tablets (1) favorable outcome (1) feces samples (COVI-BIOME ancillary study) (1) fingertip tests for POC assays (1) fostamatinib (1) fsfi survey (1) further processing of health data (1) gammaCore® (Vagus nerve stimulation) (1) gammaCore® Sapphire (non-invasive vagus nerve stimulator) (1) global survey (1) hAd5-S-Fusion+N-ETSD vaccine (1) high flow nasal cannula (HFNC) (1) high flow nasal cannula device (1) high-titer anti-Sars-CoV-2 plasma (1) home care monitoring (1) home spirometry (1) hormones (1) hospitalisation, necessity of ICU, mortality rate, lung involvement (1) hospitalization for premature birth (1) hospitalized children with Covid19 (1) human cord tissue mesenchymal stromal cells (1) hydrocortisone (1) hydroxychloroquine + azithromycin (1) hydroxychloroquine in combination with camostat mesylate (1) hydroxychloroquine placebo (1) hydroxychloroquine sulfate 200 MG (1) hyper immunoglobulins containing anti-Corona VS2 immunoglobulin (1) hyperbaric oxygen therapy (HBOT) (1) hyperimmune plasma (1) hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint (1) iAMP test (1) iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System (1) identify SARS-CoV-2 infection by serology (1) imPulse™ Una e-stethoscope (1) imaging, blood tests (1) immunoSEQ Dx (1) impliminting Online Distance Learning (1) in-hospital mortality rate (1) indirect calorimetry (1) inhalable hydroxychloroquine (HCQ) (1) inhaled hydroxychloroquine (1) inhaled type I interferon (1) inspiratory muscle traiing (1) insurance navigation (1) intensive care unit admission ratio (1) interleuken 6 level measurment (1) intermediate dose Enoxaparin/ unfractionated heparin (1) intermittent theta burst stimulation (iTBS) (1) intradermal injection of BCG Vaccine (1) intravenous immunoglobulin therapy (1) intubation (1) ioveraº (1) ioveraº sham (1) it is a survey (1) iv Tocillizumab (TCZ) (1) laboratory biomarkers (1) labs (1) lanadelumab (1) laparoscopic or open appendicectomy (1) lay telephone coaching (1) less-frequency hemodialysis (1) leucovorin (1) life questionnaires (1) lifestyle modification (1) liposomal lactoferrin (1) lopinavir/ritonavir (1) lopinavir/ritonavir group (1) lopinavir/ritonavir tablets or Arbidol or chloroquine phosphate (1) low-dose (1) low-molecular-weight heparin (1) lulizumab pegol (1) lung mechanics at different PEEP (1) lung ultrasound (1) lung ultrasound (LUS) (1) mHealth Assessments (1) mMRC (Modified Medical Research Council) Dyspnea Scale (1) mRNA in urine test (1) management strategy of outpatient with mild to moderate SARS-CoV-2 pneumonia (1) mavrilimumab (1) measurement of circulating sFlt1 concentration (1) mechanical ventilation (1) mechanical ventilator settings and position (1) media multi-task (1) media package (1) melatonin (1) meplazumab for injection (1) mesenchymal stem cells (1) metenkefalin + tridecactide (1) methylprednisolone (1) methylprednisolone therapy (1) mind. body. voice (1) mindfulness, emotion didactics, interpersonal skills, experiential learning (1) miniprobe Alveoflex (1) mobile internet survey on self-test (1) modification of the planned therapeutic management (1) modified IPAC-UHN PPE (1) molecular testing for virus RNA using RT-PCR (1) mometasone furoate nasal spray (1) monthly serologic IgM/G test (1) morning Yoga-based breathing support (1) mortality (1) mouthrinse with bêta-cyclodextrin and citrox (1) mouthrinse without bêta-cyclodextrin and citrox (1) multipeptide cocktail (1) muscle ultrasound (1) mycophenolate mofetil (1) mycophenolate mofetil (MMF) (1) mycophenolic acid (1) nCapp, a cell phone-based auto-diagnosis system (1) nangibotide (1) nasal pharyngeal (NP) swab samples (1) nasopharyngeal Covid 19 RT-PCR (1) nasopharyngeal and throat swab (1) nebulised recombinant tissue-Plasminogen Activator (rt-PA) (1) nebulization (1) newborns from covid 19 positive mothers (1) no intervention-mechanistic study (1) no intervention. observational cohort study (1) no interventional study (1) non (1) non applicable (1) non e-cigarette TV commercials (1) non interventional (1) non-RAS blocking antihypertensives (1) non-contact magnetically-controlled capsule endoscopy (1) non-interventional (1) none - observational (1) none, this study is observational (1) noninvasive ventilation (1) normal saline (1) nosocomial infection/hospital acquired infection (1) not applicable (observational study) (1) nutritional intervention (1) oSOC (1) observation (1) observation of covid 19 pneumonia (1) olfactory and gustatory tests (1) olfactory device (1) online KKH Sports Singapore Program with Usual Care (1) online mindfulness group (1) online questionnaires (1) online survey (1) oral co-trimoxazole (1) oral polio vaccine + information (1) oropharyngeal swabs (1) oxygen treatment (1) oxyhydrogen (1) pathogen reduced SARS-CoV-2 convalescent plasma (1) patients COVID 19 (1) patients receiving nasal high flow (1) performance evaluation study of RealDetect RT-PCR Kit for COVID-19 detection (1) peripheral blood draw (1) phone call (1) photobiomodulation and photodynamic therapy (1) pirfenidone (1) placebo (hartmann plus albumine) (1) placebo capsules (1) placebo for clazakizumab (1) placebo for risankizumab IV (1) placebo rinse (1) placebo+rHuPH20 (1) plasma from convalescent patients with COVID-19 (1) plasma hyperimmune (1) plasma therapy using convalescent plasma with antibody against SARS-CoV-2 (1) poractant alfa (1) positive psychological intervention (1) power breathe (1) prayer (1) pre-operative screening (1) pre_dinner Yoga-based breathing support (1) pre_lunch Yoga-based breathing support (1) predict admission of covid-19 patients to ICU and death with routine and quickly avalaible clinical, biological and radiological variables? (1) prednisolone (1) proper diet (1) prophylactic heparin (1) prophylactic lactoferrin daily (1) psycho-education video (1) psychological and sociological interviews (1) psychological assessment (1) pulmonary anomalies 4 months after documented COVID-19 pneumonia (1) pulmonary ultrasound (1) pulse oximeter (1) qRT-PCR and serology (1) quality of life questionnaires (1) quality of live assessment (1) quesionnair (1) questionaire to husband and wife (1) questionnair about Emerging Legal and Ehical Disputes Over Patient Confidentiality (1) questionnaire and optional interview (1) questionnaire filling (1) quetionnary (1) rDirectCAM (1) rapid salivary test (1) rapid serological test (1) reSET-O (1) realtime PCR (1) recombinant human interferon Alpha-1b (1) recovered covid 19 patients plasma (1) rectal swab (1) regular care (1) remdesivir (1) research specific blood sample (1) respiratory function rehabilitation training (1) retrospective metagenomics on clinical samples collected during hospitalization (1) rhDNase I (1) rhPTH(1-84) (1) risankizumab (1) risk factors (1) rosuvastatin (1) saint george respiratory questionnaire (1) saliva collection (1) saliva sample (1) samling of oropharynx and nasopharynx (1) sample of blood and saliva (1) self-administered structured questionnaire (1) self-care tools (1) semaglutide (1) semen analysis (1) serological test (1) serology test (1) sertraline (1) serum NGAL and cystatin c (1) serum chemistry analysis (1) serum inflammatory biomarkers (1) service of questionnaire (1) severe covid-19 pneumonia with ET (1) severity of lung involvement with COVID-19. (1) sham TMS (1) slow-wave disruption (1) smell household Items (1) smell the odors of the olfactory rehabilitation kit according to the classic or intensive method (1) sodium chloride 0.9% (1) sofosbuvir (1) some risk factors that might be correlated with TMD (1) specific exercise rehabilitation treatment (1) spirometry (1) spirometry, thoracic CT, CPET, 6 minute walking test, SF-36 questionnaire (1) standard chemotherapy (1) standard concomitant therapy (1) standard medical treatment (1) standard newborn and infant care (1) standard operating procedures (1) standard procedure (1) standard prophylactic dose Enoxaparin/ unfractionated heparin (1) standard protocol (1) standard treatment (1) standard western medicine treatment (1) standardized Lung Ultrasound (LUS) examination (1) stem cells (1) stress and anxiety questionnaire (1) supportive and symptomatic treatment (1) surveys and questionnaires (1) suspected of COVID-19 infection (1) sweat samples (COVIDOG ancillary study) (1) systemic treatment (1) tacrolimus (1) teleconsultation (1) telehealth applications (1) telemedicine (1) telephone consult (1) telmisartan 40 mg/amlodipine 5 mg (1) telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg (1) telmisartan 40 mg/indapamide 2.5 mg (1) thalidomide (1) therapeutic plasmaexchnage (1) theraputic heparin (1) this study is non- interventional (1) thoracic CT-scan (1) thoracic computed tomography scan (1) thoracic lung ultrasound (1) thromboprofylaxis protocol (1) thromboprophylaxis with low-molecular-weight heparin or fondaparinux (1) thymosin alpha 1 (1) topical steroids and cyclosporin-A (1) tracheostomy (1) traditional communication tools (1) transparent sheet (1) treated with hyperimmune plasma (1) turkish physicians (1) unfractionated heparin (1) urinary NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic (1) use and exposure to disinfectants during the coronavirus pandemic (1) vaccine (1) vaccine BCG (1) vaccine candidate MVA-MERS-S (1) vadadustat (1) venipuncture in peripheral vein (1) ventilatory support with oxygen therapy (1) virgin coconut oil (VCO) (1) vitamin D (1) vitamin d (1) von Willebrand factor (Recombinant) (1) vv-ECMO (1) washed microbiota transplantation (1) web based survey (1) wedged insole (1) zinc (1) zinc gluconate and ascorbic acid (1) ıt will be compared pain, sleep, fatigue, physical activity level and quality of life and questioning exercise habits before and after the covid-19 outbreak in patients with Behçet and FMF. (1) γ-Globulin (1) Оxygen therapy (1)

    Placebo

    Developed by Shray Alag, The Harker School
    Sections: Correlations, Clinical Trials, and HPO

    Correlations computed by analyzing all clinical trials.

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    Correlated Drug Terms (974)

    Name (Synonyms) Correlation
    drug1775 Hydroxychloroquine Wiki 0.12
    drug2093 LY3819253 Wiki 0.11
    drug2552 Nitazoxanide Wiki 0.10
    Name (Synonyms) Correlation
    drug212 Ad26.COV2.S Wiki 0.10
    drug2709 Ontamalimab Wiki 0.09
    drug3319 Remdesivir Wiki 0.08
    drug4122 UC-MSCs Wiki 0.08
    drug3384 Rivaroxaban Wiki 0.08
    drug4187 VPM1002 Wiki 0.07
    drug4256 Vitamin Super B-Complex Wiki 0.07
    drug3223 REGN10933+REGN10987 combination therapy Wiki 0.07
    drug2351 Mesenchymal stromal cells Wiki 0.07
    drug455 BCG vaccine Wiki 0.07
    drug2094 LY3832479 Wiki 0.07
    drug444 BAY1817080 Wiki 0.07
    drug3312 Relamorelin Wiki 0.07
    drug4251 Vitamin D Wiki 0.07
    drug927 Clazakizumab Wiki 0.07
    drug514 Baricitinib Wiki 0.06
    drug454 BCG Vaccine Wiki 0.06
    drug1152 Dapagliflozin Wiki 0.06
    drug3074 Presatovir Wiki 0.06
    drug2029 Ivermectin Wiki 0.06
    drug1511 Favipiravir Wiki 0.06
    drug3874 TD-0903 Wiki 0.06
    drug1334 Ebselen Wiki 0.06
    drug1248 Disulfiram Wiki 0.06
    drug2231 MEDI3506 Wiki 0.06
    drug1362 Electronic questionnaire Wiki 0.06
    drug465 BI 474121 Wiki 0.06
    drug1406 Ensifentrine Wiki 0.06
    drug4405 blood samples Wiki 0.06
    drug167 AZD5718 Wiki 0.06
    drug1876 Ibrutinib Wiki 0.06
    drug3746 Standard of care treatment Wiki 0.06
    drug3968 Tezepelumab Wiki 0.06
    drug3231 RO6889450 Wiki 0.06
    drug1290 Duvelisib Wiki 0.06
    drug1806 Hydroxychloroquine Sulfate Regular dose Wiki 0.06
    drug4037 Tofacitinib 10 mg Wiki 0.06
    drug2541 Niclosamide Oral Tablet Wiki 0.06
    drug1539 Fisetin Wiki 0.06
    drug1608 GSK3640254 Wiki 0.06
    drug2540 Niclosamide Wiki 0.06
    drug1597 GLPG3970 Wiki 0.06
    drug2421 Molnupiravir Wiki 0.06
    drug2677 Olokizumab 64 mg Wiki 0.06
    drug819 CYT107 Wiki 0.06
    drug832 Camostat Mesilate Wiki 0.06
    drug3442 SARS-CoV-2 rS/Matrix-M1 Adjuvant Wiki 0.06
    drug2439 Moxifloxacin Wiki 0.06
    drug4026 Tocilizumab (TCZ) Wiki 0.06
    drug2800 PUL-042 Inhalation Solution Wiki 0.06
    drug1805 Hydroxychloroquine Sulfate Loading Dose Wiki 0.06
    drug3248 RTB101 Wiki 0.06
    drug834 Canakinumab Wiki 0.06
    drug3287 Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki 0.06
    drug1265 Doxycycline Wiki 0.06
    drug3728 Standard of Care Wiki 0.05
    drug1127 DAS181 Wiki 0.05
    drug493 BNT162b2 Wiki 0.05
    drug1141 DWRX2003 Wiki 0.05
    drug2859 Pentoxifylline Wiki 0.05
    drug2117 Lenzilumab Wiki 0.05
    drug910 Chloroquine or Hydroxychloroquine Wiki 0.05
    drug3837 Suspension of heat killed (autoclaved) Mycobacterium w Wiki 0.05
    drug492 BNT162b1 Wiki 0.05
    drug1306 EIDD-2801 Wiki 0.05
    drug928 Clazakizumab 12.5 mg Wiki 0.04
    drug3463 SCB-2019 Wiki 0.04
    drug472 BIIB133 (Dapirolizumab pegol) Wiki 0.04
    drug166 AZD2693 Wiki 0.04
    drug1230 Digital oximeter monitoring Wiki 0.04
    drug1448 Exercise training group Wiki 0.04
    drug3297 Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) Wiki 0.04
    drug889 ChAdOx1-HPV Wiki 0.04
    drug84 ABTL0812 Wiki 0.04
    drug4044 Tracheostomy Wiki 0.04
    drug475 BIO101 Wiki 0.04
    drug2771 PF-07304814 Wiki 0.04
    drug303 Anti-COVID-19 human immunoglobulin Wiki 0.04
    drug2176 Losartan Wiki 0.04
    drug2564 Nitric Oxide-Releasing Drug Wiki 0.04
    drug3393 Rosuvastatin (Inhibitor arm) Wiki 0.04
    drug2710 Opaganib Wiki 0.04
    drug2756 PDS-08 Wiki 0.04
    drug3482 SNDX-6352 Wiki 0.04
    drug4116 Two doses of placebo at the routine vaccination schedule Wiki 0.04
    drug228 Aerolized Hydroxychloroquine Sulfate Wiki 0.04
    drug1349 Eicosapentaenoic acid gastro-resistant capsules Wiki 0.04
    drug2179 Lovenox 40 MG in 0.4 mL Prefilled Syringe Wiki 0.04
    drug4574 melatonin Wiki 0.04
    drug4697 recombinant human interferon Alpha-1b Wiki 0.04
    drug3379 Risperidone Wiki 0.04
    drug3636 Sirukumab Wiki 0.04
    drug4091 Treatment with Dexmedetomidine Wiki 0.04
    drug4703 respiratory function rehabilitation training Wiki 0.04
    drug2201 Low nitrite/NDMA meals Wiki 0.04
    drug2790 PRV-015 Wiki 0.04
    drug4099 Two COVID-19 vaccine candidate (TMV-083) administrations - High dose Wiki 0.04
    drug4104 Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule Wiki 0.04
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    Correlated MeSH Terms (251)

    Name (Synonyms) Correlation
    D018352 Coronavirus Infections NIH 0.32
    D045169 Severe Acute Respiratory Syndrome NIH 0.25
    D007239 Infection NIH 0.21
    Name (Synonyms) Correlation
    D003141 Communicable Diseases NIH 0.17
    D011014 Pneumonia NIH 0.16
    D055371 Acute Lung Injury NIH 0.15
    D012128 Respiratory Distress Syndrome, Adult NIH 0.14
    D012127 Respiratory Distress Syndrome, Newborn NIH 0.13
    D013577 Syndrome NIH 0.12
    D055370 Lung Injury NIH 0.10
    D001249 Asthma NIH 0.10
    D007674 Kidney Diseases NIH 0.09
    D003092 Colitis NIH 0.09
    D003093 Colitis, Ulcerative NIH 0.09
    D011658 Pulmonary Fibrosis NIH 0.09
    D014777 Virus Diseases NIH 0.09
    D018357 Respiratory Syncytial Virus Infections NIH 0.09
    D000437 Alcoholism NIH 0.08
    D008173 Lung Diseases, Obstructive NIH 0.08
    D012141 Respiratory Tract Infections NIH 0.08
    D002446 Celiac Disease NIH 0.07
    D058186 Acute Kidney Injury NIH 0.07
    D005355 Fibrosis NIH 0.07
    D007249 Inflammation NIH 0.07
    D029424 Pulmonary Disease, Chronic Obstructive NIH 0.07
    D014456 Ulcer NIH 0.06
    D008171 Lung Diseases, NIH 0.06
    D012507 Sarcoidosis NIH 0.06
    D018805 Sepsis NIH 0.06
    D003928 Diabetic Nephropathies NIH 0.06
    D014786 Vision Disorders NIH 0.06
    D001528 Behcet Syndrome NIH 0.06
    D015354 Vision, Low NIH 0.06
    D065626 Non-alcoholic Fatty Liver Disease NIH 0.06
    D005234 Fatty Liver NIH 0.06
    D001714 Bipolar Disorder NIH 0.06
    D014947 Wounds and Injuries NIH 0.06
    D012559 Schizophrenia NIH 0.06
    D018589 Gastroparesis NIH 0.06
    D002908 Chronic Disease NIH 0.06
    D051436 Renal Insufficiency, Chronic NIH 0.06
    D018450 Disease Progression NIH 0.06
    D007251 Influenza, Human NIH 0.05
    D008231 Lymphopenia NIH 0.05
    D000428 Alcohol Drinking NIH 0.05
    D003424 Crohn Disease NIH 0.05
    D000690 Amyotrophic Lateral Sclerosis NIH 0.05
    D012640 Seizures NIH 0.05
    D016472 Motor Neuron Disease NIH 0.05
    D003139 Common Cold NIH 0.05
    D054990 Idiopathic Pulmonary Fibrosis NIH 0.05
    D003289 Convalescence NIH 0.05
    D019966 Substance-Related Disorders NIH 0.05
    D016638 Critical Illness NIH 0.05
    D000544 Alzheimer Disease NIH 0.05
    D014808 Vitamin D Deficiency NIH 0.05
    D011024 Pneumonia, Viral NIH 0.04
    D015658 HIV Infections NIH 0.04
    D020196 Trauma, Nervous System NIH 0.04
    D004941 Esophagitis NIH 0.04
    D000550 Amblyopia NIH 0.04
    D055623 Keratosis, Actinic NIH 0.04
    D000532 Altitude Sickness NIH 0.04
    D001836 Body Weight Changes NIH 0.04
    D029481 Bronchitis, Chronic NIH 0.04
    D000071069 Multiple Chronic Conditions NIH 0.04
    D000071074 Neonatal Sepsis NIH 0.04
    D000070627 Chronic Traumatic Encephalopathy NIH 0.04
    D001991 Bronchitis NIH 0.04
    D001982 Bronchial Diseases NIH 0.04
    D053120 Respiratory Aspiration NIH 0.04
    D017565 Sarcoidosis, Pulmonary NIH 0.04
    D046152 Gastrointestinal Stromal Tumors NIH 0.04
    D009164 Mycobacterium Infections NIH 0.04
    D015817 Eye Infections NIH 0.04
    D020388 Muscular Dystrophy, Duchenne NIH 0.04
    D000741 Anemia, Aplastic NIH 0.04
    D000755 Anemia, Sickle Cell NIH 0.04
    D012817 Signs and Symptoms, Digestive NIH 0.04
    D057765 Eosinophilic Esophagitis NIH 0.04
    D019446 Endotoxemia NIH 0.04
    D006969 Hypersensitivity, Immediate NIH 0.04
    D014594 Uterine Neoplasms NIH 0.04
    D014625 Vaginal Neoplasms NIH 0.04
    D010265 Paraproteinemias NIH 0.04
    D009298 Nasal Polyps NIH 0.04
    D012859 Sjogren's Syndrome NIH 0.04
    D000067292 Alcohol Drinking in College NIH 0.04
    D012130 Respiratory Hypersensitivity NIH 0.04
    D011645 Puerperal Infection NIH 0.04
    D056660 Hereditary Autoinflammatory Diseases NIH 0.04
    D006337 Heart Murmurs NIH 0.04
    D008998 Monoclonal Gammopathy of Undetermined Significance NIH 0.04
    D016584 Panic Disorder NIH 0.04
    D007642 Keratosis NIH 0.04
    D015212 Inflammatory Bowel Diseases NIH 0.04
    D066087 Perinatal Death NIH 0.04
    D003248 Constipation NIH 0.04
    D005879 Tourette Syndrome NIH 0.04
    D003324 Coronary Artery Disease NIH 0.04
    D000275 Adjustment Disorders NIH 0.04
    D005922 Glomerulonephritis, IGA NIH 0.04
    D014846 Vulvar Neoplasms NIH 0.04
    D008218 Lymphocytosis NIH 0.04
    D010505 Familial Mediterranean Fever NIH 0.04
    D011818 Rabies NIH 0.04
    D018410 Pneumonia, Bacterial NIH 0.04
    D003371 Cough NIH 0.04
    D002006 Brucellosis NIH 0.04
    D004660 Encephalitis NIH 0.04
    D004715 Endometriosis NIH 0.04
    D001661 Biliary Tract Neoplasms NIH 0.04
    D007011 Hypoparathyroidism NIH 0.04
    D007896 Leishmaniasis NIH 0.04
    D011127 Polyps NIH 0.04
    D060050 Angina, Stable NIH 0.04
    D063130 Maternal Death NIH 0.04
    D001749 Urinary Bladder Neoplasms NIH 0.04
    D012140 Respiratory Tract Diseases NIH 0.04
    D012598 Scoliosi NIH 0.04
    D001168 Arthritis NIH 0.04
    D012120 Respiration Disorders NIH 0.04
    D001927 Brain Diseases NIH 0.04
    D001987 Bronchiectasis NIH 0.04
    D015179 Colorectal Neoplasms NIH 0.04
    D014115 Toxemia NIH 0.04
    D006333 Heart Failure NIH 0.04
    D001008 Anxiety Disorders NIH 0.04
    D059350 Chronic Pain NIH 0.04
    D007154 Immune System Diseases NIH 0.04
    D011565 Psoriasis NIH 0.04
    D001172 Arthritis, Rheumatoid NIH 0.03
    D009103 Multiple Sclerosis NIH 0.03
    D003924 Diabetes Mellitus, Type 2 NIH 0.03
    D009771 Obsessive-Compulsive Disorder NIH 0.03
    D001010 Anxiety, Separation NIH 0.03
    D065886 Neurodevelopmental Disorders NIH 0.03
    D000505 Alopecia NIH 0.03
    D015775 Fractures, Stress NIH 0.03
    D006948 Hyperkinesis NIH 0.03
    D002583 Uterine Cervical Neoplasms NIH 0.03
    D014552 Urinary Tract Infections NIH 0.03
    D000072861 Phobia, Social NIH 0.03
    D009190 Myelodysplastic Syndromes NIH 0.03
    D010149 Pain, Postoperative NIH 0.03
    D009155 Mutism NIH 0.03
    D000787 Angina Pectoris NIH 0.03
    D009128 Muscle Spasticity NIH 0.03
    D009136 Muscular Dystrophies NIH 0.03
    D053201 Urinary Bladder, Overactive NIH 0.03
    D012772 Shock, Septic NIH 0.03
    D006073 Gout NIH 0.03
    D050197 Atherosclerosis NIH 0.03
    D003015 Clostridium Infections NIH 0.03
    D015004 Yellow Fever NIH 0.03
    D009220 Myositis NIH 0.03
    D011618 Psychotic Disorders NIH 0.03
    D045888 Ganglion Cysts NIH 0.03
    D003193 Compulsive Personality Disorder NIH 0.03
    D016470 Bacteremia NIH 0.03
    D021821 Communicable Diseases, Emerging NIH 0.03
    D058345 Asymptomatic Infections NIH 0.03
    D009410 Nerve Degeneration NIH 0.03
    D003231 Conjunctivitis NIH 0.03
    D000208 Acute Disease NIH 0.03
    D005909 Glioblastoma NIH 0.03
    D004696 Endocarditis NIH 0.03
    D000379 Agoraphobia NIH 0.03
    D000370 Ageusia NIH 0.03
    D008268 Macular Degeneration NIH 0.03
    D019896 Alpha 1-Antitrypsin Deficiency NIH 0.03
    D003920 Diabetes Mellitus, NIH 0.03
    D000857 Olfaction Disorders NIH 0.03
    D013313 Stress Disorders, Post-Traumatic NIH 0.03
    D009369 Neoplasms, NIH 0.03
    D011665 Pulmonary Valve Insufficiency NIH 0.03
    D004194 Disease NIH 0.03
    D005334 Fever NIH 0.02
    D011251 Pregnancy Complications, Infectious NIH 0.02
    D010051 Ovarian Neoplasms NIH 0.02
    D058070 Asymptomatic Diseases NIH 0.02
    D004408 Dysgeusia NIH 0.02
    D002658 Developmental Disabilities NIH 0.02
    D018184 Paramyxoviridae Infections NIH 0.02
    D020529 Multiple Sclerosis, Relapsing-Remitting NIH 0.02
    D016491 Peripheral Vascular Diseases NIH 0.02
    D007035 Hypothermia NIH 0.02
    D006331 Heart Diseases NIH 0.02
    D040921 Stress Disorders, Traumatic NIH 0.02
    D002318 Cardiovascular Diseases NIH 0.02
    D060825 Cognitive Dysfunction NIH 0.02
    D058729 Peripheral Arterial Disease NIH 0.02
    D003643 Death, NIH 0.02
    D011236 Prediabetic State NIH 0.02
    D001835 Body Weight NIH 0.02
    D018746 Systemic Inflammatory Response Syndrome NIH 0.02
    D008659 Metabolic Diseases NIH 0.02
    D007410 Intestinal Diseases NIH 0.02
    D001289 Attention Deficit Disorder with Hyperactivity NIH 0.02
    D000257 Adenoviridae Infections NIH 0.02
    D008103 Liver Cirrhosis, NIH 0.02
    D003428 Cross Infection NIH 0.02
    D016739 Behavior, Addictive NIH 0.02
    D019851 Thrombophilia NIH 0.02
    D005356 Fibromyalgia NIH 0.02
    D003693 Delirium NIH 0.02
    D000073397 Occupational Stress NIH 0.02
    D009102 Multiple Organ Failure NIH 0.02
    D006967 Hypersensitivity, NIH 0.02
    D009203 Myocardial Ischemia NIH 0.02
    D020920 Dyssomnias NIH 0.02
    D001943 Breast Neoplasms NIH 0.02
    D010003 Osteoarthritis, NIH 0.02
    D012769 Shock, NIH 0.02
    D006973 Hypertension NIH 0.02
    D002659 Child Development Disorders, Pervasive NIH 0.02
    D054058 Acute Coronary Syndrome NIH 0.02
    D008180 Lupus Erythematosus, Systemic NIH 0.02
    D009461 Neurologic Manifestations NIH 0.02
    D005221 Fatigue NIH 0.02
    D013927 Thrombosis NIH 0.02
    D000860 Hypoxia NIH 0.02
    D020447 Parasomnias NIH 0.02
    D007676 Kidney Failure, Chronic NIH 0.02
    D003327 Coronary Disease NIH 0.02
    D003866 Depressive Disorder NIH 0.02
    D013315 Stress, Psychological NIH 0.02
    D003704 Dementia NIH 0.02
    D003095 Collagen Diseases NIH 0.02
    D007511 Ischemia NIH 0.02
    D004630 Emergencies NIH 0.01
    D000070642 Brain Injuries, Traumatic NIH 0.01
    D001068 Feeding and Eating Disorders NIH 0.01
    D050177 Overweight NIH 0.01
    D010300 Parkinsonian NIH 0.01
    D002055 Burnout, Professional NIH 0.01
    D011248 Pregnancy Complications NIH 0.01
    D003922 Diabetes Mellitus, Type 1 NIH 0.01
    D012216 Rheumatic Diseases NIH 0.01
    D009765 Obesity NIH 0.01
    D004417 Dyspnea NIH 0.01
    D001321 Autistic Disorder NIH 0.01
    D008175 Lung Neoplasms NIH 0.01
    D001930 Brain Injuries, NIH 0.01
    D000067877 Autism Spectrum Disorder NIH 0.01
    D017563 Lung Diseases, Interstitial NIH 0.01
    D020141 Hemostatic Disorders NIH 0.01
    D001778 Blood Coagulation Disorders NIH 0.01
    D000077062 Burnout, Psychological NIH 0.01
    D003863 Depression, NIH 0.01
    D001523 Mental Disorders NIH 0.01

    Correlated HPO Terms (112)

    Name (Synonyms) Correlation
    HP:0002090 Pneumonia HPO 0.16
    HP:0002099 Asthma HPO 0.10
    HP:0000077 Abnormality of the kidney HPO 0.09
    Name (Synonyms) Correlation
    HP:0002583 Colitis HPO 0.09
    HP:0100279 Ulcerative colitis HPO 0.09
    HP:0002206 Pulmonary fibrosis HPO 0.09
    HP:0006536 Pulmonary obstruction HPO 0.08
    HP:0011947 Respiratory tract infection HPO 0.08
    HP:0002608 Celiac disease HPO 0.07
    HP:0001919 Acute kidney injury HPO 0.07
    HP:0006510 Chronic pulmonary obstruction HPO 0.07
    HP:0002088 Abnormal lung morphology HPO 0.06
    HP:0100806 Sepsis HPO 0.06
    HP:0000505 Visual impairment HPO 0.06
    HP:0100754 Mania HPO 0.06
    HP:0012047 Hemeralopia HPO 0.06
    HP:0001397 Hepatic steatosis HPO 0.06
    HP:0002578 Gastroparesis HPO 0.06
    HP:0100753 Schizophrenia HPO 0.06
    HP:0012622 Chronic kidney disease HPO 0.06
    HP:0001888 Lymphopenia HPO 0.05
    HP:0100280 Crohn's disease HPO 0.05
    HP:0006802 Abnormal anterior horn cell morphology HPO 0.05
    HP:0007354 Amyotrophic lateral sclerosis HPO 0.05
    HP:0100512 Low levels of vitamin D HPO 0.05
    HP:0002511 Alzheimer disease HPO 0.05
    HP:0012387 Bronchitis HPO 0.04
    HP:0030127 Endometriosis HPO 0.04
    HP:0003811 Neonatal death HPO 0.04
    HP:0002037 Inflammation of the large intestine HPO 0.04
    HP:0001677 Coronary artery atherosclerosis HPO 0.04
    HP:0100574 Biliary tract neoplasm HPO 0.04
    HP:0100650 Vaginal neoplasm HPO 0.04
    HP:0000646 Amblyopia HPO 0.04
    HP:0100633 Esophagitis HPO 0.04
    HP:0000794 IgA deposition in the glomerulus HPO 0.04
    HP:0001250 Seizure HPO 0.04
    HP:0030416 Vulvar neoplasm HPO 0.04
    HP:0100827 Lymphocytosis HPO 0.04
    HP:0012133 Erythroid hypoplasia HPO 0.04
    HP:0010784 Uterine neoplasm HPO 0.04
    HP:0000829 Hypoparathyroidism HPO 0.04
    HP:0002383 Encephalitis HPO 0.04
    HP:0004469 Chronic bronchitis HPO 0.04
    HP:0012735 Cough HPO 0.04
    HP:0030148 Heart murmur HPO 0.04
    HP:0040187 Neonatal sepsis HPO 0.04
    HP:0100582 Nasal polyposis HPO 0.04
    HP:0002019 Constipation HPO 0.04
    HP:0009725 Bladder neoplasm HPO 0.04
    HP:0100723 Gastrointestinal stroma tumor HPO 0.04
    HP:0001369 Arthritis HPO 0.04
    HP:0002110 Bronchiectasis HPO 0.04
    HP:0100834 Neoplasm of the large intestine HPO 0.04
    HP:0001298 Encephalopathy HPO 0.04
    HP:0001635 Congestive heart failure HPO 0.04
    HP:0012532 Chronic pain HPO 0.04
    HP:0003765 Psoriasiform dermatitis HPO 0.04
    HP:0001370 Rheumatoid arthritis HPO 0.03
    HP:0005978 Type II diabetes mellitus HPO 0.03
    HP:0003560 Muscular dystrophy HPO 0.03
    HP:0002487 Hyperkinetic movements HPO 0.03
    HP:0001257 Spasticity HPO 0.03
    HP:0000709 Psychosis HPO 0.03
    HP:0001997 Gout HPO 0.03
    HP:0012174 Glioblastoma multiforme HPO 0.03
    HP:0100584 Endocarditis HPO 0.03
    HP:0030079 Cervix cancer HPO 0.03
    HP:0001681 Angina pectoris HPO 0.03
    HP:0000224 Hypogeusia HPO 0.03
    HP:0002863 Myelodysplasia HPO 0.03
    HP:0002293 Alopecia of scalp HPO 0.03
    HP:0000509 Conjunctivitis HPO 0.03
    HP:0100614 Myositis HPO 0.03
    HP:0002300 Mutism HPO 0.03
    HP:0002180 Neurodegeneration HPO 0.03
    HP:0000756 Agoraphobia HPO 0.03
    HP:0002621 Atherosclerosis HPO 0.03
    HP:0000819 Diabetes mellitus HPO 0.03
    HP:0000458 Anosmia HPO 0.03
    HP:0002664 Neoplasm HPO 0.03
    HP:0010444 Pulmonary insufficiency HPO 0.03
    HP:0000722 Obsessive-compulsive behavior HPO 0.02
    HP:0002045 Hypothermia HPO 0.02
    HP:0001945 Fever HPO 0.02
    HP:0100615 Ovarian neoplasm HPO 0.02
    HP:0001268 Mental deterioration HPO 0.02
    HP:0001626 Abnormality of the cardiovascular system HPO 0.02
    HP:0100724 Hypercoagulability HPO 0.02
    HP:0007018 Attention deficit hyperactivity disorder HPO 0.02
    HP:0002242 Abnormal intestine morphology HPO 0.02
    HP:0030858 Addictive behavior HPO 0.02
    HP:0001395 Hepatic fibrosis HPO 0.02
    HP:0012393 Allergy HPO 0.02
    HP:0001658 Myocardial infarction HPO 0.02
    HP:0002758 Osteoarthritis HPO 0.02
    HP:0012378 Fatigue HPO 0.02
    HP:0000822 Hypertension HPO 0.02
    HP:0002725 Systemic lupus erythematosus HPO 0.02
    HP:0003002 Breast carcinoma HPO 0.02
    HP:0012418 Hypoxemia HPO 0.02
    HP:0004950 Peripheral arterial stenosis HPO 0.02
    HP:0000716 Depressivity HPO 0.02
    HP:0000726 Dementia HPO 0.02
    HP:0100651 Type I diabetes mellitus HPO 0.01
    HP:0000717 Autism HPO 0.01
    HP:0001513 Obesity HPO 0.01
    HP:0002098 Respiratory distress HPO 0.01
    HP:0100526 Neoplasm of the lung HPO 0.01
    HP:0006515 Interstitial pneumonitis HPO 0.01
    HP:0000729 Autistic behavior HPO 0.01
    HP:0001928 Abnormality of coagulation HPO 0.01

    Clinical Trials

    Navigate: Correlations   HPO

    There are 543 clinical trials

    1 Phase I, Double-Blinded, Placebo-Controlled Dosage Escalation Study of the Safety and Immunogenicity of Adjuvanted and Non-Adjuvanted Inactivated SARS Coronavirus (SARS-CoV) Vaccine Administered by the Intramuscular Route

    Severe acute respiratory syndrome (SARS) is a viral illness that affects the respiratory (breathing) system. The purpose of this study is to evaluate the safety and protective (immune) responses to different doses of a SARS vaccine given with or without an adjuvant. An adjuvant is a substance that may be added to a vaccine to improve the immune response so that less of the vaccine may need to be given. Study participants will include 72 volunteers, ages 18-40, living in the Houston, Texas area. The study will take place at Baylor College of Medicine. Participants will receive 2 injections of vaccine or placebo (substance made to look like the study vaccine but contains no medication) given 1 month apart. Participants will fill out a memory aid (diary) to document daily temperature and illness signs and symptoms for 7-9 days after each injection. During the 9 study visits, several blood samples will be collected. Participants will be in the study for up to 211 days, including screening.

    NCT00533741
    Conditions
    1. Coronavirus (SARS-CoV)
    Interventions
    1. Drug: Aluminum hydroxide
    2. Drug: Placebo
    3. Biological: SARS-CoV
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Frequency and description of serious adverse events (SAEs).

    Time: 5 months after receipt of the booster dose of vaccine.

    Measure: Frequency of significant increases in serum antibody to CoV S protein in Enzyme Linked Immunosorbent Assay (ELISA) and in neutralization tests, and increases in Geometric Mean Titers (GMT)s in sera.

    Time: Screening, 1 and 5 months after the booster dose of vaccine.

    Measure: Frequency and severity of solicited injection site and systemic signs and symptoms and unsolicited adverse events (AE) / SAEs.

    Time: 1 month after receipt of the first and second doses of vaccine.

    Secondary Outcomes

    Measure: Frequency of significant serum antibody increases and increases in Geometric Mean Titers (GMT)s, as measured in neutralizing antibody tests and an ELISA against SARS-CoV S protein.

    Time: Collected just before the first vaccination and at 1 month (just before booster).
    2 Efficacy of Ingesting Gaia Herb's Quick Defense Product in Reducing Acute Respiratory Illness Symptomatology in Women: a 12-Week, Double Blind, Placebo-Controlled Randomized Trial

    The primary objective of this study is to evaluate the effectiveness of ingesting an alkylamide-rich echinacea root product (Quick Defense, Gaia Herbs) for 2 days immediately following each onset of acute respiratory illness (ARI) symptomatology during a 12-week period in the winter and early spring in women. Hypothesis: Subjects randomized to Quick Defense compared to placebo over a 12-week period will experience reduced ARI symptomatology, both acutely during each ARI episode and collectively over the entire 12-week study period.

    NCT02003651
    Conditions
    1. Acute Respiratory Infections
    Interventions
    1. Dietary Supplement: Quick Defense
    2. Dietary Supplement: Placebo
    MeSH:Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: The Wisconsin Upper Respiratory Symptom Survey (WURSS-24) will be used to assess common cold illness severity and symptoms (see attached questionnaire). Subjects will fill in the one-page WURSS-24 at the end of each day during the 12-week monitoring period. This 12-week period will cover the winter and early spring period of 2014. From the responses recorded during the 84-day study, an ARI severity score will be calculated by summing the daily ARI global severity score (0=not sick, 1=very mild ARI to 7=severe). The ARI symptom score for the 84-day period will be calculated by summing all 10 symptom scores for each day's entry (0=do not have this symptom, 1=very mild to 7=severe). In similar fashion, the ARI function ability score for the 84-day period will be calculated by summing all 9 function scores for each day's entry (0=do not have this symptom, 1=very mild to 7=severe). Separate scores will be calculated comparing groups for each illness episode recorded by the subjects.

    Measure: Common cold symptoms

    Time: 12-weeks
    3 A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of GS-5806 in Hematopoietic Cell Transplant (HCT) Recipients With Respiratory Syncytial Virus (RSV) Infection of the Upper Respiratory Tract

    The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV upper respiratory tract infection (URTI), the effect of presatovir on development of lower respiratory tract complication, being free of any supplemental oxygen progression to respiratory failure, and pharmacokinetics (PK), safety, and tolerability of presatovir.

    NCT02254408
    Conditions
    1. Respiratory Syncytial Virus
    Interventions
    1. Drug: Presatovir
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.

    Measure: Time-Weighted Average Change in Nasal Respiratory Syncytial Virus (RSV ) Viral Load From Baseline (Day 1) to Day 9

    Time: Baseline; Day 9

    Description: A Lower Respiratory Tract Complication (LRTC) was defined as one of the below as determined by the adjudication committee: Primary RSV lower respiratory tract infection (LRTI) Secondary bacterial LRTI LRTI due to unusual pathogens Lower respiratory tract complication of unknown etiology

    Measure: Percentage of Participants Who Developed a Lower Respiratory Tract Complication

    Time: Up to Day 28

    Secondary Outcomes

    Description: Participants were considered to have an event if either condition is met: Participant develops a respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) or; Participant dies prior to or on Day 28

    Measure: Percentage of Participants Who Developed Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality

    Time: Up to Day 28
    4 A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of GS-5806 in Hematopoietic Cell Transplant (HCT) Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract

    The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV lower respiratory tract infection (LRTI).

    NCT02254421
    Conditions
    1. Respiratory Syncytial Virus Infection
    Interventions
    1. Drug: Presatovir
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Syncytial Virus Infections

    Primary Outcomes

    Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factors.

    Measure: Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline to Day 9

    Time: Baseline to Day 9

    Secondary Outcomes

    Measure: Number of Supplemental O2-Free Days Through Day 28

    Time: Up to Day 28

    Measure: Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28

    Time: Up to Day 28

    Measure: Percentage of All-Cause Mortality Among Participants Through Day 28

    Time: Up to Day 28
    5 A Randomized Placebo Controlled Trial of Inhaled Beclomethasone After Community-acquired Respiratory Viral Infection in Lung Transplant Recipients

    The purpose of this study is to determine if the use of inhaled beclomethasone after a community-acquired respiratory viral infection in a lung transplant recipient decreases the risk of the subsequent development of chronic lung allograft dysfunction.

    NCT02351180
    Conditions
    1. Lung Transplant Infection
    Interventions
    1. Drug: Inhaled beclomethasone
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Virus Diseases

    Primary Outcomes

    Measure: Freedom from new or progressive chronic lung allograft dysfunction

    Time: 180 days

    Measure: Death

    Time: 180 days

    Secondary Outcomes

    Measure: Respiratory virus symptom score

    Time: 7 days

    Measure: Acute rejection

    Time: 180 days

    Measure: Lymphocytic bronchiolitis

    Time: 180 days

    Measure: Donor-specific antibodies

    Time: 180 days

    Measure: Chronic lung allograft dysfunction

    Time: 365 days
    6 Effects of Low-dose Corticosteroids on Survival of Severe Community-acquired Pneumonia

    Mortality of severe Community-Acquired Pneumonia (CAP) has not declined over time and is between 25 and 30% in sub-groups of patients. Corticosteroids (CTx) could down-regulate pulmonary and systemic inflammation, accelerate clinical resolution and decrease the rate of inflammation-associated systemic complications. Two recent meta-analyses suggest a positive effect on severe CAP day 28 survival when CTx are added to standard therapy. However they are based on only four trials gathering less than 300 patients, of which only one was positive. Recently published guidelines do not recommend CTx as part of CAP treatment. Therefore a well-powered trial appears necessary to test the hypothesis that CTx - and more specifically hydrocortisone - could improve day 28 survival of critically-ill patients with severe CAP, severity being assessed either on a Pulmonary Severity Index ≥ 130 (Fine class V) or by the use of mechanical ventilation or high-FiO2 high-flow oxygen therapy. A phase-III multicenter add-on randomized controlled double-blind superiority trial assessing the efficacy of hydrocortisone vs. placebo on Day 28 all-causes mortality, in addition to antibiotics and supportive care, including the correction of hypoxemia. Randomization will be stratified on: (i) centers; (ii) use of mechanical ventilation at the time of inclusion.

    NCT02517489
    Conditions
    1. Community Acquired Pneumonia
    Interventions
    1. Drug: Hydrocortisone
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Day 28 all causes mortality

    Time: at day 28

    Description: For the sub-group of patients included with COVID19, failure is defined as death or need of respiratory support (mechanical ventilation or high-flow oxygen therapy);

    Measure: Day 21 failure

    Time: at day 21

    Secondary Outcomes

    Measure: In patients non-invasively ventilated at inclusion, proportion of patients needing endotracheal intubation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: In patients non-ventilated at inclusion, proportion of patients requiring non-invasive ventilation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: In patients non-ventilated at inclusion, proportion of patients needing endotracheal intubation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Day 28 ventilator-free-days

    Time: between 0 and day 28

    Measure: Number of patients with vasopressor therapy initiation from inclusion to day 28

    Time: between 0 and day 28

    Measure: Day 28 vasopressor-free-days

    Time: between 0 and day 28

    Measure: ICU and/or intermediate care unit LOS

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: All-causes mortality at day 90

    Time: at day 90

    Measure: SF-36 Health Survey at day 90

    Time: at day 90

    Measure: Biomarkers: procalcitonin at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: Biomarkers: C-reactive protein at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: Biomarkers: plasmatic concentration of pro-inflammatory cytokines (IL-6, IL-20, IL-22, IL-22BP, HBD2, TNF) at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: P/F ratio measured daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28

    Time: measured daily from baseline to day 7, at the end of treatment i.e 14 days after the start of treatment, at the end of ICU-stay (for a maximum of 28 days) and/or day 28

    Measure: SOFA calculated daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28

    Time: calculated daily from baseline to day 7, at the end of treatment (i.e 14 days after the start of treatment), at the end of ICU-stay (for a maximum of 28 days) and/or day 28

    Measure: Proportion of patients experiencing secondary infection during their ICU-stay

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Proportion of patients experiencing gastrointestinal bleeding during their ICU-stay

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Daily amount of insulin administered to the patient from day 1 to day 7

    Time: Patients will be followed from day 1 to day 7

    Measure: Weight-gain at baseline and day 7

    Time: Patients will be followed at baseline and day 7

    Other Outcomes

    Description: Sub-group of patients included with COVID19

    Measure: P/F ratio measured daily from Day1 to Day7, at Day 14 and at Day 21 and/or at the end of ICU-stay

    Time: from day 1 to day 7, at day 14 and day 21 and/or at the end of ICU-stay

    Description: Sub-group of patients included with COVID19

    Measure: Proportion of patients needing endotracheal intubation

    Time: at day 21

    Description: Sub-group of patients included with COVID19

    Measure: Proportion of patients experiencing secondary infection during their ICU-stay

    Time: From baseline to day 21
    7 Evaluation of ColdZyme® Mouth Spray on Prevention and Alleviation of Induced Rhinovirus Upper Respiratory Tract Infection in Healthy Volunteers. A Double-blind, Randomized, Placebo-controlled Study

    This study evaluates the performance of ColdZyme® mouth spray on prevention and alleviation of induced rhinovirus upper respiratory tract infection in healthy volunteers. Half of participants will receive ColdZyme® mouth spray while the other half will receive placebo.

    NCT02522949
    Conditions
    1. Common Cold
    Interventions
    1. Device: ColdZyme® mouth spray
    2. Device: Placebo
    MeSH:Common Cold

    Primary Outcomes

    Description: Reduction in viral load in the URT(Upper Respiratory Tract), after challenge with rhinovirus, in relation to placebo

    Measure: Reduction in viral load in the URT

    Time: 7 days

    Secondary Outcomes

    Description: Reduction of number of days having a total symptom severity score of 6 or higher using a 5-graded Jackson scale, in relation to placebo.

    Measure: Prevention of symptomatic URTI (Upper Respiratory Tract Infection)

    Time: 11 days

    Description: Asymptomatic URTI will be assessed by quantification of viral load at peak day (day with highest viral load measured by oropharyngeal swab).

    Measure: Prevention of asymptomatic URTI.

    Time: 11 days

    Description: The number of days with cold is defined as the sum of all days with a total score of ≥ 6 according to the modified method of Jackson.

    Measure: Fewer days with symptomatic URTI

    Time: 11 days

    Description: The number of days with asymptomatic URTI is defined as the sum of all days with a viral load significantly different from the baseline.

    Measure: Fewer days with asymptomatic URTI.

    Time: 11 days

    Description: Nasal samples will be analysed for the quantity of IL-6 (Interleukin 6), IL-8 and IFNα (Interferon alpha).

    Measure: Lower level of proinflammatory proteins

    Time: 11 days

    Measure: Lower daily total symptom score

    Time: 11 days

    Measure: Lower daily score of individual symptoms

    Time: 11 days
    8 A Phase 2b, Randomized, Controlled Trial Evaluating GS-5806 in Lung Transplant (LT) Recipients With Respiratory Syncytial Virus (RSV) Infection

    The primary objective of this study is to evaluate the effect of presatovir on nasal respiratory syncytial virus (RSV) viral load in RSV-positive lung transplant (LT) recipients with acute respiratory symptoms.

    NCT02534350
    Conditions
    1. Respiratory Syncytial Virus (RSV)
    Interventions
    1. Drug: Presatovir
    2. Drug: Placebo
    MeSH:Infection Virus Diseases

    Primary Outcomes

    Measure: Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in Participants in the Full Analysis Set

    Time: Up to 7 days

    Measure: Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in a Subset of Participants in the Full Analysis Set Whose Duration of RSV Symptoms Prior to the First Dose of Study Drug is ≤ Median

    Time: Up to 7 days

    Secondary Outcomes

    Description: The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms) for the 5-point severity scale and 0 (never) to 4 or more times (always) for the 5-point frequency scale. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.

    Measure: Time-Weighted Average Change in FLU-PRO Score From Day 1/Baseline Through Day 7

    Time: Up to 7 days

    Description: FEV1 is defined as forced expiratory volume in the first second.

    Measure: Percent Change From Study Baseline in FEV1% Predicted Value

    Time: Baseline; Day 28
    9 MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial

    This is a placebo-controlled clinical trial to assess the efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with MERS.

    NCT02845843
    Conditions
    1. Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
    Interventions
    1. Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: 90-day mortality

    Time: 90-day

    Secondary Outcomes

    Measure: Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors)

    Time: 28 days

    Measure: RT-PCR cycle threshold value in the lower respiratory samples

    Time: At randomization and every 3 days afterwards, until 2 consecutive samples are negative or reaching a maximum of 90 days

    Measure: Sequential organ failure assessment (SOFA) scores

    Time: Days 0, 3, 7, 14, 21 and 28

    Measure: ICU-free days

    Time: Number of days in which patients are not being cared for in the ICU during the first 28 days after enrollment

    Measure: Length of stay in hospital

    Time: Up to one year from enrollment

    Measure: Number of Patients with Adverse drug reactions related to the treatment

    Time: From enrollment to 28 day

    Measure: Karnofsky Performance Scale

    Time: 90-day

    Measure: ICU mortality

    Time: Up to one year from enrollment

    Measure: Hospital mortality

    Time: Up to one year from enrollment

    Measure: 28-day mortality

    Time: 28-day
    10 CSP #2002 - Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT)

    This research will help us to learn if the medicine called metformin reduces the risk of death, heart attacks, and/or strokes in patients who have pre-diabetes and heart or blood vessel problems.

    NCT02915198
    Conditions
    1. Prediabetic State
    2. Atherosclerosis
    3. Metformin
    Interventions
    1. Drug: Metformin XR
    2. Drug: Placebo
    MeSH:Atherosclerosis Prediabetic State
    HPO:Atherosclerosis Type IV atherosclerotic lesion

    Primary Outcomes

    Description: The primary outcome measure is the time to first occurrence of death, non-fatal myocardial infarction or stroke, hospitalization for unstable angina with objective evidence of acute myocardial ischemia, or coronary revascularization driven by acute or progressive symptoms.

    Measure: Time in days to death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina, or symptom-driven coronary revascularization

    Time: through study completion, an average of 4.5 years

    Secondary Outcomes

    Description: Time to first occurrence of death, myocardial infarction, or stroke Time to first occurrence of a primary endpoint event, peripheral arterial disease event, or hospitalization for congestive heart failure Cumulative incidence of all components of the primary endpoint, including recurrent or multiple events in the same participant Cumulative incidence and time to first occurrence of each component of the primary outcome measure, peripheral arterial disease events, and hospitalization for congestive heart failure

    Measure: Time in days to Cardiovascular Outcomes

    Time: through study completion, an average of 4.5 years

    Description: Time to new or recurrent diagnosis of a malignancy or death from a malignancy

    Measure: Time in days to Oncologic Outcome

    Time: through study completion, an average of 4.5 years

    Description: Time to new diagnosis of type 2 diabetes (ADA criteria)

    Measure: Time in days to Diabetes Outcome

    Time: through study completion, an average of 4.5 years
    11 A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter, Phase 3 Study to Evaluate the Safety and Efficacy of Ad5FGF-4 in Patients With Refractory Angina Due to Myocardial Ischemia

    The purpose of this study is to determine whether a single intracoronary infusion of an adenovirus serotype 5 virus expressing the gene for human fibroblast growth factor-4 (Ad5FGF-4) is effective in improving angina-limited exercise duration, angina functional class, frequency of angina attacks, frequency of nitroglycerin usage, and quality of life. Half of the study participants will receive Ad5FGF-4, and half will receive placebo. The primary endpoint is the change from baseline to Month 6 in Exercise Tolerance Test (ETT) duration. Long-term safety of Ad5FGF-4 will also be assessed.

    NCT02928094
    Conditions
    1. Angina, Stable
    Interventions
    1. Biological: Ad5FGF-4
    2. Biological: Placebo
    MeSH:Angina Pectoris Myocardial Ischemia Coronary Artery Disease Angina, Stable Ischemia
    HPO:Angina pectoris Coronary artery atherosclerosis Myocardial infarction

    Primary Outcomes

    Description: Modified Bruce Protocol with exercise duration limited by angina or angina equivalent

    Measure: Change in Exercise Tolerance Test (ETT) duration

    Time: Baseline and Month 6

    Secondary Outcomes

    Description: Canadian Cardiovascular Society (CCS) angina classification

    Measure: Change in patient functional status (CCS class)

    Time: Baseline and Month 6

    Description: Average weekly angina episodes

    Measure: Change in weekly angina frequency

    Time: Baseline and Month 6

    Description: Average weekly nitroglycerin usage

    Measure: Change in weekly nitroglycerin usage

    Time: Baseline and Month 6

    Description: Seattle Angina Questionnaire

    Measure: Change in quality of life

    Time: Baseline and Month 6

    Description: Adverse events and clinical laboratory testing

    Measure: Safety of Ad5FGF-4

    Time: Through Month 6

    Description: Occurrence of clinically significant events

    Measure: Long-term safety of Ad5FGF-4

    Time: Through Month 60
    12 CSP #2004 - Microbiota or Placebo After Antimicrobial Therapy for Recurrent C. Difficile at Home (MATCH)

    The purpose of this study is to determine whether Fecal Microbiota Therapy (FMT) is effective vs. placebo in the prevention of C. difficile infection recurrence.

    NCT03005379
    Conditions
    1. Clostridium Difficile Infection
    Interventions
    1. Drug: Fecal Microbiota Therapy (FMT)
    2. Drug: Placebo
    MeSH:Clostridium Infections

    Primary Outcomes

    Description: The primary outcome is recurrent CDI (definite or probable) or death within 56 days of randomization. Definite recurrence is defined as any of the following: The new onset of more than three loose or watery stools in 24 hours for two consecutive days Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS Laboratory confirmation of C. difficile from a stool specimen. Probable recurrence is defined as the same clinical manifestations as above, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result).

    Measure: Recurrent CDI (definite or probable) or death

    Time: Within 56 days of randomization

    Secondary Outcomes

    Description: The incidence of recurrent CDI (definite or possible) or death within 6 months of randomization.

    Measure: Recurrent CDI (definite or possible), or death

    Time: Within 6 months of randomization

    Description: The investigators will use a brief assessment of both overall and gastrointestinal health status, using a previously validated instrument.

    Measure: Quality of Life

    Time: 56 days from randomization

    Description: The number of CDI recurrences within 6 months for a patient is the count of separate CDI recurrences from randomization to 6 months after randomization.

    Measure: Number of CDI recurrences

    Time: Within 6 months of randomization

    Description: This is similar to probable recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test and PCR, not episodes that are not tested or are uninterpretable.

    Measure: Diarrhea that is negative for C. difficile by EIA toxin test and PCR

    Time: Within 56 days of randomization

    Description: An assessment for non-diarrheal manifestations of CDI such as abdominal pain, urgency, and fecal incontinence will be performed.

    Measure: Multiple related symptoms

    Time: Within 6 months of randomization

    Description: The incidence of definite recurrent CDI within 56 days of randomization. Definite recurrence is defined as any of the following: The new onset of more than three loose or watery stools in 24 hours for two consecutive days Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS Laboratory confirmation of C. difficile from a stool specimen.

    Measure: Definite recurrent CDI

    Time: Within 56 days of randomization

    Description: The incidence of probable recurrent CDI within 56 days of randomization. Possible recurrence is defined as the same clinical manifestations as definite recurrent CDI, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result).

    Measure: Possible recurrent CDI

    Time: Within 56 days of randomization

    Description: The incidence of death within 56 days of randomization.

    Measure: Death

    Time: Within 56 days of randomization

    Description: This is similar to possible recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test, not episodes that are not tested or are uninterpretable.

    Measure: Diarrhea that is negative for C. difficile by EIA toxin testing but positive by PCR

    Time: Within 56 days of randomization

    Other Outcomes

    Description: Safety outcomes to be collected include: Serious adverse events, with a focus on SAEs involving hospitalization (new or prolonged), and all-cause mortality Adverse events which may be related to FMT treatment. This includes adverse events which Site Investigators consider related/possibly related to the study treatment and all adverse events which occur within 14 days of study treatment (since an aggregate analysis of events temporally linked to treatment could show a causal relationship when compared to placebo) Infectious transmissions which are plausibly linked to FMT treatment. Development of new conditions theoretically linked to alterations in gut microbiota.

    Measure: Adverse and Serious Adverse Events

    Time: Within 6 months of randomization
    13 A Phase 3 Multicenter, Long-Term Extension Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) in Subjects With Ulcerative Colitis

    This study is designed to evaluate the long-term safety and efficacy of Upadacitinib in participants with ulcerative colitis (UC) who have not responded at the end of the induction period in Study M14-234 Substudy 1, who have had loss of response during the maintenance period of Study M14-234 Substudy 3, or who have successfully completed Study M14-234 Substudy 3.

    NCT03006068
    Conditions
    1. Ulcerative Colitis (UC)
    Interventions
    1. Drug: Upadacitinib (ABT-494)
    2. Drug: Placebo
    MeSH:Colitis Colitis, Ulcerative Ulcer
    HPO:Colitis Ulcerative colitis

    Primary Outcomes

    Description: Treatment-emergent adverse events are defined as events that begin or worsen either on or after the first dose of the study drug and within 30 days after the last dose of the study drug in the analysis period.

    Measure: Assessing Treatment-Emergent Adverse Events

    Time: Up to 288 Weeks
    14 International Multicenter Double-blind Placebo-Controlled Parallel-Group Randomized Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children

    The international multicenter double-blind placebo-controlled randomized clinical study in parallel groups.The objective of this study is to obtain additional data on the efficacy and safety of Ergoferon in the treatment of acute respiratory viral infections (ARVI) in children aged from 6 months to 6 years old.

    NCT03039621
    Conditions
    1. Acute Respiratory Viral Infections
    Interventions
    1. Drug: Ergoferon
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Virus Diseases

    Primary Outcomes

    Description: Based on patient diary data. Criteria of alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.

    Measure: Time to Alleviation of All ARVI Symptoms.

    Time: 14 days of observation.

    Secondary Outcomes

    Description: Based on patient diary data. Oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period).

    Measure: Time to Normalization of Body Temperature.

    Time: 14 days of observation.

    Description: Based on patient diary data. Absence of flu-like nonspecific symptoms/presence of one mild flu-like nonspecific symptom.

    Measure: Time to Alleviation of Flu-like Nonspecific Symptoms.

    Time: 14 days of observation.

    Description: Based on patient diary data. Absence of respiratory symptoms/presence of one mild respiratory symptom.

    Measure: Time to Alleviation of Respiratory Symptoms.

    Time: 14 days of observation.

    Description: Based on patient diary data. The total score (TS) ranges from 0 to 30 consisting of 4 flu-like nonspecific (decreased activity/weakness, poor appetite/refusal to eat, sick appearance, sleep disturbance) and 6 respiratory (runny nose, stuffy nose/nasal congestion, sneezing, hoarseness, sore throat, cough) symptoms according to the 4-point scale for each symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.

    Measure: Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6.

    Time: On days 2-6 of the observation period.

    Description: Based on the area under the curve of TS for days 2-6, according to the patient diary. The total score (TS) will be calculated based on the severity of each ARVI symptom (sum of 11 symptoms = body temperature, flu-like nonspecific symptoms (4 symptoms) and respiratory symptoms (6 symptoms) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TS the absolute oral temperature values, measured in degrees Celsius, will be converted into relative units (or points), given the following gradations: ≤37.5С = 0 point; 37.6-38.1C = 1 point; 38.2-38.8C = 2 points; ≥38.90С = 3 points. For total score minimum and maximum scores are 0 and 33, where higher values represent a worse outcome.

    Measure: ARVI Severity.

    Time: On days 2-6 of the observation period.

    Description: Based on patient diary data. Criteria of recovery/alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale for each flu-like nonspecific and respiratory symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom).

    Measure: Percentage of Recovered Patients.

    Time: On days 2-6 of the observation period.

    Description: Based on patient diary data. The number of intakes of prescribed antipyretics.

    Measure: Rates of Antipyretics Use Per Patient.

    Time: On days 1- 5 of the treatment period.

    Description: Based on patient diary data. The disease worsening: ARVI complications, including those requiring antibiotics; hospitalization).

    Measure: Percentage of Patients With Worsening of Illness.

    Time: 14 days of observation peiod.
    15 A Multicenter, Randomized, Double Blind, Placebo Controlled Parallel Group, Pilot Study to Assess the Efficacy and Safety of H.P. Acthar® Gel in Subjects With Relapsing-remitting Multiple Sclerosis

    This is a multicenter, multiple dose study to estimate the response rate, and examine the safety of H.P. Acthar® Gel (Acthar) in subjects with RRMS who have not responded to high dose steroids. Approximately 66 subjects will be randomized.

    NCT03126760
    Conditions
    1. Relapsing, Remitting Multiple Sclerosis
    Interventions
    1. Drug: Repository Corticotropin Injection
    2. Drug: Placebo
    MeSH:Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Sclerosis

    Primary Outcomes

    Description: The EDSS is a 10 step assessment of neurological impairment/disability in MS ranging from 0 (normal neurological examination) to 10 (death due to MS) that is completed by a blinded rater. The blinded rater will not be involved in any aspects of participant care and management other than performing the EDSS/FSS evaluations in participant in the study.

    Measure: Response rate on Expanded Disability Status Scale (EDSS) at Day 42

    Time: Day 42

    Description: Data for AE and SAE will be presented.

    Measure: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time: Up to Day 42

    Description: Data will be summarized for each visit.

    Measure: Change from Baseline in diastolic/systolic blood pressures

    Time: Baseline and Up to Day 42

    Measure: Change from Baseline in respiratory rate

    Time: Baseline and Up to Day 42

    Measure: Change from Baseline in heart rate

    Time: Baseline and Up to Day 42

    Measure: Change from Baseline in body temperature

    Time: Baseline and Up to Day 42

    Measure: Change from Baseline in Clinically Significant Laboratory Test Abnormalities - Hematology

    Time: Baseline and Up to Day 42

    Measure: Change from Baseline in Clinically Significant Laboratory Test Abnormalities - blood chemistry

    Time: Baseline and Up to Day 42

    Measure: Change from Baseline in Clinically Significant Laboratory Test Abnormalities -urinalysis

    Time: Baseline and Up to Day 42

    Secondary Outcomes

    Description: The MSIS-29 measures the physical (20 items) and psychological (9 items) impact of MS from the participant's perspective. This validated questionnaire will result in a total score between 29 and 145 and can provide separate scores for physical and psychological impact. The MSIS-29 will be completed by the participant at all required times points during the study except on Study Day 14 when the MSIS-29 will be administered via telephone by a call center trained in the administration of the MSIS-29 or captured via a web portal.

    Measure: The response rates on Multiple Sclerosis Impact Scale Version 1 (MSIS-29) and 90% confidence intervals (CIs)

    Time: Days 7, 14, 21 and 42

    Description: The EDSS is a 10 step assessment of neurological impairment/disability in MS ranging from 0 (normal neurological examination) to 10 (death due to MS) that is completed by a blinded rater. The blinded rater will not be involved in any aspects of participant care and management other than performing the EDSS/FSS evaluations in participant in the study.

    Measure: The response rates on EDSS and 90% CIs on Day 7 and Day 21

    Time: Days 7 and 21

    Description: The CGI-I was developed for use in clinical research to provide a brief overview of the change in a participant's global function compared to baseline and regardless of study drug treatment. It requires a rating from 1 (very much improved) to 7 (very much worse).

    Measure: Clinical Global Impression of Improvement Scale (CGI-I) mean scores and 90% CIs

    Time: Days 7, 21 and 42
    16 A Staged Study Incorporating a Phase 1b, Multicenter, Unmasked, Dose Escalation Evaluation of Safety and Tolerability and a Phase 2, Multicenter, Unmasked, Randomized, Parallel Group, Controlled, Proof of Concept Investigation of Efficacy and Safety of ASP7317 for Atrophy Secondary to Age-related Macular Degeneration

    This study is for adults 50 years or older who are losing their clear, sharp central vision. Central vision is needed to be able to read and drive a car. They have been diagnosed with dry age-related macular degeneration (called dry AMD). The macula is the part of the eye that allows one to see fine detail. AMD causes cells in the macula to die (atrophy). This study is looking at a new treatment for slowing or reversing dry AMD, called ASP7317. ASP7317 is a specially created type of cells derived from stem cells. ASP7317 cells are injected into the macula of the eye. Immunosuppressive medicines (called IMT) are also taken around the time of injection of the cells to prevent the body from rejecting them. The study is divided into 3 stages. Stage 1 looks at the safety of ASP7317 at different dose levels. Researchers want to learn which of 3 different dose levels of ASP7317 work without causing unwanted effects. The doses are low, medium and high numbers of cells. IMT medicines will also be taken by mouth (oral) for 13 weeks around the time of the injection of ASP7317. In Stage 2, the participants are selected by chance (randomization) to be in the ASP7317 treatment group or to be in the control group (no treatment). What was learned about the dose of ASP7317 in stage 1 will be used to determine the appropriate dose(s) in this stage. In those who receive ASP7317, oral IMT medicines will also be taken for 13 weeks. 26 weeks after ASP3717 is injected, the best corrected visual acuity will be compared between participants who received ASP7317 and in those who did not (control group). Visual acuity is a test to find out what the smallest letters are that one can read on a standard chart. This test will be masked. Masked means the study opticians who measure one's visual acuity don't know whether the participant received ASP7317 or not. In Stage 3, participants in the untreated control group from stage 2 will have the option to receive treatment with ASP7317. They must have been in the study for 26 weeks and still meet the requirements for treatment.

    NCT03178149
    Conditions
    1. Age-Related Macular Degeneration
    Interventions
    1. Drug: ASP7317
    2. Other: Placebo
    3. Drug: tacrolimus
    4. Drug: mycophenolate mofetil (MMF)
    MeSH:Macular Degeneration

    Primary Outcomes

    Description: Best corrected visual acuity (BCVA) will be measured by an assessor certified to use the early treatment of diabetic retinopathy study (ETDRS) method. The BCVA score (in letter units) will be reported.

    Measure: PoC only: Change from baseline in BCVA score, measured by ETDRS method at week 26

    Time: Baseline and Week 26

    Description: Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA). Adverse event collection will begin upon the participant signing the informed consent.

    Measure: Safety as assessed by Incidence, frequency and severity of adverse events (AEs)

    Time: Up to 60 Months

    Description: An AE is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (hospitalization for treatment/observation/examination caused by AE is to be considered as serious); or other medically important events.

    Measure: Safety as assessed by Incidence, frequency and severity of Serious adverse events (SAEs)

    Time: Up to 60 Months

    Description: ATIMP events which may represent a significant hazard to the trial's participant population, and thus require expedited reporting, including but not limited to the following example ATIMPs: ectopic or proliferative cell growth (RPE or non-RPE) with adverse clinical Consequence; any new diagnosis of an immune-mediated disorder; any new cancer, irrespective of prior history; unexpected, clinically significant AEs possibly related to the cell transplant procedure, IMT or ASP7317 (e.g., graft failure or rejection).

    Measure: Safety as assessed by Incidence, frequency and severity of advanced therapy investigational medicinal product (ATIMP) events

    Time: Up to 60 Months

    Description: Evidence of graft failure or rejection will be assessed by BCVA, slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.

    Measure: Number of Participants with graft failure or rejection

    Time: Up to 60 Months

    Description: Evidence of graft failure or rejection will be assessed by BCVA, slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.

    Measure: Incidence of graft failure or rejection

    Time: Up to 60 Months

    Description: Immediate notification (within 24 hours of becoming aware) to the sponsor is required for any evidence of graft failure or rejection. AEs which are assessed as being evidence of graft failure or rejection will be summarized in additional AE tables, including time to onset relative to the start of adjunct study medication.

    Measure: Time of onset of ASP7317 to graft failure or rejection

    Time: Up to 60 Months

    Description: An abnormality identified during a medical test will be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of adjunct study medications; age-related eye disease studies (AREDS) lens grade increase from baseline by ≥ 1 grade; the abnormality or test value is clinically significant; visual acuity loss of ≥ 10 letters due to graft failure or rejection.

    Measure: Number of clinically significant objective test results in laboratory tests

    Time: Up to 26 Weeks

    Description: Clinically significant changes in blood pressure will be reported as moderate or severe.

    Measure: Number of clinically significant objective test results in blood pressure

    Time: Up to 12 Weeks

    Description: Clinically significant changes in AC cells grade will be reported with a grade ranging from 0 to 4+ (0 = good and 4+ = not good), on a scale from <1 to >50, with cells in field as the indicator (0 = <1 cells in the field and 4+ = >50 cells in the field).

    Measure: Number of clinically significant objective test results in anterior chamber (AC) cells grade

    Time: Up to 26 Weeks

    Description: Clinically significant changes in flare grade will be reported with a grade ranging from 0 to 4+ and defined as follows: none (grade 0), faint (grade 1), moderate (iris and lens details clear, grade 2), marked (iris and lens details hazy, grade 3), and intense (fibrin or plastic aqueous, grade 4).

    Measure: Number of clinically significant objective test results in AC flare grade

    Time: Up to 26 Weeks

    Description: Clinically significant changes in vitreous haze grade will be reported with a grade ranging from 0 to 4+ and defined as follows: clear (grade 0), opacities without obstruction of retinal details (grade 1), few opacities resulting in the mild burning of posterior details of optic nerve and retinal vessels (grade 2), optic nerve head and retinal vessels significantly blurred but still visible (grade 3), dense opacity obscuring optic nerve head (grade 4).

    Measure: Number of clinically significant objective test results in vitreous haze grade

    Time: Up to 26 Weeks

    Description: Intraocular pressure in both eyes will be measured by tonometry. Intraocular pressure should be measured after biomicroscopic examination and before pupil dilation approximately the same time of day, when possible.

    Measure: Number of clinically significant objective test results in intraocular pressure (IOP) in each eye

    Time: Up to 60 Months

    Secondary Outcomes

    Description: BCVA will be measured by an assessor certified to use the ETDRS method. The BCVA score (in letter units) will be reported.

    Measure: PoC only: Change from baseline in BCVA score, average of assessments from weeks 4 to 26

    Time: Baseline and up to Week 26

    Description: BCVA will be measured by an assessor certified to use the ETDRS method.

    Measure: PoC only: Participant response, defined as a confirmed ≥ 10-letter (0.2 logMAR) improvement in BCVA, at week 26

    Time: Week 26

    Description: The index quadrant is defined as the macular quadrant (superior, temporal, inferior or nasal) where ASP7317 is injected or, for the untreated control group, this is the macular quadrant recommended for ASP7317 injection by the subject selection committee (SSC).

    Measure: PoC only: Change from baseline in mean retinal sensitivity of all test points in the index quadrant at week 26

    Time: Baseline and Week 26

    Description: DDAF will be assessed by Fundus Autofluorescence Photography (FAF). The image reading center will review the FAF images for area of DDAF and pattern of hyper autofluorescence around the DDAF.

    Measure: PoC only: Change from baseline in (square root) area of definite decreased autofluorescence (DDAF) in the index quadrant at week 26

    Time: Baseline and Week 26

    Description: The FRII is a 7-item questionnaire that evaluates the effect of geographic atrophy on a patient's ability to independently perform reading activities.

    Measure: Change from baseline in the Functional Reading Independence Index (FRII) at week 26

    Time: Baseline and Week 26

    Description: The IVI-VLV questionnaire (28 questions) will be used to assess activities of daily living, mobility, safety and emotional well-being. This questionnaire measures perceived restriction of participation associated with daily living activities.

    Measure: Change from baseline in the Impact of Vision Impairment - Very Low Vision questionnaire (IVI-VLV) at week 26

    Time: Baseline and Week 26
    17 A 26 Week, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Phase 3 Trial With a 26 Week Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 5 and 10 mg, and Saxagliptin 2.5 and 5 mg in Pediatric Patients With Type 2 Diabetes Mellitus Who Are Between 10 and Below 18 Years of Age

    The purpose of this research study is to evaluate the efficacy and safety of the drugs dapagliflozin and saxagliptin in patients with Type 2 Diabetes who are aged 10 to below 18 years old and are currently taking metformin, insulin, or both drugs. Dapagliflozin and saxagliptin are both approved for use in patients with Type 2 Diabetes aged 18 years or older. Dapagliflozin (alone or in combination with other antidiabetic drugs) is available for use in adults in approximately 40 countries worldwide including the USA and Europe. Saxagliptin (alone or in combination with other antidiabetic drugs) is available for use in adults in approximately 90 countries worldwide. This study will assess how well dapagliflozin and saxagliptin work by finding out how these treatments affect blood glucose (sugar) levels compared to placebo (a pill that contains no active drug), in children and adolescents. Dapagliflozin and saxagliptin are considered investigational products in this study since while they have been approved for use in adults (patients 18 years or older), they haven't been approved for children and adolescents due to lack of clinical studies in this specific population. Patients with Type 2 Diabetes have higher levels of blood glucose (sugar) than patients who do not have this disease. The high level of sugar in the blood can lead to serious short-term and long-term medical problems. The main goal of treating diabetic patients is to lower blood glucose to a normal level. Lowering and controlling blood glucose help prevent or delay complications of diabetes, such as heart disease, kidney, eye and nerve diseases, and the possibility of amputation. Dapagliflozin is a drug that helps to reduce blood glucose (sugar) levels by helping the kidneys to remove excess glucose from the blood and excrete it in the urine. It prevents the kidneys from returning glucose from the urine back into the bloodstream. Saxagliptin increases insulin production when blood glucose levels are high. Insulin is a hormone made by the pancreas that allows the body to use sugar (glucose) from the food that is eaten for energy or to store glucose for future use. Saxagliptin helps to improve blood sugar levels in response to a meal and between meals if blood glucose levels are not lowered effectively. Saxagliptin does not work when the blood glucose is low. Saxagliptin also helps to decrease the amount of sugar made by the body. Together, these processes reduce blood glucose levels and help to control Type 2 Diabetes. The subject will either receive one of the active study drugs or a placebo (a pill that looks identical but contains inactive drug). This study will be double blind; this means that neither the subject, nor the study doctor will know which treatment the subject will receive. Which treatment the subject receives is decided by a computer, purely by chance; this is called a "random assignment". For this study, there will first be a screening phase of up to 6 months if Investigator thinks that some of the screening tests can be repeated, followed by a 2 week lead in phase. Thereafter there will be a 26W short-term treatment phase (W1-26), and a 26 W long-term treatment phase (W27-52). Following this there will be a follow-up telephone call on week 56 and a post study visit at W104. At day 1 visit after the lead in phase the subject will be randomly assigned to receive one of 3 treatments: dapagliflozin 5 mg, saxagliptin 2.5 mg or placebo in a blinded manner. This treatment will continue up to week 14. Then after week 14, and until the end of the study, the subject will be assigned to receive one of the following 5 treatments: dapagliflozin 5 mg, dapagliflozin 10 mg, saxagliptin 2.5 mg, saxagliptin 5 mg or placebo in a blinded manner. The drugs assigned after week 14 will be the same drugs as at Day 1, but some of the groups will receive them at a higher dose.Starting at W32 or W40, i.e., after the end of the primary endpoints, patients with background medication of metformin only, and an HbA1c value < 7.5% at W26 or W32, will undergo a third randomization. Eligible subjects from the treatment arms will undergo the randomized withdrawal of background medication, while eligible patients from the placebo arm will undergo, in addition to randomized withdrawal of background medication a randomized switch to active treatment. Short- and long-term period study visits can be delayed by a maximum of 11 months in total. If the duration of investigational product administration is longer than 52 (+1) weeks, the safety follow-up period should be shortened such that the complete study duration does not exceed 104 weeks. The W104 visit should not be delayed.If more than 12 weeks elapse between the HbA1c collection at W26 and the third rand at W32, or the HbA1c collection at W32 and the third rand at W40, the subject should not go through this rand as the HbA1c value would no longer be reliable to ascertain eligibility for the third rand

    NCT03199053
    Conditions
    1. Diabetes Mellitus, Type 2
    Interventions
    1. Drug: Dapagliflozin
    2. Drug: Saxagliptin
    3. Drug: Placebo
    MeSH:Diabetes Mellitus Diabetes Mellitus, Type 2
    HPO:Diabetes mellitus Type II diabetes mellitus

    Primary Outcomes

    Description: To determine if there will be a greater mean reduction from baseline in HbA1c achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin 5 mg or saxagliptin 2.5 mg (with titration to the high-dose for those who do not achieve the glycemic target of HbA1c < 7% at 12 weeks) compared to placebo in pediatric T2DM subjects with HbA1c levels of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

    Measure: Change from baseline in HbA1c at Week 26

    Time: 26 weeks

    Secondary Outcomes

    Description: To determine if there will be a greater mean reduction from baseline in Fasting Plasma Glucose (FPG) achieved after 26 weeks of oral double-blind add-on therapy of dapagliflozin 5 mg or saxagliptin 2.5 mg (with titration to the high-dose for those who do not achieve the glycemic target of HbA1c <7% at 12 weeks) compared to placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin

    Measure: Change from baseline in Fasting Plasma Glucose at Week 26

    Time: 26 weeks

    Description: To compare the percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% after 26 weeks of oral double-blind add-on therapy of dapagliflozin 5 mg or saxagliptin 2.5 mg (with titration to the high-dose for those who do not achieve the glycemic target of HbA1c <7% at 12 weeks) versus placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin

    Measure: Percentage of subjects with baseline HbA1c ≥ 7%, who achieve an HbA1c level < 7.0% at Week 26

    Time: 26 weeks

    Other Outcomes

    Description: To compare the percentage of subjects requiring glycemic rescue medication or discontinuing study medication due to lack of efficacy with dapagliflozin or saxagliptin against the percentage with placebo during 26 weeks of oral double-blind add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

    Measure: Percentage of subjects who require glycemic rescue medication or discontinue the study medication due to lack of efficacy during the 26-week treatment period

    Time: 26 weeks

    Description: To assess the mean change from baseline in HbA1c achieved with dapagliflozin therapy versus placebo, and separately, achieved with saxagliptin therapy versus placebo after 52 weeks of oral blinded add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

    Measure: Change from baseline in HbA1c at Week 52

    Time: 52 weeks

    Description: To assess the mean change from baseline in FPG achieved with dapagliflozin therapy versus placebo, and separately, achieved with saxagliptin therapy versus placebo after 52 weeks of oral blinded add-on treatment in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin

    Measure: Change from baseline in FPG at Week 52

    Time: 52 weeks

    Description: To assess the percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% after 52 weeks of oral blinded add-on therapy with dapagliflozin versus placebo, or saxagliptin versus placebo in pediatric T2DM subjects with HbA1c of 6.5 to 10.5% on diet and exercise and metformin (IR or XR), insulin, or metformin (IR or XR) plus insulin.

    Measure: Percentage of subjects with baseline HbA1c ≥ 7% who achieve an HbA1c level < 7.0% at Week 52

    Time: 52 weeks
    18 A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis (FIGARO UC 302)

    The purpose of this study is to evaluate the efficacy of SHP647 in inducing remission, based on composite score of patient-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis (UC).

    NCT03259308
    Conditions
    1. Ulcerative Colitis
    Interventions
    1. Drug: Ontamalimab
    2. Drug: Placebo
    MeSH:Colitis Colitis, Ulcerative Ulcer
    HPO:Colitis Ulcerative colitis

    Primary Outcomes

    Description: Remission is defined as a composite score of patient-reported symptoms using daily ediary and centrally read endoscopy as stool frequency subscore of 0 or 1 with at least a 1-point change from baseline, rectal bleeding subscore of 0 and endoscopic subscore of 0 or 1 (modified, excludes friability). The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA: 0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

    Measure: Number of Participants With Remission at Week 12

    Time: Week 12

    Secondary Outcomes

    Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

    Measure: Number of Participants With Endoscopic Remission at Week 12

    Time: Week 12

    Description: Clinical remission is defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0. The stool frequency subscore and rectal bleeding subscore range from 0 to 3 with higher scores indicating more severe disease.

    Measure: Number of Participants With Clinical Remission at Week 4, 8, 12

    Time: Week 4, 8, 12

    Description: Clinical response (composite) is defined as a decrease from baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the subscore for rectal bleeding greater than or equal to (>=) 1 point or a subscore for rectal bleeding less than or equal to (<=) 1. The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

    Measure: Number of Participants With Clinical Response (Composite) at Week 12

    Time: Week 12

    Description: Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of <=2. The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

    Measure: Number of Participants With Mucosal Healing at Week 12

    Time: Week 12

    Description: Remission is defined as a total mayo score of less than or equal to <=2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and PGA) exceeding 1, at the Week 12. The total mayo score ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

    Measure: Number of Participants With Remission Based on Total Mayo Score at Week 12

    Time: Week 12

    Description: Clinical response (Mayo) is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding >=1 point or an absolute subscore for rectal bleeding <=1. The total mayo score ranges from 0 to 12 points and consists of the following 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

    Measure: Number of Participants With Clinical Response Based on Total Mayo Score at Week 12

    Time: Week 12

    Description: The partial mayo score ranges from 0 to 9 points and consists of the following 3 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); PGA (0-3). The partial Mayo score does not include the endoscopy subscore. Here participants with partial Mayo score <= 2 with no individual subscore >1 at the Week 4, 8, and 12 will be assessed.

    Measure: Number of Participants With Partial Mayo Score Less than or Equal to (<=) 2 with no Individual Subscore Greater than (>) 1 at Week 4, 8, 12

    Time: Week 4, 8, 12

    Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Here number of participants with endoscopic remission at week 12 with a subscore of 0 will be assessed.

    Measure: Number of Participants with Endoscopic Remission at Week 12 With Endoscopic Subscore of 0

    Time: Week 12

    Description: Clinical remission with both rectal bleeding and stool frequency subscores of 0 at week 4, 8, 12 will be assessed. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

    Measure: Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Subscores of 0 at Week 4, 8, 12

    Time: Week 4, 8, 12

    Description: Deep remission is defined as both endoscopic and rectal bleeding subscores of 0, and stool frequency subscore <=1 and a centrally read Geboes score of <=2.. The stool frequency subscore, rectal bleeding subscore and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

    Measure: Number of Participants With Deep Remission at Week 12

    Time: Week 12

    Description: Participants will be asked to record the abdominal pain worst severity using 0-10 numeric rating scale, with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Abdominal Pain Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the diarrhea frequency (enter number of loose or watery bowel movements) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Diarrhea Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the urgency frequency (enter number of bowel movements with urgency) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Urgency Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the stool frequency (enter number of bowel movements passed) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Absolute Stool Frequency Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the rectal bleeding severity and frequency (enter number of bowel movements with blood) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Absolute Rectal Bleeding Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: The total sign/symptom score (average of rectal bleeding, stool frequency, abdominal pain, diarrhea, and urgency) ranges from 0 to 10 with higher scores indicating higher severity.

    Measure: Change From Baseline Total Sign/Symptom Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: The IBDQ is a psychometrically validated participant-reported outcome (PRO) instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, including UC. The IBDQ consists of 32 items, which are grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains are scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement.

    Measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains and Total Absolute Scores in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 8, 12

    Time: Baseline, Week 8, 12

    Description: The SF-36 is a generic quality-of-life instrument that has been widely used to assess health-related quality of life (HRQL) of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

    Measure: Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores and Individual Domain Scores) at Week 12

    Time: Baseline, Week 12

    Description: Incidence of hospitalizations during the entire study period will be assessed.

    Measure: Incidence of Hospitalizations

    Time: From start of study up to follow up (Week 29)

    Description: Incidence of total inpatient days during the entire study period will be assessed.

    Measure: Incidence of Total Inpatient Days

    Time: From start of study up to follow up (Week 29)
    19 A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis (FIGARO UC 301)

    The purpose of this study is to evaluate the efficacy of SHP647 in inducing remission, based on composite score of participant-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis (UC).

    NCT03259334
    Conditions
    1. Ulcerative Colitis
    Interventions
    1. Drug: Ontamalimab
    2. Other: Placebo
    MeSH:Colitis Colitis, Ulcerative Ulcer
    HPO:Colitis Ulcerative colitis

    Primary Outcomes

    Description: Remission is defined as a composite score of participant-reported symptoms using daily e-diary and centrally read endoscopy as stool frequency subscore of 0 or 1 with at least a 1-point change from baseline, rectal bleeding subscore of 0 and endoscopic subscore of 0 or 1 (modified, excludes friability). The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA: 0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

    Measure: Number of Participants With Remission at Week 12

    Time: Week 12

    Secondary Outcomes

    Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

    Measure: Number of Participants With Endoscopic Remission at Week 12

    Time: Week 12

    Description: Clinical remission is defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0. The stool frequency subscore and rectal bleeding subscore range from 0 to 3 with higher scores indicating more severe disease.

    Measure: Number of Participants With Clinical Remission at Week 4, 8, 12

    Time: Week 4, 8, 12

    Description: Clinical response (composite) is defined as a decrease from baseline in the composite score of participant-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the subscore for rectal bleeding greater than or equal to (>=) 1 point or a subscore for rectal bleeding less than or equal to (<=) 1. The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

    Measure: Number of Participants With Clinical Response (Composite) at Week 12

    Time: Week 12

    Description: Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of <=2. The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

    Measure: Number of Participants With Mucosal Healing at Week 12

    Time: Week 12

    Description: Remission is defined as a total mayo score of less than or equal to <=2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and physician's global assessment) exceeding 1, at the Week 12. The total mayo score ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

    Measure: Number of Participants With Remission Based on Total Mayo Score at Week 12

    Time: Week 12

    Description: Clinical response (Mayo) is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding >=1 point or an absolute subscore for rectal bleeding <=1. The total mayo score ranges from 0 to 12 points and consists of the following 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

    Measure: Number of Participants With Clinical Response Based on Total Mayo Score at Week 12

    Time: Week 12

    Description: The partial mayo score ranges from 0 to 9 points and consists of the following 3 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); PGA (0-3). The partial Mayo score does not include the endoscopy subscore. Number of participants with partial mayo score <=2 with no individual subscore >1 at the Week 4, 8, 12 will be assessed.

    Measure: Number of Participants With Partial Mayo Score Less than or Equal (<=) 2 with no individual subscore Greater than (>) 1 at Week 4, 8, 12

    Time: Week 4, 8, 12

    Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Here number of participants with endoscopic remission at week 12 with a subscore of 0 will be assessed.

    Measure: Number of Participants with Endoscopic Remission at Week 12 With Endoscopic Subscore of 0

    Time: Week 12

    Description: Clinical remission with both rectal bleeding and stool frequency subscores of 0 at week 4, 8, 12 will be assessed. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

    Measure: Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Subscores of 0 at Week 4, 8, 12

    Time: Week 4, 8, 12

    Description: Deep remission is defined as both endoscopic and rectal bleeding subscores of 0, and stool frequency subscore <=1 and a centrally read Geboes score of <=2.. The stool frequency subscore, rectal bleeding subscore and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

    Measure: Number of Participants With Deep Remission at Week 12

    Time: Week 12

    Description: Participants will be asked to record the abdominal pain worst severity using 0-10 numeric rating scale, with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Abdominal Pain Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the diarrhea frequency (enter number of loose or watery bowel movements) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Diarrhea Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the urgency frequency (enter number of bowel movements with urgency) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Urgency Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the stool frequency (enter number of bowel movements passed) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Absolute Stool Frequency Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: Participants will be asked to record the rectal bleeding severity and frequency (enter number of bowel movements with blood) as experienced over the previous 24 hours, in the e-diary.

    Measure: Change From Baseline in Absolute Rectal Bleeding Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: The total sign/symptom score (average of rectal bleeding, stool frequency, abdominal pain, diarrhea, and urgency) ranges from 0 to 10 with higher scores indicating higher severity.

    Measure: Change From Baseline Total Sign/Symptom Score Based on Participant e-Diary at Week 12

    Time: Baseline, Week 12

    Description: The IBDQ is a psychometrically validated participant-reported outcome (PRO) instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, including UC. The IBDQ consists of 32 items, which are grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains are scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement.

    Measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains and Total Absolute Scores in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 8, 12

    Time: Baseline, Week 8, 12

    Description: The SF-36 is a generic quality-of-life instrument that has been widely used to assess health-related quality of life (HRQL) of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

    Measure: Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores and Individual Domain Scores) at Week 12

    Time: Baseline, Week 12

    Description: Incidence of hospitalizations during the entire study period will be assessed.

    Measure: Incidence of Hospitalizations

    Time: From start of study up to follow up (Week 29)

    Description: Incidence of total inpatient days during the entire study period will be assessed.

    Measure: Incidence of Total Inpatient Days

    Time: From start of study up to follow up (Week 29)
    20 A 12-week, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis

    This study will evaluate the safety and efficacy of Relamorelin compared to placebo in patients with diabetic gastroparesis. Patients will report daily severity scores of their diabetic gastroparesis symptoms.

    NCT03285308
    Conditions
    1. Gastroparesis
    2. Diabetes Mellitus
    Interventions
    1. Drug: Relamorelin
    2. Drug: Placebo
    MeSH:Gastroparesis
    HPO:Gastroparesis

    Primary Outcomes

    Description: Patients will assess severity of diabetic gastroparesis symptoms daily using an 11-point ordinal scale with 0 being least and 10 being the worst possible score. Patients will enter the score using an electronic diary.

    Measure: To compare the efficacy of relamorelin with placebo in participants with respect to their diabetic gastroparesis symptoms during the 12 weeks of treatment

    Time: Baseline, 12 Weeks

    Description: Vomiting episodes will be patient-recorded daily using an electronic diary.

    Measure: Percentage of patients meeting the vomiting symptom responder criterion in each of the last 6 of the 12 weeks of treatment

    Time: 12 Weeks

    Secondary Outcomes

    Description: A Nausea Responder is defined as an improvement of at least 2-points in the weekly symptom scores for nausea at each of the last 6 weeks of the 12-week Treatment Period. Nausea is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no nausea, and 10 meaning the worst possible nausea.

    Measure: Percentage of Patients Meeting the Nausea Responder Criterion

    Time: Baseline to Week 12

    Description: An Abdominal Pain Responder is defined as an improvement of at least 2-points in the weekly symptom scores for Abdominal Pain at each of the last 6 weeks of the 12-week Treatment Period. Abdominal Pain is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no abdominal Pain, and 10 meaning the worst possible abdominal pain.

    Measure: Percentage of Patients Meeting the Abdominal Pain Responder Criterion

    Time: Baseline to Week 12

    Description: A Bloating Responder is defined as an improvement of at least 2-points in the weekly symptom scores for bloating at each of the last 6 weeks of the 12-week Treatment Period. Bloating is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no bloating, and 10 meaning the worst possible bloating.

    Measure: Percentage of Patients Meeting the Bloating Responder Criterion

    Time: Baseline to Week 12

    Description: A Postprandial Fullness Responder is defined as an improvement of at least 2-points in the weekly symptom scores for Postprandial Fullness at each of the last 6 weeks of the 12-week Treatment Period. Postprandial Fullness is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no feeling of fullness until finishing a meal, and 10 meaning felling full after only a few bites

    Measure: Percentage of Patients Meeting the Postprandial Fullness Responder Criterion

    Time: Baseline to Week 12

    Description: The number of patients who experienced one or more TEAE during the 12 week treatment period.

    Measure: Number of Patients who experienced one or more Treatment Emergent Adverse Event (TEAE)

    Time: Baseline to Week 12
    21 A Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Co-administered MERS-CoV Antibodies REGN3048 and REGN3051 vs. Placebo in Healthy Adults

    This is a Phase 1, first-in-human (FIH), single site, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single ascending doses of a co-administered (1:1, w/w) combination of REGN3048 and REGN3051 mAb's, administered IV in healthy adult volunteers. Study duration of approximately 16 months. Approximately 48 evaluable subjects will be enrolled in the study, eight (8) subjects in each one of 6 sequential ascending IV dose cohorts. In each cohort, subjects will be randomized to receive mAb's REGN3048 and REGN3051 (6 subjects) or placebo (2 subjects). Primary Objective: To assess the safety and tolerability of REGN3048 and REGN3051 following co-administration of single, ascending IV doses of 1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's.

    NCT03301090
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Other: Placebo
    2. Biological: REGN3048
    3. Biological: REGN3051
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Changes from baseline in abbreviated physical examination

    Time: Days 1-2

    Measure: Changes from baseline in clinical safety laboratory values

    Time: From Day 2 up to Day 121

    Measure: Changes from baseline in Electrocardiogram (ECG) parameters

    Time: 15 mins after infusion

    Measure: Changes from baseline in Electrocardiogram (ECG) parameters

    Time: 24 hrs after infusion

    Measure: Changes from baseline in symptom-directed physical examination

    Time: From Day 1 up to Day 121

    Measure: Changes from baseline in vital signs

    Time: From Day 1 up to Day 121

    Measure: The incidence of Adverse Events

    Time: From Day 1 up to Day 121

    Measure: The incidence of treatment-emergent Serious Adverse Events

    Time: From Day 1 up to Day 121

    Measure: The severity of Adverse Events assessed by toxicity grading criteria

    Time: From Day 1 up to Day 121

    Measure: The severity of treatment-emergent Serious Adverse Events assessed by toxicity grading criteria

    Time: From Day 1 up to Day 121

    Measure: The type of treatment-emergent Serious Adverse Events

    Time: From Day 1 up to Day 121

    Secondary Outcomes

    Measure: AUC for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: AUC for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: AUC(0-infinity) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: AUC(0-infinity) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: CL for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: CL for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: CMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: CMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: K(e) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: K(e) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: t(1/2) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: t(1/2) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: The change from baseline of antibodies against REGN3048 and REGN3051 (anti-drug antibodies, ADA), as measured in serum using validated bridging assays

    Time: Day 121

    Measure: The change from baseline of antibodies against REGN3048 and REGN3051 (anti-drug antibodies, ADA), as measured in serum using validated bridging assays

    Time: Day 57

    Measure: TMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: TMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: V(ss) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121

    Measure: V(ss) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

    Time: From Day 1 up to Day 121
    22 Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease: The GPAD-3 Study

    Peripheral artery disease (PAD) is a disease in which plaque builds up in the arteries that carry blood to the head, organs, and limbs. PAD usually occurs in the arteries in the legs, but can affect any arteries. Over time, plaque can harden and narrow the arteries which limits the flow of oxygen-rich blood to organs and other parts of the body. Blocked blood flow to the arteries can cause pain and numbness. The pain is usually worse with exercise and gets better with rest. PAD can raise the risk of getting an infection which could lead to tissue death and amputation. This study is investigating whether granulocyte-macrophage colony stimulating factor (GM-CSF) improves symptoms and blood flow in people with PAD. GM-CSF is a drug that is used to stimulate the bone marrow to release stem cells. Participants in the study will be randomly selected to receive GM-CSF or a placebo. After a four-week screening phase, participants will receive injections of GM-CSF or a placebo three times a week for three-weeks. Three months later, participants will again receive injections of GM-CSF or placebo three times a week for three-weeks. At six months, the study team will follow up to see if the group that received GM-CSF had more improvement than the group that received placebo.

    NCT03304821
    Conditions
    1. Peripheral Artery Disease (PAD)
    Interventions
    1. Drug: GM-CSF
    2. Drug: Placebo
    MeSH:Peripheral Arterial Disease Peripheral Vascular Diseases
    HPO:Peripheral arterial stenosis

    Primary Outcomes

    Description: Participants will be walk up and down a 100-foot hallway for 6 minutes to cover the maximum distance possible. The distance, measured in feet, completed after 6 minutes will be recorded.

    Measure: Change in 6-minute walk distance

    Time: Baseline, Month 3, Month 6, Month 9

    Secondary Outcomes

    Description: Graded treadmill exercise testing will be performed using the Gardner protocol where the treadmill speed is kept at 2 mph and the grade starts at 0 and inclines by 2% every two minutes. The peak walking time (PWT) is the time until exercise is terminated because of severe claudication. Exercise testing will be performed twice and longest time will be used as the PWT for that study visit.

    Measure: Change in Peak Walking Time (PWT)

    Time: Baseline, Month 3, Month 6, Month 9

    Description: The Walking Impairment Questionnaire (WIQ) domain of walking distance asks respondents to rate how difficult it is to walk around home, as well as distances of 50, 150, 300, 600, 900 and 1500 feet. Possible responses are: not hard (4), slightly difficult (3), somewhat difficult (2), very difficult (1), and unable to do (0). Total raw scores range from 0 to 28 with higher scores indicating increased ability to walk further distances.

    Measure: Change in Walking Impairment Questionnaire (WIQ): Walking Distance Score

    Time: Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

    Description: The Walking Impairment Questionnaire (WIQ) domain of walking speed asks respondents to rate how difficult it is to walk the distance of one block slowly, at an average speed, quickly, and running/jogging. Possible responses are: not hard (4), slightly difficult (3), somewhat difficult (2), very difficult (1), and unable to do (0). Total raw scores range from 0 to 16 with higher scores indicating increased ability to walk fast.

    Measure: Change in Walking Impairment Questionnaire (WIQ): Walking Speed Score

    Time: Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

    Description: The Walking Impairment Questionnaire (WIQ) domain of stair climbing asks respondents to rate how difficult it is to climb 1, 2, and 3 flights of stairs. Possible responses are: not hard (4), slightly difficult (3), somewhat difficult (2), very difficult (1), and unable to do (0). Total raw scores range from 0 to 12 with higher scores indicating better ability to climb stairs.

    Measure: Change in Walking Impairment Questionnaire (WIQ): Stair Climbing Score

    Time: Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

    Description: 36-item Short-Form Health Survey (SF-36) consists of eight scaled scores for the domains of: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Study participants respond to questions relating to their health and activity level by selecting from a variety of Likert scale and yes/no response options. Each scale is directly transformed into a 0-100 scale and lower scores indicate more disability (a score of 0 equates to maximum disability while a score of 100 indicates no disability).

    Measure: Change in 36-item Short-Form Health Survey (SF-36) Score

    Time: Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

    Description: Claudication onset time (COT) during the treadmill exercise will be recorded along with the peak walking time (PWT). The claudication onset time (COT) is the duration of exercise until onset of the participant's typical claudication. This is differentiated from the peak walking time (PWT) which is the time until exercise is terminated because of severe claudication. Graded treadmill exercise testing will be performed using the Gardner protocol where the treadmill speed is kept at 2 mph and the grade starts at 0 and inclines by 2% every two minutes.

    Measure: Change in Claudication Onset Time (COT)

    Time: Baseline, Month 3, Month 6, Month 9

    Description: To obtain the ankle-brachial index (ABI), bilateral upper and lower extremity blood pressure cuffs are inflated about 30 millimeters of mercury (mmHg) above the systolic pressure. Doppler flow signals are used to detect the reappearing perfusion while reducing the cuff pressure. The results is expressed as a segmental/arm pressure ratio (ABI index). The highest pressure of the two arms will be used for calculating the ABI. The average ratio is about 1.0+/-0.10; an index of 0.90 or lower is considered abnormal. In patients with calcific, non-compressible arteries (certain diabetics) where ABI measurements are unreliable, a toe/ arm pressure index ratio will be performed, with a 2.5 cm cuff used on the great or second toes. A toe/arm index less than 0.65 is considered abnormal.

    Measure: Change in Ankle-Brachial Index (ABI)

    Time: Baseline, Month 3, Month 6, Month 9

    Description: Foot transcutaneous oxygen tension (TcPO2) is a noninvasive way to measure peripheral arterial disease. TcPO2 is obtained with a monitor before exercise after the patients have been standing for three minutes and is monitored throughout exercise. Values are recorded at initial claudication distance, absolute claudication distance, and after recovery from exercise. A commonly used cut point is 60 millimeters of mercury (mmHg), with values below this indicating the presence of peripheral arterial disease.

    Measure: Change in Foot Transcutaneous Oxygen Tension (TcPO2)

    Time: Baseline, Month 3, Month 6, Month 9
    23 A Phase 4, Multicenter, Randomized, Double Blind, Placebo Controlled Pilot Study to Assess the Efficacy and Safety of Acthar Gel in Subjects With Pulmonary Sarcoidosis

    The purpose of this study is to find out if Acthar Gel is safe and effective to treat pulmonary sarcoidosis. Participants will be randomly assigned (like flipping a coin) to receive a shot under their skin of Acthar Gel or a matching placebo gel that has no drug in it. They will receive their assigned shot twice a week for 24 weeks. All participants who complete the 24-week treatment period will be eligible to receive Acthar Gel for 24 more weeks, even if they were originally in the placebo group.

    NCT03320070
    Conditions
    1. Sarcoidosis, Pulmonary
    Interventions
    1. Drug: Acthar Gel
    2. Drug: Placebo
    MeSH:Sarcoidosis, Pulmonary Sarcoidosis

    Primary Outcomes

    Description: Based on absolute change of percent predicted, FVC is evaluated to determine if the condition is: Improved (+1) [≥ 5% absolute change] Unchanged (0) [>- 5% to < 5% absolute change], or Worse (-1) [≤ -5% absolute change]

    Measure: Number of Participants in each Category of Assessment based on Forced Vital Capacity, a Pulmonary Function Test Parameter

    Time: 24 weeks

    Description: Based on absolute change of percent predicted, FVC is evaluated to determine if the condition is: Improved (+1) [≥ 5% absolute change] Unchanged (0) [>- 5% to < 5% absolute change], or Worse (-1) [≤ -5% absolute change]

    Measure: Number of Participants in each Category of Assessment based on Forced Vital Capacity, a Pulmonary Function Test Parameter

    Time: 48 weeks

    Description: Based on absolute change of percent predicted, DLCO is evaluated to determine if the condition is: Improved (+1) [≥ 5% absolute change] Unchanged (0) [>- 5% to < 5% absolute change], Worse (-1) [≤ -5% absolute change]

    Measure: Number of Participants in each Category of Assessment based on the Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO), a Pulmonary Function Test Parameter

    Time: 24 weeks

    Description: Based on absolute change of percent predicted, DLCO is evaluated to determine if the condition is: Improved (+1) [≥ 5% absolute change] Unchanged (0) [>- 5% to < 5% absolute change], Worse (-1) [≤ -5% absolute change]

    Measure: Number of Participants in each Category of Assessment based on the Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO), a Pulmonary Function Test Parameter

    Time: 48 weeks

    Description: HRCT imaging will be evaluated by the investigator/radiology and the central reader to determine if the condition is improved (+1), unchanged (0), or worse (-1).

    Measure: Number of Participants in each Category of Assessment based on High Resolution Computer Tomography (HRCT)

    Time: 24 weeks

    Description: HRCT imaging will be evaluated by the investigator/radiology and the central reader to determine if the condition is improved (+1), unchanged (0), or worse (-1).

    Measure: Number of Participants in each Category of Assessment based on High Resolution Computer Tomography (HRCT)

    Time: 48 weeks

    Description: King's Sarcoidosis Questionnaire (General Health) is a 28-item questionnaire for participants to indicate the status of their sarcoidosis and treatment. Higher scores indicate improvement, and a change of 4 points is considered clinically meaningful. The score on the scale is evaluated to determine if the condition is: Improved (+1) based on a change of ≥ 4 points Unchanged (0) based on a change of >- 4 to < 4 points Worse (-1) based on a change of ≤ -4 points

    Measure: Number of participants in each Category of Assessment based on the King's Sarcoidosis Questionnaire (General Health), a Quality of Life Parameter

    Time: 24 weeks

    Description: King's Sarcoidosis Questionnaire (General Health) is a 28-item questionnaire for participants to indicate the status of their sarcoidosis and treatment. Higher scores indicate improvement, and a change of 4 points is considered clinically meaningful. The score on the scale is evaluated to determine if the condition is: Improved (+1) based on a change of ≥ 4 points Unchanged (0) based on a change of >- 4 to < 4 points Worse (-1) based on a change of ≤ -4 points

    Measure: Number of participants in each Category of Assessment based on the King's Sarcoidosis Questionnaire (General Health), a Quality of Life Parameter

    Time: 48 weeks

    Description: The FAS is a 10-item checklist for participants to indicate the level of their fatigue. Lower scores indicate improvement (less fatigue) and a change of 4 points is considered clinically meaningful. The score on the scale is evaluated to determine if the condition is: Improved (+1) based on a change of ≤ -4 points Unchanged (0) based on a change of >- 4 to < 4 points Worse (-1) based on a change of ≥ 4 points

    Measure: Number of participants in each Category of Assessment based on the Fatigue Assessment Score (FAS), a Quality of Life Parameter

    Time: 24 weeks

    Description: The FAS is a 10-item checklist for participants to indicate the level of their fatigue. Lower scores indicate improvement (less fatigue) and a change of 4 points is considered clinically meaningful. The score on the scale is evaluated to determine if the condition is: Improved (+1) based on a change of ≤ -4 points Unchanged (0) based on a change of >- 4 to < 4 points Worse (-1) based on a change of ≥ 4 points

    Measure: Number of participants in each Category of Assessment based on the Fatigue Assessment Score (FAS), a Quality of Life Parameter

    Time: 48 weeks

    Description: Corticosteroids are typically the first-line when treatment of sarcoidosis is required. Concerns of significant corticosteroid toxicity results in efforts to taper as early as possible. Participants are evaluated at each visit following randomization, and an algorithm is used to taper them off prednisone using incremental doses of 40, 30, 20, 10, 7.5, 5, 2.5 and 0 mg. When the clinical status is: Improvement, they go down by one level First stable visit without toxicity, they continue the same dose Second stable visit without toxicity, the go down by one level Stable visit with toxicity, their toxicity is treated and they may go down by one level Worsening, they go up by one or two levels, but do not exceed 40 mg/day

    Measure: Number of Participants Receiving each Dose of Prednisone

    Time: 24 weeks

    Description: Corticosteroids are typically the first-line when treatment of sarcoidosis is required. Concerns of significant corticosteroid toxicity results in efforts to taper as early as possible. Participants are evaluated at each visit following randomization, and an algorithm is used to taper them off prednisone using incremental doses of 40, 30, 20, 10, 7.5, 5, 2.5 and 0 mg. When the clinical status is: Improvement, they go down by one level First stable visit without toxicity, they continue the same dose Second stable visit without toxicity, the go down by one level Stable visit with toxicity, their toxicity is treated and they may go down by one level Worsening, they go up by one or two levels, but do not exceed 40 mg/day

    Measure: Number of Participants Receiving each Dose of Prednisone

    Time: 48 weeks
    24 A Randomized, Double-blind, Placebo-controlled, Adaptive Study to Evaluate Symptom Improvement and Metabolic Control Among Adult Subjects With Symptomatic Hypoparathyroidism Treated With Recombinant Human Parathyroid Hormone [rhPTH(1-84)]

    The purpose of this study is to evaluate whether adding an investigational medication called recombinant human parathyroid hormone (rhPTH[1-84]) to standard hypoparathyroidism therapy (oral calcium and active vitamin D tablets) may result in superior improvements in symptoms of hypoparathyroidism assessed by hypoparathyroidism symptom diary (HPT-SD) symptom scale compared with standard therapy.

    NCT03324880
    Conditions
    1. Hypoparathyroidism
    Interventions
    1. Biological: rhPTH(1-84)
    2. Biological: Placebo
    MeSH:Hypoparathyroidism
    HPO:Hypoparathyroidism

    Primary Outcomes

    Description: The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. For symptom subscale score, the average score of the symptom items 1-7 will be calculated.

    Measure: Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Subscale Score at Week 26

    Time: Baseline, Week 26

    Secondary Outcomes

    Description: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire contains 13 fatigue-related questions. The responses to the 13 items on the FACIT-Fatigue questionnaire are each measured on a 4-point Likert scale. Thus, the total score ranges from 0 to 52. High scores represent less fatigue.

    Measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26

    Time: Baseline, Week 26

    Description: The SF-36 is a validated instruments that question participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in PCS derived from SF-36v2 at Week 26 will be reported.

    Measure: Change From Baseline in Physical Component Summary (PCS) Derived From 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores at Week 26

    Time: Baseline, Week 26

    Description: The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. For Impact subscale, the average score of the impact items 10-13 will be calculated.

    Measure: Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Impact Subscale Score at Week 26

    Time: Baseline, Week 26

    Description: The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2.

    Measure: Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Impact Items Score at Week 26

    Time: Baseline, Week 26

    Description: The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2.

    Measure: Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Item Anxiety (item 8) Score at Week 26

    Time: Baseline, Week 26

    Description: The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2.

    Measure: Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Item Sadness or Depression (Item 9) Score at Week 26

    Time: Baseline, Week 26

    Description: The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. The change in individual symptom item scores will be reported.

    Measure: Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Items Score at Week 26

    Time: Baseline, Week 26

    Description: Response is defined as a 30% reduction in HPT-SD symptom subscale score from baseline. The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. For symptom subscale score, the average score of the symptom items 1-7 will be calculated.

    Measure: Number of Participants With Response at Week 26

    Time: Baseline to Week 26

    Description: The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. The Most Bothersome Symptom Score will be analyzed.

    Measure: Change From Baseline in the Most Bothersome Symptom Score at Week 26

    Time: Baseline, Week 26

    Description: The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) assessment is a 37-item instrument. Each item will be scored from 0=Not at all to 4=Very much.

    Measure: Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Score at Week 26

    Time: Baseline, Week 26

    Description: The SF-36 is a validated instruments that question participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in the score of individual domains of SF-36v2 at Week 26 will be reported.

    Measure: Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26

    Time: Baseline, Week 26

    Description: The SF-36 is a validated instruments that question participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. Change in the MCS of SF-36v2 at Week 26 will be reported.

    Measure: Change From Baseline in Mental Component Summary (MCS) Score of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26

    Time: Baseline, Week 26

    Description: The WPAI:Hypoparathyroidism will be used to assess how hypoparathyroidism affects partcipants' ability to work and perform regular activities. Concepts that the WPAI:Hypoparathyroidism measures include time missed from work and impairment of work and other regular activities due to specific health problems. The change from baseline in the questionnaire response will be reported.

    Measure: Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI:Hypoparathyroidism) Score at Week 26

    Time: Baseline, Week 26

    Description: The PGI-S is a verbal rating scale asks the respondent to best describe how their symptoms severity. Response options are no symptoms, mild, moderate, severe and very severe. Mean change in scores of PGI-S at Week 26 will be reported.

    Measure: Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Severity (PGI-S) at Week 26

    Time: Baseline, Week 26

    Description: The PGI-C is verbal rating scale asks the respondent to best describe change in symptoms compared to the beginning of study. Response options are very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse. Mean change in scores of PGI-C at Week 26 will be reported.

    Measure: Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Change (PGI-C) at Week 26

    Time: Baseline, Week 26

    Description: The neurocognitive test battery will include tests evaluating the frontal-executive domain, which encompasses functions attributable to the prefrontal cortex and its connections to the basal ganglia (mostly striatum). The tests will include the CogState (CS) Brief Battery (including the Detection: speed [range from 2.001 to 6; lower scores (LS) indicate improvement (IMP)], Identification: speed [range from 2.001 to 6; LS indicate IMP], One Card Learning: accuracy [range from 0 to 1.5708; higher scores (HS) indicate IMP], One Back: speed [range from 2.001 to 6; LS indicate IMP]), CS Groton Maze Learning Test: total errors (range from 0 to infinity; LS indicate IMP), CS International Shopping List Task (ISLT): number of correct responses (range from 0 to infinity; HS indicate IMP), and CS ISLT -Delayed Recall:number of correct responses (range from 0 to infinity; HS indicate IMP). Change in in-clinic neurocognitive assessment scores at Week 24 will be reported.

    Measure: Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24

    Time: Baseline, Week 24

    Description: The neurocognitive test battery will include tests evaluating the frontal-executive domain, which encompasses functions attributable to the prefrontal cortex and its connections to the basal ganglia (mostly striatum). The tests will include the CogState (CS) Brief Battery (including the Detection: speed [range from 2.001 to 6; lower scores (LS) indicate improvement (IMP)], Identification: speed [range from 2.001 to 6; LS indicate IMP], One Card Learning: accuracy [range from 0 to 1.5708; higher scores (HS) indicate IMP], One Back: speed [range from 2.001 to 6; LS indicate IMP]), CS Groton Maze Learning Test: total errors (range from 0 to infinity; LS indicate IMP), CS International Shopping List Task (ISLT): number of correct responses (range from 0 to infinity; HS indicate IMP), and CS ISLT -Delayed Recall:number of correct responses (range from 0 to infinity; HS indicate IMP). Changes in at-home neurocognitive assessment scores (CS Brief Battery) at Week 24 will be reported.

    Measure: Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 24

    Time: Baseline, Week 24

    Description: Change in 24-hour urine calcium excretion at Week 26 will be reported.

    Measure: Change From Baseline in 24-hour Urine Calcium Excretion at Week 26

    Time: Baseline, Week 26

    Description: Change in serum phosphate level at Week 26 will be reported.

    Measure: Change From Baseline in Serum Phosphate Level at Week 26

    Time: Baseline, Week 26

    Description: Changes in doses of active vitamin D and calcium supplements at Week 26 will be reported.

    Measure: Change From Baseline in Doses of Active Vitamin D and Calcium Supplements at Week 26

    Time: Baseline, Week 26

    Description: Number of participants with albumin-corrected serum calcium between 1.875 millimoles per liter (mmol/L) (7.5 milligram per decilitre [mg/dL]) and upper limit of normal (ULN) for the central laboratory normal range at Week 26 will be reported.

    Measure: Number of Participants With Albumin-corrected Serum Calcium Control at Week 26

    Time: Week 26

    Description: Number of participants achieving composite criteria of the following: albumin-corrected serum calcium between 1.875 mmol/L (7.5 mg/dL) and the ULN for the central laboratory normal range, dose of active vitamin D decreased by 50% and at least a 50% reduction from the baseline oral calcium supplement dose at Week 26 will be reported.

    Measure: Number of Participants who Achieve Composite Criteria for Albumin-corrected Serum Calcium Concentration, Vitamin D Dose and Oral Calcium Supplement Dose at Week 26

    Time: Baseline to Week 26

    Description: Bone turnover markers includes serum bone-specific alkaline phosphatase, procollagen amino-terminal peptide, C-terminal telopeptide of type 1 collagen, and osteocalcin.

    Measure: Change From Baseline in Bone Turnover Markers at Week 26

    Time: Baseline, Week 26

    Description: An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as AEs that started or worsened on or after the date and time of the first dose of investigational product.

    Measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    Time: From start of study drug administration up to Week 30
    25 A Phase 1 Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI7219 in Healthy Subjects, Including Assessment of the Impact of Changes to the Oral Formulation and Determination of Intravenous Pharmacokinetics

    This is a 6-part study to evaluate the safety, tolerability, and PK of MEDI7219 in healthy subjects. Parts A, B, C & E are the single-dose parts of the study. Parts D & F are the multiple ascending dose (MAD) parts of the study. The starting dose and formulation for Parts D & F will be selected from data emerging from Parts A, B and E. Enrollment of approximately 198 subjects is anticipated.

    NCT03362593
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: MEDI7219
    2. Drug: Placebo
    3. Drug: Formulation without Active Drug

    Primary Outcomes

    Description: Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)

    Measure: Number of subjects with Adverse Events as a measure of safety and tolerability of MEDI7219

    Time: Baseline to last follow up visit (Parts A and C - Day 28) (Part D & F Day 63) and (Parts B and E 28 days post last dose)

    Secondary Outcomes

    Description: PK parameters will be calculated from the plasma concentration versus time data for Cmax (maximum observed concentration)

    Measure: Pharmacokinetics of MEDI7219: Cmax

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit

    Description: PK parameters will be calculated from the plasma concentration versus time data for Tmax (time to maximum observed concentration)

    Measure: Pharmacokinetics of MEDI7219: Tmax

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit, Parts F cohort 2 ONLY: Pre-dose and 8 hours post-dose

    Description: PK parameters will be calculated from the plasma concentration versus time data for T1/2 (terminal half-life)

    Measure: Pharmacokinetics of MEDI7219: t1/2

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit

    Description: PK parameters will be calculated from the plasma concentration versus time data for AUC (0-inf) [area under the curve (AUC) extrapolated to infinity]

    Measure: Pharmacokinetics of MEDI7219: AUC (0-inf)

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit

    Description: PK parameters will be calculated from the plasma concentration versus time data for AUC (0-last) [area under the curve (AUC) from time 0 to last measurable concentration]

    Measure: Pharmacokinetics of MEDI7219: AUC(0-last)

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit

    Description: PK parameters will be calculated from the plasma concentration versus time data for (AUC 0-24) [area under the curve (AUC) from time 0 to 24 hours post dose]

    Measure: Pharmacokinetics of MEDI7219: AUC(0-24h)

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Parts D & F pre-dose to Day 63/EOS visit

    Description: PK parameters will be calculated from the plasma concentration versus time data for AUC%extrapolated [The percentage of AUC(0-inf) accounted for by extrapolation]

    Measure: Pharmacokinetics of MEDI7219: AUC (%extrap)

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only)

    Description: PK parameters will be calculated from the plasma concentration versus time data for Lambda-z [Slope of the regression line passing through the apparent elimination phase in a concentration vs time plot]

    Measure: Pharmacokinetics of MEDI7219: Lambda-z

    Time: Pre-dose to 144 hours post-dose (Parts A, B, C and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only)

    Description: PK parameters will be calculated from the plasma concentration for CL/F (apparent clearance)

    Measure: Pharmacokinetics of MEDI7219: CL/F

    Time: Pre-dose to 144 hours post-dose (Parts A, B and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only)

    Description: PK parameters will be calculated from the plasma concentration for Vz/F (volume of distribution)

    Measure: Pharmacokinetics of MEDI7219: Vz/F

    Time: Pre-dose to 144 hours post-dose (Parts A, B and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only); Pre-dose to Day 63/EOS visit (Parts D & F)

    Description: PK parameters will be calculated from the plasma concentration for Frel (relative bioavailability)

    Measure: Pharmacokinetics of MEDI7219: Frel

    Time: Pre-dose to 144 hours post-dose (Parts B and Part E cohorts 1 & 2 only); Pre-dose to 168 hours post-dose (Part E optional cohorts only)

    Description: PK parameters will be calculated from the plasma concentration for Vd (volume of distribution)

    Measure: Pharmacokinetics of MEDI7219: Vd

    Time: Pre-dose to 144 hours (Part C)

    Description: PK parameters will be calculated from the plasma concentration for F (absolute bioavailability)

    Measure: Pharmacokinetics of MEDI7219: F

    Time: Pre-dose to 144 hours (Part C )

    Description: PK parameters will be calculated from the plasma concentration versus time data for AUC (0-tau) [area under the curve (AUC) for a dosing interval]

    Measure: Pharmacokinetics of MEDI7219: AUC (0-tau)

    Time: Pre-dose to Day 63/EOS visit (Parts D & F)

    Description: Presence of Anti-drug antibody to MEDI7219

    Measure: Immunogenicity

    Time: Day -1 to Day 28/EOS Visit (Parts A and C); Day -1 to Day 63/EOS Visit (Parts D & F); Day -1 to 28 days post last dose of final period/EOS Visit (Parts B and E)

    Description: PK parameters will be calculated from the plasma concentration versus time data for Cmax (maximum observed concentration)

    Measure: Pharmacokinetics of Formulation Component: Cmax

    Time: Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively)

    Description: PK parameters will be calculated from the plasma concentration versus time data for Tmax (time to maximum observed concentration)

    Measure: Pharmacokinetics of Formulation Component: Tmax

    Time: Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively)

    Description: PK parameters will be calculated from the plasma concentration versus time data for T1/2 (terminal half-life)

    Measure: Pharmacokinetics of Formulation Component: T(1/2)

    Time: Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively)

    Description: PK parameters will be calculated from the plasma concentration versus time data for AUC (0-inf) [area under the curve (AUC) extrapolated to infinity]

    Measure: Pharmacokinetics of Formulation Component: AUC (0-inf)

    Time: Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively)

    Description: PK parameters will be calculated from the plasma concentration versus time data for AUC (0-last) [area under the curve (AUC) from time 0 to last measurable concentration]

    Measure: Pharmacokinetics of Formulation Component: AUC (0-last)

    Time: Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively)

    Description: PK parameters will be calculated from the plasma concentration versus time data for (AUC 0-24) [area under the curve (AUC) from time 0 to 8 hours post dose]

    Measure: Pharmacokinetics of Formulation Component: AUC (0-8h)

    Time: Predose to 8 hours post dose Day 1 (Parts A, B and E); Pre-dose to 8 hours post dose on Days 1, 7, 8, 14, 15, 21, 22, 28, 29 and 35 (Part D and F Cohort 1); Pre-dose to 24 hours post dose on Days 1, 14, 28 and 35 (Part F Cohort 2, respectively)

    Description: PK parameters will be calculated from the plasma concentration from CL (apparent clearance)

    Measure: Pharmacokinetics of MEDI7219: CL

    Time: Pre-dose to 144 hours post-dose (Part C)
    26 A 52-week, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis

    A 52-week study to compare the efficacy of relamorelin with that of placebo in participants with diabetic gastroparesis (DG) with respect to the core signs and symptoms of diabetic gastroparesis.

    NCT03383146
    Conditions
    1. Gastroparesis
    2. Diabetes Mellitus
    Interventions
    1. Drug: Relamorelin
    2. Drug: Placebo
    MeSH:Gastroparesis
    HPO:Gastroparesis

    Primary Outcomes

    Description: Participants will assess severity of diabetic gastroparesis symptoms daily using an 11-point ordinal scale with 0 being least and 10 being the worst possible score using an electronic diary

    Measure: Change from Baseline to Week 12 in the weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS)

    Time: Baseline to Week 12

    Description: Participants will assess severity of diabetic gastroparesis symptoms daily using an 11-point ordinal scale with 0 being least and 10 being the worst possible score using an electronic diary

    Measure: Change from Baseline to Week 52 in weekly average DGSSS

    Time: Baseline to Week 52

    Description: Incidence of AEs

    Measure: Number of participants with adverse events (AEs)

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS clinical laboratory values during the 52 week treatment period

    Measure: Number of clinically significant (CS) clinical laboratory values

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS vital sign values during the 52 week treatment period

    Measure: Vital sign values (heart rate, blood pressure, respiratory rate, and temperature)

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS ECG values during the 52 week treatment period

    Measure: Electrocardiogram (ECG) Heart Rate

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS ECG values during the 52 week treatment period

    Measure: ECG PR Interval

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS ECG values during the 52 week treatment period

    Measure: ECG QRS Interval

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS ECG values during the 52 week treatment period

    Measure: ECG QT Interval

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS ECG values during the 52 week treatment period

    Measure: ECG QTc Interval

    Time: Baseline to Week 52

    Description: The number of participants who experienced CS HbA1c levels during the 52 week treatment period

    Measure: Change from Baseline in hemoglobin A1c (HbA1c) levels

    Time: Baseline to Week 52

    Description: The number of participants who experienced anti-relamorelin antibodies during the 52 week treatment period

    Measure: Change from Baseline in anti-relamorelin antibodies

    Time: Baseline to Week 52
    27 A Randomized, 24-week Parallel-group Placebo-controlled Multicenter (Phase 2) Study of Anthocyanins in People at Risk for Dementia

    The aim of this project is to study the safety and efficacy of anthocyanins in improving key dementia-related mechanisms and cognitive functioning in older people at risk for dementia. Secondary analyses will include a variety of biological measures, including biochemistry, imaging and cardiovascular measures.

    NCT03419039
    Conditions
    1. Dementia
    2. Inflammation
    3. Mild Cognitive Impairment
    4. Coronary Artery Disease
    Interventions
    1. Dietary Supplement: Anthocyanins
    2. Dietary Supplement: Placebo
    MeSH:Dementia Coronary Artery Disease Inflammation Cognitive Dysfunction
    HPO:Cognitive impairment Coronary artery atherosclerosis Dementia Mental deterioration

    Primary Outcomes

    Description: A composite measure from the CogTrack battery

    Measure: Quality of episodic memory.

    Time: Baseline to 24 weeks

    Secondary Outcomes

    Description: CogTrack evaluates attentional intensity index, sustained intensity index, cognitive reaction time, attentional fluctuation index, quality of working memory, quality of episodic memory and speed of memory retrieval.

    Measure: Secondary endpoints from CogTrack

    Time: Baseline to 24 weeks

    Description: Lipid profile, fatty acids, cytokines ( among others: IL-1, IL-2, IL-6, TNF-a), plasma antoxidant status and vitamins (lipid peroxidation markers, vitamins E, C, A, total plasma antioxidant capacity, glutathion)., carinthine, blood glucose, HbA1c, anthocyanins and metabolites, mapping of a-beta degradation products.

    Measure: Blood outcome analysis

    Time: Baseline to 24 weeks

    Description: Flow-mediated dilation (FMD), Cardiac-ankle vascular index (CAVI), photoplethysmogram (PPG).

    Measure: Cardiovascular parameters

    Time: Baseline to 24 weeks

    Description: Microbiota

    Measure: Fecal analysis

    Time: Baseline to 24 weeks

    Description: kyrinin

    Measure: Urine analysis

    Time: Baseline to 24 weeks

    Description: anthocyanin metabolites

    Measure: CSF measurements

    Time: Baseline to 24 weeks

    Description: Diagnosing and follow-up of cerebrovascular disease

    Measure: MR-imaging/CT

    Time: Baseline to 24 weeks
    28 A 12-week, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis

    This study will evaluate the safety and efficacy of Relamorelin compared to placebo in patients with diabetic gastroparesis. Patients will report daily severity scores of their diabetic gastroparesis symptoms.

    NCT03426345
    Conditions
    1. Gastroparesis
    2. Diabetes Mellitus
    Interventions
    1. Drug: Relamorelin
    2. Drug: Placebo
    MeSH:Gastroparesis
    HPO:Gastroparesis

    Primary Outcomes

    Description: Patients will assess severity of diabetic gastroparesis symptoms daily using an 11-point ordinal scale with 0 being least and 10 being the worst possible score. Patients will enter the score using an electronic diary.

    Measure: To compare the efficacy of relamorelin with placebo in participants with respect to their diabetic gastroparesis symptoms during the 12 weeks of treatment

    Time: Baseline to Week 12

    Description: Vomiting episodes will be patient-recorded daily using an electronic diary.

    Measure: Percentage of patients meeting the vomiting symptom responder criterion in each of the last 6 of the 12 weeks of treatment

    Time: Baseline to Week 12

    Secondary Outcomes

    Description: A Nausea Responder is defined as an improvement of at least 2-points in the weekly symptom scores for nausea at each of the last 6 weeks of the 12-week Treatment Period. Nausea is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no nausea, and 10 meaning the worst possible nausea.

    Measure: Percentage of Patients Meeting the Nausea Responder Criterion

    Time: Baseline to Week 12

    Description: An Abdominal Pain Responder is defined as an improvement of at least 2-points in the weekly symptom scores for Abdominal Pain at each of the last 6 weeks of the 12-week Treatment Period. Abdominal Pain is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no abdominal pain, and 10 meaning the worst possible abdominal pain.

    Measure: Percentage of Patients Meeting the Abdominal Pain Responder Criterion

    Time: Baseline to Week 12

    Description: A Bloating Responder is defined as an improvement of at least 2-points in the weekly symptom scores for bloating at each of the last 6 weeks of the 12-week Treatment Period. Bloating is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no bloating, and 10 meaning the worst possible bloating.

    Measure: Percentage of Patients Meeting the Bloating Responder Criterion

    Time: Baseline to Week 12

    Description: A Postprandial Fullness Responder is defined as an improvement of at least 2-points in the weekly symptom scores for Postprandial Fullness at each of the last 6 weeks of the 12-week Treatment Period. Postprandial Fullness is assessed on an 11-point ordinal scale from 0 to 10, with 0 meaning no feeling of fullness until finishing a meal, and 10 meaning felling full after only a few bites.

    Measure: Percentage of Patients Meeting the Postprandial Fullness Responder Criterion

    Time: Baseline to Week 12

    Description: The number of patients who experienced one or more TEAE during the 12 week treatment period.

    Measure: Number of Patients who experienced one or more Treatment Emergent Adverse Event (TEAE)

    Time: Baseline to Week 12
    29 Noradrenergic Biomarkers in PTSD: Precision Medicine & Mechanisms

    Posttraumatic stress disorder (PTSD) affects many individuals who experience a traumatic event. There are a variety of treatment options for PTSD, including psychotherapy (talk therapy) options, as well as medications, such as the drug prazosin. Each of the treatment options available is effective at significantly reducing the symptoms of PTSD in some, but not all, individuals with PTSD. However, investigators are not yet able to predict in advance who is likely to respond to which of the available treatments. Neither are the investigators able to explain what changes in the brain after exposure to a traumatic stressors, and why it results in persistent symptoms of PTSD for some people, but not for others. In this study, the investigators are testing two things: First, is testing whether two simple, easy tests of how an individual's blood pressure changes with standing and how an individual's eye reacts to a pulse of light may be able to predict whether that person is likely to respond to the medication prazosin for PTSD. Second, is testing whether those who have been exposed to a traumatic stress show differences in how their body regulates the response to the stress-signal noradrenaline.

    NCT03539614
    Conditions
    1. Posttraumatic Stress Disorder
    Interventions
    1. Drug: Prazosin
    2. Drug: Placebo
    MeSH:Stress Disorders, Post-Traumatic

    Primary Outcomes

    Description: The PTSD Checklist for DSM 5 is a self-reported rating scale where an individual rates the severity of each symptom of PTSD on a likert scale. The ratings on individual items are summed to create a total score, which ranges from 0 to 80, with higher scores indicating more symptoms. The relationship between changes in participants' total PCL scores at different time points and prazosin exposure - and whether this relationship is moderated by baseline biomarker values - will be analyzed using a linear mixed effects model.

    Measure: Change in total PTSD Checklist for DSM 5 (PCL5) score

    Time: The PCL5 total score is assessed at baseline, during each stage of the study, and at the endpoint of the study. Thus, measurements will be scheduled to occur at the following time points, relative to the baseline visit: 0, 4, 8, 9-12, 16, and 20 weeks
    30 A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 305)

    The purpose of this study is to evaluate the efficacy and safety of ontamalimab in inducing clinical remission and endoscopic response in participants with moderate to severe Crohn's Disease.

    NCT03559517
    Conditions
    1. Crohn's Disease
    Interventions
    1. Biological: Ontamalimab
    2. Other: Placebo
    MeSH:Crohn Disease
    HPO:Crohn's disease

    Primary Outcomes

    Description: Clinical remission is determined by meeting the criteria for remission using the 2-item patient reported outcome (PRO) subscores of average worst daily abdominal pain (based on 11 point numeric rating scale [NRS] ranging from 0 [No pain] to 10 [Worst imaginable pain]) and average daily stool frequency of type 6/7 as per the Bristol Stool Form Scale (BSFS) (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

    Measure: Number of Participants With Clinical Remission at Week 16

    Time: Week 16

    Description: Endoscopic response is measured by a decrease from baseline in simple endoscopic score for Crohn's disease (SES-CD) (ranging from 0 to 56, with higher values indicating more severe disease). Number of participants with endoscopic response will be reported.

    Measure: Number of Participants With Endoscopic Response at Week 16

    Time: Week 16

    Secondary Outcomes

    Description: Clinical remission is defined by Crohn's Disease Activity Index CDAI score. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical remission as measured by CDAI will be reported.

    Measure: Number of Participants With Clinical Remission as Measured by Crohn's Disease Activity Index (CDAI) at Week 16

    Time: Week 16

    Description: Enhanced endoscopic response is measured by a decrease from baseline in SES-CD (range from 0 to 56, with higher values indicating more severe disease). Number of participants with enhanced endoscopic response will be reported.

    Measure: Number of Participants With Enhanced Endoscopic Response at Week 16

    Time: Week 16

    Description: Clinical remission is determined by meeting the criteria for clinical remission using the 2-item PRO subscores of average worst daily abdominal pain (based on the 4-point scale ranging from 0 = none to 3 = severe) and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

    Measure: Number of Participants With Clinical Remission by 2-item Patient Reported Outcome (PRO) at Week 16

    Time: Week 16

    Description: Clinical response as per 2-item PRO score is to meet at least 1 of the 2 criteria over the 7 most recent days: 1. A decrease in the average daily abdominal pain based on 11-point NRS ranging 0 (No pain) to 10 (Worst imaginable pain), with stool frequency of type 6/7 (very soft/liquid stools) either: a) not worsening from baseline and/or b) meeting the criteria for clinical remission, that is based on the average daily stool frequency of type 6/7 as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]). 2. A decrease from baseline in the average daily stool frequency of type 6/7 as per the BSFS, with the average daily worst abdominal pain either: a) not worsening from baseline and/or b) meeting the criteria for clinical remission (based on average daily abdominal pain using a 11-point NRS). Number of participants with clinical response will be reported.

    Measure: Number of Participants With Clinical Response at Week 16

    Time: Week 16

    Description: Number of participants with both clinical remission by 2-item PRO as determined by meeting the criteria for clinical remission using the 2-item PRO subscores of average worst daily abdominal pain (based on the 4-point scale ranging from 0 = none to 3 = severe) and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days and endoscopic response, as measured by a decrease in SES-CD (range from 0 to 56, with higher values indicating more severe disease).

    Measure: Number of Participants With Clinical Remission and Endoscopic Response at Week 16

    Time: Week 16

    Description: Complete endoscopic healing at Week 16 as measured by SES-CD (ranging from 0 to 56, with higher values indicating more severe disease) will be assessed. Number of participants with complete endoscopic healing will be reported.

    Measure: Number of Participants With Complete Endoscopic Healing at Week 16

    Time: Week 16

    Description: Clinical response as measured by at least a 100-point reduction in the CDAI from baseline (CDAI-100 response) will be assessed. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical response CDAI -100 at Week 16 will be reported.

    Measure: Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -100 at Week 16

    Time: Week 16

    Description: Clinical response as measured by at least a 70-point reduction in the CDAI from baseline (CDAI-70 response) will be assessed. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical response CDAI -70 at Week 16 will be reported.

    Measure: Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -70 at Week 16

    Time: Week 16

    Description: Clinical remission is determined by meeting the criteria for remission using the 2-item patient reported outcome (PRO) subscores of average worst daily abdominal pain (based on 11-point numeric rating scale [NRS] ranging from 0 [No pain] to 10 [Worst imaginable pain]) and average daily stool frequency of type 6/7 as per the Bristol Stool Form Scale (BSFS) (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

    Measure: Number of Participants With Clinical Remission Over Time

    Time: Baseline up to Week 16

    Description: Patient-reported CD clinical signs and symptom data will be collected using a daily e-diary. Participants record abdominal pain severity (numeric rating scale [NRS]), very soft stool/liquid stool frequency (as shown by BSFS [ranging from type 1 {separate hard lumps-like stools} to type 7 {entirely liquid stools}] type 6/7), total stool frequency, rectal bleeding frequency, rectal urgency frequency, nausea severity (none to severe), vomiting frequency, incontinence frequency, abdominal pain used in CDAI and general wellbeing (generally well to terrible).

    Measure: Change From Baseline in Individual and Total Sign/Symptom Score Based on Participant Daily e-Diary Entries at Week 16

    Time: Baseline, Week 16

    Description: Endoscopic healing at Week 16 measured as SES-CD (ranging from 0 to 56, with higher values indicating more severe disease) individual variables (Size of Ulcers, Ulcerated surface, Affected surface and Presence of Narrowing) will be assessed as well. Number of participants with endoscopic healing will be reported.

    Measure: Number of Participants With Endoscopic Healing at Week 16

    Time: Week 16

    Description: The IBDQ consists of 32 items grouped into 4 domains scored as bowel (10 to 70), systemic (5 to 35), emotional (12 to 84), and social function (5 to 35). The total score ranges from 32 to 224. For each domain and the total score, a higher score indicates better health-related quality of life

    Measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score

    Time: Baseline, Week 8, Week 12, up to Week 16, or early termination

    Description: The Short form-36 health survey is used to assess HRQL. It consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role- emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

    Measure: Change From Baseline in Short Form (SF)-36 at Week 16

    Time: Baseline, Week 16

    Description: Incidence of all cause hospitalizations will be assessed.

    Measure: Incidence of Hospitalizations

    Time: Baseline up to Week 32

    Description: Incidence of total inpatient days will be assessed.

    Measure: Incidence of Total Inpatient Days

    Time: Baseline up to Week 32

    Description: Incidence of Crohn's disease-related surgeries and other surgical procedures.

    Measure: Incidence of Crohn's Disease (CD)-related and Other Surgeries

    Time: Baseline up to Week 32
    31 A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 306)

    The purpose of this study is to evaluate the efficacy and safety of Ontamalimab in inducing clinical remission and endoscopic response in participants with moderate to severe Crohn's Disease.

    NCT03566823
    Conditions
    1. Crohn's Disease
    Interventions
    1. Biological: Ontamalimab
    2. Other: Placebo
    MeSH:Crohn Disease
    HPO:Crohn's disease

    Primary Outcomes

    Description: Clinical remission is determined by meeting the criteria for remission using the 2-item patient reported outcome (PRO) subscores of average worst daily abdominal pain (based on 11 point numeric rating scale [NRS] ranging from 0 [No pain] to 10 [Worst imaginable pain]) and average daily stool frequency of type 6/7 as per the Bristol Stool Form Scale (BSFS) (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

    Measure: Number of Participants With Clinical Remission at Week 16

    Time: Week 16

    Description: Endoscopic response is measured by a decrease from baseline in simple endoscopic score for Crohn's disease (SES-CD) (ranging from 0 to 56, with higher values indicating more severe disease). Number of participants with endoscopic response will be reported.

    Measure: Number of Participants With Endoscopic Response at Week 16

    Time: Week 16

    Secondary Outcomes

    Description: Clinical remission is defined by Crohn's Disease Activity Index CDAI score. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical remission as measured by CDAI will be reported.

    Measure: Number of Participants With Clinical Remission as Measured by Crohn's Disease Activity Index (CDAI) at Week 16

    Time: Week 16

    Description: Enhanced endoscopic response is measured by a decrease from baseline in SES-CD (range from 0 to 56, with higher values indicating more severe disease). Number of participants with enhanced endoscopic response will be reported.

    Measure: Number of Participants With Enhanced Endoscopic Response at Week 16

    Time: Week 16

    Description: Clinical remission is determined by meeting the criteria for clinical remission using the 2-item PRO subscores of average worst daily abdominal pain (based on the 4-point scale ranging from 0 = none to 3 = severe) and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

    Measure: Number of Participants With Clinical Remission by 2-item Patient Reported Outcome (PRO) at Week 16

    Time: Week 16

    Description: Clinical response as per 2-item PRO score is to meet at least 1 of the 2 criteria over the 7 most recent days: 1. A decrease in the average daily abdominal pain based on 11-point NRS ranging 0 (No pain) to 10 (Worst imaginable pain), with stool frequency of type 6/7 (very soft/liquid stools) either: a) not worsening from baseline and/or b) meeting the criteria for clinical remission, that is based on the average daily stool frequency of type 6/7 as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]). 2. A decrease from baseline in the average daily stool frequency of type 6/7 as per the BSFS, with the average daily worst abdominal pain either: a) not worsening from baseline and/or b) meeting the criteria for clinical remission (based on average daily abdominal pain using a 11-point NRS). Number of participants with clinical response will be reported.

    Measure: Number of Participants With Clinical Response at Week 16

    Time: Week 16

    Description: Number of participants with both clinical remission by 2-item PRO as determined by meeting the criteria for clinical remission using the 2-item PRO subscores of average worst daily abdominal pain (based on the 4-point scale ranging from 0 = none to 3 = severe) and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per the BSFS (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days and endoscopic response, as measured by a decrease in SES-CD (range from 0 to 56, with higher values indicating more severe disease).

    Measure: Number of Participants With Clinical Remission and Endoscopic Response at Week 16

    Time: Week 16

    Description: Complete endoscopic healing at Week 16 as measured by SES-CD (ranging from 0 to 56, with higher values indicating more severe disease) will be assessed. Number of participants with complete endoscopic healing will be reported.

    Measure: Number of Participants With Complete Endoscopic Healing at Week 16

    Time: Week 16

    Description: Clinical response as measured by at least a 100-point reduction in the CDAI from baseline (CDAI-100 response) will be assessed. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical response CDAI -100 at Week 16 will be reported.

    Measure: Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -100 at Week 16

    Time: Week 16

    Description: Clinical response as measured by at least a 70-point reduction in the CDAI from baseline (CDAI-70 response) will be assessed. CDAI is used to assess CD which range from 0-149 points: Asymptomatic remission, 150-220 points: Mild to moderate active CD, 221-450 points: Moderate to severe active CD, >451 points: Severely active to fulminant disease. Number of participants with clinical response CDAI -70 at Week 16 will be reported.

    Measure: Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -70 at Week 16

    Time: Week 16

    Description: Clinical remission is determined by meeting the criteria for remission using the 2-item patient reported outcome (PRO) subscores of average worst daily abdominal pain (based on 11-point numeric rating scale [NRS] ranging from 0 [No pain] to 10 [Worst imaginable pain]) and average daily stool frequency of type 6/7 as per the Bristol Stool Form Scale (BSFS) (ranging from type 1 [separate hard lumps-like stools] to type 7 [entirely liquid stools]) over the 7 most recent days. Number of participants with clinical remission will be reported.

    Measure: Number of Participants With Clinical Remission Over Time

    Time: Baseline up to Week 16

    Description: Patient-reported CD clinical signs and symptom data will be collected using a daily e-diary. Participants record abdominal pain severity (numeric rating scale [NRS]), very soft stool/liquid stool frequency (as shown by BSFS [ranging from type 1 {separate hard lumps-like stools} to type 7 {entirely liquid stools}] type 6/7), total stool frequency, rectal bleeding frequency, rectal urgency frequency, nausea severity (none to severe), vomiting frequency, incontinence frequency, abdominal pain used in CDAI and general wellbeing (generally well to terrible).

    Measure: Change From Baseline in Individual and Total Sign/Symptom Score Based on Participant Daily e-Diary Entries at Week 16

    Time: Baseline, Week 16

    Description: Endoscopic healing at Week 16 measured as SES-CD (ranging from 0 to 56, with higher values indicating more severe disease) individual variables (Size of Ulcers, Ulcerated surface, Affected surface and Presence of Narrowing) will be assessed as well. Number of participants with endoscopic healing will be reported.

    Measure: Number of Participants With Endoscopic Healing at Week 16

    Time: Week 16

    Description: The IBDQ consists of 32 items grouped into 4 domains scored as bowel (10 to 70), systemic (5 to 35), emotional (12 to 84), and social function (5 to 35). The total score ranges from 32 to 224. For each domain and the total score, a higher score indicates better health-related quality of life

    Measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score

    Time: Baseline, Week 8, Week 12, up to Week 16, or early termination

    Description: The Short form-36 health survey is used to assess HRQL. It consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role- emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

    Measure: Change From Baseline in Short Form (SF)-36 at Week 16

    Time: Baseline, Week 16

    Description: Incidence of all cause hospitalizations will be assessed.

    Measure: Incidence of Hospitalizations

    Time: Baseline up to Week 32

    Description: Incidence of total inpatient days will be assessed.

    Measure: Incidence of Total Inpatient Days

    Time: Baseline up to Week 32

    Description: Incidence of Crohn's disease-related surgeries and other surgical procedures.

    Measure: Incidence of Crohn's Disease (CD)-related and Other Surgeries

    Time: Baseline up to Week 32
    32 CSP #2008 - Pentoxifylline in Diabetic Kidney Disease

    Pentoxifylline (PTX) is a medication that has been on the market since 1984 for use in disease in the blood vessels of the legs. There is some preliminary information that it may protect the kidneys from damage due to diabetes and other diseases. "Pentoxifylline in Diabetic Kidney Disease" is a study to bee conducted in 40 VA hospitals across the nation to determine definitively whether or not PTX can prevent worsening of kidney disease and delay death in patients with diabetic kidney disease.

    NCT03625648
    Conditions
    1. Diabetic Kidney Disease
    Interventions
    1. Drug: Pentoxifylline
    2. Drug: Placebo
    MeSH:Kidney Diseases Diabetic Nephropathies
    HPO:Abnormality of the kidney Nephropathy

    Primary Outcomes

    Description: ESRD will be defined as need for chronic dialysis or renal transplantation.

    Measure: Time to ESRD or death

    Time: 5 to 9 years

    Secondary Outcomes

    Description: Quality of life as measured by the Kidney Disease Quality of Life Short Form (KDQoL-SF)

    Measure: Quality of life (KDQoL-SF)

    Time: 5 to 9 years

    Description: Time until doubling of serum creatinine

    Measure: Time until doubling of serum creatinine

    Time: 5 to 9 years

    Description: The risk of a CHF hospitalization will be based on the participant-time data, specifically, the number of events per years.

    Measure: Incidence of congestive heart failure hospitalization (CHF)

    Time: 5 to 9 years

    Description: The risk of a MACE event will be based on participant-time data, specifically, the number of events per participant years.

    Measure: Incidence of a three-point MACE

    Time: 5 to 9 years

    Description: The risk of a PVD event will be based on participant-time data, specifically, the number of events per participant years.

    Measure: Incidence of a peripheral vascular disease (PVD)

    Time: 5 to 9 years

    Description: Percentage of participants with 50% reduction in UACR from baseline

    Measure: Percentage of participants with 50% reduction in UACR from baseline

    Time: 5 to 9 years

    Description: Rate of change in eGFR per year during the study period.

    Measure: Rate of change in eGFR per year during the study period

    Time: 5 to 9 years
    33 Targeting Inflammation and Alloimmunity in Heart Transplant Recipients With Tocilizumab (RTB-004)

    The purpose of this research study is to see if a study drug called Tocilizumab will, when given with standard anti-rejection medicines, lead to better heart transplantation outcomes at 1 year after the transplant. Specifically, the investigators will evaluate whether taking tocilizumab leads to less rejection, less development of unwanted antibodies, and better heart function.

    NCT03644667
    Conditions
    1. Heart Transplant
    Interventions
    1. Biological: tocilizumab
    2. Biological: Placebo
    3. Drug: Standard of Care Triple IS

    Primary Outcomes

    Description: This outcome is defined by a composite 1 year post-transplant endpoint of: detection of de novo donor-specific antibodies (dnDSA) (Core Laboratory), acute cellular rejection (ACR) ≥ ISHLT 2R rejection (Core Laboratory), antibody mediated rejection (AMR) ≥ ISHLT AMR 1 (Core Laboratory), hemodynamic compromise rejection in the absence of a biopsy or histological rejection, death, or re-transplantation.

    Measure: Proportion of Participants Positive for Event of dnDSA, ACR, AMR, Hemodynamic Compromise, Death or Re-Transplantation - By Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Secondary Outcomes

    Description: A comparison by treatment group of the incidence of freedom from development of de novo donor-specific antibodies (dnDSA). dnDSA is a newly developed alloantibody that is against the donor organ.

    Measure: Freedom of Detection of de Novo Donor-Specific Antibodies (dnDSA) - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: A comparison by treatment group of the incidence of freedom from development of acute cellular rejection ≥2R (Reference: International Society of Heart and Lung Transplantation [ISHLT] acute cellular rejection-grade 2R or greater severity).

    Measure: Freedom from Acute Cellular Rejection (ACR) ≥ International Society of Heart and Lung Transplantation (ISHLT) 2R Rejection - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: A comparison by treatment group of the incidence of freedom from development of antibody-mediated rejection defined as ISHLT grade AMR 1 or greater severity.

    Measure: Freedom from Antibody Mediated Rejection (AMR) ≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1 - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: A comparison by treatment group of the incidence of freedom from development of hemodynamic compromise (HDC). Hemodynamic compromise is defined by: - Need for inotropic agents due to a Cardiac Index (CI) <2.0 L/min/m^2 or a 25% decrease from baseline, in addition to one of the following: ejection fraction of <40% or a 20% decrease from baseline, and the need for inotropic agents OR fractional shortening of <20% or a 25% decrease from baseline, and the need for inotropic agents.

    Measure: Freedom from Hemodynamic Compromise Rejection in the Absence of a Biopsy or Histological Rejection - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: A comparison by treatment group of the incidence of freedom from development of episode of rejection requiring treatment. Reference: Acute cellular rejection as defined by the 2004 International Society of Heart and Lung Transplantation (ISHLT) grading scale.

    Measure: Freedom from Any-Treated Rejection - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: A comparison by treatment group of the incidence of freedom from acute cellular rejection (ACR) ≥ ISHLT 2R rejection. Reference: 2004 International Society of Heart and Lung Transplantation [ISHLT [ grading scale).

    Measure: Freedom from Acute Cellular Rejection (ACR) ≥ International Society of Heart and Lung Transplantation (ISHLT) 2R Per Patient - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: Time from transplant, free of antibody mediated rejection, defined as ISHLT grade AMR 1 or greater will be compared between the treatment groups. Hemodynamic compromise is defined as the need for inotropic agents due to a Cardiac Index (CI) <2.0 L/min/m2 or a 25% decrease from baseline in addition to one of the following: Ejection fraction of <40% or a 20% decrease from baseline, and the need for inotropic agents Fractional shortening of <20% or a 25% decrease from baseline, and the need for inotropic agents

    Measure: Freedom from Antibody Mediated Rejection (AMR) (≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1) Per Participant - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)]

    Description: Time from transplant, free of antibody mediated rejection, defined as ISHLT grade AMR 1 or greater will be compared between the treatment groups

    Measure: Freedom from Hemodynamic Compromise Rejection in the Absence of a Biopsy or Histological Rejection Per Participant - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: Incidence of all-cause mortality will be compared between the treatment groups.

    Measure: Occurrence of Death - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: Incidence of participant(s) being re-listed for transplant will be compared between the treatment groups.

    Measure: Occurrence of Re-Listed for Transplantation - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)

    Description: Incidence of participant(s) re-transplantation will be compared between the treatment groups.

    Measure: Occurrence of Re-Transplantation - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)]

    Description: The frequency of events will be compared between the treatment groups.

    Measure: Number of Acute Cellular Rejection (≥ International Society of Heart and Lung Transplantation (ISHLT) 2R) Per Patient - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)]

    Description: The frequency of events will be compared between the treatment groups.

    Measure: Number of Antibody Mediated Rejection (AMR) (≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1) Per Participant - by Treatment Group

    Time: 12 months post-transplantation

    Description: The frequency of events will be compared between the treatment groups.

    Measure: Number of Rejection Episodes Associated with Hemodynamic Compromise (HDC) Per Participant - by Treatment Group

    Time: From transplant through 12 months post transplant surgery (12 months)]

    Description: Per protocol, per clinical research site standard of care.

    Measure: Change in Intravascular Ultrasound (IVUS) Measurements From Baseline to 1 Year Post-Transplant- by Treatment Group

    Time: Baseline (4 to 8 weeks post-transplant), 1 year post-transplant

    Description: In accordance with the International Society of Heart and Lung Transplantation (ISHLT) Cardiac Allograft Vasculopathy (CAV) angiographic grading scale.

    Measure: Angiographic Evidence of Cardiac Allograft Vasculopathy (CAV) - by Treatment Group

    Time: 12 months post-transplantation

    Description: Incidence of participant loss to follow up will be compared between the treatment groups.

    Measure: Participant Loss to follow up - by Treatment Group

    Time: 12 months post-transplantation

    Description: The frequency of serious infections requiring intravenous antimicrobial therapy and need for hospitalization will be compared between treatment groups.

    Measure: Occurrence of Serious Infections Requiring Intravenous Antimicrobial Therapy and Need for Hospitalization - by Treatment Group

    Time: Through 24 months post transplant surgery

    Description: The incidence of tuberculosis will be compared between treatment groups.

    Measure: Incidence of Tuberculosis - by Treatment Group

    Time: Through 24 months post transplant surgery

    Description: The incidence of CMV infection will be compared between treatment groups.

    Measure: Incidence of Cytomegalovirus (CMV) Infection - by Treatment Group

    Time: Through 24 months post transplant surgery

    Description: The incidence of PTLD will be compared between treatment groups.

    Measure: Incidence of Post-Transplant Lymphoproliferative Disease (PTLD) - by Treatment Group

    Time: Through 24 months post transplant surgery

    Description: The number of participants who discontinue study drug, per protocol, will be compared between treatment groups.

    Measure: Tolerability (Discontinuation of Study Drug) of Tocilizumab (TCZ) - by Treatment Group

    Time: Through 24 months post transplant surgery
    34 A Phase 2, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Relationships of Different Doses of JNJ-53718678 in Children >=28 Days and <=3 Years of Age With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus Infection

    The purpose of this study is to evaluate the antiviral activity, clinical outcomes, safety, tolerability, and pharmacokinetic/pharmacodynamic relationships of different oral dose levels of JNJ-53718678 in children greater than or equal to 28 days and less than or equal to 3 years of age with respiratory syncytial virus (RSV) disease (hospitalized participants [Cohort 1] or outpatients [Cohort 2]).

    NCT03656510
    Conditions
    1. Respiratory Syncytial Virus Infections
    Interventions
    1. Drug: JNJ-53718678
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Virus Diseases Respiratory Syncytial Virus Infections

    Primary Outcomes

    Description: RSV viral load AUC will be determined from immediately prior to first dose of study drug through Day 5. The RSV viral load is measured by the RSV viral load as measured by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assay of nasal swabs.

    Measure: Respiratory Syncytial Virus (RSV) Viral Load Area Under Curve (AUC) from Immediately Prior to First Dose of Study Drug Through Day 5

    Time: Baseline through Day 5

    Secondary Outcomes

    Description: RSV viral load and change from baseline over time will be measured by qRT-PCR assay in the mid-turbinate nasal swab specimens.

    Measure: RSV Viral Load and Change from Baseline Over Time

    Time: Baseline through Day 21

    Description: RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.

    Measure: RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 3, 8, and 14

    Time: Baseline through Days 3, 8 and 14

    Description: Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.

    Measure: Time to Undetectable RSV Viral Load

    Time: Up to 21 days

    Description: Proportion of participants with undetectable RSV viral load will be reported.

    Measure: Proportion of Participants with Undetectable RSV Viral Load at each timepoint

    Time: Up to 21 days

    Description: Duration of signs and symptoms of RSV disease will be assessed by PRESORS. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues).

    Measure: Duration of Signs and Symptoms of RSV Disease Assessed by the Pediatric RSV Electronic Severity and Outcome Rating Scale (PRESORS)

    Time: Up to 21 days

    Description: Severity of RSV disease will be assessed by PRESORS. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues).

    Measure: Severity of RSV Disease Assessed by PRESORS

    Time: Up to 21 days

    Description: Change from baseline in parent(s)/caregiver(s) PRESORS scores (worsening or improvement) will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) daily by parent/caregiver.

    Measure: Change from Baseline in Parent(s)/Caregiver(s) PRESORS Scores

    Time: Baseline up to 21 days

    Description: Change from baseline in clinician PRESORS scores (worsening or improvement) will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) by clinician.

    Measure: Change from Baseline in Clinician PRESORS Scores

    Time: Baseline up to 21 days

    Description: Time to resolution (that is, to none or mild) of RSV symptoms will be recorded.

    Measure: Time to Resolution of RSV Symptoms

    Time: Up to 21 days

    Description: Time to improvement based on general questions on overall health will be reported.

    Measure: Time to Improvement on Overall Health

    Time: Up to 21 days

    Description: Proportion of participants with improvement or worsening of RSV disease based on general questions on overall health will be reported.

    Measure: Proportion of Participants with Improvement or Worsening of RSV Disease

    Time: Up to 21 days

    Description: Time to return to pre-RSV health as rated by the parent(s)/caregiver(s) will be recorded.

    Measure: Time to Return to Pre-RSV Health as Rated by the Parent(s)/Caregiver(s)

    Time: Up to 21 days

    Description: Proportion of participants with vital signs (heart rate, respiratory rate, body temperature and peripheral capillary oxygen saturation [SpO2]) abnormalities will be reported.

    Measure: Proportion of Participants with Vital Sign Abnormalities

    Time: Up to 28 days

    Description: Proportion of participants with abnormal body temperature will be reported.

    Measure: Proportion of Participants with Abnormal Body Temperature as Measured by the Parent(s)/Caregiver(s)

    Time: Up to 28 days

    Description: Proportion of participants who require (re)hospitalization during treatment and follow-up will be reported.

    Measure: Proportion of Participants who Require (re)Hospitalization During Treatment and Follow-up

    Time: Up to 21 days

    Description: Time return to age-adjusted normal values for vital signs (heart rate, respiratory rate, and/or blood oxygen) for participants with risk factors for severe RSV Disease will be recorded.

    Measure: Time Return to Age-Adjusted Normal Values for vital signs (Heart Rate, Respiratory Rate, and/or Blood Oxygen) for Participants with Risk Factors for Severe RSV Disease

    Time: Up to 21 days

    Description: Time to discharge (from initial admission and from initiation of treatment) will be recorded for Cohort 1 only.

    Measure: Cohort 1: Time to Discharge

    Time: Up to 21 days

    Description: Proportion of participants who require to be admitted to the ICU will be reported for Cohort 1 only.

    Measure: Cohort 1: Proportion of Participants who Require to be Admitted to Intensive Care Unit (ICU)

    Time: Up to 21 days

    Description: In the event that a participant requires ICU, admission, the duration of need for ICU stay will be reported for Cohort 1 only.

    Measure: Cohort 1: Duration of ICU Stay

    Time: Up to 21 days

    Description: Proportion of participants who require supplemental oxygen will be reported for Cohort 1 only.

    Measure: Cohort 1: Proportion Participants who Require Supplemental Oxygen

    Time: Up to 21 days

    Description: Duration of the oxygen supplementation in participants requiring will be reported for Cohort 1 only.

    Measure: Cohort 1: Duration of Supplemental Oxygen

    Time: Up to 21 days

    Description: Proportion of participants who require non-invasive ventilator support (for example [e.g], continuous positive airway pressure) status will be reported for Cohort 1 only.

    Measure: Cohort 1: Proportion of Participants who Require Non-invasive Ventilator Support

    Time: Up to 21 days

    Description: Proportion of participants who require invasive ventilator support (e.g, endotracheal-mechanical ventilation) will be reported for Cohort 1 only.

    Measure: Cohort 1: Proportion of Participants who Require Invasive Mechanical Ventilation Support

    Time: Up to 21 days

    Description: Duration of non-invasive ventilator support (e.g, continuous positive airway pressure) to deliver oxygen will be measured for Cohort 1 only.

    Measure: Cohort 1: Duration of Non-invasive Ventilator Support

    Time: Up to 21 days

    Description: Duration of invasive ventilator support (e.g, endotracheal-mechanical ventilation) to deliver oxygen will be measured for Cohort 1 only.

    Measure: Cohort 1: Duration of Invasive Ventilator Support

    Time: Up to 21 days

    Description: Proportion of participants who need (defined by <50% of normal oral intake) hydration and/or feeding by IV administration or nasogastric tube will be reported for Cohort 1 only.

    Measure: Cohort 1: Proportion of Participants who Need Hydration and/or Feeding by Intravenously (IV) Administration or Nasogastric Tube

    Time: Up to 21 days

    Description: Time to clinical stability is defined as the time from initiation of study treatment until the time at which the following criteria are met: Time to return to age-adjusted normal values for otherwise healthy and pre-RSV infection status for participants with risk factor for severe RSV disease (heart rate, respiratory rate, blood oxygen level), no more oxygen supplementation or otherwise healthy participants and with risk factor(s) for severe RSV disease and no more intravenously (IV)/nasogastric tube feeding/hydration) in otherwise healthy participants or return to pre-RSV status of IV/nasogastric tube feeding/hydration in participants with risk factor for severe RSV disease for Cohort 1 only.

    Measure: Cohort 1: Time to Clinical Stability with Clinical Stability Evaluated by the Investigator

    Time: Up to 21 days

    Description: Time from initiation of study treatment until SpO2 >=92 percentage (%) and SpO2 >= 95% on room air among participants who were not on supplemental oxygen prior to the onset of respiratory symptoms will be reported for Cohort 1 only.

    Measure: Cohort 1: Time From Initiation of Study Treatment Until Peripheral Capillary Oxygen Saturation (SpO2) >= 92% and SpO2 >= 95% on Room Air Among Participants who Were not on Supplemental Oxygen Prior to Onset of Respiratory Symptoms

    Time: Up to 21 days

    Description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    Measure: Percentage of Participants with Adverse Events

    Time: Up to 28 days

    Description: Percentage of participants with abnormal laboratory (serum chemistry, hematology and urinalysis) findings will be reported.

    Measure: Percentage of Participants with Abnormal Laboratory Findings

    Time: Up to 28 days

    Description: Percentage of participants with abnormal ECGs findings will be reported.

    Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings

    Time: Up to 21 days

    Description: Plasma Concentrations of JNJ-53718678 will be evaluated and determined by population pharmacokinetics (popPK) modelling.

    Measure: Plasma Concentrations of JNJ-53718678

    Time: Days 1 and 3

    Description: Number of medical care encounters and treatments (including physician or emergency room visits, tests and procedures, and medications, surgeries and other procedures) will be reported.

    Measure: Medical Resource Utilization

    Time: Up to 28 days

    Description: Acceptability and palatability of the JNJ-53718678 formulation will be assessed through a questionnaire asking about the child's reaction when given the medicine, completed by parent(s)/caregiver(s) after last dosing.

    Measure: Acceptability and Palatability of the JNJ-53718678 Formulation as Assessed by Parent(s)/Caregiver(s)

    Time: Day 8

    Description: Number of participants with changes in the RSV F-gene compared with baseline sequences will be assessed by sequencing of the viral genome.

    Measure: Number of Participants with Post-baseline Changes in the RSV F-gene Compared with Baseline Sequences

    Time: Up to 21 days
    35 Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Effects of RO6889450 (Ralmitaront) in Patients With Schizophrenia or Schizoaffective Disorder and Negative Symptoms

    This study investigates the effects of RO6889450 on the negative symptoms associated with schizophrenia and schizoaffective disorder.

    NCT03669640
    Conditions
    1. Schizophrenia, Schizoaffective Disorder
    Interventions
    1. Drug: RO6889450
    2. Drug: Placebo
    MeSH:Schizophrenia Psychotic Disorders
    HPO:Psychosis Schizophrenia

    Primary Outcomes

    Measure: Change from Baseline at Week 12 in Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore

    Time: Baseline to Week 12

    Secondary Outcomes

    Measure: Change from Baseline in Clinical Global Impression Severity (CGI-S) Overall Scores

    Time: Baseline to week 12

    Measure: Change from Baseline in CGI-S Negative Symptoms Scores

    Time: Baseline to week 12

    Measure: Clinical Global Impression - Improvement (CGI-I) Overall Scores

    Time: Week 12

    Measure: CGI-I Negative Symptoms Scores

    Time: Week 12

    Measure: Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Total Scores

    Time: Baseline to week 12

    Measure: Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Symptom Factor Scores

    Time: Baseline to week 12

    Measure: Change from Baseline in Brief Negative Symptom Scale (BNSS) Total Scores

    Time: Baseline to week 12

    Measure: Change from Baseline in Brief Negative Symptom Scale (BNSS) Symptom Factor Scores

    Time: Baseline to week 12

    Measure: Change from Baseline in Defeatist Performance Attitude Scale (DPAS) Scores

    Time: Baseline to week 12

    Measure: Percentage of Participants with Adverse Events (AE)

    Time: Baseline through the end of the follow-up period (approximately 16 weeks)

    Measure: Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Scores

    Time: Baseline through the end of the follow-up period (approximately 16 weeks)

    Measure: Change from Baseline in Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A)

    Time: Baseline through the end of the follow-up period (approximately 16 weeks)

    Measure: Area Under the Curve at Steady State (AUCss) of RO6889450

    Time: At pre-defined intervals from Day 7 through the end of the follow-up period (approximately 16 weeks)

    Measure: Maximum Serum Concentration (Cmax) of RO6889450

    Time: At pre-defined intervals from Day 7 through the end of the follow-up period (approximately 16 weeks)
    36 A Phase 2, Randomized, Double-blind, Parallel Group, Placebo Controlled Study to Evaluate the Effect of Tezepelumab on Airway Inflammation in Adults With Inadequately Controlled Asthma on Inhaled Corticosteroids and at Least One Additional Asthma Controller (CASCADE)

    A phase 2, multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of tezepelumab on airway inflammation in adults with inadequately controlled asthma.

    NCT03688074
    Conditions
    1. Asthma
    2. Bronchial Diseases
    3. Respiratory Tract Diseases
    4. Lung Diseases, Obstructive
    5. Lung Diseases
    6. Respiratory Hypersensitivity
    7. Hypersensitivity, Immediate
    8. Hypersensitivity
    9. Immune System Diseases
    Interventions
    1. Biological: Tezepelumab
    2. Other: Placebo
    MeSH:Asthma Lung Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Bronchial Diseases Respiratory Hypersensitivity Hypersensitivity Immune System Diseases Hypersensitivity, Immediate Inflammation
    HPO:Abnormal lung morphology Allergy Asthma Pulmonary obstruction

    Primary Outcomes

    Description: The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies.

    Measure: The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies.

    Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

    Secondary Outcomes

    Description: The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies

    Measure: The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies

    Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

    Description: The change in % airway epithelial integrity from baseline determined by microscopic evaluation of bronchoscopic biopsies

    Measure: The change in % airway epithelial integrity from baseline determined by microscopic evaluation of bronchoscopic biopsies

    Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

    Description: The change in number of airway submucosal inflammatory cells per mm2 from baseline, across the spectrum of T2 status, determined by microscopic evaluation of bronchoscopic biopsies

    Measure: The change in number of airway submucosal inflammatory cells per mm2 from baseline, across the spectrum of T2 status, determined by microscopic evaluation of bronchoscopic biopsies

    Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.
    37 A Phase III Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Lower Respiratory Tract Parainfluenza Infection in Immunocompromised Subjects

    This study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection. It also contains a sub-study to enroll patients with severe COVID-19.

    NCT03808922
    Conditions
    1. Lower Respiratory Tract Infection
    2. Parainfluenza
    3. Immunocompromised
    4. COVID-19
    Interventions
    1. Drug: DAS181
    2. Drug: Placebo
    3. Drug: DAS181 COVID-19
    4. Drug: DAS181 OL
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Paramyxoviridae Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: Removal of all oxygen support (with stable SpO2)

    Measure: Percent of subjects who Return to Room Air (RTRA) (main study)

    Time: by Day 28

    Measure: Percent of subjects with improved COVID-19 Clinical Status Scale (sub-study)

    Time: Day 14

    Secondary Outcomes

    Measure: All-cause mortality rate (main study)

    Time: at Day 28

    Measure: Percent of subjects who Return to Room Air (RTRA) (main study)

    Time: by Day 21

    Measure: Time (in days) to RTRA (main study)

    Time: Days 10, 14, 21, 28

    Measure: Percent of subjects who achieve clinical stability (main study)

    Time: by Day 28

    Measure: Percent of subjects discharged (without mortality and hospice) (main study)

    Time: by Days 14, 21, 28 and 35

    Measure: Time (in days) to first hospital discharge (without hospice) (main study)

    Time: through Day 35

    Measure: Total number of inpatient days (main study)

    Time: up to Day 35

    Measure: Baseline SAD-RV infection-related mortality rate (main study)

    Time: at Day 28

    Measure: Baseline SAD-RV infection-related mortality rate (main study)

    Time: at Day 35

    Measure: All-cause mortality rate (main study)

    Time: at Day 35

    Measure: Change in pulmonary function (FEV1% predicted) (main study)

    Time: Day 1, Day 7, Day 14, Day 28

    Measure: Time to improved COVID19 clinical status (Sub-study)

    Time: Day 5, Day 10, Day 21, Day 28

    Measure: Time to RTRA

    Time: Day 10, Day 14, Day 21, Day 28

    Measure: Time to Clinical stability

    Time: Day 14, Day 21, Day 28

    Measure: Time to SARS-CoV-2 RNA in the respiratory specimens being undetectable

    Time: Day 5, Day 10, Day 14, Day 21, Day 28

    Measure: Time to Clinical deterioration

    Time: Day 5, Day 10, Day 14, Day 21, Day 28

    Measure: Time to Discharge from hospital (without readmission before Day 28).

    Time: Day 14, Day 21, Day 28

    Measure: Time to Death (all causes)

    Time: Day 14, Day 21, Day 28
    38 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging, Multi-Center Trial to Evaluate the Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Upper Limb Spasticity in Adults After Stroke or Traumatic Brain Injury

    This is a randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging, trial to Evaluate the Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Upper Limb Spasticity in Adults After Stroke or Traumatic Brain Injury. The study will be conducted in the U.S.A. , approximately 128 adult subjects from approximately 30 study centers will be randomly assigned (1:1:1:1) to one of four treatment groups. The study consists of a 21-day screening period, a treatment visit and follow-up visits.The study enrollment is discontinued early due to the impact of COVID-19 on enrollment.

    NCT03821402
    Conditions
    1. Upper Limb Spasticity
    Interventions
    1. Biological: DAXI for injection dose LOW DOSE
    2. Biological: DAXI for injection dose MEDIUM DOSE
    3. Biological: DAXI for injection Dose HIGH DOSE
    4. Other: Placebo
    MeSH:Muscle Spasticity
    HPO:Spasticity

    Primary Outcomes

    Description: Mean change from baseline in muscle tone measured with the Modified Ashworth Scale (MAS) in the suprahypertonic muscle group (SMG) of the elbow, wrist, OR finger flexors at Week 6. Score range: 0 (Normal tone, no in tone) to 4 (Affected part{s} rigid in flexion or extension)

    Measure: Change from Baseline from suprahypertonic muscle group (SMG) score

    Time: Week 6

    Description: Mean score on of the the Physician Global Impression of Change (PGIC) at Week 6. Score range: -4 (Markedly worse) to +4 (Markedly improved).

    Measure: Change from Baseline Physician Global Impression of Change (PGIC) score

    Time: Week 6

    Secondary Outcomes

    Description: Proportion of subjects who improve by a full point on the Modified Ashworth Scale (MAS) in the suprahypertonic muscle group (SMG). Score range: 0 (Normal tone, no increase in tone) to 4 (Affected part{s} rigid in flexion or extension)

    Measure: Muscle tone improvement

    Time: Weeks 6 and 12

    Description: Proportion of subjects with improvement (score ≥ 1) on the Physician Global Impression of Change (PGIC). Score range: 0 (Normal tone, no increase in tone) to 4 (Affected part{s} rigid in flexion or extension)

    Measure: Physician Global Impression of Change (PGIC) improvement

    Time: Weeks 6 and 12

    Description: Change in functional impairment as measured by the Disability Assessment Scale (DAS) for the principal treatment target (PTT). Score range: 0 (No disability) to 3 (Severe disability - normal activities limited).

    Measure: Disability Assessment Scale (DAS) functional impairment

    Time: Weeks 6 and 12

    Description: Duration of effect

    Measure: Duration of effect

    Time: Up to 36 weeks

    Description: Number of subjects with potential Botulinum Toxin type A distant spread of toxin adverse events, and number of subjects who develop neutralizing antibodies to Botulinum Toxin Type A will be assessed.

    Measure: Safety and immunogenicity assessment

    Time: Up to 36 weeks
    39 Promotion of Maternal Gut Microbiota and Psychological Stimulation on Child Cognitive Development at 6 Months of Age

    Probiotics is suggested to play several roles in promoting health, including alleviating disease symptoms, protection against atopic disease, and modulating the immune system by improving the beneficial gut microbiota colonization. The discovery of the gut microbiota-brain axis suggested that there is a reciprocal influence between the brain and the gut through a constant communication. This bi-directional axis enables signals to be transferred from brain to influence sensory, motor, and secretory modalities of the GI tract, also permits signal from the gut to influence brain function. The establishment of intestinal microbiota during early neurodevelopmental period suggests the colonization and maturation of gut microbiota may influence brain development. Several studies have shown there is an association between shifts in the gut microbiota composition in children with neurodevelopmental disorders. This study aims to investigate how maternal probiotic + LC-PUFA supported with government program supplements, healthy eating, and psychosocial stimulation could affect fetal brain development and later child brain functions and cognitive development. Intervention would be delivered to pregnant women for 9 months, starting at the end of second trimester of gestational period.

    NCT03851120
    Conditions
    1. Maternal Exposure
    2. Health Behavior
    3. Infant Development
    Interventions
    1. Dietary Supplement: Probiotic and LC-PUFA
    2. Dietary Supplement: Placebo
    3. Behavioral: Psychosocial stimulation and healthy eating education

    Primary Outcomes

    Description: measured in parenchymal and cortical regions

    Measure: Total brain volume

    Time: 1 year

    Description: Myelination index

    Measure: Fetal brain development

    Time: 1 year

    Description: Looking time (s) as a response to stimuli differentiation at 4 months of age

    Measure: Child cognitive and brain function at 4 months of age

    Time: 1 year

    Description: BSID-III

    Measure: Child cognitive at 6 months of age

    Time: 1 month

    Description: BERA

    Measure: Brain function at 6 months of age

    Time: 1 month

    Secondary Outcomes

    Description: Edinburgh Postnatal Depression Scale (EPDS)

    Measure: Mother depression scale

    Time: 1 year

    Description: Visual acuity

    Measure: Cognitive development and brain function at 4-months of age

    Time: 1 year

    Description: Baby weighing scale

    Measure: Birth weight

    Time: 1 month

    Description: Change in weight-for-age z-score

    Measure: Child's Growth

    Time: 6 months

    Description: Change in Length-for-age z-score

    Measure: Child's linear growth

    Time: 6 months

    Description: Change in Head-circumference-for-age

    Measure: Head circumference

    Time: 6 months

    Description: Change in weight-for-length z score

    Measure: Child nutritional status

    Time: 6 months

    Description: Maternal involvement using HOME inventory questionnaires

    Measure: Quality of interaction with parents

    Time: 1 year

    Description: Zinc, iron, folate blood level

    Measure: Maternal micronutrient status

    Time: 1 year

    Description: Blood glucose

    Measure: Gestational diabetes

    Time: 1 year

    Description: Diagnosed by doctor

    Measure: Pre-eclampsia

    Time: 1 year

    Description: Gestational age

    Measure: Preterm birth

    Time: 1 year

    Description: actual dietary intake, dietary pattern and quality

    Measure: Mother's dietary quality

    Time: 1 year

    Description: Microbiota composition by S16rRNA analysis

    Measure: Fecal microbiota composition

    Time: 1 year
    40 A Phase II Randomized, Double-blinded, Placebo-controlled Parallel Group Trial to Examine the Efficacy and Safety of BI 425809 Once Daily With Adjunctive Computerized Cognitive Training Over 12 Week Treatment Period in Patients With Schizophrenia

    The primary objective of this Phase II exploratory trial is to provide Proof of Concept (PoC) data to assess the effect on cognition of oral once daily administration of BI 425809 given for 12 weeks in patients with schizophrenia on stable antipsychotic treatment and adjunctive Computerized Cognitive Training (CCT).

    NCT03859973
    Conditions
    1. Schizophrenia
    Interventions
    1. Drug: BI 425809
    2. Drug: Placebo
    MeSH:Schizophrenia
    HPO:Schizophrenia

    Primary Outcomes

    Measure: Change from baseline in neurocognitive function as measured by the neurocognitive composite score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)

    Time: Up to 12 weeks

    Secondary Outcomes

    Measure: Change from baseline in cognitive function as measured by the overall MCCB composite score (including social cognition)

    Time: Up to 12 weeks

    Description: Schizophrenia Cognition Rating Scale (SCoRS)

    Measure: Change from baseline in the effect of cognitive deficit on day-to-day functioning as measured by SCoRS total score

    Time: Up to 12 weeks

    Description: Positive and Negative Syndrome Scale (PANSS)

    Measure: Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score

    Time: Up to 12 weeks

    Measure: Percentage of patients with (S)AEs

    Time: Up to 12 weeks
    41 Prevention of Maternal and Neonatal Death/Infections With a Single Oral Dose of Azithromycin in Women in Labor (in Low- and Middle-income Countries): a Randomized Controlled Trial

    Maternal and neonatal infections are among the most frequent causes of maternal and neonatal deaths, and current antibiotic strategies have not been effective in preventing many of these deaths. Recently, a randomized clinical trial conducted in a single site in The Gambia showed that treatment with oral dose of 2 g azithromycin vs. placebo for all women in labor reduced selected maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. The A-PLUS trial includes two primary hypotheses, a maternal hypothesis and a neonatal hypothesis. First, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce maternal death or sepsis. Second, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce intrapartum/neonatal death or sepsis.

    NCT03871491
    Conditions
    1. Maternal Death
    2. Maternal Infections Affecting Fetus or Newborn
    3. Neonatal SEPSIS
    4. Maternal Sepsis During Labor
    5. Neonatal Death
    6. Postpartum Sepsis
    Interventions
    1. Drug: Azithromycin
    2. Drug: Placebo
    MeSH:Infection Sepsis Toxemia Neonatal Sepsis Pregnancy Complications, Infectious Puerperal Infection Perinatal Death Maternal Death Death
    HPO:Neonatal death Neonatal sepsis Sepsis

    Primary Outcomes

    Description: Incidence of maternal death or sepsis within 6 weeks (42 days) post-delivery in intervention vs. placebo group.

    Measure: Maternal: Incidence of maternal death or sepsis within 6 weeks (42 days) post-delivery in intervention vs. placebo group.

    Time: within 6 weeks (42 days)

    Description: Incidence of intrapartum/neonatal death or sepsis within 4 weeks (28 days) post-delivery in intervention vs. placebo group

    Measure: Neonatal: Incidence of intrapartum/neonatal death or sepsis within 4 weeks (28 days) post-delivery in intervention vs. placebo group

    Time: 4 weeks (28 days) post-delivery

    Secondary Outcomes

    Description: Fever (>100.4°F/38°C) in addition to one or more of the following: fetal tachycardia ≥160 bpm, maternal tachycardia >100 bpm, tender uterus between contractions, or purulent/foul smelling discharge from uterus prior to delivery.

    Measure: Incidence of chorioamnionitis

    Time: prior to delivery

    Description: Fever (>100.4°F/38°C) in addition to one or more of maternal tachycardia >100 bpm, tender uterine fundus, or purulent/foul smelling discharge from uterus after delivery.

    Measure: Incidence of endometritis

    Time: within 42 days post-delivery

    Description: Wound infection (Purulent infection of a perineal or Cesarean wound with or without fever. In the absence of purulence, requires presence of fever >100.4°F/38°C and at least one of the following signs of local infection: pain or tenderness, swelling, heat, or redness around the incision/laceration); Abdominopelvic abscess (Evidence of pus in the abdomen or pelvis noted during open surgery, interventional aspiration or imaging); Pneumonia (Fever >100.4°F/38°C and clinical symptoms suggestive of lung infection including cough and/or tachypnea >24 breaths/min or radiological confirmation); Pyelonephritis (Fever >100.4°F/38°C and one or more of the following: urinalysis/dip suggestive of infection, costovertebral angle tenderness, or confirmatory urine culture); Mastitis/breast abscess or infection (Fever >100.4°F/38°C and one or more of the following: breast pain, swelling, warmth, redness, or purulent drainage).

    Measure: Incidence of other infections

    Time: within 42 days post-delivery

    Description: Use of subsequent maternal antibiotic therapy after randomization to 42 days postpartum for any reason.

    Measure: Incidence of use of subsequent maternal antibiotic therapy

    Time: after randomization to 42 days post-delivery

    Description: Time from drug administration until initial discharge after delivery (time may vary by site).

    Measure: Maternal initial hospital length of stay

    Time: within 42 days post-delivery

    Description: Maternal readmissions within 42 days of delivery

    Measure: Incidence of maternal readmissions

    Time: within 42 days post-delivery

    Description: Maternal admission to special care units

    Measure: Incidence of maternal admission to special care units

    Time: within 42 days post-delivery

    Description: Maternal unscheduled visit for care

    Measure: Incidence of maternal unscheduled visit for care

    Time: within 42 days post-delivery

    Description: Maternal GI symptoms including nausea, vomiting, and diarrhea and other reported side effects.

    Measure: Incidence of maternal GI symptoms

    Time: within 42 days post-delivery

    Description: Maternal death due to sepsis using the Global Network algorithm for cause of death

    Measure: Incidence of maternal death due to sepsis

    Time: within 42 days post-delivery

    Description: Incidence of other neonatal infections.

    Measure: Incidence of other neonatal infections (e.g. eye infection, skin infection)

    Time: within 42 days post-delivery

    Description: Neonatal initial hospital length of stay, defined as time of delivery until initial discharge (time may vary by site).

    Measure: Neonatal initial hospital length of stay

    Time: within 28 days of delivery

    Description: Neonatal readmissions within 42 days of delivery

    Measure: Incidence of neonatal readmissions

    Time: within 42 days of delivery

    Description: Neonatal admission to special care units

    Measure: Incidence of neonatal admission to special care units

    Time: within 28 days of delivery

    Description: Neonatal unscheduled visit for care

    Measure: Incidence of neonatal unscheduled visit for care

    Time: within 42 days post-delivery

    Description: Neonatal death due to sepsis using the Global Network algorithm for causes of death

    Measure: Incidence of neonatal death due to sepsis

    Time: within 28 days of delivery

    Description: Pyloric stenosis within 42 days of delivery, defined as clinical suspicion based on severe vomiting leading to death, surgical intervention (pyloromyotomy) as verified from medical records, or radiological confirmation.

    Measure: Incidence of pyloric stenosis within 42 days of delivery

    Time: within 42 days of delivery
    42 A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease

    This study will be conducted to evaluate the efficacy of BAN2401 in participants with early Alzheimer's disease (EAD) by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of BAN2401 in participants with EAD in the Extension Phase and whether the long-term effects of BAN2401 as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase.

    NCT03887455
    Conditions
    1. Early Alzheimer's Disease
    Interventions
    1. Drug: BAN2401
    2. Drug: Placebo
    MeSH:Alzheimer Disease
    HPO:Alzheimer disease

    Primary Outcomes

    Measure: Core Study: Change from Baseline in the CDR-SB at 18 Months

    Time: Baseline, 18 months

    Description: Here MRI means magnetic resonance imaging, ECG means electrocardiogram, and ADAs means antidrug antibodies.

    Measure: Extension Phase: Number of Participants With Adverse Events (AEs), Clinically Significant Change From Baseline in Vital Signs Values, Abnormal MRI and ECG Values, Clinically Significant Findings in Laboratory Values, Positive ADAs, and any Suicidality

    Time: Month 18 up to Month 45

    Measure: Extension Phase: Change from Core Study Baseline in CDR-SB

    Time: Baseline up to Month 45

    Secondary Outcomes

    Measure: Core Study: Change from Baseline in the Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) Composite at 18 Months

    Time: Baseline, 18 months

    Measure: Core Study: Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months

    Time: Baseline, 18 months

    Measure: Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months

    Time: Baseline, 18 months
    43 A Phase 1b Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Pharmacokinetics, and Anti-viral Effects of Galidesivir Administered Via Intravenous Infusion to Subjects With Yellow Fever or COVID-19

    This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics, safety and antiviral activity of galidesivir in subjects with yellow fever (YF) or COVID-19.

    NCT03891420
    Conditions
    1. COVID-19
    2. Yellow Fever
    Interventions
    1. Drug: Galidesivir
    2. Drug: Placebo
    MeSH:Yellow Fever Fever
    HPO:Fever

    Primary Outcomes

    Measure: number of subjects with treatment emergent adverse events and serious adverse events

    Time: absolute number through the end of the study, approximately 56 days

    Measure: number of subjects with change in laboratory parameters

    Time: absolute number and change from baseline through the end of the study, approximately 56 days

    Measure: exposure of galidesivir as measured by plasma concentrations

    Time: 24 hours post dose on Day 1 through 12 hours post dose on Day 7

    Secondary Outcomes

    Measure: yellow fever virus (YFV) titer (Group A)

    Time: change in YFV titer from baseline through Day 21

    Measure: antiviral effect on SARS-CoV-2 in the respiratory tract - COVID-19 (Group B)

    Time: change in SARS-CoV-2 from baseline through Day 21

    Measure: changes in clinical status using 8-point ordinal scale in COVID-19 (Group B)

    Time: through Day 21

    Measure: changes from baseline and time to improvement using NEWS in COVID-19 (Group B)

    Time: through Day21

    Measure: mortality

    Time: mortality at Day 56
    44 A Phase 1, Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB091, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Healthy Adult Participants

    This study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of BIIB091 in healthy participants.This study will also determine the effect of food on the single oral dose pharmacokinetic (PK).

    NCT03943056
    Conditions
    1. Healthy Volunteer
    Interventions
    1. Drug: BIIB091
    2. Drug: Placebo

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.

    Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time: Baseline up to Day 9 for SAD Cohorts; Baseline up to Day 24 for MAD Cohorts

    Secondary Outcomes

    Measure: Area Under the Curve from Time 0 to the Time of the Last Measurable Concentration (AUClast)

    Time: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts

    Measure: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)

    Time: Baseline and multiple timepoints up to Day 3

    Measure: Maximum Observed Concentration (Cmax)

    Time: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 14 for MAD Cohorts

    Measure: Time to Reach Maximum Observed Concentration (Tmax)

    Time: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 14 for MAD Cohorts

    Measure: Elimination Half-Life (t½)

    Time: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts

    Measure: Apparent Total Body Clearance (CL/F)

    Time: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts

    Measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F)

    Time: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts

    Measure: Amount of BIIB091 Excreted in Urine per Sampling Interval (Aeu)

    Time: Baseline and multiple timepoints up to Day 3

    Measure: Percentage of BIIB091 Excreted in Urine per Sampling Interval (%Feu)

    Time: Baseline and multiple timepoints up to Day 3

    Measure: Renal clearance (CLr)

    Time: Baseline and multiple timepoints up to Day 3

    Measure: Area Under the Concentration-Time Curve Within a Dosing Interval (AUCtau)

    Time: Baseline and multiple timepoints up to Day 16

    Measure: Accumulation Ratio (R)

    Time: Baseline and multiple timepoints up to Day 16

    Measure: Trough concentration (Ctrough)

    Time: Baseline and multiple timepoints up to Day 16
    45 A Phase IIIB, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Clinical Efficacy Study of Baloxavir Marboxil for the Reduction of Direct Transmission of Influenza From Otherwise Healthy Patients to Household Contacts

    Otherwise healthy index patients (IP) are randomized to either baloxavir marboxil or placebo if their influenza symptoms onset was within 48 hours of screening. Their households are enrolled within 24 hours of randomization if at least 2 household contacts (HHC) have not received influenza vaccine within 6 months of screening and if all HHC screen negative for influenza infection. The main endpoints are assessed based on multiple respiratory swabs, obtained from both IP and HHC up to 9 (+/-1) days post IP randomization, and through the assessment of symptoms.

    NCT03969212
    Conditions
    1. Influenza
    Interventions
    1. Drug: Baloxavir Marboxil
    2. Drug: Placebo
    MeSH:Influenza, Human

    Primary Outcomes

    Description: Defined as the percentage of Household Contacts (HHCs) who become Polymerase Chain Reaction Positive (PCR+) for Influenza by Day 5 post IP randomization. HHCs may be symptomatic or asymptomatic and their virus subtype must match that of the index patient (IP) in their household. The primary efficacy analysis population will consist of all enrolled unvaccinated HHCs of the randomized IPs.

    Measure: Virological Transmission by Day 5

    Time: Baseline to Day 5 (5 days)

    Secondary Outcomes

    Description: Defined as the percentage of HHCs who become PCR+ for Influenza by Day 5 post IP randomization and develop Influenza symptoms at any time during the study. HHCs ≥12 years old were defined symptomatic if (1) Presence of temperature ≥38.0 Celsius and one respiratory symptom (cough, sore throat, nasal congestion) or (2) Presence of one respiratory symptom and one general systemic symptom (headache, feverishness or chills, muscle or joint pain, fatigue), with or without fever. HHCs ≥2 and <12 years old were defined symptomatic if presence of temperature ≥38.0 Celsius and cough, nasal congestion, or rhinorrhea. Note: For HHCs of any age, respiratory or general systemic symptoms had to be either (1) new, or (2) worsened versus baseline with baseline symptoms due to a pre-existing comorbidity. HHCs must have their virus subtype match that of the IP.

    Measure: Symptomatic Transmission by Day 5

    Time: Baseline to Day 5 (5 days)

    Description: Defined as the percentage of households with at least one HHC who meets the primary endpoint.

    Measure: Virological Transmission at the Household Level by Day 5

    Time: Baseline to Day 5 (5 days)

    Description: Defined as the percentage of households with at least one HHC who meets the "Symptomatic transmission by Day 5 endpoint.

    Measure: Symptomatic Transmission at the Household Level by Day 5

    Time: Baseline to Day 5 (5 days)

    Description: Defined as the percentage of HHCs who become PCR+ for Influenza by Day 9 post IP randomization. HHCs must have their virus subtype match that of the IP, and include: (1) all HHC meeting primary endpoint, AND (2) all HHC cases detected after Day 5 Visit meeting the following criteria: (2a) included HHC case is in a household where another HHC has already met the primary endpoint, OR (2b) included HHC case is PCR (+) for influenza bearing treatment-emergent amino acid substitutions in the PA protein that have been associated with reduced susceptibility to baloxavir marboxil.

    Measure: Virological Transmission by Day 9

    Time: Baseline to Day 9 (9 days)

    Description: Defined as the percentage of HHCs who meet the "Virological transmission by Day 9" endpoint AND are symptomatic per the definition for symptoms in the "Symptomatic transmission by Day 5" endpoint.

    Measure: Symptomatic Transmission by Day 9

    Time: Baseline to Day 9 (9 Days)

    Description: Defined as the percentage of HHCs who become PCR (+) for influenza (confirmed at central laboratory) by Day 9.

    Measure: Any Virological Infection by Day 9

    Time: Baseline to Day 9 (9 Days)

    Description: Defined as the percentage of households with at least one HHC who meets the "Any virological infection by Day 9" endpoint.

    Measure: Any Virological Infection at the Household Level by Day 9

    Time: Baseline to Day 9 (9 Days)

    Description: Defined as the percentage of HHCs who meet the "Any virological infection by Day 9" endpoint AND are symptomatic per the definition for symptoms in the "Symptomatic transmission by Day 5" endpoint.

    Measure: Any Symptomatic Infection by Day 9

    Time: Baseline to Day 9 (9 Days)

    Description: Defined as the percentage of households with at least one HHC who meets the "Any symptomatic infection by Day 9" endpoint.

    Measure: Any Symptomatic Infection at the Household Level by Day 9

    Time: Baseline to Day 9 (9 Days)

    Measure: Percentage of IPs With Adverse Events (AEs)

    Time: Baseline to Day 9 (≥12 years old) and Day 21 (<12 years old)

    Description: The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.

    Measure: Change from baseline in health-related quality of life according to EuroQol 5 dimensions 5 (EQ-5D-5L; Appendix 3) questionnaire at Day 3 and Day 9 Visits (IPs only)

    Time: Baseline, Day 3 and Day 9

    Description: The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment.

    Measure: Change From Baseline in Work Productivity and Activity Impairment According to Work Productivity and Activity Impairment (WPAI) plus Classroom Impairement Questions Score (IPs only)

    Time: Baseline and Day 9
    46 Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 706321 in Healthy Male Subjects (Single-blind, Randomised, Placebo-controlled, Parallel Group Design)

    The main objectives are: - Part I: To investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy male subjects following oral administration of single rising doses. - Part II: The relative bioavailability of BI 706321 after administration of tablets and capsules under fasted conditions will be compared with each other and the effect of food on the tablet bioavailability will be investigated.

    NCT03971695
    Conditions
    1. Healthy
    Interventions
    1. Drug: BI 706321
    2. Drug: Placebo

    Primary Outcomes

    Measure: Part I: Safety and tolerability of BI 706321 is the percentage of subjects with drug-related adverse events

    Time: Up to 22 Days

    Measure: Part II: AUC0-tz (area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 to the last quantifiable data point)

    Time: Up to 22 Days

    Measure: Part II: Cmax (maximum measured concentration of BI 706321 in plasma)

    Time: Up to 22 Days

    Secondary Outcomes

    Measure: Part I: AUC0-∞ (area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity)

    Time: Up to 22 Days

    Measure: Part I: Cmax (maximum measured concentration of BI 706321 in plasma)

    Time: Up to 22 Days

    Measure: Part I: tmax (time from dosing to the maximum measured concentration of BI 706321 in plasma)

    Time: Up to 22 Days

    Measure: Part II: AUC0-∞ (area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity)

    Time: Up to 22 Days
    47 A Pilot Study to Evaluate the Gastrointestinal Response to Increasing Doses of a Resistant Starch Blend in Healthy Subjects

    This study aims to test the hypothesis that a unique blend of resistant starches and fiber will promote gastrointestinal health, as measured by an increase in short-chain fatty acids and improvement in quality of life measures in conjunction with microbial community changes. This study specifically evaluates the impact on short-chain fatty acids and gut microbiota and the impact on quality of life from a resistant starch blend in healthy adult humans with occasional gastrointestinal distress.

    NCT03983772
    Conditions
    1. Quality of Life
    2. Health, Subjective
    Interventions
    1. Dietary Supplement: RS blend
    2. Other: Placebo

    Primary Outcomes

    Description: Concentration of total short-chain fatty acids, including valerate, isovalerate and isobutyrate, and individually-reported n-butyrate concentration as well as propionate and acetate % will be reported by Genova Diagnostics Report

    Measure: Change in Concentration of short-chain fatty acids from baseline to each product intervention

    Time: Baseline (2 week period) compared to each product completion period of 2 weeks

    Secondary Outcomes

    Description: Fecal frequency (time in hours between stools) will be evaluated for each time period and compared between baseline (2 week period) and product intervention period (each 2 week period)

    Measure: Change in fecal frequency (hours between stools) from baseline at each intervention

    Time: Baseline (2 week period) to end of product completion (2 week intervention for each dose and time combination)

    Description: Response pattern score on PROMIS Scale v1.0 - GI Diarrhea will be compared between baseline and each intervention period

    Measure: Change in Response pattern score for Frequency and Severity of Gastrointestinal Symptoms (PROMIS Scale v1.0 - GI Diarrhea 6a)

    Time: Baseline (2 week period) to end of product completion (2 week intervention for each dose and time combination)

    Description: Response pattern score on PROMIS Scale v1.0 - GI Constipation will be compared between baseline and each intervention period

    Measure: Change in Response pattern score for Frequency and Severity of Gastrointestinal Symptoms (PROMIS Scale v1.0 - GI Constipation)

    Time: Baseline (2 week period) to end of product completion (2 week intervention for each dose and time combination)

    Description: Response pattern score on PROMIS Scale v1.0 - GI Gas and Bloating 13a 09-02-2016 will be compared between baseline and each intervention period

    Measure: Change in Response pattern score for Frequency and Severity of Gastrointestinal Symptoms (PROMIS Scale v1.0 - GI Gas and Bloating 13a 09-02-2016)

    Time: Baseline (2 week period) to end of product completion (2 week intervention for each dose and time combination)
    48 A Phase 1, Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects

    This is a single-center, observer-blinded, dosage-escalation trial to evaluate the safety, tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT in rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49. There are 4 dose groups: Group A will receive ChAd155-RG at the lower dosage (5x1010vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group B will receive ChAd155-RG at the higher dosage (1x1011vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group C will receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and 15, and placebo injections on Days 8 and 22; Group D will receive RABAVERT at the standard dose (1 mL) on Days 1, 8, and 22, and a placebo injection on Day 15. Since this is a dosage-escalation study, sentinel subjects will be used at each dosage level before non-sentinel subjects will be enrolled. The study will be conducted at Emory University Vaccine and Treatment Evaluation Unit (VTEU). This trial is expected to take approximately 48 months to complete. The duration of each subject's participation is approximately 13 months, from recruitment through the last study visit. The primary objectives of this study are: 1) Assessment of the safety, tolerability, and reactogenicity of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of ChAd155-RG at 1x1011vp per dose; 2) Comparison of the safety, tolerability, and reactogenicity of one or two doses of ChAd155-RG, with three doses of RABAVERT.

    NCT04019444
    Conditions
    1. Rabies
    2. Rabies Immunisation
    Interventions
    1. Biological: ChAd155-RG
    2. Other: Placebo
    3. Biological: Rabies Vaccine
    MeSH:Rabies

    Primary Outcomes

    Measure: Frequency of any Serious Adverse Events (SAEs)

    Time: Day 1 through Day 381

    Measure: Frequency of Serious Adverse Events (SAEs) considered study vaccine-related

    Time: Day 1 through Day 381

    Measure: Frequency of solicited injection site events

    Time: Day 1 through Day 29

    Measure: Frequency of study vaccine-related lab Adverse Events (AEs)

    Time: Day 1 through Day 22

    Measure: Frequency of systemic reactogenicity events

    Time: Day 1 through Day 29

    Measure: Frequency of unsolicited study vaccine-related Adverse Events (AEs)

    Time: Day 1 through Day 50

    Measure: Number of subjects with new onset of a chronic medical condition

    Time: Day 1 through Day 381

    Measure: Severity of any Serious Adverse Events (SAEs)

    Time: Day 1 through Day 381

    Measure: Severity of Serious Adverse Events (SAEs) considered study vaccine-related

    Time: Day 1 through Day 381

    Measure: Severity of solicited injection site events

    Time: Day 1 through Day 29

    Measure: Severity of study vaccine-related lab Adverse Events (AEs)

    Time: Day 1 through Day 22

    Measure: Severity of systemic reactogenicity events

    Time: Day 1 through Day 29

    Measure: Severity of unsolicited study vaccine-related Adverse Events (AEs)

    Time: Day 1 through Day 50

    Secondary Outcomes

    Measure: Geometric Mean Titer (GMT) (as measured by rabies VNA using a standard, WHO-approved, RFFIT)

    Time: Day 1 through Day 381

    Measure: Peak Geometric Mean Titer (GMT) (defined as highest GMT measured across all post-vaccination antibody time points)

    Time: Day 1 through Day 381

    Measure: Proportion of subjects seroconverting to rabies virus (defined as VNA concentration > / = 0.5 IU/mL)

    Time: Day 1 through Day 381
    49 A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) (COURSE)

    A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

    NCT04039113
    Conditions
    1. Chronic Obstructive Pulmonary Disease (COPD)
    Interventions
    1. Biological: Tezepelumab
    2. Other: Placebo
    MeSH:Pulmona Pulmonary Disease, Chronic Obstructive Lung Diseases Lung Diseases, Obstructive
    HPO:Abnormal lung morphology Chronic pulmonary obstruction Pulmonary obstruction

    Primary Outcomes

    Description: The exacerbation rate is based on exacerbations reported by the investigator over 52 weeks.

    Measure: Moderate or severe COPD exacerbation rate ratio (tezepelumab vs placebo)

    Time: Over 52 Weeks

    Secondary Outcomes

    Description: Time to first occurrence of moderate/severe exacerbation post randomization. Outcome measures: Hazard ratio

    Measure: Time to first moderate or severe COPD exacerbation

    Time: By Week 52

    Description: Proportion of subjects with at least one moderate/severe exacerbation reported by the Investigator over 52 weeks Outcome measure: Odds Ratio

    Measure: Proportion with at least one moderate/severe COPD exacerbation

    Time: Over 52 Weeks

    Description: The severe exacerbation rate is based on severe exacerbations reported by the Investigator over 52 weeks.

    Measure: Severe COPD exacerbation rate ratio (tezepelumab vs. placebo)

    Time: Over 52 Weeks

    Description: Difference in change from baseline in pre-BD forced expiratory volume in 1 second (FEV1) in tezepelumab arm as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of forced expiration.

    Measure: Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1)

    Time: Baseline, Week 52

    Description: Proportion of subjects achieving a decrease of 4 units or more in the St. George's Respiratory Questionnaire (SGRQ) total score at Week 52, i.e. minimum clinically important difference (MCID). Outcome measure: odds ratio

    Measure: Change in respiratory health status/health-related quality of life

    Time: Baseline, Week 52

    Description: Difference (tezepelumab vs. placebo) in SGRQ from baseline at Week 52. SGRQ is a 50-item patient reported outcome questionnaire. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0% indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment. Decrease of 4 units is associated with a minimum clinically important difference (MCID).

    Measure: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score

    Time: Baseline, Week 52

    Description: Difference (tezepelumab vs. placebo) in COPD assessment tool (CAT) from baseline at Week 52. CAT is an 8-item patient reported outcome questionnaire developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. The score ranges from 0 to 40, with higher scores indicating greater COPD impact on health status.

    Measure: Change from baseline in the COPD Assessment Test (CAT) Total Score

    Time: Baseline, Week 52

    Description: Serum trough concentration of tezepelumab

    Measure: Evaluate pharmacokinetics of tezepelumab

    Time: Weeks 0, 4, 12, 24, 36, 52, 64

    Description: Incidence of anti-drug antibodies (ADA)

    Measure: Evaluate immunogenicity of tezepelumab

    Time: Over 52 weeks
    50 A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Clinical Outcomes, Antiviral Activity, Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics/Pharmacodynamics of JNJ-53718678 in Adult and Adolescent Hematopoietic Stem Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

    The purpose of this study is to evaluate the effect of JNJ-53718678 on the development of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTIs) in adult hematopoietic stem cell transplant (HSCT) recipients with RSV upper RTI.

    NCT04056611
    Conditions
    1. Respiratory Syncytial Virus Infections
    Interventions
    1. Drug: JNJ-53718678 250 mg
    2. Drug: Placebo
    3. Drug: JNJ-53718678 125 mg
    MeSH:Infection Virus Diseases Respiratory Syncytial Virus Infections

    Primary Outcomes

    Description: The proportion of participants who develop RSV LRTI through Visit Day 28 per the Endpoint Adjudication Committee (EAC) assessment will be reported.

    Measure: Proportion of Participants who Develop Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI)

    Time: Up to Day 28

    Secondary Outcomes

    Description: The proportion of participants who develop RSV-associated LRTC through Visit Day 28 per the EAC's assessment will be reported.

    Measure: Proportion of Participants who Develop RSV-associated Lower Respiratory Tract Complication (LRTC)

    Time: Up to Day 28

    Description: An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

    Measure: Number of Participants with Adverse Events (AEs)

    Time: Up to 49 days

    Description: Percentage of participants with abnormal clinical laboratory findings will be reported.

    Measure: Percentage of Participants with Abnormal Clinical Laboratory Findings

    Time: Up to 49 days

    Description: Percentage of participants with abnormal ECGs findings will be reported.

    Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings

    Time: Up to 49 days

    Description: Percentage of participants with abnormal vital signs findings will be reported.

    Measure: Percentage of Participants with Abnormal Vital Signs Findings

    Time: Up to 49 days

    Description: The proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

    Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment

    Time: Up to 49 days

    Description: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, (all-cause mortality) will be reported.

    Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, (all-cause Mortality)

    Time: Up to 49 days

    Description: Proportion of participants progressing to death (all-cause mortality), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

    Measure: Proportion of Participants Progressing to Death (All-cause Mortality), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment

    Time: Up to 49 days

    Description: Proportion of participants progressing to death (all-cause mortality) will be reported.

    Measure: Proportion of Participants Progressing to Death (All-cause Mortality)

    Time: Up to 1 year

    Description: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

    Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment

    Time: Up to 49 days

    Description: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) will be reported.

    Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive)

    Time: Up to 49 days

    Description: Number of supplemental O2 free days will be reported.

    Measure: Number of Supplemental Oxygen (O2) Free Days Through Day 28

    Time: Through Day 28

    Description: Incidence of supplemental oxygen requirement in participants will be reported.

    Measure: Incidence of Supplemental Oxygen Requirement

    Time: Up to 28 days

    Description: Duration of supplemental oxygen requirement in participants will be reported.

    Measure: Duration of Supplemental Oxygen

    Time: Up to 28 days

    Description: Change from baseline in respiratory rate as measured by the investigator during scheduled visits will be reported.

    Measure: Change from Baseline in Respiratory Rate

    Time: Baseline up to 49 days

    Description: Change from baseline in heart rate as measured by the investigator during scheduled visits will be reported.

    Measure: Change from Baseline in Heart Rate

    Time: Baseline up to 49 days

    Description: Change from baseline in SpO2 as measured by the investigator during scheduled visits will be reported.

    Measure: Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2)

    Time: Baseline up to 49 days

    Description: Change from baseline in body temperature as measured by the investigator during scheduled visits will be reported.

    Measure: Change from Baseline in Body Temperature

    Time: Baseline up to 49 days

    Description: Proportion of participants hospitalized (of participants who were not hospitalized at baseline) will be reported.

    Measure: Proportion of Participants Hospitalized (of Participants who Were not Hospitalized at Baseline)

    Time: Up to 1 year

    Description: Proportion of participants re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline, required hospitalization, and were discharged during the study) will be reported.

    Measure: Proportion of Participants Re-hospitalized

    Time: Up to 1 year

    Description: Total length of hospital stay (time in hospital from first dosing) will be reported.

    Measure: Total Length of Hospital Stay

    Time: Up to 49 days

    Description: Total time in the ICU (time in ICU from first dosing) will be reported.

    Measure: Total Time in the Intensive Care Unit (ICU)

    Time: Up to 49 days

    Description: Incidence of Grade 3 and Grade 4 AEs will be assessed by system organ class where Grade 3: Severe and Grade 4: Life-threatening.

    Measure: Incidence of Grade 3 and Grade 4 Adverse Events (AEs)

    Time: Up to 49 days

    Description: Incidence of respiratory AEs will be reported.

    Measure: Incidence of Respiratory AEs

    Time: Up to 49 days

    Description: Incidence of thoracic-related AEs will be reported.

    Measure: Incidence of Thoracic-related AEs

    Time: Up to 49 days

    Description: Incidence of antibiotic use in participants who develop and in those who do not develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

    Measure: Incidence of Antibiotic use in Participants who Develop and in Those who do not Develop RSV LRTI or RSV-Associated LRTC per the EAC's Assessment

    Time: Up to 49 days

    Description: Time to resolution of symptoms, assessed through an instrument for participant-reported symptoms (RiiQ Symptom Scale) will be reported.

    Measure: Time to Resolution of Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale

    Time: Up to 49 days

    Description: Change from baseline in severity of symptoms reported by participants in the RiiQ symptom scale through Day 28 will be reported.

    Measure: Change from Baseline in Severity of Symptoms Reported by Participants in the RiiQ Symptom Scale Through Day 28

    Time: Baseline up to Day 28

    Description: Time to resolution of respiratory illness, through the PGI-S Scale, will be reported.

    Measure: Time to Resolution of Respiratory Illness as Assessed by Patient Global Impression of Severity (PGI-S) Scale

    Time: Up to 49 days

    Description: Change from baseline in PGI-H scale through Day 28 will be reported.

    Measure: Change from Baseline in Patient Global Impression of Health (PGI-H) Scale Through Day 28

    Time: Baseline up to Day 28

    Description: Change from baseline in PGI-C scale through Day 28 will be reported.

    Measure: Change from Baseline in Patient Global Impression of Change (PGI-C) Scale Through Day 28

    Time: Baseline up to Day 28

    Description: AUC (0-24h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose.

    Measure: Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours Postdose (AUC [0-24]) of JNJ-53718678

    Time: Up to 24 hours postdose (on Days 1 and 8)

    Description: Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.

    Measure: Trough Plasma Concentration (Ctrough) of JNJ-53718678

    Time: Predose on Days 1 and 8

    Description: Cmax is defined as the maximum observed plasma concentration of JNJ-53718678 in the dosing interval.

    Measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678

    Time: Day 1

    Description: The potential association of plasma concentration-time data of JNJ-53718678 with antiviral activity (RSV viral kinetics) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

    Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Antiviral Activity

    Time: Up to 49 days

    Description: The potential association of plasma concentration-time data of JNJ-53718678 with selected safety (including AEs and laboratory abnormalities) parameters will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

    Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Safety Parameters

    Time: Up to 49 days

    Description: The potential association of plasma concentration-time data of JNJ-53718678 with clinical outcomes (proportion of participants developing LRTI) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

    Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Clinical Outcomes

    Time: Up to 49 days

    Description: RSV viral load and change from baseline over time will be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in the mid-turbinate nasal swab specimens.

    Measure: RSV Viral Load and Change from Baseline Over Time

    Time: Baseline up to Day 28

    Description: RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.

    Measure: RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 8, 11, 15, 22 and 28

    Time: Baseline up to Days 8, 11, 15, 22 and 28

    Description: Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.

    Measure: Time to Undetectable RSV Viral Load

    Time: Up to 49 days

    Description: Proportion of participants with undetectable RSV viral load at each time point throughout the study will be reported.

    Measure: Proportion of Participants with Undetectable RSV Viral Load at Each Timepoint

    Time: Up to 49 days

    Description: Change from baseline for the HRQOL assessment as assessed through the EQ-5D-5L through Day 28 will be reported.

    Measure: Change from Baseline for the Health-related Quality of Life (HRQOL) as Assessed by 5-level EuroQol 5-Dimension (EQ-5D-5L) Through Day 28

    Time: Baseline up to Day 28

    Description: Change from baseline for the HRQOL assessment as assessed through RiiQ impact scales through Day 28 will be reported.

    Measure: Change from Baseline for the HRQOL as Assessed by RiiQ Impact Scales Through Day 28

    Time: Baseline up to Day 28

    Description: Change from baseline in the RSV F gene sequence will be reported.

    Measure: Change from Baseline in the RSV F Gene Sequence

    Time: Baseline up to 49 days
    51 A Two-Part Study With a Birth Cohort (Observational Stage) for Early Diagnosis of Respiratory Syncytial Virus (RSV), Followed by an Optional Phase 2a, Randomized, Double-blind, Placebo-controlled Study (Interventional Stage) to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of JNJ-53718678 in Infants With Acute Respiratory Tract Infection Due to RSV

    The purpose of this two-part designed study is to assess in the setting of a planned early interception of pediatric RSV disease, early viral and disease kinetics (observational stage) and the antiviral effects of an Respiratory Syncytial Virus (RSV) fusion inhibitor, JNJ-53718678 (interventional stage). In the observational stage the infant is closely monitored for early symptoms by the parent(s)/caregiver(s) and thus may be brought in for diagnosis earlier than in the typical setting.

    NCT04068792
    Conditions
    1. Respiratory Syncytial Viruses
    Interventions
    1. Other: RSV Mobile Application
    2. Drug: Placebo
    3. Drug: JNJ-53718678 2.5 mg/kg
    4. Drug: JNJ-53718678 3 mg/kg
    5. Drug: JNJ-53718678 4.5 mg/kg
    MeSH:Virus Diseases

    Primary Outcomes

    Description: Respiratory Syncytial Virus (RSV) viral load AUC will be determined from immediately prior to first dose of study drug through Day 5. The RSV viral load is measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in mid-turbinate nasal swab specimens.

    Measure: Part 2: RSV Viral Load Area Under Curve (AUC) from Immediately Prior to First Dose of Study Drug Through Day 5

    Time: On the day of diagnosis (Baseline) through Day 5 of interventional stage

    Secondary Outcomes

    Description: Total Respiratory Symptom Score over time will be captured by RSV mobile Application (App) during the pre-diagnostic phase and the post-diagnostic phase for RSV positive participants that do not enter in the interventional stage.

    Measure: Part 1: Total Respiratory Symptom Score Over Time

    Time: Up to 21 Days of observational stage

    Description: Clinician PRESORS scores will be reported for hospitalized RSV positive participants. Clinician PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) by clinician.

    Measure: Part 1: Change from Baseline in Clinician Pediatric RSV Electronic Severity and Outcome Rating Scale (PRESORS) Scores

    Time: On the day of RSV diagnosis (Baseline) up to Discharge post-diagnosis (21 Days) of observational stage

    Description: RSV Viral load during pre-diagnostic phase will be determined based on measurements of RSV viral load in nasal secretions by a qRT-PCR assay in mid-turbinate nasal swab specimens.

    Measure: Part 1: RSV Viral Load

    Time: Pre-diagnostic phase: Within 24hrs of Observation Day 1

    Description: RSV viral load kinetics from Day 1 to Day 8 after RSV diagnosis over time (if not participating in the interventional stage) will be measured by real-time qRT-PCR assay in the mid-turbinate nasal swab specimens.

    Measure: Part 1: RSV Viral Load Kinetics from Day 1 to Day 8

    Time: On the day of diagnosis (Baseline) through Day 8 of observational stage

    Description: Change from baseline in Parent(s)/Caregiver(s) PRESORS scores (worsening or improvement) will be reported.

    Measure: Part 1: Change from Baseline in Parent(s)/Caregiver(s) PRESORS Scores Over Time

    Time: On the day of diagnosis (Baseline) up to 21 Days of the observational stage

    Description: RSV viral load and change from baseline over time will be measured by qRT-PCR assay in mid-turbinate nasal swab specimens.

    Measure: Part 2: RSV Viral Load and Change from Baseline Over Time

    Time: On the day of diagnosis (Baseline) through Day 21 of interventional stage

    Description: RSV viral load AUC will be determined by qRT-PCR assay in mid-turbinate nasal swab specimens.

    Measure: Part 2: RSV Viral Load Area Under the curve (AUC) from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 3, 8, and 14

    Time: On the day of diagnosis (Baseline) through Days 3, 8 and 14 of interventional stage

    Description: Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.

    Measure: Part 2: Time to Undetectable RSV Viral Load

    Time: Up to 21 days of interventional stage

    Description: Percentage of participants with undetectable RSV viral load will be reported.

    Measure: Part 2: Percentage of Participants with Undetectable RSV Viral Load at each timepoint

    Time: Up to 21 days of interventional stage

    Description: Duration of signs and symptoms of RSV disease will be assessed by PRESORS. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues).

    Measure: Part 2: Duration of Signs and Symptoms of RSV Disease Assessed by the PRESORS

    Time: Up to 21 days of interventional stage

    Description: Severity of RSV disease will be assessed by PRESORS. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues).

    Measure: Part 2: Severity of RSV Disease Assessed by PRESORS

    Time: Up to 21 days of interventional stage

    Description: Change from baseline in parent(s)/caregiver(s) PRESORS scores (worsening or improvement) will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) daily by parent/caregiver.

    Measure: Part 2: Change from Baseline in Parent(s)/Caregiver(s) PRESORS Scores

    Time: On the day of diagnosis (Baseline) up to 21 days of interventional stage

    Description: Change from baseline in clinician PRESORS scores (worsening or improvement) will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) by clinician.

    Measure: Part 2: Change from Baseline in Clinician PRESORS Scores

    Time: On the day of diagnosis (Baseline) up to 21 days of interventional stage

    Description: Time to resolution (that is, to none or mild) of RSV symptoms will be recorded.

    Measure: Part 2: Time to Resolution of RSV Symptoms

    Time: Up to 21 days of interventional stage

    Description: Time to improvement based on general questions on overall health will be reported.

    Measure: Part 2: Time to Improvement on Overall Health

    Time: Up to 21 days of interventional stage

    Description: Percentage of participants with improvement or worsening of RSV disease based on general questions on overall health will be reported.

    Measure: Part 2: Percentage of Participants with Improvement or Worsening of RSV Disease

    Time: Up to 21 days of interventional stage

    Description: Time to return to pre-RSV health as rated by the parent(s)/caregiver(s) will be recorded.

    Measure: Part 2: Time to Return to Pre-RSV Health as Rated by the Parent(s)/Caregiver(s)

    Time: Up to 21 days of interventional stage

    Description: Percentage of participants with vital signs (heart rate, respiratory rate, body temperature and peripheral capillary oxygen saturation [SpO2]) abnormalities will be reported.

    Measure: Part 2: Percentage of Participants with Vital Sign Abnormalities

    Time: Up to 28 days of interventional stage

    Description: Percentage of participants who require (re)hospitalization during treatment and follow-up will be reported.

    Measure: Part 2: Percentage of Participants who Require (re)Hospitalization During Treatment and Follow-up

    Time: Up to 28 days of interventional stage

    Description: An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    Measure: Part 2: Percentage of Participants with Adverse Events as a Measure of Safety and Tolerability

    Time: Up to 28 days of interventional stage

    Description: Percentage of participants with abnormal laboratory findings (hematology, biochemistry, urinalysis) will be reported.

    Measure: Part 2: Percentage of Participants with Abnormal Laboratory Findings

    Time: Up to 28 days of interventional stage

    Description: Percentage of participants with abnormal ECGs findings will be reported.

    Measure: Part 2: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings

    Time: Up to 28 days of interventional stage

    Description: Plasma Concentrations of JNJ-53718678 will be evaluated and determined by population pharmacokinetics (popPK) modelling.

    Measure: Part 2: Plasma Concentrations of JNJ-53718678

    Time: Day 1 and Day 3 of interventional stage
    52 A Phase 4, Multicenter, 2-part Study Composed of a 1-Year Randomized, Double-blind, Parallel-group, Placebo-controlled, Active-comparator, Dose-optimization Evaluation Followed by a 1-Year Open-label Evaluation to Assess the Safety and Efficacy of Guanfacine Hydrochloride Prolonged-release (SPD503) in Children and Adolescents Aged 6 to 17 Years With Attention-deficit/Hyperactivity Disorder

    This interventional multicenter dose-optimization Phase IV PASS conducted in Europe and the USA evaluates the comparative long-term safety and efficacy of SPD503 in children and adolescents aged 6 to 17 years diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) for whom stimulants are not suitable, not tolerated, or shown to be ineffective. The study will be conducted in two parts: Study Part A (randomized, double-blinded, parallel-group, placebo- and active comparator-controlled, 3-treatment arm safety and efficacy evaluation of SPD503) and Study Part B (open label SPD503 treatment).

    NCT04085172
    Conditions
    1. Attention Deficit Hyperactivity Disorder (ADHD)
    Interventions
    1. Drug: Guanfacine hydrochloride (SPD503)
    2. Drug: Atomoxetine hydrochloride
    3. Other: Placebo
    MeSH:Hyperkinesis Attention Deficit Disorder with Hyperactivity
    HPO:Attention deficit hyperactivity disorder Hyperactivity Hyperkinetic movements

    Primary Outcomes

    Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 10 in both Part A and Part B of the study.

    Measure: Change from Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 10

    Time: Baseline, Week 10

    Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 18 in Part A of the study.

    Measure: Change from Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 18

    Time: Baseline, Week 18

    Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 49 in both Part A and Part B of the study.

    Measure: Change from Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 49

    Time: Baseline, Week 49

    Secondary Outcomes

    Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. Cognitive domain, sustained attention will be measured by the CANTAB RVP task. RVP measures the ability to sustain attention over time and is a sensitive measure of frontal-parietal function. In this task, single digits appear in a pseudo--random order at a rate of 100 digits per minute in a box at the center of the screen. Participants are to detect a 3-digit target sequence (e.g. 2-4-6) and respond by pressing a button at the bottom of the screen when the final number of the sequence appears on the screen.

    Measure: Change from Baseline in the Rapid Visual Information Processing (RVP) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

    Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

    Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments, SWM is a component of cognitive executive function which is measured by SWM task of CANTAB between the errors. The ability to retain spatial information and manipulate remembered items in working memory will be measured with the SWM task of CANTAB which is self-ordered and assesses the individual's ability to strategize heuristically. The test is a sensitive measure of frontal lobe and executive dysfunction.

    Measure: Change from Baseline in the Spatial Working Memory (SWM) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

    Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

    Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments.Response control or inhibition cognitive domain will be measured by the CANTAB SST. SST measure response inhibition. The participant must respond to an arrow stimulus by touching either of 2 choices depending on the direction the arrow points. If an audio tone is present, the participant is not to respond.

    Measure: Change from Baseline in the Stop Signal Task (SST) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

    Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

    Description: The neurocognitive function effects of SPD503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. Recognition memory of cognition domain will be measured by the CANTAB DMS task. DMS measures both simultaneous matching and short-term visual memory. The participant is shown a complex visual pattern (the sample) and after a brief delay, 4 similar patterns. The participant must identify the pattern that matches the sample.

    Measure: Change from Baseline in the Delayed Matching to Sample (DMS) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) in Both Part A and Part B at Specified Time Points

    Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

    Description: Sexual maturation will be measured by Tanner stage. The stage of puberty or sexual maturation will be evaluated for each participant according to Tanner staging. The Tanner stage for genitals (male, stages I-V), breasts (females, stages I-V), and pubic hair (both sexes, stages I-V) will be documented at the specified times.

    Measure: Tanner Stage in Both Part A and Part B at Specified Time Points

    Time: Part A: Baseline, Week 10, Week 18, Week 49 Part B: Baseline, Week 10, Week 49

    Description: Physical examinations will include height and weight. Growth will be measured by weight, height, and BMI. Body mass index is a measure of body fat based on height and weight. Vital signs will be assessed based on blood pressure, pulse rate, respiratory rate and body temperature in both Part A and Part B. The HR, PR interval, QRS interval, and QT interval will be measured from all ECGs and the QTcB and QTcF assessed at specified time points in both Part A and Part B of the study.

    Measure: Number of participants with clinically significant changes in Vital signs, ECG, Physical Examination

    Time: From start of study drug administration up to follow up (week 52)

    Description: Psychiatric symptoms will be measured by the Brief Psychiatric Rating Scale for Children (BPRS-C) total score. The 21 items of the clinician-rated BPRS-C are grouped into the following 7 scales: depression, anxiety, psychomotor excitation, behavior problems, withdrawal retardation, thinking disturbance, and organicity. Each item of the 21 items is clinician-graded using the following 7-point severity Likert-scale from 0 to 6 (not present=0; very mild=1; mild=2; moderate=3; moderately severe=4; severe=5; extremely severe=6. BPRS-C will be assessed at specified time points in both Part A and Part B.

    Measure: Brief Psychiatric Rating Scale for Children (BPRS-C)

    Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

    Description: The C-SSRS is a structured tool to assess suicidal ideation and behavior. A maximum of 19 items will be completed as follows: 7 items are required, a potential 10 additional items will be completed upon a positive response to a required item, and 2 items completed if suicide or suicide-like behavior is observed during the interview. The C-SSRS uses dichotomous scales (i e, yes or no), Likert scales, and text or narrative to further describe thoughts or behaviors. C-SSRS Score will be assessed at specified time points in both Part A and Part B.

    Measure: Columbia- Suicide Severity Rating Scale (CSSRS)

    Time: Baseline (from start of study drug administration) to Week 52

    Description: UKU rating scale was developed for clinicians to assess side effects of psychopharmacological medications based on interviews and other relevant source information. UKU items relevant to the established safety profile of SPD503 such as Increased Duration of Sleep, Asthenia or Lassitude or lncreased Fatigability, Sleepiness or Sedation, and Orthostatic Dizziness. UKU rating scale will be assessed at specified time points in both Part A and Part B.

    Measure: Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale

    Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36, Week 49, Week 50, Week 51 and Week 52 Part B: Baseline, Week 10, Week 23, Week 36, Week 49, Week 50, Week 51 and Week 52

    Description: Sedative effects will be measured by participant ratings on the Pediatric Daytime Sleepiness Scale (PDSS). The PDSS is a self-reported assessment of daytime sleepiness in children aged 11 to 15 years. PDSS questionnaire was designed to be easy to administer, score, and interpret. Sleepiness-related questions are based on previous research of situations that can be sensitive to sleep loss in this age group. The 8 questions are scored on Likert-scale from 0 to 4 (never=0; seldom=1; sometimes=2; frequently=3; always=4). The total score on the PDSS can range from 0 (never sleepy) to 32 (always sleepy). PDSS will be assessed at specified time points in both Part A and Part B.

    Measure: Pediatric Daytime Sleepiness Scale (PDSS)

    Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

    Description: The ADHD-RS-5 (DuPaul et al., 2016) is used widely by mental health, educational, and medical practitioners in screening, diagnosis, and treatment evaluation to determine the frequency and severity of ADHD symptoms and impairments in children and adolescents. Attention-deficit/hyperactivity disorder symptoms is measured by the investigator-administered ADHD Rating Scale-5 (ADHD-RS-5) total score and hyperactivity/impulsivity and inattentiveness symptoms as subscale scores. The ADHD-RS-5 is based on the diagnostic criteria for ADHD as described in the DSM-5 and consists of 2 symptom subscales, inattention and hyperactivity-impulsivity, each with 9 items and a total scale of 18 items. Each item in the subscale is scored with a value ranging from 0 (no symptoms) to 3 (severe symptoms). The total score can range from 0 to 54. ADHD-RS-5 Total Score and Subscales wiil be assessed at specified time points in both Part A and Part B.

    Measure: ADHD Rating Scale-5 (ADHD-RS-5) Total Score and Subscales

    Time: Part A: Baseline, Week 1, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

    Description: Global clinical measurement of ADHD improvement as measured by Clinical Global Impression-Improvement (CGI-I) using the Clinical Global Impression-Severity (CGI-S) to establish baseline. The CGI scale will be used to evaluate the severity of mental illness over time. The CGI-S will be administered to assess the severity of mental illness at baseline. The CGI-S is scored on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The CGI-I is also scored on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). CGI-I will be measured at specified time points in both Part A and Part B.

    Measure: Clinical Global Impression-Improvement (CGI-I)

    Time: Part A: Week 1, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Week 10, Week 23, Week 36 and Week 49

    Description: The Parent Report Form of the Child Health and Illness Profile - Child Edition (CHIP-CE:PRF) will be administered to provide information on self-esteem and school functioning in pediatric participants diagnosed with ADHD. The 5 domains and 12 subdomains covered in the 76 items comprising the CHIP-CE:PRF. Satisfaction: with health (7 items) and self (4 items); Comfort: physical (9 items) and emotional symptoms (9 items) and activity restrictions (4 items) due to illness; Resilience: behaviors and family involvement (8 items) in activities likely to enhance health, Social problem-solving (5 items),Physical activity (6 items); Risk avoidance: behaviors that if not avoided are likely to pose risks to health: Individual risk avoidance (4 items), Threats to achievement (10 items); Achievement: developmentally appropriate role functioning in school and with peers: Academic performance (5 items), Peer relations (5 items). CHIP-CE: PRF will be assessed in both Part A and Part B.

    Measure: Child Health and Illness Profile - Child Edition: Parent Report Form (CHIP-CE:PRF)

    Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49

    Description: School performance will be measured by teacher ratings of academic skills using the APRS at specified time points in both Part A and Part B. The APRS is a reliable rating scale that has been shown to be valid in assessing teacher perceptions of the quality of a student's academic competency. The scale includes 19 items that are directed toward work performance in various participant areas; academic success, behavioral control in academic situations, and attention to assignments. Teachers mark responses in a Likert-scale format from 1 (never or poor) to 5 (very often or excellent). From the APRS, a total score and the following 3 subscale scores are calculated: academic success, impulse control, and academic productivity.

    Measure: Academic Performance Rating Scale (APRS)

    Time: Part A: Baseline, Week 10, Week 18, Week 23, Week 36 and Week 49 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49
    53 A Randomized, Placebo-controlled, Subject and Investigator Blinded Study Investigating the Safety, Tolerability and Preliminary Efficacy of 8-week Treatment With Intra-articular LRX712 to Regenerate Articular Cartilage in Patients With Mild/Moderate Knee Osteoarthritis

    This study will explore the preliminary efficacy of multiple intra-articular injections of LRX712 by evaluating the ability of the drug to restore structural integrity of articular cartilage. Efficacy will be evaluated in the context of the systemic safety and local tolerability of the investigational drug.

    NCT04097379
    Conditions
    1. Osteoarthritis (OA)
    Interventions
    1. Drug: LRX712
    2. Drug: Placebo
    MeSH:Osteoarthritis
    HPO:Osteoarthritis

    Primary Outcomes

    Description: Efficacy of multiple intra-articular injections of LRX712 in regenerating cartilage as measured with 7T MRI

    Measure: Changes in articular cartilage [23Na] content from baseline compared to placebo at week 28

    Time: Baseline and Week 28

    Secondary Outcomes

    Description: Efficacy of multiple intra-articular injections of LRX712 measured with 7T MRI

    Measure: Changes in articular cartilage [23Na] content from baseline compared to placebo at Week 16 and 52

    Time: Baseline, Week 16 and 52

    Description: Efficacy of multiple intra-articular injections of LRX712 measured with 7T MRI

    Measure: Changes from baseline in cartilage morphometrics (volume and thickness) in the medial femoral condyle at Week 16, 28 and 52

    Time: Baseline, Week 16, 28 and 52

    Description: The observed time to reach max (Tmax) plasma concentration following drug administration

    Measure: Time to Reach the Maximum Plasma Concentration (Tmax)

    Time: Pre-dose to 28 weeks

    Description: The observed maximum (Cmax) plasma concentration following drug administration

    Measure: Maximum Observed Plasma Concentration (Cmax)

    Time: Pre-dose to 28 weeks

    Description: The observed minimum (Cmin) plasma concentration following drug administration

    Measure: Minimum Observed Plasma Concentration (Cmin)

    Time: Pre-dose to 28 weeks

    Description: The observed synovial concentration following drug administration

    Measure: Concentration in synovial fluid

    Time: Day 1; week 4; week 8
    54 Improving Everyday Functioning in Adults Aged 70 and Over Using a Multivitamin Supplement

    Investigation of the chronic effect of 12 week multivitamin supplementation on markers of everyday function in adults aged 70 and over.

    NCT04112732
    Conditions
    1. Aging
    2. Stress
    Interventions
    1. Dietary Supplement: Multivitamin
    2. Other: Placebo

    Primary Outcomes

    Description: An overall outcome measure which is a composite measure made up of four personal well-being questions used in the Measuring National Well-being programme plus one additional question. These five questions are: Overall, how satisfied are you with your life nowadays? Overall, to what extent do you feel the things you do in your life are worthwhile? Overall, how happy did you feel yesterday? Overall, how anxious did you feel yesterday? Overall, how well did you feel yesterday?

    Measure: Overall Well-Being (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Secondary Outcomes

    Description: Systolic and Diastolic blood pressure measured via Portapres a non-invasive, continuous beat-to-beat blood pressure monitoring system.

    Measure: Cardiovascular reactivity- Blood pressure (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Beats per minute, measured via Portapres a non-invasive, continuous beat-to-beat blood pressure monitoring system.

    Measure: Cardiovascular reactivity- Heart rate (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: C-Reactive Protein (CRP)

    Measure: Immune/inflammatory response (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Secretory Immunoglobulin-A (s-IgA)

    Measure: Immune/inflammatory response(change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: The Kingston Caregiver Stress Scale.This tool is designed to assess levels of perceived stress associated with caregiving in informal carers. The scale comprises three sections that assess levels of stress in relation to care-related feelings; family matters; and financial stresses. Higher scores indicate higher levels of stress

    Measure: Self-Reported Stress (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: The Perceived Stress Scale (PSS), The PSS is a 10-item scale which measures the extent to which participants perceive their lives to be overwhelming, uncontrollable and unpredictable.Scale responses range from 0 (never) to 4 (very often) and items are summed to yield a total score. Higher scores indicate greater perceived levels of stress, experienced over the previous month

    Measure: Self-Reported Stress (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Cohen Hoberman Inventory of Physical Symptoms.The CHIPS was designed as a measure of perceived burden due to the experience of a range of physical symptoms. The scale comprises a list of 33 common everyday symptoms (e.g. 'acne', 'diarrhoea', 'heart pounding or racing') and asks respondents 'how much that problem has bothered or distressed you during the past two weeks including today'. Items are scored for 1-5, then summed across all items. Higher scores indicate worse health

    Measure: General health(change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: SF-20. The survey measures health across 6 domains: physical functioning (6 questions), role functioning (2 questions), social functioning (1 question), mental health (5 questions), health perceptions (5 questions), and pain (1 question).Scores across each of these domains are reported on a 0% to 100% scale, with 0% representing the worst possible score in that domain and 100% the best possible score. Raw scores are transformed to fit the 0% to 100% interval as described in the original publication (note that for question #1 on general health, an initial transformation is performed as follows: 1 = 5, 2 = 4.36, 3 = 3.43, 4 = 1.99, 5 = 1). Reversal of scoring is completed as necessary such that the highest score always represents the best possible score. The exception to this scoring pattern is the pain score, for which 0% represents the best possible score and 100% the worst possible score,

    Measure: General health (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Instrumental Activities of Daily Living Scale. is an appropriate instrument to assess independent living skills.There are eight domains of function measured with the Lawton IADL scale. Women are scored on all 8 areas of function; historically, for men, the areas of food preparation, housekeeping, laundering are excluded. Clients are scored according to their highest level of functioning in that category. A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women, and 0 through 5 for men.

    Measure: Daily functioning and care behaviours (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Hospital Anxiety and Depression Scale, this is a 14 item scales, with scale responsed rangin from 0 to 5. Scores are summed to produce separate scores for anxiety and depression. Higher scores indicate more frequent feelings of anxiety and depressive symptoms. Scores between 0 and 7 are considered normal. Scores between 8 and 10 are indicative of borderline mood disorder and scores > 11 indicates probable mood disorder

    Measure: Mood trait measures (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Profile of Moods States (POMS). This comprises 37 items with response ranging from 'not at all' to 'extremely'. Scores from the POMS-SF are used to derive a total score for 'mood disturbance', as well as subscores for the domains of 'tension', 'depressed', 'anger', 'vigour', 'fatigue' and 'concentration'. A total score disturbance score can also be calculated by adding the scores from the first five of these global scores and subtracting 'vigour

    Measure: Mood trait measures (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: State-Trait Anxiety Inventory (STAI) The STAI is a widely used instrument consisting of two subscales assessing 'State' and 'Trait' anxiety respectively. Each subscale contains 20 statements (e.g. 'I am calm') each with a 4-point Likert scale, giving a range of potential scores from 20 to 80. Participants rate how much they feel like each statement at the time of making the response (State subscale), and how much they generally feel like each statement (Trait subscale). Higher scores indicate greater anxiety.

    Measure: Acute measures of subjective state in responses to a stressor (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: NASA-Task Load Index. The NASA-TLX comprises a set of six scales anchored with 'Low' and 'High' at the extreme points. Three of the scales reflect the demand placed upon the respondent by the task (Mental Demand, Physical Demand, Temporal Demand), whereas three reflect the interaction between the respondent and the task (Effort, Perceived Performance, Frustration).

    Measure: Acute measures of subjective state in responses to a stressor (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Task performance on the Multi-Tasking Framework (MTF),

    Measure: Cognitive function (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Prospective and Retrospective memory Questionnaire, The PRMQ is a 16 item scale that quantifies memory failures for everyday tasks over two subscales: prospective memory (e.g., do you forget appointments if you are not prompted by someone else or by a reminder such as a calendar or diary?) and retrospective memory (e.g., do you fail to do something you were supposed to do a few minutes later even though it's there in front of you, like take a pill or turn off the kettle?). Scale responses range from 1 (never) to 5 (very often), and higher scores indicate poorer everyday memory.

    Measure: Cognitive function (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: A covert measure of prospective memory, whereby participants will be asked to remember to return a reminder slip with their 'participant number' written on, which will be posted out before testing visits.

    Measure: Cognitive function (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Pittsburgh Sleep Quality Index. The PSQI assesses seven factors - subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication and daytime dysfunction - via questions regarding sleep timings and zero to three-point scales in which participants rate whether they have experienced a number of issues (e.g. 'During the past week, how often have you had trouble sleeping because you have had bad dreams?') from 'not during the past week' to '3 or more times in the past week'. A global sleep score is created by totalling the seven subfactor scores, with higher scores indicating poorer sleep quality.

    Measure: Sleep quality (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Yale Physical Activity Scale, The YPAS is an interviewer-administered questionnaire developed to assess physical activity in older adults. The YPAS is divided into two sections: in the first section, there is a comprehensive physical work, exercise, and recreational activities checklist to assess time spent in these types of activities during a typical week in the past month. The second section contains questions to quickly assess an individual's participation in five activity dimensions: vigorous activity, leisurely walking, moving on feet, standing, and sitting. Responses on the YPAS allow eight summary indices to be calculated: total time spent per week in all physical activities, weekly energy expenditure in kcal per week, five individual indices for the activity dimensions, and an activity dimension summary index

    Measure: Mobility (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Falls Efficacy Scale, measures of "fear of falling" or, more properly, "concerns about falling.To calculate the FES-I score when all items are completed, simply add the scores for each item together to give a total that ranges from a minimum 16 (no concern about falling) to maximum 64 (severe concern about falling).

    Measure: Mobility (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Timed up and Go Test, length of time in seconds it takes participants to stand form a chair, walk 3 metres, turn around and sit back down in chair.

    Measure: Mobility(change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Grip Strength. 3 trials on non dominant hand. Measured in kg.

    Measure: Mobility (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Balance tests. Measured to see if participants can hold 3 stances for 10s. If they can they are awarded 1 point, if not 0 points.

    Measure: Mobility(change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Lubben Social Network Scale, This measure uses 6 questions: 3 key questions evaluate the size of 3 different aspects of social network that are attributable to family ties and a parallel set attributable to friendship ties. Each LSNS-6 question is scored on a 0 to 5 scale. The total score is an equally weighted sum of these 6 questions, with scores ranging from 0 to 30.

    Measure: Social network size (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Convoy Method. • Respondents are presented with a set of three concentric circles, with the word 'You' contained within a smaller circle in the middle. Respondents are asked to think about "people who are important in your life right now, but who are not equally close". Respondents are then asked to think about "people to whom you feel so close it is hard to imagine life without them"; these people are entered into the innermost circle. For the next circle respondents are asked to consider "people to whom you may not feel quite that close but who are still very important to you". Finally, in the outer circle respondents are asked to place "People whom you haven't already mentioned but who are close enough and important enough in your life that they are part of your personal network". The numbers of people within each network are counted and can be used to represent support networks in each of the categories and / or summed to produce an index of total social network size

    Measure: Social network size (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: The De Jong Gierveld Loneliness Scale,This tool can be used to provide a single index of loneliness in addition to indices of 'Emotional Loneliness' and 'Social Loneliness' . To score the answers to the scale, the neutral and positive answers are scored as "1" on the negatively worded questions and On the positively worded items, the neutral and negative answers are scored as "1"

    Measure: Loneliness (change from baseline)

    Time: Measured at baseline and then following chronic (12 weeks) treatment

    Description: Blood biomarkers taken to assess impact of nutritional status, this will measure vitmain B12, ferritin and folate.

    Measure: Nutrition Status

    Time: Measured at baseline and then following chronic (12 weeks) treatment
    55 A Randomized, Double-blind, Placebo-controlled, Three-period Two-treatment Incomplete-block Crossover Study to Investigate the Effects of Intravenous GSK3858279 on a Battery of Evoked Pain Tests in Healthy Participants

    This study will evaluate the mechanistic basis for the analgesic effects of GSK3858279 in humans by using a battery of experimental pain assessments in healthy participants. This will be placebo-controlled, three-period two-treatment crossover study. In each period, participants will receive either GSK3858279 or placebo in a 1:1 ratio. Only healthy male participants will be enrolled into the study. The duration of the study will be approximately 6 months.

    NCT04114656
    Conditions
    1. Pain
    Interventions
    1. Drug: Placebo
    2. Drug: GSK3858279

    Primary Outcomes

    Description: The thermal pain tests will be performed first on normal skin contralateral to the site of UVB irradiation, then on UVB irradiated skin. A thermode will be placed on the participant's back. The initial temperature will be 32 degree Celsius and will be increased by 0.5 degree Celsius per second until the participant indicates the stimulus as painful, or when a temperature of 50 degree Celsius is reached.

    Measure: Temperature required to detect Ultraviolet B (UVB) heat pain threshold at Day 1

    Time: Day 1

    Description: The thermal pain tests will be performed first on normal skin contralateral to the site of UVB irradiation, then on UVB irradiated skin. A thermode will be placed on the participant's back. The initial temperature will be 32 degree Celsius and will be increased by 0.5 degree Celsius per second until the participant indicates the stimulus as painful, or when a temperature of 50 degree Celsius is reached.

    Measure: Temperature required to detect UVB heat pain threshold at Day 2

    Time: Day 2

    Description: The thermal pain tests will be performed first on normal skin contralateral to the site of UVB irradiation, then on UVB irradiated skin. A thermode will be placed on the participant's back. The initial temperature will be 32 degree Celsius and will be increased by 0.5 degree Celsius per second until the participant indicates the stimulus as painful, or when a temperature of 50 degree Celsius is reached.

    Measure: Temperature required to detect UVB heat pain threshold at Day 8

    Time: Day 8

    Description: Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (Electronic Visual Analogue Scale [eVAS] slider at 100 millimeters [mm]) or when a time limit (120 seconds) is reached.

    Measure: Time to intolerable pain threshold by cold pressor pain method at Day 1

    Time: Day 1

    Description: Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (eVAS slider at 100 mm) or when a time limit (120 seconds) is reached.

    Measure: Time to intolerable pain threshold by cold pressor pain method at Day 2

    Time: Day 2

    Description: Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (eVAS slider at 100 mm) or when a time limit (120 seconds) is reached.

    Measure: Time to intolerable pain threshold by cold pressor pain method at Day 8

    Time: Day 8

    Description: Time to intolerable pain threshold will be assessed by cold pressor pain method. In this method, participants will place their non-dominant hand into a water bath (35 ± 0.5 degree Celsius). After 2 minutes, participant will then move their hand from the warm water bath, directly placing their hand into a similar sized bath (1.0 ± 0.5 degree Celsius). The participants will be instructed to indicate when pain detection threshold is reached; first change in sensation from cold non-painful to painful and the increase in pain intensity. This endpoint will look at the pain tolerance on when it is no longer tolerable (eVAS slider at 100 mm) or when a time limit (120 seconds) is reached.

    Measure: Time to intolerable pain threshold by cold pressor pain method at Day 15

    Time: Day 15

    Description: For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 mm distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-hertz [Hz] tetanic pulse with a duration of 0.2 millisecond [ms]) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 milliamp (mA) is reached.

    Measure: Electrical pain tolerance threshold for single stimulus at Day 1

    Time: Day 1

    Description: For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 mm distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-Hz tetanic pulse with a duration of 0.2 ms) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 mA is reached.

    Measure: Electrical pain tolerance threshold for single stimulus at Day 2

    Time: Day 2

    Description: For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 mm distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-Hz tetanic pulse with a duration of 0.2 ms) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 mA is reached.

    Measure: Electrical pain tolerance threshold for single stimulus at Day 8

    Time: Day 8

    Description: For cutaneous electrical pain, two electrodes will be placed on clean (scrubbed) skin overlying the left tibial bone 100 mm distal from the caudal end of the patella. For single (stair) stimulus, each stimulus (10-Hz tetanic pulse with a duration of 0.2 ms) will be controlled by a computer-controlled constant current stimulator. The pain intensity after each stimulation will be measured using the eVAS, until pain tolerance level is reached, or a maximum of 50 mA is reached.

    Measure: Electrical pain tolerance threshold for single stimulus at Day 15

    Time: Day 15
    56 A Two-center, Randomized, Double-blind, Placebo-controlled, Phase Ib Study to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-MERS-S_DF-1 in Healthy Study Subjects

    The study will be a two center, randomized, double blind, placebo controlled study of the MVA MERS S_DF-1 candidate delivered by i.m. injection. To evaluate the MERS-S-specific antibody responses and safety profile induced by the two dosage levels of MVA-MERS-S_DF-1 the data will be compared to a placebo control group.

    NCT04119440
    Conditions
    1. MERS (Middle East Respiratory Syndrome)
    Interventions
    1. Biological: MVA-MERS-S_DF1 - Low Dose
    2. Biological: MVA-MERS-S_DF1 - High Dose
    3. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Safety and reactogenicity will be assesssed by observation, questionaire and diary. Changes from baseline for safety laboratory measures will be monitored. Occurence of SAE will be collected throughout the entire study duration.

    Measure: Frequency of adverse events associated with MVA-MERS-S_DF-1.

    Time: day 1, 14, 29, 42, 56, 84, 168, 336, 364

    Measure: Frequency and severity of local injection site reactogenicity signs and symptoms

    Time: day 1, 14, 29, 42, 84, 336

    Secondary Outcomes

    Description: Magnitude of MERS-S-specific antibody re-sponses (ELISA and neutralization assays) monitored in a centralized approved laboratory

    Measure: Immunogenicity

    Time: day 0, 14, 28, 42, 56, 70, 84, 168, 336, 364 (dependent on vaccination scheme)
    57 A Phase II, Randomised, Observer-blind, Placebo Controlled Multi-country Study to Assess the Safety, Reactogenicity and Immunogenicity of a Single Intramuscular Dose of GSK Biologicals' Investigational RSV Maternal Unadjuvanted Vaccine (GSK3888550A), in Healthy Pregnant Women Aged 18 to 40 Years and Infants Born to Vaccinated Mothers

    The purpose of this study is to evaluate the safety and immune response to a single intramuscular (IM) dose of GSK Biologicals' investigational RSV maternal vaccine (RSVPreF3) in healthy pregnant women 18-40 years of age and in infants born to vaccinated mothers.

    NCT04126213
    Conditions
    1. Respiratory Syncytial Virus Infections
    Interventions
    1. Biological: RSVPreF3 formulation 2
    2. Biological: RSVPreF3 formulation 3
    3. Drug: Placebo
    MeSH:Respiratory Syncytial Virus Infections

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Solicited administration site events are: pain, redness and swelling.

    Measure: Percentage of maternal subjects reporting solicited administration site events

    Time: From Day 1 to day 7

    Description: Solicited systemic events are: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache.

    Measure: Percentage of maternal subjects reporting solicited systemic events

    Time: From Day 1 to day 7

    Description: The hematological assays are: Complete Blood Count (CBC) with differential and platelet count. The biochemical assays are: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), creatinine and blood urea nitrogen.

    Measure: Percentage of maternal subjects with hematological and biochemical laboratory abnormality at baseline

    Time: At baseline (Day -15)

    Description: The hematological assays are: Complete Blood Count (CBC) with differential and platelet count. The biochemical assays are: alanine amino-transferase Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), creatinine and blood urea nitrogen.

    Measure: Percentage of maternal subjects with hematological and biochemical laboratory abnormality at Day 8

    Time: At Day 8 (visit 2)

    Description: An unsolicited AE is any AE reported in addition to those solicited during the clinical study and that was spontaneously communicated by a maternal subject. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE.

    Measure: Percentage of maternal subjects with unsolicited adverse events (AEs)

    Time: From Day 1 to Day 30

    Description: An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject or abnormal pregnancy outcomes (spontaneous abortion, foetal death, stillbirth, congenital anomalies, ectopic pregnancy).

    Measure: Percentage of maternal subjects with at least one serious adverse event (SAE)

    Time: From Day 1 to Day 43 post-delivery

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measure: Percentage of maternal subjects with AEs leading to study withdrawal

    Time: From Day 1 to Day 43 post-delivery

    Description: An MAE is a symptom or illness requiring hospitalisation, emergency room visit, or visit to/by a health care provider.

    Measure: Percentage of maternal subjects with at least one medically attended AE (MAE)

    Time: From Day 1 to Day 43 post-delivery

    Description: Pregnancy outcomes include live birth with no congenital anomalies, live birth with congenital anomalies, foetal death/still birth (antepartum or intrapartum) with no congenital anomalies, foetal death/still birth (antepartum or intrapartum) with congenital anomalies, elective/therapeutic termination with no congenital anomalies and elective/therapeutic termination with congenital anomalies.

    Measure: Percentage of maternal subjects with pregnancy outcomes

    Time: From Day 1 to Day 43 post-delivery

    Description: Pregnancy-related AESIs include maternal death, hypertensive disorders of pregnancy (gestational hypertension, pre-eclampsia, pre-eclampsia with severe features including eclampsia), antenatal bleeding (morbidly adherent placenta, placental abruption, caesarean scar pregnancy, uterine rupture), postpartum hemorrhage, foetal growth restriction, gestational diabetes mellitus, non-reassuring foetal status, pathways to preterm birth (premature preterm rupture of membranes, preterm labor, provider-initiated preterm birth), chorioamnionitis, oligohydramnios, polyhydramnios, gestational liver disease (intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy), maternal sepsis.

    Measure: Percentage of maternal subjects with pregnancy-related Adverse Events of Special Interest (AESIs)

    Time: From Day 1 to Day 43 post-delivery

    Description: Neonatal AESIs, reported up to 6 weeks after birth, include small for gestational age, low birth weight including very low birth weight, neonatal encephalopathy, congenital microcephaly (postnatally or prenatally diagnosed), congenital anomalies (major external structural defects, internal structural defects, functional defects), neonatal death (in a preterm live birth or in a term live birth), neonatal infections (blood stream infections, meningitis, respiratory infection), respiratory distress in the neonate, preterm birth, failure to thrive, large for gestational age, macrosomia.

    Measure: Percentage of infant subjects with neonatal AESIs

    Time: From birth to Day 43 post-birth

    Description: An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.

    Measure: Percentage of infant subjects with at least one SAE

    Time: From birth to Day 43 post-birth

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measure: Percentage of infant subjects with AEs leading to study withdrawal

    Time: From birth to Day 43 post-birth

    Description: A MAE is an AE that needs medical supervision.

    Measure: Percentage of infant subjects with at least one MAE

    Time: From birth to Day 43 post-birth

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by Enzyme-linked immunosorbent assay (ELISA). The corresponding antibody concentration is expressed in ELISA units per milliliter (ELU/mL). The assay is performed for each group and for each age category (18 -<35 years; ≥ 35 years; overall)

    Measure: RSVPreF3 Immunoglobulin G (IgG)-specific antibody concentration in terms of Geometric Mean Concentrations (GMCs) at Day 1, before vaccination for each group and by age category

    Time: At Day 1 (before vaccination)

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL. The assay is performed for each group and for each age category (18 -<35 years; ≥ 35 years; overall)

    Measure: RSVPreF3 IgG antibody GMCs at Day 31

    Time: At Day 31

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL. The assay is performed for each group and for each age category (18 -<35 years; ≥ 35 years; overall)

    Measure: RSVPreF3 IgG antibody GMCs at delivery

    Time: At delivery(Visit 5)

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The assay is performed for each group and for each age category (18 -<35 years; ≥ 35 years; overall)

    Measure: RSV-A neutralizing antibody Geometric Mean Titers (GMTs) at Day 1, before vaccination

    Time: At Day 1 (before vaccination)

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The assay is performed for each group and for each age category (18 -<35 years; ≥ 35 years; overall)

    Measure: RSV-A neutralizing antibody GMTs at Day 31

    Time: At Day 31

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The assay is performed for each group and for each age category (18 -<35 years; ≥ 35 years; overall)

    Measure: RSV-A neutralizing antibody GMTs at delivery

    Time: At delivery (Visit 5)

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL. The antibodies are measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample can be obtained).

    Measure: RSVPreF3 IgG antibody GMCs in infants born to maternal subjects

    Time: At birth (Visit Day 1 for infants)

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The antibodies are measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample can be obtained).

    Measure: RSV-A neutralizing antibody GMTs in infants born to maternal subjects

    Time: At birth (Visit Day 1 for infants)

    Description: The placental transfer ratio is determined between cord blood or an infant blood sample collected within 3 days after birth (if no cord blood sample can be obtained) and maternal RSVPreF3 IgG-specific antibody concentrations. Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA.

    Measure: Geometric Mean Ratio between cord blood and maternal RSVPreF3 IgG-specific antibody concentrations

    Time: At delivery (visit 5 for maternal subjects) or birth (visit Day 1 for infants)

    Secondary Outcomes

    Description: An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject or abnormal pregnancy outcomes (spontaneous abortion, foetal death, stillbirth, congenital anomalies, ectopic pregnancy).

    Measure: Percentage of maternal subjects with at least one SAE

    Time: From Day 1 to Day 181 post-delivery

    Description: An MAE is a symptom or illness requiring hospitalisation, emergency room visit, or visit to/by a health care provider.

    Measure: Percentage of maternal subjects with at least one MAE

    Time: From Day 1 to Day 181 post-delivery

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measure: Percentage of maternal subjects with at least one AE leading to study withdrawal

    Time: From Day 1 to Day 181 post-delivery

    Description: An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.

    Measure: Percentage of infant subjects with at least one SAE from birth through 6 months after birth

    Time: From birth to Day 181 post-birth

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measure: Percentage of infant subjects with at least one AE leading to study withdrawal from birth through 6 months after birth

    Time: From birth to Day 181 post-birth

    Description: An MAE is a symptom or illness requiring hospitalisation, emergency room visit, or visit to/by a health care provider.

    Measure: Percentage of infant subjects with at least one MAE from birth through 6 months after birth

    Time: From birth to Day 181 post-birth

    Description: An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.

    Measure: Percentage of infant subjects with at least one SAE from birth through 1 year after birth

    Time: From birth to Month 12 post-birth

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measure: Percentage of infant subjects with at least one AE leading to study withdrawal from birth through 1 year after birth

    Time: From birth to Month 12 post-birth

    Description: A MAE is a symptom or illness requiring hospitalisation, emergency room visit, or visit to/by a health care provider.

    Measure: Percentage of infant subjects with at least one MAE from birth through 1 year after birth

    Time: From birth to Month 12 post-birth

    Description: A maternal MA-RTI occurs when the maternal subject visits a healthcare professional for any respiratory symptom, including cough, sputum production and difficulty breathing. An RSV associated MA-RTI is characterised by a medically attended visit for RTI symptoms (runny nose or blocked nose or cough) and a confirmed RSV infection.

    Measure: Percentage of maternal subjects with at least one RSV-associated Medically Attended RSV-associated Respiratory Tract Illnesses (MA-RTI)

    Time: From delivery (visit 5) to Day 181 post-delivery

    Description: An RSV-associated LRTI is characterised by a history of cough or difficulty in breathing, a blood oxygen saturation by pulse oximetry (SpO2) < 95% or respiratory rate increase and a confirmed RSV infection.

    Measure: Percentage of infant subjects with at least one RSV-associated LRTI

    Time: From birth (Visit at Day 1) to Day 181 post-birth

    Description: A RSV-associated severe LRTI is characterised by a history of cough or difficulty in breathing, a SpO2 < 93 % or lower chest wall in-drawing and a confirmed RSV infection.

    Measure: Percentage of infant subjects with at least one RSV-associated severe LRTI

    Time: From birth (Visit Day 1) to Day 181 post-birth

    Description: A RSV-associated very severe LRTI is characterised by a history of cough or difficulty in breathing, a SpO2 < 90 % or inability to feed or failure to respond / unconscious and a confirmed RSV infection.

    Measure: Percentage of infant subjects with at least one RSV-associated very severe LRTI

    Time: From birth (Visit Day 1) to Day 181 post-birth

    Description: An RSV-associated hospitalization is characterised by a confirmed RSV infection and a hospitalisation for an acute medical condition.

    Measure: Percentage of infant subjects with at least one RSV-associated hospitalisation

    Time: From birth (Visit Day 1) to Day 181 post-birth

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL.

    Measure: RSVPreF3 IgG antibody GMCs in maternal subjects, at day 43

    Time: At Day 43 post-delivery

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay.

    Measure: RSV-A neutralizing antibody GMTs in maternal subjects, at day 43

    Time: At Day 43 post-delivery

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay.

    Measure: RSV-B neutralizing antibody GMTs in maternal subjects at Day 1

    Time: At Day 1 (before vaccination)

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-B neutralizing antibody GMTs in maternal subjects at Day 31

    Time: At Day 31

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-B neutralizing antibody GMTs in maternal subjects at delivery

    Time: At delivery (Visit 5)

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-B neutralizing antibody GMTs in maternal subjects at Day 43 post-delivery

    Time: At Day 43 post-delivery

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL.

    Measure: RSVPreF3 IgG antibody GMCs in infants born to maternal subjects, at Day 43 after birth

    Time: At Day 43 after birth

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL.

    Measure: RSVPreF3 IgG antibody GMCs in infants born to maternal subjects, at Day 121 after birth

    Time: At Day 121 after birth

    Description: Serological assays for the determination of IgG antibodies against RSVPreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL.

    Measure: RSVPreF3 IgG antibody concentration at Day 181 after birth

    Time: At Day 181 after birth

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-A neutralizing antibody GMTs at Day 43 after birth

    Time: At Day 43 after birth

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-A neutralizing antibody GMTs at Day 121 after birth

    Time: At Day 121 after birth

    Description: Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-A neutralizing antibody GMTs at Day 181 after birth

    Time: At Day 181 after birth

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU. The antibodies are measured on the cord blood sample collected at delivery, or on a blood sample collected from the infant within 3 days after birth (if no cord blood sample can be obtained).

    Measure: RSV-B neutralizing antibody GMTs at birth

    Time: At birth (Visit at Day 1)

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-B neutralizing antibody GMTs at Day 43 after birth

    Time: At Day 43 after birth

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-B neutralizing antibody GMTs at Day 121 after birth

    Time: At Day 121 after birth

    Description: Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers are expressed in ED60 and/or IU.

    Measure: RSV-B neutralizing antibody GMTs at Day 181 after birth

    Time: At Day 181 after birth
    58 A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of VIB4920 in Subjects With Sjögren's Syndrome (SS)

    The purpose of the study is to evaluate the efficacy, safety, and tolerability of VIB4920 (formerly MEDI4920) in adult participants with Sjögren's Syndrome (SS).

    NCT04129164
    Conditions
    1. Sjögren's Syndrome
    Interventions
    1. Drug: VIB4920
    2. Drug: Placebo
    MeSH:Sjogren's Syndrome Syndrome

    Primary Outcomes

    Measure: Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) at Day 169 in Population 1

    Time: Baseline (Day 1) and Day 169

    Measure: Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at Day 169 in Population 2

    Time: Baseline (Day 1) and Day 169

    Secondary Outcomes

    Measure: Change From Baseline in ESSPRI at Day 169 in Population 1

    Time: Baseline (Day 1) and Day 169

    Measure: Percentage of Participants achieving ESSDAI [3] and ESSDAI [4] response in Population 1

    Time: Baseline (Day 1) to Day 169

    Measure: Percentage of Participants achieving ESSPRI response in Population 2

    Time: Baseline (Day 1) to Day 169

    Measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Day 169 in Populations 1 and 2

    Time: Baseline (Day 1) and Day 169

    Measure: Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 in Populations 1 and 2

    Time: Baseline (Day 1) and Day 169

    Measure: Patient's Global Impression of Severity at Day 169 in Populations 1 and 2

    Time: Day 169

    Measure: Number of participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Populations 1 and 2

    Time: From Baseline (Day 1) up to Day 365

    Measure: Number of participants With Adverse Events of Special Interest (AESIs) in Populations 1 and 2

    Time: From Baseline (Day 1) up to Day 365

    Measure: Number of Participants With Abnormal Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Reported as TEAEs in Populations 1 and 2

    Time: From Baseline (Day 1) up to Day 365

    Measure: Plasma Concentration of VIB4920

    Time: Day 1 to Day 365

    Measure: Percentage of Participants With Positive Antibody Titer to VIB4920 in Populations 1 and 2

    Time: Day 1 to Day 365
    59 Investigator- and Subject-blinded, Randomized, Placebo-controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy Trial of CFZ533 in Pediatric and Young Adult Subjects With New Onset Type 1 Diabetes (T1DM)

    The study is a Phase 2, multicounty, multicenter, non-confirmatory, investigator- and subject masked, randomized, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of CFZ533 on preservation of residual pancreatic β-cell function in new onset T1DM in pediatric and young adult subjects.

    NCT04129528
    Conditions
    1. Type 1 Diabetes Mellitus
    Interventions
    1. Drug: CFZ533
    2. Other: Placebo
    MeSH:Diabetes Mellitus Diabetes Mellitus, Type 1
    HPO:Diabetes mellitus Type I diabetes mellitus

    Primary Outcomes

    Description: To evaluate safety and tolerability of CFZ533 in new onset T1DM.

    Measure: Proportion of subjects with adverse events (AE)/serious adverse events (SAE) in treatment groups.

    Time: at 16 months

    Description: To evaluate the treatment effect of CFZ533 on pancreatic beta cell function.

    Measure: Stimulated C-peptide AUC by mixed meal tolerance test (MMTT).

    Time: at 12 months

    Secondary Outcomes

    Description: To evaluate the pharmacokinetics (PK) of CFZ533.

    Measure: Free CFZ533 plasma concentration.

    Time: at day 1

    Description: To evaluate the pharmacokinetics (PK) of CFZ533.

    Measure: Free CFZ533 plasma concentration.

    Time: at 1 week

    Description: To evaluate the pharmacokinetics (PK) of CFZ533.

    Measure: Free CFZ533 plasma concentration.

    Time: at 12 months

    Description: To evaluate the treatment effect of CFZ533 on full or partial remission.

    Measure: Proportion of subjects with full or partial remission.

    Time: at 12 months

    Description: To evaluate durability of effects of CFZ533 on pancreatic beta cell function.

    Measure: Stimulated C-peptide AUC by MMTT.

    Time: at 3 years
    60 A Phase I, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD2693 Following Single Ascending Dose Administration in Male and Female Subjects of Non-childbearing Potential in Overweight But Otherwise Healthy Subjects, and Healthy Chinese and Japanese Subjects

    This Phase 1, first-in-human (FiH), single-ascending-dose (SAD) study, will assess the safety and tolerability and characterize the pharmacokinetics (PK) of AZD2693, following subcutaneous (SC) SAD administration of AZD2693 in male and female subjects of non-childbearing potential in overweight but otherwise healthy subjects, and healthy Chinese and Japanese subjects.

    NCT04142424
    Conditions
    1. Metabolic Disorders
    2. Non-alcoholic Steatohepatitis
    Interventions
    1. Drug: AZD2693
    2. Drug: Placebo
    MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease Metabolic Diseases Overweight
    HPO:Hepatic steatosis

    Primary Outcomes

    Description: To investigate the safety and tolerability of SC administration of SAD of AZD2693

    Measure: Number of subjects experiencing adverse events and serious adverse events

    Time: From baseline (Day 1) until Day 112 (Week 16, Final follow-up)

    Secondary Outcomes

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Area under the concentration-time curve from time zero extrapolated to infinity (AUC)

    Time: At Day 1 pre-dose, 0.25 hours [h], 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC(0-48h)]

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable analyte concentration divided by the dose administered (AUClast/D)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUC/D)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Maximum observed plasma drug concentration (Cmax) of AZD2693

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Observed maximum plasma concentration divided by the dose administered (Cmax/D)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Time to reach maximum observed concentration following drug administration (tmax)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693.

    Measure: Apparent terminal elimination half-life associated with the terminal slope (λz) of the semi-logarithmic concentration-time curve, estimated as (ln2)/λz (t½λz)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Apparent total body clearance of drug from plasma after extravascular administration calculated as Dose/AUC (CL/F)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Apparent volume of distribution for parent drug at terminal phase (extravascular administration), estimated by dividing CL/F by λz (Vz/F)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Mean residence time (MRT)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Terminal elimination rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve (λz)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Time delay between drug administration and the first observed concentration in plasma (tlag)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Time of the last quantifiable concentration (tlast)

    Time: At Day 1 pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h and 72h post-dose and 1, 2, 4, 8, 12 and 16 weeks post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Cumulative fraction (%) of dose excreted unchanged into the urine from time zero to the last measured time point [fe(0-last)]

    Time: At Day 1 pre-dose, 0-6h, 6-12h and then 0-12h intervals up to 72h post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Cumulative amount of analyte excreted into the urine from time zero through the last sampling interval [Ae(0-last)]

    Time: At Day 1 pre-dose, 0-6h, 6-12h and then 0-12h intervals up to 72h post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Renal clearance of drug from plasma, estimated by dividing Ae(0-t) by AUC(0-t) where the 0-t interval is the same for both Ae and AUC [CLR]

    Time: At Day 1 pre-dose, 0-6h, 6-12h and then 0-12h intervals up to 72h post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)]

    Time: At Day 1 pre-dose, 0-6h, 6-12h and then 0-12h intervals up to 72h post-dose

    Description: To characterize the PK of AZD2693 following SC administration of SAD of AZD2693

    Measure: Fraction of dose excreted unchanged into the urine from time t1 to t2 [fe(t1-t2)]

    Time: At Day 1 pre-dose, 0-6h, 6-12h and then 0-12h intervals up to 72h post-dose
    61 A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of a Single Dose of Exebacase in Patients Receiving Standard-of-Care Antibiotics for the Treatment of Staphylococcus Aureus Bloodstream Infections (Bacteremia), Including Right-Sided Infective Endocarditis

    The purpose of this superiority study is to evaluate the efficacy and safety of exebacase in addition to standard of care antibiotics (SoCA) compared with SoCA alone for the treatment of patients with Staphylococcus aureus (S. aureus) bloodstream infections (BSI), including right-sided infective endocarditis (IE). Patients will be randomized to receive a single intravenous dose of exebacase or placebo. Patients will receive SoCA selected by the investigators based on the protocol. Exebacase, a direct lytic agent, is an entirely new treatment modality against S. aureus. Exebacase is a recombinantly-produced, purified cell wall hydrolase enzyme that results in rapid bacteriolysis, potent biofilm eradication, synergy with antibiotics, low propensity for resistance, and the potential to suppress antibiotic resistance when used together with antibiotics. Exebacase represents a first-in-field, first-in-class treatment with the potential to improve clinical outcome when used in addition to SoCA to treat S. aureus BSI including IE.

    NCT04160468
    Conditions
    1. Staphylococcus Aureus Bacteremia
    2. Staphylococcus Aureus Endocarditis
    Interventions
    1. Drug: Exebacase
    2. Drug: Placebo
    MeSH:Bacteremia Endocarditis
    HPO:Endocarditis

    Primary Outcomes

    Measure: Clinical responder rate at Day 14 in the methicillin-resistant Staphylococcus aureus (MRSA) population

    Time: Day 14

    Description: TEAEs will be summarized by treatment group.

    Measure: Treatment-emergent adverse events (TEAEs) through Day 60

    Time: Through Day 60

    Secondary Outcomes

    Measure: Clinical responder rate at Day 14 in all S. aureus patients

    Time: Day 14

    Measure: 30-day survival in the MRSA population

    Time: Through Day 30

    Measure: Clinical responder rate at Day 60 in the MRSA population

    Time: Day 60

    Measure: Clinical responder rate at Day 60 in all S. aureus patients

    Time: Day 60

    Measure: Clinical responder rate at Day 60 in right-sided IE patients (all S. aureus and MRSA populations)

    Time: Day 60
    62 A Phase 2b Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of MEDI3506 in Subjects With Diabetic Kidney Disease

    A Phase 2b Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of MEDI3506 in Subjects with Diabetic Kidney Disease

    NCT04170543
    Conditions
    1. Diabetic Kidney Disease
    Interventions
    1. Drug: MEDI3506
    2. Drug: Placebo
    3. Drug: Dapagliflozin
    MeSH:Kidney Diseases Diabetic Nephropathies
    HPO:Abnormality of the kidney Nephropathy

    Primary Outcomes

    Description: Change compared to placebo

    Measure: Urine albumin:creatinine ratio (UACR)

    Time: Baseline to Day 169 (24 weeks)

    Secondary Outcomes

    Description: To assess the number Treatment Emergent Adverse events (TEAEs), Serious Adverse Events (SAEs), Treatment Emergent Adverse Events of Special Interest (AESIs)

    Measure: Safety and Tolerability by assessment of adverse events

    Time: Visit 1 (Screening) to Day 230 (End of Study)

    Description: MEDI3506 serum PK concentrations throughout the study

    Measure: PK profile of MEDI3506

    Time: Day 1 to Day 230

    Description: Anti-drug antibodies (ADAs) incidence throughout the study

    Measure: Immunogenicity of MEDI3506

    Time: Day 1 to Day 230

    Description: Proportion of subjects with > 30%, 40% or 50% reduction

    Measure: UACR

    Time: At Day 169, baseline to Day 85 (12 weeks) or Day 85 to Day 169

    Description: To assess systolic and diastolic blood pressure, heart rate, respiratory rate, temperature, 12-lead electrocardiogram, echocardiogram and physical exam

    Measure: Safety and tolerability by assessment of vital signs

    Time: Visit 1(Screening) to End of study

    Description: To assess hematology, serum chemistry, urinalysis

    Measure: Safety and tolerability by clinical laboratory evaluations

    Time: Visit 1(Screening) to End of study
    63 Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 1: Interleukin-5 Antagonists - Mepolizumab and Reslizumab

    This study is designed to assess pharmacokinetics and pharmacodynamics of mepolizumab and reslizumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies. This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (mepolizumab or reslizumab) or placebo.

    NCT04183192
    Conditions
    1. Healthy Subjects
    2. Pharmacokinetics
    3. Pharmacodynamics
    Interventions
    1. Biological: Mepolizumab
    2. Biological: Mepolizumab
    3. Biological: Mepolizumab
    4. Biological: Mepolizumab
    5. Biological: Reslizumab
    6. Biological: Reslizumab
    7. Biological: Reslizumab
    8. Biological: Reslizumab
    9. Biological: Placebo

    Primary Outcomes

    Description: 1. The values and variability of standard pharmacodynamic metrics (AUEC and maximal difference at a single time-point) for eosinophils at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab

    Measure: Area under effect curve and maximum change from baseline for eosinophils for mepolizumab and reslizumab

    Time: 63 or 123 days, depending on treatment arm

    Secondary Outcomes

    Description: 1. The values and variability of pharmacokinetic characteristics (Cmax and area under the curve of free drug concentration) at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab.

    Measure: Maximum concentration and area under the curve for mepolizumab and reslizumab

    Time: 63 or 123 days, depending on treatment arm

    Description: 2. Parameters (Emax, and EC50) calculated by the model after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab or reslizumab with placebo data.

    Measure: Pharmacodynamic model parameters for mepolizumab and reslizumab

    Time: 63 or 123 days, depending on treatment arm
    64 An Electrophysiological Predictor of SSRI Response in Veterans With PTSD

    This is a research study to examine the effectiveness of a brief screening method that may predict which people with posttraumatic stress disorder (PTSD) are most likely to show a positive response to selective serotonin reuptake inhibitor (SSRI) medications. Participants will be recruited over approximately 3.25 years, until at least 94 participants complete the 17 week study.

    NCT04183205
    Conditions
    1. Posttraumatic Stress Disorder
    Interventions
    1. Diagnostic Test: LDAEP
    2. Drug: Placebo
    3. Drug: sertraline
    MeSH:Stress Disorders, Traumatic Stress Disorders, Post-Traumatic

    Primary Outcomes

    Description: The CAPS-5 is the "gold standard" clinical interview for assessing PTSD. This measure will be used to characterize the sample regarding PTSD diagnosis and as a measure of PTSD severity. Each of the 20 symptoms of PTSD included in DSM-5 is rated on a 5-point scale ranging from 0-4, with a 0 or 1 indicating that the symptom is absent or subthreshold and a score of 2-4 indicating that a symptom has reached the threshold to be included as a symptom and ranges in severity from moderate to extreme. The total range of the CAPS-5 is 0-80.

    Measure: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Change

    Time: Administered at screening session 1, and weeks 0, 2, 6, and 14

    Secondary Outcomes

    Description: The QIDS-SR will be used to measure the severity of depressive symptoms. The QIDS provides equivalent weightings (0-3) for each symptom item, gives clearly stated anchors that estimate the frequency and severity of symptoms, and includes all items required to diagnose a major depressive episode.

    Measure: Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR) Change

    Time: Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14

    Description: The HAM-D is the most widely used clinician-administered scale for assessing severity of depression symptoms. The 6-item unidimensional core Melancholia subscale of the HAM-D will be used as the primary depression outcome variable.

    Measure: Hamilton Depression Rating Scale (HAM-D) Change

    Time: Administered at weeks 0, 2, 6 and 14

    Description: DASS-21 is a 21-item measure that assesses the severity of a range of symptoms common to depression, anxiety, and stress. The total score can be used as a measure of general distress or depression, anxiety, and stress subscales can be scored separately.

    Measure: Depression Anxiety Stress Scales (DASS-21) Change

    Time: Administered at screening session 1, and weeks 0, 2, 6, and 14

    Description: The PCL-5 is a 20-item measure that assesses DSM-5 symptoms of PTSD. Participants will rate how much they experienced each symptom on a 5-point Likert-type scale (0 = "not at all" to 4 = "extremely") during the past week (total range=0-80). The PCL-5 will be anchored to participants' worst traumatic event. In addition to the administration of these measures during the four assessment sessions, the PCL-5 will also be administered bi-weekly at each psychiatrist check-in visit.

    Measure: PTSD Checklist for DSM-5 (PCL-5) Change

    Time: Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14

    Description: The PANAS consists of two, 10-item mood scales that measure positive (e.g., 'enthusiastic') and negative (e.g., 'upset') affect separately.

    Measure: The Positive and Negative Affect Schedule (PANAS) Change

    Time: Administered at screening session 1, and weeks 0, 2, 6, and 14

    Description: SCL-90-R measures the following nine primary psychiatric symptom dimensions: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. The Global Severity Index (GSI) is the average rating given to all 90 items and provides a measure of general psychopathology.

    Measure: Symptom Checklist (SCL-90-R) Change

    Time: Administered at screening session 1, and weeks 0, 2, 6, and 14
    65 Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 3 - Interferon Beta-1A and Peginterferon Beta-1A

    This study is designed to assess pharmacokinetics and pharmacodynamics of interferon beta-1a and peginterferon beta-1a across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies. This is a randomized, placebo-controlled, single-dose, parallel arm study in 84 healthy subjects assigned to one of three dose groups (low, intermediate, and high) of each drug (interferon beta-1a and peginterferon beta-1a) or placebo.

    NCT04183491
    Conditions
    1. Healthy Subjects
    2. Pharmacokinetics
    3. Pharmacodynamics
    Interventions
    1. Biological: Interferon beta-1a
    2. Biological: Interferon beta-1a
    3. Biological: Interferon beta-1a
    4. Biological: Peginterferon beta-1a
    5. Biological: Peginterferon beta-1a
    6. Biological: Peginterferon beta-1a
    7. Biological: Placebo

    Primary Outcomes

    Description: The values and variability of standard pharmacodynamic (PD) metrics (AUEC and maximal difference at a single time-point) for neopterin at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

    Measure: Area under effect curve (AUEC) and maximum change from baseline for neopterin for interferon beta-1a and peginterferon beta-1a

    Time: 7 or 14 days, depending on treatment arm

    Secondary Outcomes

    Description: 2. The values and variability of pharmacokinetic characteristics (Cmax and AUC of free drug concentration) at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

    Measure: Maximum concentration (Cmax) and area under the curve (AUC) for interferon beta-1a and peginterferon beta-1a

    Time: 7 or 14 days, depending on treatment arm

    Description: 1. The values and variability of standard PD metrics (AUEC and maximal difference at a single time-point) for MxA at low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a

    Measure: Area under effect curve and maximum change from baseline for Myxovirus-resistance protein A (MxA) for interferon beta-1a and peginterferon beta-1a

    Time: 7 or 14 days, depending on treatment arm

    Description: 3. Parameters (Emax [maximum effect], and EC50 [half maximal effect concentration]) calculated by the model after combining data from low, intermediate, and high doses of interferon beta-1a and peginterferon beta-1a with placebo data

    Measure: Pharmacodynamic model parameters for interferon beta-1a and peginterferon beta-1a

    Time: 7 or 14 days, depending on treatment arm
    66 A Randomized, Double Blind, Placebo-Controlled Phase 1b Study With Open-Label Extension to Assess the Safety, Tolerability and Preliminary Efficacy of ASP0367 (MA-0211) in Pediatric Male Patients With Duchenne Muscular Dystrophy (DMD)

    The primary purpose of this study is to evaluate the safety and tolerability of ASP0367. This study will also evaluate the pharmacokinetics, pharmacodynamics and efficacy on muscle function of ASP0367.

    NCT04184882
    Conditions
    1. Duchenne Muscular Dystrophy (DMD)
    Interventions
    1. Drug: ASP0367
    2. Drug: Placebo
    MeSH:Muscular Dystrophies Muscular Dystrophy, Duchenne
    HPO:Muscular dystrophy

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a subject administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE observed after starting administration of the investigational product (IP) to 14 days after the last dose of IP for the double blind part or moving to the open-label extension part, whichever comes first. An IP-related TEAE is defined as any TEAE with a causal relationship of "yes" by the investigator.

    Measure: Number of participants with Treatment Emergent Adverse Events (TEAEs)

    Time: Up to Week 28

    Description: Number of participants with potentially clinically significant vital sign values.

    Measure: Number of participants with vital sign abnormalities and/or AEs

    Time: Up to Week 28

    Description: Number of participants with potentially clinically significant body weight.

    Measure: Number of participants with body weight change abnormalities and/or AEs

    Time: Up to Week 28

    Description: Number of participants with potentially clinically significant 12-ECG values.

    Measure: Number of participants with electrocardiogram (ECG) abnormalities

    Time: Up to Week 28

    Description: Number of participants with potentially clinically significant echocardiography values.

    Measure: Number of participants with echocardiography abnormalities and/or AEs

    Time: Up to Week 28

    Description: Number of participants with potentially clinically significant laboratory values.

    Measure: Number of participants with laboratory value abnormalities and/or AEs

    Time: Up to Week 28

    Description: The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response provided to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 6 items for suicidal behavior (1. Actual attempt, 2. Interrupted attempt, 3. Aborted attempt, 4. Preparatory acts or behavior, 5. Suicidal Behavior 6. Completed suicide,) will be reported.

    Measure: Number of participants with suicidal ideation and/or behavior as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)

    Time: Baseline and up to Week 28

    Description: The Digit span test is a subtest of Wechsler Intelligence Scale for children (WISC). This test comprises 3 parts on the fifth edition (WISC-V). Digit Span Forward requires the subject to repeat numbers in the same order as presented by the interviewer. Digit Span Backward requires the subject to repeat the numbers in the reverse order of that presented by the interviewer. Digit Span Sequencing requires the subject to sequentially order the numbers presented by the interviewer. Scores of this test are based on each raw score and total raw score.

    Measure: Change from baseline in digit span test

    Time: Baseline and up to Week 24

    Secondary Outcomes

    Description: AUCtau will be recorded from the PK plasma samples collected.

    Measure: Pharmacokinetics (PK) of ASP0367 in plasma: AUC from the time of dosing to the start of next dosing interval (AUCtau)

    Time: Up to Week 2

    Description: Cmax will be recorded from the PK plasma samples collected.

    Measure: PK of ASP0367 in plasma: maximum concentration (Cmax)

    Time: Up to Week 2

    Description: Whole blood cell samples will be collected to measure percent change in target gene expressions.

    Measure: Pharmacodynamics (PD) of ASP0367: Percent change from baseline in peroxisome proliferator-activated receptor (PPAR) delta target genes expression levels in blood

    Time: Baseline and up to Week 4

    Description: Serum samples will be collected to record myostatin/follistatin ratio.

    Measure: PD of ASP0367: Percent change from baseline in serum myostatin/follistatin ratio

    Time: Baseline and up to Week 12

    Description: The PUL Assessment v2.0 includes a total of 23 upper limb test items, with the first entry item A used to define the starting functional level. The remaining 22 items are subdivided into 3 major dimension levels as following; shoulder level (6 items, maximum score of 12), elbow level (9 items, maximum score of 17) and distal level dimension (7 items, maximum score of 13). Positive change in scores indicates an improvement.

    Measure: Change from baseline in Performance of Upper Limb Module (PUL) (v2.0) assessment score

    Time: Baseline and up to Week 12

    Description: PedsQL Multidimensional Fatigue Scale comprises the General Fatigue Scale (6 items), Sleep/Rest Fatigue Scale (6 items) and Cognitive Fatigue Scale (6 items). A 5-point response scale in each item is utilized (0 never a problem; 1 almost never a problem; 2 sometimes a problem; 3 often a problem; 4 almost always a problem). Negative change in scores indicates an improvement. This scale is based on the subject's age and will be assessed by both subject and parent or legal guardian.

    Measure: Change from baseline on Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale

    Time: Baseline and up to Week 12

    Description: The 2-minute walk test (2MWT) is a measurement of endurance that assesses walking distance over 2 minutes. Only ambulatory subjects conduct the 2MWT in this study.

    Measure: Change from baseline in distance walked in 2 minutes assessed in meters

    Time: Baseline and up to Week 12

    Description: The a6MCT has been developed as a submaximal endurance test for both legs (leg-cycling) and arms (arm-cranking) for children who are expected to lose their walking ability in the near future or are wheel chair dependent. Only arm-cranking will be applied to this study.

    Measure: Percent change from baseline in the assisted 6 minute cycling test (a6MCT) maximal attained revolutions

    Time: Baseline and up to Week 12

    Description: The a6MCT has been developed as a submaximal endurance test for both legs (leg-cycling) and arms (arm-cranking) for children who are expected to lose their walking ability in the near future or are wheel chair dependent. Only arm-cranking will be applied to this study.

    Measure: Change from baseline in the a6MCT maximal attained revolutions

    Time: Baseline and up to Week 12

    Description: The fat fraction by MRS will be assessed for the vastus lateralis (VL) and soleus (SOL) muscles.

    Measure: Change from baseline in fat fraction by magnetic resonance spectroscopy (MRS)

    Time: Baseline, Week 12 and Week 24
    67 A Phase 1 Multiple Ascending Intradermal Dose Study to Assess the Safety, Tolerability and Immunological Response of ASP2390 in Adult Subjects Allergic to House Dust Mites

    The purpose of this study is to evaluate the safety and tolerability of multiple ascending intradermal doses of ASP2390 in adult male and female participants allergic to house dust mites (HDM). This study will also evaluate the effect of multiple ascending intradermal doses of ASP2390 on HDM-specific immunoglobulin G subclass 4 (IgG4) levels in adult male and female participants allergic to HDM.

    NCT04184895
    Conditions
    1. Allergic to House Dust Mites
    Interventions
    1. Biological: ASP2390
    2. Biological: Placebo

    Primary Outcomes

    Description: AEs will be coded using medical dictionary for regulatory activities(MedDRA). An AE is any untoward medical occurrence in a participant administered a study drug which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with use of a medicinal product whether or not considered related to the medicinal product. Confirmed and suspected SARS-CoV-2 infection and COVID-19 will be recorded as an AE. An AE is considered serious if the event: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); or other medically important events.

    Measure: Number of participants with Adverse Events (AEs)

    Time: Up to 5 years

    Description: Number of participants with potentially clinically significant laboratory values.

    Measure: Number of participants with laboratory value abnormalities and/or AEs

    Time: Up to week 63

    Description: Number of participants with potentially clinically significant vital sign values.

    Measure: Number of participants with vital sign abnormalities and/or AEs

    Time: Up to week 63

    Description: Routine 12-lead ECGs will be taken after the participant has been resting in the supine position for at least 5 minutes. Routine 12-lead ECGs will be taken in triplicate.

    Measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs

    Time: Up to week 63

    Description: Subcutaneous immunotherapy systemic reaction events will be graded using the World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. Each grade is based on organ system involved and severity. Organ systems are defined as cutaneous, conjunctival, upper respiratory, lower respiratory, gastrointestinal, cardiovascular and other. A reaction from a single organ system such as cutaneous, conjunctival or upper respiratory, but not asthma, gastrointestinal, or cardiovascular is classified as a grade 1. Symptom(s)/sign(s) from more than 1 organ system or asthma, gastrointestinal, or cardiovascular are classified as grades 2 or 3. Respiratory failure or hypotension with or without loss of consciousness define grade 4 and death grade 5. The grade is determined by the physician's clinical judgement.

    Measure: Number of participants with subcutaneous immunotherapy systemic reaction events

    Time: Up to week 11

    Description: Participants will be asked to record local reactogenicity (pain, tenderness, erythema/redness, Induration/Swelling) on a daily basis for 7 consecutive days after the injection, each treatment will be summarized. Grades range from 1 (mild) to 4 (potentially life-threatening).

    Measure: Number of participants with specific local reactogenicity events

    Time: Up to week 12

    Description: Participants will be asked to record systemic reactogenicity (nausea/vomiting, diarrhea, headache, fatigue, myalgia) on a daily basis for 7 consecutive days after the injection, each treatment will be summarized. Grades range from 1 (mild) to 4 (potentially life-threatening).

    Measure: Number of participants with specific systemic reactogenicity events

    Time: Up to week 12

    Secondary Outcomes

    Description: The house dust mite (HDM) allergen-specific IgG4 immunological response for all participants will be presented for each treatment by visit using descriptive statistics.

    Measure: Change from baseline in immunological response to ASP2390 as assessed by HDM allergen-specific IgG4 levels

    Time: Baseline and up to week 24
    68 Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 2: PCSK9 Inhibitors - Alirocumab and Evolocumab

    This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies. This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab and alirocumab ) or placebo.

    NCT04189484
    Conditions
    1. Healthy Subjects
    2. Pharmacokinetics
    3. Pharmacodynamics
    Interventions
    1. Biological: Evolocumab
    2. Biological: Evolocumab
    3. Biological: Evolocumab
    4. Biological: Evolocumab
    5. Biological: Alirocumab
    6. Biological: Alirocumab
    7. Biological: Alirocumab
    8. Biological: Alirocumab
    9. Biological: Placebo

    Primary Outcomes

    Description: The values and variability of AUEC for LDL-C at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

    Measure: Area under effect curve (AUEC) for LDL-C for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm

    Description: The values and variability of maximum change from baseline for LDL-C at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

    Measure: Maximum change from baseline for LDL-C for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm

    Secondary Outcomes

    Description: The values and variability of AUEC for ApoB at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

    Measure: AUEC for Apolipoprotein B (ApoB) for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm

    Description: The values and variability of maximal difference at a single time-point for ApoB at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

    Measure: Maximum change from baseline for apoB for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm

    Description: The values and variability of Cmax at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

    Measure: Maximum concentration (Cmax) for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm

    Description: The values and variability of AUC at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

    Measure: Area under the curve (AUC) for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm

    Description: Model parameters (Emax) calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.

    Measure: Pharmacodynamic model parameters (maximum effect [Emax]) for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm

    Description: Model parameters (EC50) calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.

    Measure: Pharmacodynamic model parameters (half maximum effect concentration [EC50]) for evolocumab and alirocumab

    Time: 42, 56, or 84 days, depending on treatment arm
    69 A Randomised, Single-blind, Placebo-controlled Trial to Investigate Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 474121 Administered as Oral Solution and Tablets to Healthy Male Subjects (SRD Part), and a Randomised, Open-label, Single-dose, Three-way Cross-over Bioavailability Comparison of BI 474121 as Tablet Versus Oral Solution and Tablet With and Without Food (BA Part)

    The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 474121 in healthy male subjects following oral administration of single rising doses.

    NCT04194645
    Conditions
    1. Healthy
    Interventions
    1. Drug: BI 474121
    2. Drug: Placebo

    Primary Outcomes

    Measure: Percentage of subjects with drug-related adverse events (Single-rising dose (SRD) part)

    Time: Up to 15 days

    Measure: BA part: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)

    Time: Up to 96 hours

    Measure: BA part: Cmax (maximum measured concentration of the analyte in plasma)

    Time: Up to 96 hours

    Secondary Outcomes

    Measure: SRD part: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)

    Time: Up to 96 hours

    Measure: SRD part: Cmax (maximum measured concentration of the analyte in plasma)

    Time: Up to 96 hours

    Measure: BA part: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

    Time: Up to 96 hours
    70 Single-Centre, Randomised, Double-Blind, 3-Period Cross-Over Study to Investigate Effects on QTcF Interval of Verinurad ER 24 mg or IR 40 mg in Combination With Allopurinol 300 mg, Compared to Matching Placebos In Healthy Volunteers

    This study will be conducted to investigate the safety of verinurad in healthy volunteers in combination with allopurinol 300 mg, compared with placebo in particular its effect on electrocardiogram (ECG), with focus on the QT/QTc interval

    NCT04256629
    Conditions
    1. Healthy Volunteers (Intended Indication: Chronic Kidney Disease)
    Interventions
    1. Drug: Verinurad
    2. Drug: Placebo
    3. Drug: Allopurinol
    MeSH:Kidney Diseases Renal Insufficiency, Chronic
    HPO:Abnormality of the kidney Chronic kidney disease Nephropathy

    Primary Outcomes

    Description: To assess the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supra-therapeutic exposure), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF interval analysis

    Measure: Maximum observed plasma concentration (Cmax)

    Time: Visit 2,3,4:- Day 1: Pre-dose, 0.5,1,1.5,2, 3, 4, 5, 6, 7, 8 and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose

    Description: To assess the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supra-therapeutic exposure), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF interval analysis

    Measure: Baseline-corrected and placebo-adjusted QTcF interval (ΔΔQTcF)

    Time: Screening; Visit 2,3,4:- Day -1, 1,2, 3; Follow up visit (7 to 10 days after the last dose)

    Secondary Outcomes

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation(supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected heart rate (ΔHR)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected and placebo-adjusted heart rate (ΔΔHR)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected RR interval (ΔRR interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected and placebo-adjusted RR interval (ΔΔRR interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected PR interval (ΔPR interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected and placebo-adjusted PR interval (ΔΔPR interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected and placebo-adjusted QRS interval (ΔQRS interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected and placebo-adjusted QRS interval (ΔΔQRS interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected QT interval (ΔQT interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected and placebo-adjusted QT interval (ΔΔQT interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected QTcF interval (ΔQTcF interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

    Measure: Baseline-corrected and placebo-adjusted QTcF interval (ΔΔQTcF interval)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To assess the pharmacokinetics (PK) of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Area under plasma concentration-time curve from zero to infinity (AUC)

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects.

    Measure: Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUC0-t)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Maximum observed plasma concentration (Cmax)

    Time: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Time to reach maximum observed plasma concentration (tmax)

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Time delay between drug administration and the first observed concentration in plasma (tlag)

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Time of last quantifiable plasma concentration (tlast)

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Apparent total body clearance of drug from plasma after extravascular administration (parent drug only) [CL/F]

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Apparent volume of distribution during the terminal phase after extravascular administration (parent drug only) [Vz/F]

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Apparent volume of distribution at steady state (Vss/F)

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

    Measure: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)

    Time: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose

    Description: To assess clinical chemistry/hematology/urinalysis as a variable of safety and tolerability of verinurad and allopurinol

    Measure: Number of subjects with abnormal haematology, clinical chemistry and urinalysis

    Time: Screening; Visit 2,3 and 4:- Day -1, Day 3: 48 h post-dose, Follow up period

    Description: To assess vital signs as a variable of safety and tolerability of verinurad and allopurinol

    Measure: Number of subjects with abnormal blood pressure and pulse rate

    Time: Screening; Visit 2,3 and 4:- Day -1, Day 1: pre-dose, 1 and 6 h post-dose; Day 2: 24 h post-dose; Day 3: 48 h post-dose, Follow up visit
    71 MitoQ for Fatigue in Multiple Sclerosis: A Placebo Controlled Trial

    The purpose of this study is to determine whether MS patients who receive Oral mitoquinone (MitoQ) have less fatigue than those receiving a placebo. A comparison between patient's fatigue scored at baseline and fatigue scored 12 weeks after drug initiation will assess if MitoQ has a significant change in fatigue.

    NCT04267926
    Conditions
    1. Multiple Sclerosis
    2. Fatigue
    Interventions
    1. Drug: 20 mg MitoQ
    2. Drug: Placebo
    3. Drug: 40mg of MitoQ
    MeSH:Multiple Sclerosis Sclerosis Fatigue
    HPO:Fatigue

    Primary Outcomes

    Description: MFIS is a self -reported fatigue survey. Scale 0 - 84

    Measure: Modified Fatigue Inventory Scale (MFIS)

    Time: 12 weeks

    Secondary Outcomes

    Description: SDMT measures cognitive function. Scale 0-110

    Measure: Symbol Digit Modalities Test (SDMT)

    Time: 12 weeks

    Description: EDSS measures neurological function. Scale 0-10

    Measure: Expanded Disability Status Scale (EDSS)

    Time: 12 weeks

    Description: BDI is a self-reported questionnaire measuring depression. Scale 0-21

    Measure: Beck's Depression Inventory (BDI)

    Time: 12 weeks
    72 Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe COVID-19

    The novel coronavirus pneumonia is a kind of new emerging respiratory infectious disease, characterized by fever, dry cough, and chest tightness, and caused by the infection of the 2019 novel coronavirus (2019-nCoV). In severe cases, there will be rapid respiratory system failure. The novel coronavirus pneumonia is extremely contagious and the disease progresses rapidly. It has become a urgent and serious public health event that threatens human life and health globally. Among them, severe pneumonia caused by novel coronavirus is characterized by extensive acute inflammation of the lungs and the patient is critically ill. At present, there is no effective treatment in clinical practice.Most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for severe pneumonia patients infected with 2019-nCoV.

    NCT04273646
    Conditions
    1. 2019 Novel Coronavirus Pneumonia
    2. COVID-19
    Interventions
    1. Biological: UC-MSCs
    2. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of Pneumonia Improvement

    Measure: Pneumonia severity index

    Time: From Baseline (0W) to 12 week after treatment

    Description: Evaluation of Pneumonia Improvement

    Measure: Oxygenation index (PaO2/FiO2)

    Time: From Baseline (0W) to 12 week after treatment

    Secondary Outcomes

    Description: Incidence of acute and chronic treatment-related adverse events in patients with novel coronavirus severe pneumonia receiving UC-MSCs infusion as assessed.

    Measure: Side effects in the UC-MSCs treatment group

    Time: From Baseline (0W) to 96 week after treatment

    Description: Marker for efficacy of treatment

    Measure: 28-days survival

    Time: Day 28

    Description: Markers of organ function（Score each criterion on a scale of 0 to 4, and the higher the score, the worse the prognosis.）

    Measure: Sequential organ failure assessment

    Time: Day 28

    Description: Markers of Infection

    Measure: C-reactive protein

    Time: From Baseline (0W) to 12 week after treatment

    Description: Markers of Infection

    Measure: Procalcitonin

    Time: From Baseline (0W) to 12 week after treatment

    Description: Marker of Immunological function

    Measure: Lymphocyte count

    Time: From Baseline (0W) to 12 week after treatment

    Description: Marker of Immunological function

    Measure: CD3+, CD4+ and CD8+ T celll count

    Time: From Baseline (0W) to 12 week after treatment

    Description: Marker of Immunological function

    Measure: CD4+/CD8+ratio

    Time: From Baseline (0W) to 12 week after treatment
    73 The Efficacy of Treating Pulmonary Fibrosis and Pulmonary Function Injury in COVID-19 With the Fuzheng Huayu Tablets: a Multicenter Randomized Controlled Trial

    According to previous studies, viral pneumonia can develop into pulmonary fibrosis, which can affect patients'lung function and even life health.This study aims to observe the efficacy and safety of Fuzheng Huayu Tablets in the treatment of pulmonary fibrosis after COVID-19.

    NCT04279197
    Conditions
    1. Pulmonary Fibrosis Due to COVID-19
    Interventions
    1. Drug: Fuzheng Huayu Tablet
    2. Drug: Vitamin C tablets
    3. Other: Placebo
    4. Other: respiratory function rehabilitation training
    MeSH:Pulmonary Fibrosis Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Evaluation of pulmonary fibrosis Improvement. pulmonary fibrosis judged by HRCT score.HRCT images are divided into four grades according to the score, and a reduction of one grade is an improvement.

    Measure: The improvement proportion of pulmonary fibrosis

    Time: Week 24

    Secondary Outcomes

    Description: Evaluation of Lung Function Improvement

    Measure: Blood oxygen saturation

    Time: Week 24

    Description: Discomfort symptoms include dyspnea, cough, exhausted, fatigue, insomnia, sweating, poor appetite, diarrhea, etc., which are common manifestations of patients with COVID-19

    Measure: Clinical symptom score

    Time: Week 24

    Description: This scale can reflect the quality of life of patients to some extent.

    Measure: Quality of Life-BREF (QOL-BREF)

    Time: Week 24

    Description: This scale can reflect the quality of life of patients to some extent.

    Measure: Patient Health Questionnaire-9(PHQ-9)

    Time: Week 24

    Description: This scale can reflect the quality of life of patients to some extent.

    Measure: Generalized anxiety disorder-7(GAD-7)

    Time: Week 24

    Description: Evaluation of Lung Function Improvement

    Measure: The 6-minute walk distance

    Time: Week 24
    74 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

    This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.

    NCT04280705
    Conditions
    1. COVID-19
    Interventions
    1. Other: Placebo
    2. Drug: Remdesivir

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.

    Measure: Time to Recovery

    Time: Day 1 through Day 29

    Secondary Outcomes

    Description: Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Alanine Transaminase (ALT)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Aspartate Transaminase (AST)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Creatinine

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Glucose

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Hemoglobin

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Platelets

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Prothrombin Time (PT)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Total Bilirubin

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in White Blood Cell Count (WBC)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Neutrophils

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Lymphocytes

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Monocytes

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Basophils

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Eosinophils

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome.

    Measure: Change in National Early Warning Score (NEWS) From Baseline

    Time: Days 1, 3, 5, 8, 11, 15, 22, and 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1

    Time: Day 1

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3

    Time: Day 3

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5

    Time: Day 5

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8

    Time: Day 8

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11

    Time: Day 11

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15

    Time: Day 15

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22

    Time: Day 22

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29

    Time: Day 29

    Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

    Measure: Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)

    Time: Day 1 through Day 29

    Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

    Measure: Percentage of Participants Reporting Serious Adverse Events (SAEs)

    Time: Day 1 through Day 29

    Description: Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses.

    Measure: Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics

    Time: Day 1 through Day 10

    Description: Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.

    Measure: Duration of Hospitalization

    Time: Day 1 through Day 29

    Description: Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die

    Measure: Duration of New Non-invasive Ventilation or High Flow Oxygen Use

    Time: Day 1 through Day 29

    Description: Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die .

    Measure: Duration of New Oxygen Use

    Time: Day 1 through Day 29

    Description: Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die

    Measure: Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use

    Time: Day 1 through Day 29

    Description: New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.

    Measure: Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use

    Time: Day 1 through Day 29

    Description: The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline

    Measure: Percentage of Participants Requiring New Oxygen Use

    Time: Day 1 through Day 29

    Description: The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline

    Measure: Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement.

    Measure: Mean Change in the Ordinal Scale

    Time: Day 1, 3, 5, 8, 11, 15, 22, and 29

    Description: The mortality rate was determined as the proportion of participants who died by study Day 15.

    Measure: 14-day Participant Mortality

    Time: Day 1 through Day 15

    Description: The mortality rate was determined as the proportion of participants who died by study Day 29.

    Measure: 29-day Participant Mortality

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant

    Measure: Time to an Improvement by at Least One Category Using an Ordinal Scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant

    Measure: Time to an Improvement of at Least Two Categories Using an Ordinal Scale

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.

    Measure: Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First

    Time: Day 1 through Day 29
    75 Human Umbilical Cord Mesenchymal Stem Cells Treatment for Pneumonia Patients Infected by 2019 Novel Coronavirus

    The 2019 novel coronavirus pneumonia outbroken in Wuhan, China, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, there is no effective treatment in clinical practice. The present clinical trial is to explore the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for novel coronavirus pneumonia patients.

    NCT04293692
    Conditions
    1. COVID-19
    Interventions
    1. Biological: UC-MSCs
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of Pneumonia change

    Measure: Size of lesion area by chest imaging

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Evaluation of Pneumonia change

    Measure: Blood oxygen saturation

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Secondary Outcomes

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: 0-4 score, the higher the score is, the poor of the prognosis will be.

    Measure: Sequential organ failure assessment

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Number of participants with treatment-related adverse events

    Measure: Side effects in the UC-MSCs treatment group

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Markers of the heart function

    Measure: Electrocardiogram, the changes of ST-T interval mostly

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Markers of infection

    Measure: Concentration of C-reactive protein C-reactive protein, immunoglobulin

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Marker of Immunology and inflammation

    Measure: CD4+ and CD8+ T cells count

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Marker of Immunology and inflammation

    Measure: Concentration of the blood cytokine (IL-1β, IL-6, IL-8,IL-10,TNF-α)

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Markers of the heart function

    Measure: Concentration of the myocardial enzymes

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
    76 A Phase IIb Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Severe Influenza Infection

    This is a Phase IIb study consisting of two cohorts to evaluate efficacy, safety and pharmacokinetics of DAS181 in IFV infection. An approximate total of 280 subjects will be enrolled into this study.

    NCT04298060
    Conditions
    1. Influenza Infection
    2. SAD-RV Infection and COVID-19
    Interventions
    1. Drug: DAS181
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Influenza, Human

    Primary Outcomes

    Description: Percent of subjects who have returned to room air

    Measure: Percent of subjects who have returned to room air

    Time: 7 days

    Description: Percent change of subjects return to baseline oxygen requirement by Day 7 compared to Day 1

    Measure: Percent change of subjects return to baseline oxygen requirement

    Time: 7 days
    77 Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting; a Randomised, Placebo-controlled Prophylaxis Study (COPCOV)

    The study is a double-blind, randomised, placebo-controlled trial that will be conducted in healthcare settings and other facilities directly involved in COVID-19 case management. We will recruit healthcare workers and other staff working in a facility where there are cases of either proven, or suspected, COVID-19, who can be followed reliably for 5 months. 40,000 participants will be recruited and we predict an average of 400-800 participants per site in 50-100 sites. The participant will be randomised to receive either chloroquine or placebo (1:1 randomisation), or to hydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10mg base/kg (four 155mg tablets for a 60kg subject), followed by 155 mg daily (250mg chloroquine phosphate salt/ 200mg hydroxychloroquine sulphate) will be taken for 3 months. If the participant is diagnosed with COVID-19, they will take continue to take the study medication until: - 90 days after enrolment (i.e., completion of kit) - hospitalised due to COVID-19 disease (i.e., not for quarantine purposes) in which case they will stop, or - advised to stop by their healthcare professional for other reasons Episodes of symptomatic respiratory illness, including symptomatic COVID-19, and clinical outcomes will be recorded in the Case Record Form during the follow-up period.

    NCT04303507
    Conditions
    1. COVID19
    2. Coronavirus
    3. Acute Respiratory Illnesses
    Interventions
    1. Drug: Chloroquine or Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups

    Measure: Number of symptomatic COVID-19 infections

    Time: Approximately 90 days

    Secondary Outcomes

    Description: Symptoms severity of COVID-19 will be compared between the two groups using a respiratory severity score.

    Measure: Symptoms severity of COVID-19

    Time: Approximately 90 days

    Description: Number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of follow up.

    Measure: Number of asymptomatic cases of COVID-19

    Time: Approximately 90 days

    Description: Number of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.

    Measure: Number of symptomatic acute respiratory illnesses

    Time: Approximately 90 days

    Description: Severity of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.

    Measure: Severity of symptomatic acute respiratory illnesses

    Time: Approximately 90 days

    Other Outcomes

    Description: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, Acute Respiratory Infection and disease severity.

    Measure: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity.

    Time: Approximately 90 days

    Description: Number of days lost to work in relation to the treatment arm

    Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic.

    Time: Approximately 90 days

    Description: The trial will collect data on monetary costs associated with the use of healthcare resources and determine the effects between treatment groups.

    Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs

    Time: Approximately 90 days

    Description: The trial will collect data on health-related quality of life using the quality of life questionnaire (EQ-5D-3L) to determine the effects between treatment groups.

    Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on quality of life measures using the quality of life questionnaire (EQ-5D-3L)

    Time: Approximately 90 days
    78 Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

    Study Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.

    NCT04308668
    Conditions
    1. Corona Virus Infection
    2. Acute Respiratory Distress Syndrome
    3. SARS-CoV Infection
    4. Coronavirus
    5. Coronavirus Infections
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Number of participants at 14 days post enrollment with active COVID19 disease.

    Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline

    Time: 14 days

    Description: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

    Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline

    Time: 14 days

    Secondary Outcomes

    Description: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.

    Measure: Incidence of Hospitalization

    Time: 14 days

    Description: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.

    Measure: Incidence of Death

    Time: 90 days

    Description: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.

    Measure: Incidence of Confirmed SARS-CoV-2 Detection

    Time: 14 days

    Description: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.

    Measure: Incidence of Symptoms Compatible with COVID19 (possible disease)

    Time: 90 days

    Description: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.

    Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal

    Time: 14 days

    Description: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

    Measure: Overall symptom severity at 5 and 14 days

    Time: 5 and 14 days

    Description: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.

    Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry

    Time: 14 days
    79 Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization

    This is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).

    NCT04311177
    Conditions
    1. Corona Virus Infection
    2. Acute Respiratory Distress Syndrome
    3. SARS-CoV Infection
    Interventions
    1. Drug: Losartan
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.

    Measure: Hospital Admission

    Time: 15 days

    Secondary Outcomes

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.

    Measure: Change in PROMIS Dyspnea Functional Limitations

    Time: baseline, 10 days

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

    Measure: Change in PROMIS Dyspnea Severity

    Time: baseline, 10 days

    Description: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.

    Measure: Daily Maximum Temperature

    Time: 10 days

    Description: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.

    Measure: Emergency Department/Clinic Presentations

    Time: 28 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating Day 7

    Time: 7 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating Day 15

    Time: 15 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating Day 28

    Time: 28 days

    Description: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Oropharyngeal Swab Day 9

    Time: 9 days

    Description: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Oropharyngeal Swab Day 15

    Time: 15 days

    Description: Outcome reported as the mean number of days participants in each arm did not require ventilator use.

    Measure: Ventilator-Free Days

    Time: 28 days

    Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.

    Measure: Therapeutic Oxygen-Free Days

    Time: 28 days

    Description: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.

    Measure: Need for Hospital Admission at 15 Days

    Time: 15 days

    Description: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.

    Measure: Need for Oxygen Therapy at 15 Days

    Time: 15 days
    80 Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization

    This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.

    NCT04312009
    Conditions
    1. Corona Virus Infection
    2. Acute Respiratory D
    3. Acute Respiratory Distress Syndrome
    4. SARS-CoV Infection
    Interventions
    1. Drug: Losartan
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.

    Measure: Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days

    Time: 7 days

    Secondary Outcomes

    Description: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.

    Measure: Daily Hypotensive Episodes

    Time: 10 days

    Description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

    Measure: Hypotension Requiring Vasopressors

    Time: 10 days

    Description: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.

    Measure: Acute Kidney Injury

    Time: 10 days

    Description: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.

    Measure: Sequential Organ Failure Assessment (SOFA) Total Score

    Time: 10 days

    Description: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.

    Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S)

    Time: 10 days

    Description: Outcome reported as the number of participants who have expired at 28 days post enrollment.

    Measure: 28-Day Mortality

    Time: 28 days

    Description: Outcome reported as the number of participants who have expired at 90 days post enrollment.

    Measure: 90-Day Mortality

    Time: 90 days

    Description: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

    Measure: ICU Admission

    Time: 10 days

    Description: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.

    Measure: Number of Ventilator-Free Days

    Time: 10 days

    Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.

    Measure: Number of Therapeutic Oxygen-Free Days

    Time: 10 days

    Description: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.

    Measure: Number of Vasopressor-Free Days

    Time: 10 days

    Description: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.

    Measure: Length of ICU Stay

    Time: 10 days

    Description: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.

    Measure: Length of Hospital Stay

    Time: 10 days

    Description: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.

    Measure: Incidence of Respiratory Failure

    Time: 10 days

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.

    Measure: Change in PROMIS Dyspnea Functional Limitations

    Time: 10 days

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

    Measure: Change in PROMIS Dyspnea Severity

    Time: 10 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating

    Time: 10 days

    Description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Nasopharyngeal Swab Day 9

    Time: 9 days

    Description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Nasopharyngeal Swab Day 15

    Time: 15 days

    Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Blood Day 9

    Time: 9 days

    Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Blood Day 15

    Time: 15 days
    81 A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 Inhalation Solution in Reducing the Severity of COVID-19 in Adults Positive for SARS-CoV-2 Infection

    Adults who have tested positive for SARS-CoV-2 infection and who do not require supplemental oxygen will receive PUL-042 Inhalation Solution or placebo 3 times over a one week period in addition to their normal care. Subjects will be be followed and assessed for their clinical status over 28 days to see if PUL-042 Inhalation Solution improves the clinical outcome

    NCT04312997
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PUL-042 Inhalation Solution
    2. Drug: Placebo
    MeSH:Infection Respiratory Aspiration

    Primary Outcomes

    Description: To determine the efficacy of PUL-042 Inhalation Solution in decreasing the severity of COVID-19 in subjects: 1) who have documented SARS-CoV-2 infection and, 2) who do not require supplemental oxygen (Ordinal Scale for Clinical Improvement 3 or less) at the time of enrollment. The primary endpoint is the difference in the proportion of patients with clinically meaningful worsening of COVID-19 within 28 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.

    Measure: Severity of COVID-19

    Time: 28 days

    Secondary Outcomes

    Description: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy

    Measure: SARS-CoV-2 infection

    Time: 28 days

    Description: To determine the difference in the proportion of COVID-19 patients with clinically meaningful worsening of COVID-19 within 14 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.

    Measure: Severity of COVID-19 over 14 days

    Time: 14 days

    Description: To assess the progression of COVID-19 severity during the study as measured by the SARS-CoV-2 Symptom Score. The SARS-CoV-2 Symptom Score measures 3 elements on a 0-3 scale (cough, shortness of breath or difficulty breathing, and muscle aches or fatigue) ranging from 0 for none to 3 for severe. The fourth element is fever and it is rated on a 0-4 scale with 0 being no fever and 4 being life-threatening.

    Measure: Severity of COVID-19 symptoms

    Time: 28 days

    Description: The requirement for ICU admission within 28 days from the start of the experimental therapy.

    Measure: ICU admission

    Time: 28 days

    Description: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.

    Measure: Mechanical Ventilation

    Time: 28 days

    Description: All cause mortality at 28 days from the start of experimental therapy

    Measure: Mortality

    Time: 28 days
    82 A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 Inhalation Solution in Reducing the Infection Rate and Progression to COVID-19 in Adults Exposed to SARS-CoV-2

    Subjects who have documented exposure to SARS-CoV-2 (COVID-19) will receive 4 doses of PUL-042 Inhalation Solution or 4 doses of a placebo solution by inhalation over 10 days. Subjects will be followed for the incidence and severity of COVID-19 over 28 days. Subjects will be tested for infection with SARS-CoV-2 at the beginning, middle and end of the study.

    NCT04313023
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PUL-042 Inhalation Solution
    2. Drug: Placebo
    MeSH:Infection Disease Progression

    Primary Outcomes

    Description: To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-CoV-2 infection and, 2) are asymptomatic at enrollment. The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 28 days from the start of experimental therapy.

    Measure: Severity of COVID-19

    Time: 28 days

    Secondary Outcomes

    Description: Positive test for SARS-CoV-2 infection 28 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit

    Measure: Incidence of SARS-CoV-2 infection

    Time: 28 days

    Description: Positive test for SARS-CoV-2 infection 14 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit

    Measure: Incidence of SARS-CoV-2 infection

    Time: 14 days

    Description: The severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 14 days from the start of experimental therapy.

    Measure: Severity of COVID-19

    Time: 14 days

    Description: The requirement for ICU admission within 28 days from the start of experimental therapy.

    Measure: ICU admission

    Time: 28 days

    Description: The requirement for mechanical ventilation within 28 days from the start of experimental therapy.

    Measure: Mechanical ventilation

    Time: 28 days

    Description: All cause mortality at 28 days from the start of experimental therapy.

    Measure: Mortality

    Time: 28 days
    83 An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19

    Phase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of disease severity strata. Phase 3 Cohort 1: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with critical COVID-19 receiving mechanical ventilation at baseline. Phase 3 Cohort 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 receiving mechanical ventilation at baseline.

    NCT04315298
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Sarilumab
    2. Drug: Placebo

    Primary Outcomes

    Description: Phase 2

    Measure: Percent change in C-reactive protein (CRP) levels in patients with serum IL-6 level greater than the upper limit of normal

    Time: Day 4

    Description: Phase 3 Cohort 1 7-point Ordinal Scale: Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized

    Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with critical COVID-19 receiving mechanical ventilation at baseline

    Time: Up to day 22

    Description: Phase 3 Cohort 2

    Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with COVID-19 receiving mechanical ventilation at baseline

    Time: Up to day 22

    Secondary Outcomes

    Description: Phase 2

    Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale in severe or critical patients with serum IL-6 levels greater than the upper limit of normal

    Time: Up to day 29

    Description: Phase 2

    Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale reporting in severe or critical patients with all IL-6 levels

    Time: Up to day 29

    Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Documented fever defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic), or ≥37.6°C (temporal or axillary)

    Measure: Time to resolution of fever for at least 48 hours without antipyretics in patients with documented fever

    Time: Up to day 29

    Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

    Measure: Time to resolution of fever for at least 48 hours without antipyretics by clinical severity

    Time: Up to day 29

    Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

    Measure: Time to resolution of fever for at least 48 hours without antipyretics by baseline IL-6 levels

    Time: Up to day 29

    Description: Phase 2 Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to improvement in oxygenation for at least 48 hours

    Time: Up to day 29

    Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to improvement in oxygenation for at least 48 hours by clinical severity

    Time: Up to day 29

    Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to improvement in oxygenation for at least 48 hours by baseline IL-6 levels

    Time: Up to day 29

    Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to resolution of fever and improvement in oxygenation for at least 48 hours

    Time: Up to day 29

    Description: Phase 2

    Measure: Mean change in the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 2

    Measure: Percentage of patients in each clinical status category using the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 2 NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)

    Measure: Time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours

    Time: Up to day 29

    Description: Phase 2

    Measure: Change from baseline in NEWS2 scoring system

    Time: Up to day 29

    Description: Phase 2 Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)

    Measure: Number of days with fever

    Time: Up to day 29

    Description: Phase 2

    Measure: Proportion of patients alive, off oxygen

    Time: At day 29

    Description: Phase 2

    Measure: Number of days of resting respiratory rate >24 breaths/min

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of days with hypoxemia

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of days of supplemental oxygen use

    Time: Up to day 29

    Description: Phase 2

    Measure: Time to saturation ≥94% on room air

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of ventilator free days in the first 28 days

    Time: Baseline to day 29

    Description: Phase 2

    Measure: Number of patients requiring initiation of mechanical ventilation

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of patients requiring non-invasive ventilation

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of patients requiring the use of high flow nasal cannula

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of patients admitted into an intensive care unit (ICU)

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of days of hospitalization among survivors

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of deaths due to any cause

    Time: Up to day 60

    Description: Phase 3

    Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale

    Time: Up to day 22

    Description: Phase 3 Defined as discharged, or alive without supplemental oxygen use or at pre-COVID oxygen use

    Measure: Proportion of patients who recover

    Time: Up to day 22

    Description: Phase 3

    Measure: Proportion of deaths

    Time: Through day 29

    Description: Phase 3

    Measure: Proportion of patients alive not receiving mechanical ventilation

    Time: At day 22

    Description: Phase 3

    Measure: Proportion of patients alive not requiring extracorporeal membrane oxygenation (ECMO)

    Time: At day 22

    Description: Phase 3

    Measure: Proportion of patients with a 2-point improvement in clinical status on the 7-point ordinal scale

    Time: Up to day 22

    Description: Phase 3

    Measure: Time to at least 1-point improvement in clinical status assessment on the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 3

    Measure: Time to at least 2-point improvement in clinical status assessment on the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 3

    Measure: Proportion of patients receiving mechanical ventilation

    Time: Up to day 22

    Description: Phase 3

    Measure: Proportion of patients receiving ECMO

    Time: Up to day 22

    Description: Phase 3

    Measure: Proportion of patients discharged and alive

    Time: At day 22

    Description: Phase 3 Defined as discharged or alive without supplemental oxygen use or at pre-COVID oxygen use

    Measure: Time to recovery

    Time: Up to day 29

    Description: Phase 3

    Measure: Proportion of deaths

    Time: Through day 60

    Description: Phase 3

    Measure: Time to death due to any cause

    Time: Through day 60

    Description: Phase 3

    Measure: Number of ventilator free days

    Time: Up to day 29

    Description: Phase 3

    Measure: Number of days of hospitalization among survivors

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with serious adverse events

    Time: Up to Day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with Grade 4 neutropenia (ANC <500/mm3)

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with Grade 4 neutropenia (ANC <500/mm3)

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with hypersensitivity reactions

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with infusion reactions

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with gastrointestinal perforation

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: White blood cell count

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Hemoglobin levels

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Platelet count

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Creatinine levels

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Total bilirubin level

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Alanine aminotransferase (ALT) level

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Aspartate aminotransferase (AST) level

    Time: Up to day 29 if still hospitalized
    84 Exploratory Clinical Study to Assess the Efficacy of NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia

    This is phase II study to assess the efficacy of NestaCell® (mesenchymal stem cell) to treat severe COVID-19 pneumonia.

    NCT04315987
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: NestaCell®
    2. Biological: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Ordinal scale (WHO ordinal scale that measures illness severity over time)

    Measure: Change in Clinical Condition

    Time: 10 days

    Secondary Outcomes

    Description: Evaluation of Pneumonia change

    Measure: Rate of mortality within 10-days

    Time: 10 days

    Description: Evaluation of Pneumonia change

    Measure: Change of Clinical symptoms - respiratory rate

    Time: 10 days

    Description: oxygen saturation

    Measure: Hypoxia

    Time: 10 days

    Description: oxygen saturation

    Measure: PaO2 / FiO2 ratio

    Time: 10 days

    Description: Marker of Immunological function

    Measure: CD4+ and CD8+ T cell count

    Time: Days 1, 2, 4, 6 and 8.

    Description: PaO2 / FiO2 ratio

    Measure: Changes of blood oxygen

    Time: 10 days

    Description: Number of participants with treatment-related adverse events

    Measure: Side effects in the treatment group

    Time: 10 days

    Description: Complete blood count, ALT, AST, GGT, CK, CKmB and creatinine

    Measure: Complete blood count, cardiac, hepatic and renal profiles;

    Time: Days 1, 2, 4, 6 and 8.
    85 A Multicentre, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of GSK2982772 in Participants With Moderate to Severe Plaque Psoriasis

    Plaque psoriasis is a chronic relapsing inflammatory skin disease that is characterized by keratinocyte hyper-proliferation and epidermal hyperplasia. Standard treatment for psoriasis generally requires long-term use of topical therapies, psoralen and ultraviolet A (PUVA), ultraviolet B (UVB) and/or systemic immunosuppressant therapies to achieve and maintain adequate disease control. This is a multicenter, randomized, double-blind study conducted in participants with moderate to severe plaque psoriasis. The study will evaluate the efficacy, safety, pharmacokinetic and pharmacodynamics profile of 960 milligram (mg) GSK2982772 administered as a once daily modified release (MR) formulation. Participants will be randomized in a 2:1 ratio to receive either 960 mg GSK2982772 or placebo for 12 weeks. The duration of the study, including Screening and follow-up, will be approximately 21 weeks for each participant.

    NCT04316585
    Conditions
    1. Psoriasis
    Interventions
    1. Drug: GSK2982772
    2. Drug: Placebo
    MeSH:Psoriasis
    HPO:Palmoplantar pustulosis Psoriasiform dermatitis

    Primary Outcomes

    Description: Psoriatic lesions will be assessed using the PASI scoring system. Erythema, induration, and scale are each graded on a 5-point scale (0-4), and the percent body Surface Area (BSA) affected is scored on a 7-point scale (0-6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). The body region scores are each multiplied by a weighted factor; and the sum of the region scores give the overall PASI score. Higher scores indicate more severe disease.

    Measure: Percentage of participants who achieve >=75 percent improvement from Baseline in Psoriasis Area Severity Index (PASI) score at Week 12

    Time: Baseline and Week 12

    Secondary Outcomes

    Description: Psoriatic lesions will be assessed using the PASI scoring system. Erythema, induration, and scale are each graded on a 5-point scale (0-4), and the percent BSA affected is scored on a 7-point scale (0-6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). The body region scores are each multiplied by a weighted factor; and the sum of the region scores give the overall PASI score. Higher scores indicate more severe disease.

    Measure: Percentage of participants who achieve >=50 percent improvement from Baseline in PASI score at Week 12

    Time: Baseline and Week 12

    Description: Psoriatic lesions will be assessed using the PASI scoring system. Erythema, induration, and scale are each graded on a 5-point scale (0-4), and the percent BSA affected is scored on a 7-point scale (0-6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). The body region scores are each multiplied by a weighted factor; and the sum of the region scores give the overall PASI score. Higher scores indicate more severe disease

    Measure: Percentage of participants who achieve >=90 percent improvement from Baseline in PASI score at Week 12

    Time: Baseline and Week 12

    Description: Psoriatic lesions will be assessed using the PASI scoring system. Erythema, induration, and scale are each graded on a 5-point scale (0-4), and the percent BSA affected is scored on a 7-point scale (0-6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). The body region scores are each multiplied by a weighted factor; and the sum of the region scores give the overall PASI score. Higher scores indicate more severe disease

    Measure: Percentage of participants who achieved >=100 percent improvement from Baseline in PASI score at Week 12

    Time: Baseline and Week 12

    Description: Psoriatic lesions will be assessed using the PASI scoring system. Erythema, induration, and scale are each graded on a 5-point scale (0-4), and the percent BSA affected is scored on a 7-point scale (0-6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). The body region scores are each multiplied by a weighted factor; and the sum of the region scores give the overall PASI score. Higher scores indicate more severe disease

    Measure: Change from Baseline PASI scores at Week 12

    Time: Baseline and Week 12

    Description: The Investigator or physician designee only will complete a global assessment of disease activity using the physician global assessment item. A 5-point scoring system will be used to measure the severity of psoriatic lesions over the entire body at the time of evaluation. Percentage of participants who have a sIGA score of 0=clear or 1=almost clear at Week 12 will be summarized.

    Measure: Percentage of participants who have a Static Investigator's Global Assessment (sIGA) score of 0 or 1 at Week 12

    Time: At Week 12

    Description: The BSA affected with psoriasis will be evaluated at all study visits by the Investigator or suitably trained delegate. As a reference, the area of the whole palm is counted as 1 percent BSA.

    Measure: Change from Baseline in psoriatic BSA at Week 12

    Time: Baseline and Week 12
    86 A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment

    The study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult subjects who are diagnosed with severe and critical COVID 19. Arm A: CD24Fc/Best Available Treatment; Arm B: placebo/ Best Available Treatment. CD24Fc will be administered as single dose of 480 mg via IV infusion on Day 1. Total of 270 subjects will be enrolled and randomized in 1:1 ratio to receive CD24Fc or placebo. All subjects will be treated with the best available treatment. The follow up period is 28 days.

    NCT04317040
    Conditions
    1. Covid19
    Interventions
    1. Drug: CD24Fc
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to improve in clinical status: the time (days) required from the start of treatment to the improvement of clinical status "severe" to "moderate/mild"; or improvement from "scale 2, 3, or 4" to "scale 5 or higher" based on NIAID ordinal scales.

    Measure: Improvement of COVID-19 disease status

    Time: 29 days

    Secondary Outcomes

    Description: Proportion of patients who died or had respiratory failure, defined as the need for mechanical ventilation, ECMO, non-invasive ventilation, or high flow oxygen devices, at Day 29

    Measure: Proportion of patients who died or had respiratory failure.

    Time: 29 days

    Description: Time for disease progression from NIAID scale 3 or 4 to need to be on invasive mechanical ventilation, or ESMO, or death, or from NIAID scale 2 to death.

    Measure: Disease progression of COVID-19

    Time: 29 days

    Description: All cause of death

    Measure: All cause of death

    Time: 15 days and 29 days

    Description: Proportion of clinical relapse, as defined by rate of return to oxygen support for more than 1 day within 29 days from randomization after initial recovery

    Measure: Proportion of clinical relapse

    Time: 29 days

    Description: Conversion rate of clinical status on days 8 (proportion of subjects who changed from NIAID ordinal "scale 3 or 4" to "scale 5 or higher")

    Measure: Conversion rate of clinical status at Day 8

    Time: 8 days

    Description: Conversion rate of clinical status on days 15 (proportion of subjects who changed from NIAID ordinal "scale 3 or 4" to "scale 5 or higher")

    Measure: Conversion rate of clinical status at Day 15

    Time: 15 days

    Description: The discharge time, calculated after the randomization.

    Measure: Hospital discharge time

    Time: 29 days

    Description: Duration of mechanical ventilation (IMV, NIV) (days)

    Measure: Duration of mechanical ventilation

    Time: 29 days

    Description: Duration of pressors (days)

    Measure: Duration of pressors

    Time: 29 days

    Description: Duration of extracorporeal membrane oxygenation (days)

    Measure: Duration of ECMO

    Time: 29 days

    Description: Duration of oxygen therapy (oxygen inhalation by high flow nasal cannula or mask) (days)

    Measure: Duration of high flow oxygen therapy

    Time: 29 days

    Description: Changes of absolute lymphocyte count in peripheral blood

    Measure: Absolute lymphocyte count

    Time: 29 days

    Description: The changes of plasma concentration of D-dimers

    Measure: Change of D-dimers

    Time: 15 and 29 days
    87 Clinical Trial of Favipiravir Tablets Combine With Chloroquine Phosphate in the Treatment of Novel Coronavirus Pneumonia

    This study is a multi-centered, three-armed, randomized, double-blinded, controlled study, namely, the oral trial drug favipiravir tablets plus chloroquine phosphatetablets tablets group (combined group), the oral trial drug favipiravir tablets group (pirovir group), and the oral placebo treatment group (control group). The total number of enrolled cases in this study was set at 150. During the treatment, the clinical data of the subjects were collected, the changes of viral load and biochemical indicators were detected, and the outcome of the subjects was monitored. The main indicators of efficacy include improvement or recovery of respiratory symptoms and viral nucleic acid shedding. The rate of progression to severe disease, duration of fever, peripheral blood index and improvement time of pulmonary imaging were the secondary indicators to evaluate the efficacy. Statistical analysis was performed at the middle and final stages of the study to evaluate the efficacy and safety of favipiravir tablets combined with chloroquine phosphatetablets tablets in the treatment of novel coronavirus pneumonia.

    NCT04319900
    Conditions
    1. Novel Coronavirus Pnuemonia
    Interventions
    1. Drug: favipiravir tablets+chloroquine phosphatetablets tablets
    2. Drug: Favipiravir tablets
    3. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time of improvement or recovery of respiratory symptoms

    Measure: Time of Improvement or recovery of respiratory symptoms

    Time: 10 days during the intervention period

    Description: Number of days from positive to negative for test of swab or sputum virus nucleic acid

    Measure: Number of days virus nucleic acid shedding

    Time: 10 days during the intervention period

    Description: Frequency of improvement or recovery of respiratory symptoms

    Measure: Frequency of Improvement or recovery of respiratory symptoms

    Time: 10 days during the intervention period

    Secondary Outcomes

    Description: Duration of fever after recruitment

    Measure: Duration of fever

    Time: 10 days during the intervention period

    Description: Disease is defined as severe if it meets any of the following criteria: 1.Respiratory rate ≥30/min; 2. Oxygen saturation ≤93%; 3. Arterial partial oxygen pressure (PaO2)/oxygen absorption concentration (FiO2) ≤300 mmHg (1 mmHg=0.133 kPa)

    Measure: Frequencies of progression to severe illness

    Time: 10 days during the intervention period

    Description: Time of improvement of pulmonary imaging

    Measure: Time of improvement of pulmonary imaging

    Time: 10 days during the intervention period

    Description: Peripheral blood c-reactive protein concentration

    Measure: Peripheral blood c-reactive protein concentration

    Time: day-1,3,7,14 after the intervention period

    Description: Absolute value of peripheral blood lymphocytes

    Measure: Absolute value of peripheral blood lymphocytes

    Time: day-1,3,7,14 after the intervention period

    Description: percentage of peripheral blood lymphocytes

    Measure: percentage of peripheral blood lymphocytes

    Time: day-1,3,7,14 after the intervention period
    88 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia

    This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.

    NCT04320615
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Tocilizumab (TCZ)
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Clinical Status Assessed Using a 7-Category Ordinal Scale

    Time: Day 28

    Secondary Outcomes

    Measure: Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of Time: Up to 60 days

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

    Time: Up to 60 days

    Measure: Incidence of Mechanical Ventilation

    Time: Up to 60 days

    Measure: Ventilator-Free Days to Day 28

    Time: Up to Day 28

    Measure: Incidence of Intensive Care Unit (ICU) Stay

    Time: Up to 60 days

    Measure: Duration of ICU Stay

    Time: Up to 60 days

    Measure: Time to Clinical Failure

    Time: From first dose to time of death, mechanical ventilation, ICU admission, or study withdrawal (whichever occurs first, for up to 60 days). If already in ICU on ventilation, failure = a one-category worsening on the ordinal scale, withdrawal, or death

    Measure: Mortality Rate

    Time: Days 7, 14, 21, 28, and 60

    Measure: Time to Hospital Discharge

    Time: Up to 60 days

    Measure: Time to Recovery

    Time: Up to 60 days

    Measure: Duration of Time on Supplemental Oxygen

    Time: Up to 60 days

    Measure: Percentage of Participants with Adverse Events

    Time: Up to 60 days

    Measure: COVID-19 (SARS-CoV-2) Viral Load Over Time

    Time: Up to 60 days

    Measure: Time to Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) Virus Negativity

    Time: Up to 60 days

    Measure: Proportion of Participants with Post-Treatment Infection

    Time: Up to 60 days

    Measure: Serum Concentration of IL-6

    Time: Up to 60 days

    Measure: Serum Concentration of sIL-6R

    Time: Up to 60 days

    Measure: Serum Concentration of Ferritin

    Time: Up to 60 days

    Measure: Serum Concentration of C-Reactive Protein (CRP)

    Time: Up to 60 days

    Measure: Serum Concentration of TCZ

    Time: Up to 60 days
    89 Hydroxychloroquine Versus Placebo in Patients Presenting COVID-19 Infection and at Risk of Secondary Complication: a Prospective, Multicentre, Randomised, Double-blind Study

    A new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated. Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening. The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.

    NCT04325893
    Conditions
    1. Coronavirus
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Number of death from any cause, or the need for intubation and mechanical ventilation during the 14 days following inclusion and start of treatment.

    Time: Day 14

    Secondary Outcomes

    Measure: Number of death from any cause, or the need for intubation and mechanical ventilation during the 28 days following inclusion and start of treatment.

    Time: Day 28

    Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome

    Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14

    Time: Day 14

    Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome

    Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28.

    Time: Day 28

    Measure: Number of all-cause mortality at day 14

    Time: Day 14

    Measure: Number of all-cause mortality at day 28

    Time: Day 28

    Measure: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 5

    Time: Day 5

    Measure: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 10

    Time: Day 10

    Measure: The rate of venous thromboembolic events at day 28, documented and confirmed by an adjudication committee.

    Time: Day 28

    Measure: Number of all-cause mortality at day 28 in patients aged 75 and older

    Time: day 28

    Measure: Clinical evolution on the WHO OSCI scale for COVID-19 between day 0 and day 28 for patients aged 75 or older

    Time: day 28

    Measure: Rate of severe adverse events at day 28

    Time: day 28

    Measure: Number of all-cause mortality at day 14 in patients aged 75 and older

    Time: day 14
    90 ODYSSEY: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Treating Inflammatory Lung Injury and Improving Clinical Outcomes Associated With Severe or Critical COVID-19 Infection

    This is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.

    NCT04326426
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Tradipitant
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Time to improvement on a 7-point ordinal scale as compared to baseline

    Time: 14 days or discharge

    Secondary Outcomes

    Measure: Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)

    Time: 14 days or discharge

    Measure: Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples

    Time: 14 days or discharge

    Measure: In-hospital mortality

    Time: 14 days or discharge

    Measure: Mean change in NEWS2 score from baseline

    Time: 14 days or discharge

    Measure: Understand the effect of genetics for treatment response through whole genome sequence of the participant and the COVID-19 virus

    Time: 14 days or discharge

    Measure: Reduction from baseline of NRS for cough

    Time: 14 days or discharge

    Measure: Reduction from baseline of NRS for nausea

    Time: 14 days or discharge

    Measure: Time to normalization of fever for at least 48 hours

    Time: 14 days or discharge

    Measure: Time to improvement in oxygenation for at least 48 hours

    Time: 14 days or discharge
    91 An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19

    Primary Objective: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19 Secondary Objectives: - Evaluate the 28-day survival rate - Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity - Evaluate changes in the National Early Warning Score 2 (NEWS2) - Evaluate the duration of predefined symptoms and signs (if applicable) - Evaluate the duration of supplemental oxygen dependency (if applicable) - Evaluate the incidence of new mechanical ventilation use during the study - Evaluate the duration of new mechanical ventilation use during the Study - Evaluate the proportion of patients requiring rescue medication during the 28-day period - Evaluate need for admission into intensive care unit (ICU) - Evaluate duration of hospitalization (days) - The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of: - Serious adverse events (SAEs) - Major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia - Grade ≥2 infusion related reactions - Grade ≥2 hypersensitivity reactions - Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline) - Major or opportunistic bacterial or fungal infections

    NCT04327388
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Drug: Sarilumab SAR153191
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

    Measure: Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale

    Time: Baseline to Day 29

    Secondary Outcomes

    Measure: Percent of patients alive at Day 29

    Time: Day 29

    Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

    Measure: Proportion of patients with one point improvement from baseline in clinical status assessment at days 4, 7, 15, 21, 29 using the 7-point ordinal scale

    Time: Baseline to Days 4, 7, 15, 21, 29

    Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

    Measure: Mean change in the 7-point ordinal scale from baseline to Days 4, 7, 15, 21, and 29 (or until discharge)

    Time: Baseline to Days 4, 7, 15, 21, 29 (or until discharge)

    Description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.

    Measure: Time to resolution of fever

    Time: Baseline to Day 29

    Description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is defined as SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever is sooner.

    Measure: Time to resolution of fever and improvement in oxygenation

    Time: Baseline to Day 29

    Description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period.

    Measure: Days with fever

    Time: Baseline to Day 29

    Description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

    Measure: Time to change in NEWS2 from baseline

    Time: Baseline to Day 29

    Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

    Measure: Time to NEWS2 of <2 and maintained for 24 hours

    Time: Baseline to Day 29

    Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

    Measure: Mean change from baseline to days 4, 7, 15, 21, and 29 in NEWS2

    Time: Baseline to days 4, 7, 15, 21, and 29

    Description: SpO2/FiO2 of 50 or greater compared to the nadir for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.

    Measure: Time-to-improvement in oxygenation

    Time: Baseline to Day 29

    Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.

    Measure: Alive off supplemental oxygen at day 29

    Time: Day 29

    Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.

    Measure: Days of hypoxemia

    Time: Baseline to Day 29

    Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.

    Measure: Days of supplemental oxygen use

    Time: Baseline to Day 29

    Measure: Days of resting respiratory rate >24 breaths/min

    Time: Baseline to Day 29

    Measure: Time to saturation ≥94% on room air

    Time: Baseline to Day 29

    Measure: Ventilator free days in the first 28 days (to day 29)

    Time: Baseline to Day 29

    Description: For those not requiring these interventions at baseline.

    Measure: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula

    Time: Baseline to Day 60

    Measure: Proportion of patients requiring rescue medication during the 28-day period

    Time: Baseline to Day 28

    Description: For patients are not in ICU at baseline

    Measure: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available)

    Time: Baseline to Day 60

    Measure: Days of hospitalization among survivors

    Time: Baseline to Day 60

    Measure: Incidence of serious adverse events

    Time: Baseline to Day 60

    Measure: The incidence of major or opportunistic bacterial or fungal infections

    Time: Baseline to Day 60

    Measure: The incidence of major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia

    Time: Baseline to Day 60

    Measure: The incidence of hypersensitivity reactions, infusion reactions, gastrointestinal perforation

    Time: Baseline to Day 60

    Measure: The number of patients with clinically significant laboratory abnormalities

    Time: Baseline to Day 60
    92 A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2a Clinical Trial to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Orally Administered TERN-101 Tablets in Adult Patients With Presumed Non-Cirrhotic Non-Alcoholic Steatohepatitis (NASH)

    This is a Phase 2, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of TERN-101 in non-cirrhotic NASH patients.

    NCT04328077
    Conditions
    1. NASH - Nonalcoholic Steatohepatitis
    Interventions
    1. Drug: TERN-101
    2. Other: Placebo
    MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease
    HPO:Hepatic steatosis

    Primary Outcomes

    Measure: Subject incidence of adverse events for TERN-101 versus placebo

    Time: 16 weeks

    Secondary Outcomes

    Measure: Percent change from baseline in ALT for TERN-101 versus placebo at 12 weeks

    Time: 12 weeks

    Description: Area under the curve

    Measure: Plasma concentration of TERN-101 - AUC

    Time: 12 weeks

    Description: Maximum observed concentration

    Measure: Plasma concentration of TERN-101 - Cmax

    Time: 12 weeks

    Description: Time to reach maximum measured plasma concentration

    Measure: Plasma concentration of TERN-101 - Tmax

    Time: 12 weeks

    Description: Determination of half-life

    Measure: Plasma concentration of TERN-101 - t1/2

    Time: 12 weeks
    93 Reducing Health Care Workers Absenteeism in COVID-19 Pandemic by Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial.

    Rationale: Covid-19 spreads rapidly throughout the world. A large epidemic in the Netherlands would seriously challenge the available hospital capacity, and this would be augmented by absenteeism of healthcare workers (HCW). Strategies to prevent absenteeism of HCW are, therefore, desperately needed to safeguard continuous patient care. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, and reported significant reductions in morbidity and mortality. The hypothesis is that BCG vaccination can reduce HCW absenteeism during the epidemic phase of Covid-19. Objective: Primary objective: To reduce absenteeism among HCW with direct patient contacts during the epidemic phase of Covid-19. Secondary objective: To reduce hospital admission, ICU admission or death in HCW with direct patient contacts during the epidemic phase of Covid-19. Study design: A placebo-controlled adaptive multi-centre randomized controlled trial. Study population: HCW with direct patient contacts among which nurses and physicians working at emergency rooms and wards where Covid-19-infected patients are treated. Intervention: Participants will be randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio. Main study parameters/endpoints: Primary endpoint: number of days of (unplanned) absenteeism for any reason. Secondary endpoints include the number of days of (unplanned) absenteeism because of documented Covid-19 infection, and the cumulative incidence of hospital admission, Intensive Care Admission, and death. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of Covid-19 infection. The primary endpoint and the adaptive design with frequent interim analyses facilitate maximum efficiency of the trial, so that results can inform policy making during the ongoing epidemic.

    NCT04328441
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BCG Vaccine
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of days of unplanned absenteeism for any reason

    Measure: Health Care Workers absenteeism

    Time: Maximum of 365 days

    Secondary Outcomes

    Measure: the cumulative incidence of documented COVID-19

    Time: Maximum of 365 days

    Measure: the cumulative incidence of Hospital Admission due to documented COVID-19

    Time: Maximum of 365 days

    Measure: the number of days of unplanned absenteeism, because of documented COVID-19

    Time: Maximum of 365 days

    Measure: the cumulative incidence of self-reported acute respiratory symptoms or fever

    Time: Maximum of 365 days

    Measure: the cumulative incidence of death due to documented COVID-19

    Time: Maximum of 365 days

    Measure: the cumulative incidence of Intensive Care Admission due to documented COVID-19

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of absenteeism, because of imposed quarantine as a result of exposure to COVID-19

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of absenteeism, because of imposed quarantine as a result of having acute respiratory symptoms, fever or documented COVID-19

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of unplanned absenteeism because of self-reported acute respiratory symptoms

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of self-reported fever (≥38 gr C)

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of self-reported fever (≥38 gr C)

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of self-reported acute respiratory symptoms

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of self-reported acute respiratory symptoms

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of death for any reason

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of Intensive Care Admission for any reason

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of Hospital Admission for any reason

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence and magnitude of plasma/serum antibodies (IgA,M,G) and SARS-CoV-2-specific antibodies at 12 weeks after vaccination and at the end of the study period

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence and magnitude of plasma/serum antibodies (IgA,M,G) and SARS-CoV-2-specific antibodies at 12 weeks after vaccination and at the end of the study period

    Time: 3-6 months after inclusion
    94 Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

    Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.

    NCT04328467
    Conditions
    1. COVID-19
    2. Corona Virus Infection
    3. ARDS
    4. Acute Respiratory Distress Syndrome
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.

    Measure: COVID-19-free survival

    Time: up to 12 weeks

    Secondary Outcomes

    Description: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.

    Measure: Incidence of confirmed SARS-CoV-2 detection

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.

    Measure: Incidence of possible COVID-19 symptoms

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.

    Measure: Incidence of all-cause study medicine discontinuation

    Time: up to 12 weeks

    Description: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.

    Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.

    Measure: Incidence of Hospitalization for COVID-19 or death

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.

    Measure: Incidence of study medication-related side effects

    Time: up to 12 weeks
    95 A Phase 2 Randomized, Single-Blind Study of a Single Dose of Peginterferon Lambda-1a (Lambda) Compared With Placebo in Outpatients With Mild COVID-19

    To evaluate the efficacy of a single dose of subcutaneous injections of 180 ug of Peginterferon Lambda-1a, compared with placebo in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with uncomplicated COVID-19 disease.

    NCT04331899
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Peginterferon Lambda-1a
    2. Other: Placebo

    Primary Outcomes

    Description: Time to first of two consecutive negative respiratory secretions obtained by oropharyngeal and/or anterior nare swabs for SARS-CoV-2 by qRT-PCR.

    Measure: Duration of Viral shedding of SARS-CoV-2 by qRT-PCR

    Time: 28 days

    Secondary Outcomes

    Description: Sars-CoV-2 RNA level in oropharyngeal and/or anterior nare swabs collected daily.

    Measure: Sars-CoV-2 viral load

    Time: 28 days

    Description: Area under the curve of SARSCoV-2 viral load in oropharyngeal and/or anterior nare swabs collected daily.

    Measure: Area under the curve of SARS-COV-2 viral load

    Time: 28 days

    Description: Time to alleviation of all symptoms (fever, chills, cough, nasal congestion, muscle pains), defined as the time from initiation of treatment until all symptoms are rated as absent or mild in symptomatic patients.

    Measure: Time to alleviation of all symptoms Time to alleviation of all symptoms

    Time: 28 days

    Measure: Number of participants requiring emergency department visits or hospitalizations within 28 days of initiation of treatment

    Time: 28 days
    96 Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease

    ORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.

    NCT04332991
    Conditions
    1. Coronavirus
    2. Acute Respiratory Infection
    3. SARS-CoV Infection
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)

    Measure: COVID Ordinal Outcomes Scale on Day 15

    Time: assessed on study day 15

    Secondary Outcomes

    Description: Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy

    Measure: all-location, all-cause mortality assessed on day 15

    Time: assessed on study day 15

    Description: Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy

    Measure: all-location, all-cause mortality assessed on day 29

    Time: assessed on study day 29

    Description: We will determine the COVID Ordinal Scale for all patients on study day 3

    Measure: COVID Ordinal Outcomes Scale on Study Day 3

    Time: assessed on study day 3

    Description: We will determine the COVID Ordinal Scale on study day 8

    Measure: COVID Ordinal Outcomes Scale on Study Day 8

    Time: assessed on study day 8

    Description: We will determine the COVID Ordinal Scale on study day 29

    Measure: COVID Ordinal Outcomes Scale on Study Day 29

    Time: assessed on study day 29

    Description: We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28

    Measure: Number of patients dead or with receipt of ECMO between enrollment and Day 28

    Time: Enrollment to Day 28

    Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.

    Measure: Oxygen-free days through Day 28

    Time: 28 days after randomization

    Description: Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.

    Measure: Ventilator-free days through Day 28

    Time: 28 days after randomization

    Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.

    Measure: Vasopressor-free days through Day 28

    Time: 28 days after randomization

    Description: The number of days spent out of the ICU to day 28.

    Measure: ICU-free days to Day 28

    Time: 28 days after randomization

    Description: Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.

    Measure: Hospital-free days to Day 28

    Time: 28 days after randomization

    Other Outcomes

    Description: We will determine the number of patients that experience seizure between randomization and day 28

    Measure: Number of patients with seizures to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28

    Measure: Number of patients with atrial or ventricular arrhythmia to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience cardiac arrest between randomization and day 28

    Measure: Number of patients with cardiac arrest to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28

    Measure: Number of patients with elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience acute pancreatitis between randomization and day 28

    Measure: Number of patients with acute pancreatitis arrest to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience acute kidney injury between randomization and day 28

    Measure: Number of patients with acute kidney injury to day28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience renal replacement therapy between randomization and day 28

    Measure: Number of patients with receipt of renal replacement therapy to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28

    Measure: Number of patients with symptomatic hypoglycemia to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience neutropenia, lymphopenia, anemia, or thrombocytopenia between randomization and day 28

    Measure: Number of patients with neutropenia, lymphopenia, anemia, or thrombocytopenia to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28

    Measure: Number of patients with severe dermatologic reaction to day 28

    Time: 28 days after randomization

    Description: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge

    Measure: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge

    Time: 28 days after randomization
    97 Piclidenoson for Treatment of COVID-19 - A Randomized, Double-Blind, Placebo-Controlled Trial

    Patients with documented moderate COVID-19 infection will be randomized 1:1 to receive piclidenoson 2 mg Q12H orally with standard supportive care (SSC - intervention arm) or placebo orally with SSC (control arm) for up to 28 days.

    NCT04333472
    Conditions
    1. COVID-19
    2. Coronavirus Infection
    Interventions
    1. Drug: Piclidenoson
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of subjects alive and free of respiratory failure (defined as need for non-invasive or invasive mechanical ventilation, high-flow oxygen, or extracorporeal membrane oxygenation) at Day 29

    Measure: Proportion of subjects alive and free of respiratory failure

    Time: 29 days

    Description: Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29

    Measure: Proportion of subjects discharged home alive

    Time: 29 days

    Description: Proportion of patients experiencing AEs

    Measure: Treatment-emergent adverse events (AEs)

    Time: 29 days

    Secondary Outcomes

    Description: • Clinical status at Day 29 on NIAID 8-point ordinal scale (NIH 2020): Not hospitalized, no limitations Not hospitalized, with limitations Hospitalized, no active medical problems Hospitalized, not on oxygen Hospitalized, on oxygen Hospitalized, on high-flow oxygen or noninvasive mechanical ventilation Hospitalized, on mechanical ventilation or ECMO Death

    Measure: Clinical status

    Time: 29 days

    Description: Time (days) to improvement of 2 points on 7-point ordinal clinical scale

    Measure: Time to improvement

    Time: 29 days

    Description: Proportion of patients who require mechanical ventilation

    Measure: Incidence of mechanical ventilation

    Time: 29 days

    Description: Ventilator-free days to Day 29

    Measure: Ventilator-free days

    Time: 29 days

    Description: Proportion of patients who require ICU admission

    Measure: Incidence of Intensive Care Unit (ICU) admission

    Time: 29 days

    Description: Duration (days) of ICU stay

    Measure: Duration of ICU stay

    Time: 29 days

    Description: Time (days) to hospital discharge

    Measure: Time to hospital discharge

    Time: 29 days

    Description: Duration (days) of need for supplemental oxygen

    Measure: Duration of need for supplemental oxygen

    Time: 29 days

    Description: Time (days) to virus negativity by RT-PCR, defined as absence of SARS CoV 2 on 2 consecutive days of sampling

    Measure: Time to virus negativity

    Time: 29 days

    Description: SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR

    Measure: SARS-CoV-2 viral load

    Time: 29 days

    Description: Proportion of patients experiencing AEs leading to early discontinuation of trial treatment

    Measure: AEs leading to withdrawal

    Time: 29 days

    Description: Proportion of patients experiencing SAEs

    Measure: Treatment-emergent serious AEs (SAEs)

    Time: 29 days

    Description: Proportion of patients experiencing treatment-emergent changes in clinical laboratory parameters or ECGs

    Measure: Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs)

    Time: 29 days

    Description: Proportion of patients who meet study safety-related stopping rules

    Measure: Incidence of meeting safety-related stopping rules

    Time: 29 days

    Description: Plasma concentrations over time of piclidenoson

    Measure: Pharmacokinetics of piclidenoson in this patient population

    Time: 5 days

    Description: Change from baseline in serum concentrations of cytokines

    Measure: Serum cytokine levels

    Time: 29 days
    98 A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study of Hydroxychloroquine in Outpatient Adults With COVID-19

    Primary Objective: To assess the effect of hydroxychloroquine versus placebo on nasopharyngeal SARS-CoV-2 viral load in outpatient adults with COVID-19 Secondary Objectives: - To assess the effect of hydroxychloroquine versus placebo on clinical signs and symptoms and progression of disease in outpatient adults with COVID-19 - To assess the safety and tolerability of hydroxychloroquine in outpatient adults with COVID-19

    NCT04333654
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Hydroxychloroquine SAR321068
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Change from baseline to Day 3 in nasopharyngeal SARS-CoV-2 viral load (if quantitative PCR is available)

    Time: Baseline to Day 3

    Description: Viral load assessed by PCR from a nasopharyngeal swab - 2. Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Number of participants by PCR result status (positive or negative) (if quantitative PCR is not available)

    Time: Baseline to Day 3

    Secondary Outcomes

    Description: Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Change from baseline to Day 5 in nasopharyngeal SARS-CoV-2 viral load

    Time: Baseline to Day 5

    Description: Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Number of participants by PCR result status (positive or negative)

    Time: Baseline to end of study (Day14)

    Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe)

    Measure: Number of participants with COVID-19 symptoms by severity

    Time: Baseline to end of study (Day14)

    Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe). Resolution of a symptom is defined as when a symptom previously scored ≥ 1 on the scale is scored as 0

    Measure: Time to resolution of COVID-19 Symptoms

    Time: Baseline to end of study (Day14)

    Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C

    Measure: Time to resolution of fever

    Time: Baseline to end of study (Day14)

    Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C

    Measure: Percentage of participants with resolution of fever

    Time: Baseline to end of study (Day14)

    Measure: Percentage of participants hospitalized

    Time: Baseline to end of study (Day14)

    Measure: Number of participants with Adverse Events

    Time: Baseline to end of study (Day14)
    99 An International, Multi-site, Bayesian Platform Adaptive, Randomized, Placebo-controlled Trial Assessing the Effectiveness of Candidate Agents in Mitigating COVID-19 Disease in Healthcare Workers

    The objective of CROWN CORONATION is the prevention of symptomatic COVID-19 by using combinations of approved and safe repurposed interventions, with complementary mechanisms of action.

    NCT04333732
    Conditions
    1. COVID 19
    Interventions
    1. Drug: MR or M-M-R II ® vaccine
    2. Drug: Placebo

    Primary Outcomes

    Description: To determine the incidence of the trial intervention(s) in preventing laboratory test-confirmed, symptomatic COVID19 (i.e. any of the following: cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, nausea, vomiting, or diarrhea), in healthcare workers with repeated exposures to SARS-CoV-2 by day 60 after enrollment.

    Measure: Symptomatic COVID-19

    Time: 60 days

    Secondary Outcomes

    Description: Severity of COVID-19 will be graded on a simplified version of the ordinal World Health Organization COVID-19 severity scale (WHO COVID-19 severity scale).

    Measure: Severity of COVID-19 over the study period

    Time: 60 days

    Description: SARS-CoV-2 infection (by serology) over up to 5 months of follow-up

    Measure: Effectiveness of preventing/reducing SARS-CoV-2 infection

    Time: 5 months
    100 A Randomised, Double-blind, Placebo Controlled Study of Eicosapentaenoic Acid (EPA-FFA) Gastro-resistant Capsules to Treat Hospitalised Subjects With Confirmed SARS-CoV-2

    This is an double-blind, randomized, placebo controlled phase III study in hospitalized subjects with confirmed SARS-CoV-2.

    NCT04335032
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Drug: Eicosapentaenoic acid gastro-resistant capsules
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to treatment failure during the 28-day treatment period. Treatment failure is defined as additional or alternative treatment required, or intubation and invasive ventilation, or transfer to intensive care unit, or death.

    Measure: Evaluation of EPA-FFA efficacy compared to placebo

    Time: 28 days

    Secondary Outcomes

    Description: To determine whether EPA-FFA gastro-resistant capsules decreases the time to and amount of clinical improvement as determined by the WHO 9-point ordinal scale during the study.

    Measure: Time to and amount of clinical improvement

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules increases the number of subjects alive and discharged home without supplemental oxygen therapy.

    Measure: Change in recovery and survival rate

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules decreases CRP and IL-6 during the study.

    Measure: Reduction of CRP and IL-6

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules increases IFN-γ during the study

    Measure: Increase in IFN-γ

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules decreases other proinflammatory chemokines and cytokines.

    Measure: Reduction in proinflammatory chemokines and cytokines.

    Time: 28 days

    Other Outcomes

    Description: To evaluate the safety of EPA-FFA gastro-resistant capsules in the treatment of COVID-19 (SARS-CoV-2) by assessing subjects clinical lab parameters and vital signs, and the number and proportion of subjects with AEs.

    Measure: Safety - Vitals, AEs and Clinical lab parameters

    Time: throughout the study, about 3 months
    101 CORON-ACT - a Multicenter, Double-blind, Randomized Controlled Phase II Trial on the Efficacy and Safety of Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

    The mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets. There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS. The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.

    NCT04335071
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: Tocilizumab (TCZ)
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Number of patients with ICU admission

    Time: 7 days after randomisation

    Measure: Number of patients with intubation

    Time: 14 days after randomisation

    Measure: Number of patients with death

    Time: 28 days after randomisation

    Secondary Outcomes

    Description: Assessed by the 8-point WHO scale

    Measure: Illness severity

    Time: At days 2, 7, 14, 28 after randomisation

    Description: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale

    Measure: Number of patients with clinical improvement

    Time: At days 2, 7, 14, 28 after randomisation

    Description: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale

    Measure: Time to clinical improvement (days)

    Time: Up to day 28 after randomisation

    Measure: Duration of hospitalization (days)

    Time: Up to day 28 after randomisation

    Measure: Time to ICU admission (days)

    Time: Up to day 28 after randomisation

    Measure: Duration of ICU stay

    Time: Up to day 28 after randomisation

    Measure: Time to intubation

    Time: Up to day 28 after randomisation

    Measure: Duration of mechanical ventilation (days)

    Time: Up to day 28 after randomisation

    Other Outcomes

    Measure: Number of deaths

    Time: Within 28 days after randomisation

    Measure: Number of patients with ICU admission

    Time: Within 28 days after randomisation

    Measure: Number of patients with intubation

    Time: Within 28 days after randomisation

    Description: Events of special interest are defined as secondary infections, acute kidney failure, hepatic, and cardiac failure

    Measure: Number of patients with events of special interest

    Time: Within 28 days after randomisation

    Measure: Number of patients with SAEs considered by the investigator to be at least probably related to the IMP

    Time: Within 28 days after randomisation
    102 A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Patients With COVID-19-Moderate Type

    This study evaluates treatment with Favipiravir combined with supportive care for adult patients with COVID-19-moderate type.

    NCT04336904
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Other: Placebo

    Primary Outcomes

    Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72 hours.

    Measure: Time from randomization to clinical recovery

    Time: 90 days

    Secondary Outcomes

    Description: 1. Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;

    Measure: Time from randomization to negativity in RT-PCR nucleic acid test

    Time: 28 days

    Description: Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;

    Measure: Incidence of deterioration/aggravation of pneumonia

    Time: 28 days

    Description: Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;

    Measure: Time from randomization to resolution of pyrexia

    Time: 28 days

    Description: Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization; It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0: Mild: Requires non-prescription treatment; Moderate: Requires medication treatment; limits instrumental activities of daily living; Severe: Limits self-care activities of daily living

    Measure: Time from randomization to relief of cough

    Time: 28 days

    Description: Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;

    Measure: Time from randomization to relief of dyspnoea

    Time: 28 days

    Description: 6. Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization

    Measure: Rate of auxiliary oxygen therapy

    Time: 28 days

    Description: ICU admission rate within 28 days of randomization

    Measure: ICU admission rate

    Time: 28 days

    Description: All-cause mortality within 28 days of randomization

    Measure: Mortality

    Time: 28 days
    103 Efficacy and Safety of Nintedanib Ethanesulfonate Soft Capsule in the Treatment of Pulmonary Fibrosis in Patients With Moderate to Severe COVID-9(COVID 19) : a Single-center, Randomized, Placebo-controlled Study

    This center intends to conduct a single-center, randomized, placebo-controlled study to evaluate the effectiveness and safety of Nintedanib ethanesulfonate soft capsule in the treatment of pulmonary fibrosis in patients with moderate to severe COVID-19.

    NCT04338802
    Conditions
    1. COVID-19
    2. Nintedanib
    3. Safety
    4. Effect of Drugs
    Interventions
    1. Drug: Nintedanib 150 MG
    2. Other: Placebo
    MeSH:Pulmonary Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Changes in forced vital capacity (FVC) after treatment compared to baseline.

    Measure: Changes in forced vital capacity (FVC)

    Time: 8 weeks

    Secondary Outcomes

    Description: Changes incarbon monoxide dispersion (DLco%) after treatment compared to baseline.

    Measure: Changes in carbon monoxide dispersion (DLco%)

    Time: 8 weeks

    Description: Changes in the six-minute walk test (6MWT) after treatment compared to baseline.

    Measure: Changes in the six-minute walk test (6MWT)

    Time: 8 weeks

    Description: Changes in High resolution CT score after treatment compared to baseline.The minimum and maximum values are 0 and 25 , and higher scores mean a worse outcome. As for the score, it is the expected value and will be determined according to the actual result

    Measure: Changes in High resolution CT score

    Time: 8 weeks
    104 Evaluation of the Efficacy and Safety of Camostat Mesilate + Hydroxychloroquine Combination Therapy in Hospitalized Patients With Moderate COVID-19 Infection

    Evaluation of the efficacy and safety of hydroxychloroquine - camostat combination therapy in hospitalized patients with moderate COVID-19 infection, CLOCC-Trial Primary Objectives: The primary objective of this study is to demonstrate, that a combination therapy of hydroxychloroquine and camostat (Foipan®) is superior to hydroxychloroquine + placebo in participants with moderate COVID-19.

    NCT04338906
    Conditions
    1. COVID
    Interventions
    1. Drug: Camostat Mesilate
    2. Drug: Placebo
    3. Drug: Hydroxychloroquine

    Primary Outcomes

    Measure: Not hospitalized

    Time: day 14 from baseline

    Secondary Outcomes

    Measure: Time to improvement of 2 categories from admission on a 7-point ordinal scale

    Time: day 14

    Measure: Proportion of participants in each group with normalization of fever

    Time: day 7 and day 14

    Measure: Proportion of participants in each group with oxygen saturation > 94% on room air for >24h

    Time: day 7 and day 14

    Measure: Time to fever normalization (if febrile at baseline)

    Time: within 14 days

    Measure: Time to first negative SARS-CoV-2 PCR in NP swap (if pos. at baseline)

    Time: within 14 days

    Measure: Time to first negative SARS-CoV-2 PCR in lower respiratory tract specimens (sputum, bronchoalveolar lavage, tracheal aspirate) (if positive at baseline)

    Time: within 14 days

    Measure: Duration of oxygen therapy

    Time: within 28 days

    Measure: Proportion of participants in each group with need for mechanical ventilation

    Time: within 28 days

    Measure: Duration of hospitalization

    Time: within 28 days

    Measure: All cause mortality

    Time: day 28
    105 Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia

    The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.

    NCT04339660
    Conditions
    1. COVID-19
    Interventions
    1. Biological: UC-MSCs
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement and recovery time of inflammatory and immune factors

    Measure: The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP)

    Time: Observe the immune function of the participants within 4 weeks

    Description: Evaluation of Pneumonia change

    Measure: Blood oxygen saturation

    Time: Monitor blood oxygen saturation of the participants within 4 weeks

    Secondary Outcomes

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Evaluation of Pneumonia change

    Measure: Size of lesion area by chest imaging

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Marker of Immunology and inflammation

    Measure: CD4+ and CD8+ T cells count

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Degree of infection

    Measure: Peripheral blood count recovery time

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Indirect response to lung function

    Measure: Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.)

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Clearance time of COVID-19 in participant

    Measure: COVID-19 nucleic acid negative time

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
    106 Azithromycin Added to Hydrochloroquine in Patients Admitted to Intensive Care Due to Coronavirus Disease 2019 (COVID-19)- Randomised Controlled Trial

    Trial design: Prospective, multi-centre, randomised, pragmatic, double blind trial Methods: Participants: Adult (>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria: symptoms of febrile disease for ≥1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, incl. long QT syndromes, participation in another outcome-based interventional trial within last 30 days, patients taking Hydrochloroquine for other indication than COVID-19, pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydrochloroquine 800mg orally in two doses followed by 400mg daily in two doses and Azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or Hydrochloroquine+ placebo (HC group) or placebo + placebo (C-group) in addition to best standard of care, which may evolve during the trial period but will not differ between groups. Objective: To test the hypothesis that early administration of combination therapy slows disease progression and improves mechanical-ventilation free survival. Outcomes: Primary outcome: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline. ICU-LOS D28 and D 90 mortality (in hospital) Tertiary (exploratory) outcomes: Viral load at D7 of study enrolment (No of viral RNA copies/ml of blood), proportion of patients alive and rtPCR negative from nasal swab at D14, Difference of FiO2 requirement and respiratory system compliance between day 0 and 7. Randomization: In 1:1:1 ratio and stratified according to study centre and patients age (cut-off 70 years) Blinding (masking): Patients, treating clinicians, outcome assessors and data analyst will be blinded to study treatment allocation. Unblinded study pharmacist or research nurse will prepare investigational products.

    NCT04339816
    Conditions
    1. COVID-19
    2. Respiratory Failure
    Interventions
    1. Drug: Azithromycin
    2. Drug: Hydroxychloroquine
    3. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.

    Measure: Proportion of alive patients free off mechanical ventilation

    Time: 14 days after enrolment

    Secondary Outcomes

    Description: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline.

    Measure: Proportion of patients who avoided the need of mechanical ventilation

    Time: 14 days

    Description: Length of stay in intensive care unit

    Measure: ICU LOS

    Time: 28 days

    Description: Proportion of patients who died by day 28

    Measure: Mortality28

    Time: 28 days

    Description: Proportion of patients who died by day 90

    Measure: Mortality90

    Time: 90 days
    107 Hydroxychloroquine for the Treatment of Mild COVID-19 Disease

    The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In-vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 [1] replication and anecdotal reports from Chinese COVID-19 patients [2, 3] suggest that chloroquine is a good candidate for treatment. No data have been published and reported evidence is based on non-controlled use of hydroxychloroquine. The aim of this placebo-controlled trial is to assess the effect of hydroxychloroquine on duration of symptoms in mild COVID-19 patients and time of virus shedding as an important tool to reduce the risk of further community transmissions. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post- and preexposure prophylaxis of COVID-19 and as a tool for reduction of community transmission.

    NCT04340544
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Measure: Difference in time to resolution of clinical signs and symptoms of mild COVID-19 treated with hydroxychloroquine or placebo as assessed by daily self-assessment

    Time: 28±2 days

    Secondary Outcomes

    Measure: Difference between hydroxychloroquine- and placebotreated patients on an ordinal outcome scale until Day 28 (death, admission to intensive care, hospitalization, continuing disease, recovered)

    Time: 28±2 days

    Measure: All-cause mortality within 28 days

    Time: 28±2 days

    Other Outcomes

    Measure: Proportion of patients with negative COVID-19 PCR test at day 14 in per protocol population as per throat swab

    Time: 28±2 days

    Measure: Change in COVID-19 virus load from baseline to day 14

    Time: 28±2 days
    108 A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of TJ003234 in Subjects With Severe Coronavirus Disease 2019 (COVID-19)

    This is a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the safety and efficacy of TJ003234 administered as an intravenous (IV) infusion in subjects with severe COVID-19 under supportive care, and to assess the effect of TJ003234 on the levels of cytokines.

    NCT04341116
    Conditions
    1. Coronavirus Disease 2019 COVID-19
    Interventions
    1. Drug: TJ003234
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Proportion (%) of subjects recovered

    Time: Day 1 through Day 14

    Secondary Outcomes

    Measure: Proportion (%) of subjects recovered on Day 30

    Time: Day 1 through Day 30

    Measure: All-cause mortality rate by Day 30

    Time: Day 1 through Day 30

    Measure: Time to recovery among subjects alive by Day 30

    Time: Day 1 through Day 30

    Measure: Length of hospitalization

    Time: Day 1 through Day 30

    Measure: Incidence of treatment-emergent Adverse events by Day 30

    Time: Day 1 through Day 30
    109 A Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Immunogenicity of the Recombinant Novel Coronavirus Vaccine (Adenovirus Vector) in Healthy Adults Aged Above 18 Years

    This is a phase II, randomised, double-blinded and placebo-controlled clinical trial in healthy adults above 18 years of age. This clinical trial is designed to evaluate the immunogenicity and safety of Ad5-nCoV which encodes for a full-length spike (S) protein of SARS-CoV-2.

    NCT04341389
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Recombinant novel coronavirus vaccine (Adenovirus type 5 vector)
    2. Other: Placebo
    MeSH:Adenoviridae Infections

    Primary Outcomes

    Measure: Occurrence of adverse reactions

    Time: 0-14 days post vaccination

    Measure: Anti SARS-CoV-2 S IgG antibody response(ELISA)

    Time: 28 days post vaccination

    Measure: Neutralizing antibody response to SARS-CoV-2

    Time: 28 days post vaccination

    Secondary Outcomes

    Measure: Occurrence of adverse events

    Time: 0-28 days post vaccination

    Measure: Occurrence of serious adverse reaction

    Time: 0-6 months post vaccination

    Measure: Anti SARS-CoV-2 S IgG antibody response(ELISA)

    Time: 0, 14 days and 6 months post vaccination

    Measure: Neutralizing antibody response to SARS-CoV-2

    Time: 0 and 6 months post vaccination

    Measure: Neutralizing antibody response to Ad5-vector

    Time: 0, 28 days and 6 months post vaccination

    Measure: IFN-γ ELISpot responses to SARS-CoV-2 spike protein

    Time: 0 and 28 days post vaccination
    110 Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia (The SCOPE Trial)

    The main objective of our study is to determine if treatment with sirolimus can improve clinical outcomes in hospitalized patients with COVID-19. The investigators will employ a randomized, double blind, placebo-controlled study design. 30 subjects will be randomized in a 2:1 fashion to receive sirolimus or placebo. Sirolimus will be given as a 6mg oral loading dose on day 1 followed by 2mg daily for a maximum treatment duration of 14 days or until hospital discharge, whichever happens sooner. Chart reviews will be conducted daily to determine changes in clinical status, concomitant medications and laboratory parameters. Study specific biomarkers will be measured at baseline and then at days 3, 7 and 14.

    NCT04341675
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Sirolimus
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Death or progression to respiratory failure requiring advanced support measures, either due to inadequate ventilation (non-invasive or invasive mechanical ventilation) or inadequate oxygenation (CPAP* or high flow supplemental oxygen at rates ≥ 15 liters/minute), in patients given sirolimus compared to the placebo group. * CPAP use for known obstructive sleep apnea will not be considered as disease progression.

    Measure: Proportion of patients who are alive and free from advanced respiratory support measures at day 28.

    Time: 28 days

    Secondary Outcomes

    Description: Progression to a higher level of care, e.g. ICU

    Measure: Proportion of patients who require escalation in care

    Time: 14 days

    Description: Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)

    Measure: Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)

    Time: 14 days

    Description: Survival to hospital discharge

    Measure: Proportion of patients surviving to hospital discharge

    Time: days

    Description: Incidence and type of adverse events

    Measure: Drug safety profile

    Time: 14 days

    Description: Number of days spent on advanced respiratory support measures

    Measure: Duration of advanced respiratory support

    Time: days

    Description: Length of hospitalization (in patients who survive to discharge)

    Measure: Duration of hospital stay

    Time: days

    Description: Number of days between study initiation and death (in the subset of patients who die during the hospitalization)

    Measure: Time from treatment initiation to death

    Time: days

    Description: Time (in days) to resolution of fever

    Measure: Time to resolution of fever

    Time: 14 days

    Description: Patients needing off-label treatments such as Anti-IL-6 inhibitors at the discretion of primary clinicians

    Measure: Proportion of patients who require initiation of off-label therapies

    Time: 14 days
    111 Randomized Controlled Trial of Hydroxychloroquine Versus Placebo for the Treatment of Adult Patients With Acute Coronavirus Disease 2019 - COVID-19

    The current outbreak of COVID-19 caused by SARS-CoV-2 is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>9500) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 replication and anecdotal reports from COVID-19 patients in China and France suggest that chloroquine or hydroxychloroquine is a good candidate for treatment. In the French study a favourable effect was seen when hydroxychloroquine was used together with azithromycin in a small series of COVID-19 patients. However, so far all published evidence is based on non-controlled use of hydroxychloroquine. We propose to conduct a placebo-controlled trial in COVID-19 patients with mild to moderate disease in Germany to assess virological efficacy, tolerability and safety of hydroxychloroquine in the treatment of COVID-19. The objective of this trial is to identify an effect of hydroxychloroquine on viral clearance in vivo. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post-exposure prophylaxis of COVID-19.

    NCT04342221
    Conditions
    1. COVID-19, Hydroxychloroquine Sulfate
    Interventions
    1. Drug: Hydroxychloroquine Sulfate
    2. Drug: Placebo

    Primary Outcomes

    Description: Viral clearance defined as time to sustained SARS-CoV-2-specific RNA copy number ≤100, measured by real time reverse-transcription polymerase chain reaction RT-PCR in throat swabs.

    Measure: Effect of HCQ on in vivo viral clearance

    Time: 6 months

    Other Outcomes

    Measure: In-hospital mortality

    Time: 60 days

    Measure: All-cause mortality

    Time: 60 days

    Measure: Proportion requiring non-invasive or invasive ventilation

    Time: 6 months

    Measure: Proportion admitted to ICU

    Time: 6 months

    Measure: Duration of hospitalization

    Time: 6 months

    Measure: Reduction in viral RNA load in upper respiratory tract specimen as assessed by area under viral load curve

    Time: 6 months

    Measure: Reduction in viral RNA load in upper respiratory tract specimen defined as decline of RNA load by 2 log-levels or to below detection level

    Time: 6 months
    112 A Double-blind, Placebo-controlled Clinical Trial of Fluvoxamine for Symptomatic Individuals With COVID-19 Infection

    The purpose of this research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use. This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. Only residents of Missouri and Illinois may participate.

    NCT04342663
    Conditions
    1. COVID 19
    2. Coronavirus
    Interventions
    1. Drug: Fluvoxamine
    2. Drug: Placebo
    MeSH:Infecti Infection Coronavirus Infections

    Primary Outcomes

    Description: Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation >92%.

    Measure: Time to clinical worsening

    Time: RCT (approximately 15 days)

    Secondary Outcomes

    Description: (1) moderate severity of illness as defined by O2 saturation <92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation <92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.

    Measure: clinical deterioration on a Likert-type scale (1-6)

    Time: RCT (approximately 15 days)

    Description: (1) requiring supplemental oxygen; (2) requiring hospitalization; (3) requiring ventilator support.

    Measure: clinical deterioration measured by number of days

    Time: RCT (approximately 15 days)

    Description: Outcomes will be collected daily, with symptomatic data collected approximately twice daily. The most severe symptom at baseline will be the focus.

    Measure: Symptomatic severity on a likert scale (0-10 where 0= none and 10=very severe)

    Time: RCT (approximately 15 days)
    113 A Randomized, Double-blind, Placebo-controlled, Clinical Trial of LY3127804 in Patients Who Are Hospitalized With Pneumonia and Presumed or Confirmed COVID-19

    A randomized, double-blind, placebo-controlled, clinical trial of LY3127804 in participants who are hospitalized with pneumonia and presumed or confirmed COVID-19. The study may last up to 9 weeks and include daily visits up to day 28, and follow-up visits by phone.

    NCT04342897
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Drug: LY3127804
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of days on which a participant breathes without assistance

    Measure: Number of Ventilator Free Days

    Time: Day 1 to Day 28

    Secondary Outcomes

    Description: The scale is an assessment of clinical status. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities

    Measure: Number of Participants Reporting Each Severity Rating on the National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Assessment

    Time: Day 1 to Day 28

    Description: Survival without Respiratory Failure

    Measure: Percentage of Participants who are Alive and Respiratory Failure Free

    Time: Day 1 to Day 28

    Description: Mortality

    Measure: Mortality

    Time: Day 1 to Day 28

    Description: Days of Hospitalization

    Measure: Length of Hospitalization

    Time: Day 1 to Day 28

    Description: Number of Participants with any Serious Adverse Event (SAE)

    Measure: Number of Participants with any Serious Adverse Event (SAE)

    Time: Day 1 to Day 28

    Description: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

    Measure: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

    Time: Day 1 to Day 28
    114 A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post-Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses in Elderly Residents of Long-Term Care Facilities (LTCF)

    Trial to evaluate the efficacy and safety of NTZ for post-exposure prophylaxis of COVID-19 and other VRIs in elderly LTCF residents.

    NCT04343248
    Conditions
    1. COVID-19
    2. Viral Respiratory Illnesses
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    3. Dietary Supplement: Vitamin Super B-Complex

    Primary Outcomes

    Description: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the 6-week treatment period.

    Measure: Symptomatic laboratory-confirmed COVID-19

    Time: up to 6 weeks

    Description: The proportion of subjects with symptomatic laboratory-confirmed VRI identified after the start of treatment and before the end of the 6-week treatment period.

    Measure: Symptomatic laboratory-confirmed VRI

    Time: up to 6 weeks
    115 Pyridostigmine in Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2 Infection

    We will evaluate low-dose pyridostigmine as add-on therapy to best medical care in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and its related Coronavirus Disease 2019 (COVID-19) who require hospitalization. Our hypothesis is that, in comparison to the placebo, pyridostigmine will reduce in at least 10% a composite outcome [death; mechanical ventilation; >2 point-increase in the SOFA score) by day 28. We will also evaluate interleukin (IL)-6 kinetics during the first 14 days of in-hospital stay. It is estimated that 25-33% of patients hospitalized for COVID-19 are admitted to intensive care units (ICU) for severe hypoxemia. The reported mortality in those with severe disease ranges between 38% and 49%. So far, there is no pharmacological therapeutic (or else) strategy known to reduce morbidity and mortality in these patients. Mortality in COVID-19 appears to be mediated not necessarily by the direct effect of the infection, but by the disproportionate inflammatory response of the host. Pyridostigmine is an old drug that, by inhibiting acetylcholine-esterase, the enzymatic machinery that degrades acetylcholine (ACh), results in increased ACh bioavailability. ACh, in turn, ligates to nicotinic-alpha7 receptors in macrophages and T cells, resulting in reduced overactivation of these immune cells. In experimental murine sepsis, this family of drugs has resulted in reduced inflammation and mortality. Human evidence is scarce for severe inflammatory conditions. However, recent evidence from our group and others indicates that pyridostigmine has an immunomodulatory effect in people living with HIV, resulting in elevation of CD4+ T cell counts, decreased immune activation, and reduction in inflammatory mediators. Altogether, this suggests that ACh-esterase inhibitors may act as immunomodulators during viral infections, potentially reducing the inflammatory cascade (the so-called "cytokine storm") observed in critically ill COVID-19 patients. At the proposed dose (60mg/d), the rate of minor adverse events is less than 5% with no reported serious adverse effects. From that perspective, we consider that pyridostigmine can function as an immuno-modulator and reduce morbidity and mortality in COVID-19-stricken patients, with the added value of a safe pharmacological profile. Moreover, as an old drug, re-purposing it for a novel indication may be a simpler, more efficient approach than developing a novel one from the ground up.

    NCT04343963
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Drug: Pyridostigmine Bromide
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Composite of death, Need for mechanical ventilation, or an increase of 2 or more points in the SOFA score

    Measure: Critical condition or death

    Time: 28 days

    Description: Kinetics of circulating IL-6

    Measure: IL-6

    Time: 14 days in-hospital, hospital discharge, or death
    116 A Randomized Placebo-controlled Safety and Dose-finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

    In this study invetigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 80 patients will be enrolled and randomly assigned in a 1:1:1 ratio to three study arms and received clazakizumab at a dose of 12.5 mg, 25 mg or placebo. Based on interim analysis, the remaining 10 subjects at NYU will be randomly assigned to a 1:1 ratio to two arms that will receive clazakizumab at a dose of 25 mg or placebo. The NYU site will serve as the central data management site for other centers who undertake this protocol. Other sites will enroll patients based on the two arm 1:1 randomization. 60 patients at outside sites are expected to enroll.

    NCT04343989
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Clazakizumab 25 mg
    2. Drug: Clazakizumab 12.5 mg
    3. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Measure: Cumulative incidence of serious adverse events associated with clazakizumab or placebo

    Time: 60 days

    Secondary Outcomes

    Measure: Cumulative incidence of intubation

    Time: 14 days

    Measure: Time to extubation

    Time: 14 days

    Measure: Length of ICU stay

    Time: 14 days

    Measure: Number of patients who present a decrease in C-reactive protein

    Time: 14 days

    Description: Number of patients who remain alive at time point.

    Measure: Patient Survival

    Time: 28 days

    Description: Number of patients who remain alive at end of study.

    Measure: Patient Survival

    Time: 60 days
    117 SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)

    This study will the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.

    NCT04344184
    Conditions
    1. COVID-19
    2. Lung Injury, Acute
    3. Kidney Injury
    Interventions
    1. Drug: L-ascorbic acid
    2. Other: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

    Primary Outcomes

    Description: COVID disease status will be measured by the 9-point (from 0 to 8) World Health Organization (WHO) ordinal scale for disease improvement at 28 days.

    Measure: Change in COVID disease status

    Time: Baseline to 28, 60 and 90 days

    Secondary Outcomes

    Description: Change in serum oxalate levels

    Measure: Renal safety biomarkers - serum oxalate

    Time: On days 5,7 and 14

    Description: Microscopic analysis of urine for presence of oxalate stones

    Measure: Renal safety biomarkers - urine oxalate stones

    Time: On days 5,7 and 14

    Description: 24-hour urine oxalate levels

    Measure: Renal safety biomarkers - 24-hour urine oxalate levels

    Time: On days 5,7 and 14

    Description: Renal-failure free days, with AKI defined by the KDIGO criteria

    Measure: Acute Kidney Injury-free days

    Time: On day 28, 90

    Description: Mortality by all causes

    Measure: Number of deaths

    Time: On day 28, 60 and 90 days

    Description: Difference in plasma ferritin levels in ng/mL, compared to baseline levels

    Measure: Change in plasma ferritin levels

    Time: Days 1-7 compared with baseline

    Description: Difference in D-dimer levels in mcg/mL, compared to baseline levels

    Measure: Change in plasma D-dimer levels

    Time: Days 1-7 compared with baseline

    Description: Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels

    Measure: Change in serum lactate dehydrogenase (LDH) levels

    Time: Days 1-7 compared with baseline

    Description: Difference in syndecan-1 levels in ng/mL, to with baseline levels

    Measure: Change in plasma syndecan-1 levels

    Time: Days 1-7 compared with baseline

    Description: Difference in cell-free DNA levels in ng/μL, compared to baseline levels

    Measure: Change in plasma cell-free DNA levels

    Time: Days 1-7 compared with baseline

    Description: Difference in plasma IL-6 levels in pg/mL, compared to baseline levels

    Measure: Change in plasma IL-6 levels

    Time: Days 1-7 compared with baseline

    Description: Respiratory failure defined as resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation

    Measure: Proportion of patients alive and free of respiratory failure

    Time: At 28-days

    Description: Percentage of patients alive and not requiring invasive mechanical ventilation

    Measure: Proportion of patients alive and free of invasive mechanical ventilation

    Time: At 28-days
    118 A Randomized Double Blind, Placebo-Controlled Study of Auxora for the Treatment of Severe COVID-19 Pneumonia (CARDEA)

    Part 1 of this trial enrolled 30 patients to receive Auxora (formerly CM4620) in a 2:1 randomized, open label trial of patients with severe and critical COVID-19 pneumonia. Part 2 will consist of a randomized, double blind, placebo-controlled (RCT) study that will evaluate efficacy, safety, and the pharmacokinetic profile of Auxora in patients with severe COVID-19 pneumonia. Four hundred patients will be randomized 1:1 to receive Auxora or matching placebo. Patients with an estimated PaO2/FiO2 of 75-200 will be stratified to ensure balanced randomization between the Auxora and placebo arms. The number of patients with an imputed PaO2/FiO2 >200 randomized into the study will be capped at 80. Subgroup analyses will be performed to explore how time to recovery is influenced by baseline variables and to evaluate the treatment effect at different levels of each of these variables. The dose of Auxora will be 2.0 mg/kg (1.25 mL/kg) administered at 0 hour, and then 1.6 mg/kg (1 mL/kg) at 24 hours and 1.6 mg/kg (1 mL/kg) at 48 hours from the SFISD. The dose of placebo will be 1.25 mL/kg administered at 0 hour and then 1 mL/kg at 24 hours and 1 mL/kg at 48 hours from the SFISD. Remdesivir, corticosteroids and convalescent plasma will be allowed. The infusion of Auxora will start within 12 hours from the time the patient or LAR provides informed consent.

    NCT04345614
    Conditions
    1. Pneumonia
    Interventions
    1. Drug: Auxora
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Defined as the number of days hospitalized but not requiring supplemental oxygen or ongoing medical care, or; discharged and requiring supplemental oxygen, or; discharged, not requiring supplemental oxygen.

    Measure: Number of days from the Start of the First Infusion of Study Drug (SFISD) to recovery

    Time: From start of first infusion of study drug to day 30

    Secondary Outcomes

    Measure: Proportion of patients requiring invasive mechanical ventilation or dying

    Time: from start of start of first infusion of study drug and up to day 30

    Measure: Proportion of patients requiring invasive mechanical ventilation

    Time: from start of start of first infusion of study drug and up to day 30

    Description: The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen

    Measure: Differences in outcomes as measured by an 8-point ordinal scale

    Time: from randomization through Days 12 and 30

    Measure: Proportion of patients who have died at day 30 (mortality)

    Time: Day 30

    Measure: Number of days in the hospital

    Time: from admission into the hospital until discharge from the hospital

    Measure: Number of days in the Intensive Care Unit (ICU)

    Time: from admission into ICU until discharge from ICU

    Measure: Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE)

    Time: from randomization and through day 30

    Description: Concentration measured using a validated assay

    Measure: CM4620-IE serum concentration

    Time: enrollment through 72 hours
    119 Safety and Efficacy of Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells in Severe Patients With Coronavirus Disease 2019 (COVID-19): A Phase 1/2 Randomized Controlled Trial

    Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.

    NCT04346368
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Biological: BM-MSCs
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Evaluation of pneumonia improvement

    Measure: Changes of oxygenation index (PaO2/FiO2)

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: Proportion of participants with treatment-related adverse events

    Measure: Side effects in the BM-MSCs treatment group

    Time: Baseline through 6 months

    Secondary Outcomes

    Description: Improvement of clinical symptoms including duration of fever, respiratory destress, pneumonia, cough, sneezing, diarrhea.

    Measure: Clinical outcome

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: days of the patients in hospital

    Measure: Hospital stay

    Time: Baseline through 6 months

    Description: Evaluation of pneumonia improvement

    Measure: CT Scan

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: (deep sputum / pharyngeal swab / nasal swab / anal swab / tear fluid / stomach fluid / feces / blood or alveolar lavage fluid)

    Measure: Changes in viral load

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: Immunological status

    Measure: Changes of CD4+, CD8+ cells count and concentration of cytokines

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: Marker for efficacy

    Measure: Rate of mortality within 28-days

    Time: From baseline to day 28

    Description: Markers of Infection

    Measure: Changes of C-reactive protein

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
    120 BHV3500-203: Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of Zavegepant* (BHV-3500) Intranasal (IN) for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen

    The purpose of this study is to determine if a CGRP receptor antagonist may potentially blunt the severe inflammatory response at the alveolar level, delaying or reversing the path towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial ventilation or death in patients with COVID-19 on supplemental oxygen. * BHV-3500, formerly "vazegepant", is now referred to as "zavegepant" (za ve' je pant). The World Health Organization (WHO) International Nonproprietary Names (INN) Expert Committee revised the name to "zavegepant" which was accepted by the United States Adopted Names (USAN ) Council for use in the U.S. and is pending formal adoption by the INN for international use.

    NCT04346615
    Conditions
    1. COVID-19 Infection
    Interventions
    1. Drug: Zavegepant (BHV-3500)
    2. Drug: Placebo

    Primary Outcomes

    Description: a. Efficacy will be measured by the difference between groups in the meah 6-point severity rating at Day 15. The severity ratings are: Death Hospitalized, on invasive mechanical ventilation or ECMO Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: To compare the efficacy of zavegepant (BHV-3500) to placebo in subjects hospitalized with COVID-19 infection requiring supplemental oxygen, using a six-point rating scale at Day 15. .

    Time: Baseline to Day 15

    Secondary Outcomes

    Measure: Proportion of subjects who have a 6-point severity rating of 5 or 6, are alive, and do not use supplemental oxygen as a procedure at Day 29.

    Time: Baseline to Day 29

    Measure: Proportion of subjects who have a 6-point severity rating of 2 or 3, or use any ventilation or high-flow nasal cannula as procedures, on any day through Day 29.

    Time: Baseline to Day 29

    Measure: Proportion of subjects admitted into an ICU on any day through Day 29 from AE eCRFs.

    Time: Baseline to Day 29

    Measure: Proportion of subjects who have a 6-point severity rating of 3, 4, 5, or 6, are alive, and do not use invasive mechanical ventilation as a procedure at Day 15. The analogous definition is applied to Day 29.

    Time: Baseline at Day 15 and at Day 29

    Measure: Proportion of subjects who have a 6-point severity rating of 4, 5 or 6, or use a low- or high-flow nasal, are alive, and do not use any ventilation at Day 15. The analogous definition is applied to Day 29.

    Time: Baseline at Day 15 and at Day 29

    Measure: Difference between treatment groups in the mean 6-point severity rating at Day 29

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 with any 6-point severity rating greater than baseline.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first of any 2 consecutive days through Day 29 with all SpO2/FiO2 ratios > 400 on both days.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 with ≥ 1-point decrease in any NEWS2 score from baseline.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 with all NEWS2 scores < 2 on that day.

    Time: Baseline to Day 29

    Measure: Mean change from baseline in NEWS2 score at Days 15 and 29 for subjects who are alive at these time points

    Time: Baseline at Day 15 and at Day 29.

    Measure: Proportion of subjects who have a 6-point severity rating of 5 or 6, are alive, and do not use supplemental oxygen as a procedure at Day 15.

    Time: Baseline to Day 15

    Measure: Proportion of subjects who are discharged from the hospital, have a 6-point severity rating of 6 on any day after discharge, and use supplemental oxygen on any day after discharge.

    Time: Baseline to Day 60

    Measure: Mean number of days with respiratory rate > 24 breaths/minute through Day 29 for subjects who are alive at Day 29 and do not use invasive mechanical ventilation.

    Time: Baseline to Day 29

    Measure: Mean number of days with supplemental oxygen use through Day 29 for subjects who are alive at Day 29. A day in which any 6-point severity rating is 2, 3, or 4, or supplemental oxygen is used as a procedure counts.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 on which any SpO2 ≥ 90%, any 6-point severity rating is 5 or 6, and no supplemental oxygen is used as a procedure.

    Time: Baseline to Day 29

    Measure: Mean number of ventilator-free days through Day 29 for subjects who are alive at Day 29.

    Time: Baseline to Day 29

    Measure: Mean SOFA total scores at ICU admission and Day 29 (if still in ICU), from SOFA and AE eCRFs.

    Time: Baseline to Day 29

    Measure: Mean number of days of hospitalization through Day 29 for subjects who are alive on Day 29. All days on study on or before hospitalization discharge are days of hospitalization, from 6-point severity rating scale eCRFs

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first of any 2 consecutive days through Day 29 in which all temperatures show lack of fever on both days and no antipyretics are used on either day.

    Time: Baseline to Day 29

    Measure: Number of subjects with deaths, SAEs, severe AEs, and Grade 3 or 4 laboratory test abnormalities at any time on study.

    Time: Screening to Day 60

    Measure: Number and percentage of subjects with severe or life-threatening bacterial, invasive fungal, or opportunistic infections at any time through Day 29 from AE/SAE eCRFs.

    Time: Baseline to Day 29

    Measure: Number and percentage of subjects with intranasal administration reactions at any time through Day 29 from AE/SAE eCRFs.

    Time: Baseline to Day 29

    Measure: Proportion of subjects with ≥ 50% reduction in eGFR from baseline at any time on study from laboratory test eCRFs.

    Time: Baseline to Day 60
    121 A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Favipiravir Compared to Standard Supportive Care in Subjects With Mild or Asymptomatic COVID-19

    The objective of this study is to evaluate the efficacy of oral favipiravir plus standard of care treatment (SOC) compared with placebo plus SOC in reducing the duration of shedding of SARS-CoV2 virus in patients with mild or asymptomatic COVID-19.

    NCT04346628
    Conditions
    1. Sars-CoV2
    2. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Drug: Placebo
    3. Other: Standard of care treatment

    Primary Outcomes

    Description: Time in days from randomization to the first two negative results of nasal and/or oropharyngeal swab.

    Measure: Time until cessation of oral shedding of SARS-CoV-2 virus

    Time: Up to 28 days

    Secondary Outcomes

    Description: Viral load (nucleic acid) will be assessed by RT-PCR over time.

    Measure: Sars-CoV-2 viral load

    Time: Up to 28 days

    Description: Clinical worsening will be determined by clinician assessment.

    Measure: Count of participants with clinical worsening of COVID-19 disease

    Time: Up to 28 days

    Measure: Count of participants with development of SARS-CoV-2 antibodies

    Time: Up to 28 days

    Measure: Time until cessation of symptoms

    Time: Up to 28 days

    Description: This outcome will be assessed in patient who are asymptomatic of COVID-19 infection at the time of enrollment

    Measure: Count of participant with absence of development of any symptoms

    Time: Up to 28 days

    Description: Cmax is a pharmacokinetic parameter that measures the maximum concentration of drug in plasma.

    Measure: Cmax of favipiravir

    Time: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)

    Description: Cmin is a pharmacokinetic parameter that measures the minimum concentration of drug in plasma.

    Measure: Cmin of favipiravir

    Time: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)
    122 Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Real Time Polymerase Chain Reaction (RT-PCR) Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate

    To create a protocol for treatment of Pakistani patients with SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different quinone drug dosing regimens in controlling SARS-CoV-2 infection for asymptomatic patients.

    NCT04346667
    Conditions
    1. SARS-CoV-2
    2. Coronavirus Infection
    3. Asymptomatic Condition
    4. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine Sulfate Regular dose
    2. Drug: Hydroxychloroquine Sulfate Loading Dose
    3. Drug: Chloroquine
    4. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Asymptomatic Diseases

    Primary Outcomes

    Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7

    Measure: RT-PCR negative status

    Time: 6-7 days

    Secondary Outcomes

    Description: Time to progression to next stage of SARS-CoV-2 disease severity index

    Measure: Progression of symptoms

    Time: 7 days

    Description: Time to onset of fever (temperature greater than 100 degree F), cough, or shortness of breath (respiratory rate >22 per minute).

    Measure: Development of Symptoms

    Time: 7 days

    Description: Drug related adverse events as determined by data safety and monitoring board (DSMB)

    Measure: Adverse events

    Time: 7 days
    123 A Single Blind, Randomized, Placebo-controlled, Multi-center Phase 2 Study to Evaluate the Safety and Efficacy of Clevudine in Patients Diagnosed With Moderate COVID-19

    The purpose of this clinical trial is to assess the safety and efficacy of Clevudine 120 mg versus placebo once daily administration with standard of care therapy for 14 days (maximum up to 21 days) in patients with moderate COVID-19.

    NCT04347915
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Clevudine
    2. Drug: Placebo

    Primary Outcomes

    Description: The primary efficacy endpoint for this clinical trial is the rate of patients with negative SARS-Coronavirus-2 (SARS-CoV-2) in a two-day continuous Real-Time-RT-PCR test from baseline to before the 15th day.

    Measure: The rate of subjects tested as negative SARS-Coronavirus-2 (SARS-CoV-2)

    Time: within 15days

    Secondary Outcomes

    Measure: The rate of subjects tested as negative SARS-Coronavirus-2 (SARS-CoV-2) in consecutive two days of Real-Time RT-PCR tests

    Time: Day 4, 8, 11, 15, 22, 29(or EOT) day comparing the baseline

    Measure: The rate of subjects indicated by the improvement of lung invasive

    Time: within Day 29 (or EOT)

    Measure: The change of viral load

    Time: Day 4, 8, 11, 15, 22, and 29(or EOT) comparing the baseline
    124 Proof of Concept, Multicentre, Parallel, Randomized, Double-blind Clinical Trial to Assess the Safety and Efficacy of Nitazoxanide 600 mg Compared to Placebo in the Treatment of Hospitalized Patients With COVID-19 in Moderate Condition.

    This is a proof of concept study to evaluate the efficacy of nitazoxanide (600 mg BID) to treat hospitalized patients with moderate COVID-19.

    NCT04348409
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitazoxanide Tablets
    2. Drug: Placebo

    Primary Outcomes

    Description: PCR will be done to evaluate the change in viral load

    Measure: Viral load

    Time: day 1, 4, 7, 14 and 21

    Secondary Outcomes

    Description: Time to wean off oxygen supplementation

    Measure: Evolution of acute respiratory syndrome

    Time: 21 days

    Description: WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)

    Measure: Change in Clinical Condition

    Time: 21 days

    Description: Time to be discharged from hospital

    Measure: Hospital discharge

    Time: 21 days

    Description: Evaluation of change in acute respiratory syndrome

    Measure: Rate of mortality within 21-days

    Time: 21 days

    Description: Evaluation of change in acute respiratory syndrome

    Measure: Need of mechanical ventilation

    Time: 21 days
    125 Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection (Thy-Support)

    This study is a phase II, parallel, prospective, randomized, double-blind, placebo controlled trial. The present study will aim to address the efficacy and safety of acute administration of triiodothyronine on ICU patients diagnosed with pulmonary infection due to COVID-19 and require mechanical respiratory support or ECMO.

    NCT04348513
    Conditions
    1. Pulmonary Infection
    2. Covid-19
    Interventions
    1. Drug: T3 solution for injection
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Description: The primary objective of the study is to determine whether the administration of intravenous triiodothyronine in ICU patients diagnosed with pulmonary infection due to COVID-19 facilitates weaning from cardiorespiratory support compared to placebo. Successful weaning is defined as no requirement for ventilatory support after extubation (mechanical support) or support from ECMO for 48 hours. The primary objective will be measured as percentage of patients successfully weaned after 30 days of follow-up.

    Measure: Assessment of weaning from cardiorespiratory support

    Time: 30 days

    Secondary Outcomes

    Description: Hemodynamic status will be assessed by continuous blood pressure measurements (systolic BP in mmHg)

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Hemodynamic status will be assessed by continuous blood pressure measurements (diastolic BP in mmHg)

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Hemodynamic status will be assessed by continuous blood pressure measurements (mean BP in mmHg)

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Hemodynamic status will be assessed by the number of participants with use of inotropic and vasoactive drugs

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of oxygen in mmHg)

    Measure: Assessment of pulmonary function

    Time: 30 days

    Description: Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of carbon dioxide in mmHg)

    Measure: Assessment of pulmonary function

    Time: 30 days

    Description: Pulmonary function will be assessed by arterial measurement of lactate levels (in mmol/L)

    Measure: Assessment of pulmonary function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in aspartate aminotransferase (AST in IU/L) will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in alanine aminotransferase (ALT in IU/L) will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in gamma-glutamyl transpeptidase (γ-GT in IU/L) will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in bilirubin in mg/dL will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in fibrinogen in mg/dL will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in d-dimers in ng/ml will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Urine volume during 24 hours (in ml) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Changes in urea (in mg/dL) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Changes in uric acid (in mg/dL) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Changes in creatinine (in mg/dL) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Echocardiographic assessment of cardiac left ventricular ejection fraction (LVEF, %)

    Measure: Assessment of cardiac function

    Time: 30 days

    Description: Measurements of cardiac troponin I (in μg/L) will be used to assess myocardial injury

    Measure: Assessment of cardiac injury

    Time: 30 days

    Description: COVID-19 infection will be assessed by inflammatory indices in blood (white blood cells in number per μL)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by inflammatory indices in blood (CRP in mg/L)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by inflammatory indices in blood (erythrocyte sedimentation rate in mm/hr)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by temperature monitoring (in degrees Celsius)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by time needed (in days) for the patient to become negative in COVID-19

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: Number of participants with major (death, cardiac Arrest, electromechanical dissociation, pulmonary embolism, new myocardial infarction, stroke, pulmonary edema, cardiogenic shock and hypotension, septic shock, pulmonary embolism, serious bleeding) events be recorded during the follow up period

    Measure: Assessment of clinical outcome and safety

    Time: 30 days

    Description: Number of participants with minor (myocarditis, Venous Thromboembolism, left Ventricular mural thrombus, renal failure, hepatic failure, stress ulcers, minor bleeding, paroxysmal supraventricular tachycardia and atrial fibrillation, rhythm disturbances) events will be recorded during the follow up period

    Measure: Assessment of clinical outcome and safety

    Time: 30 days
    126 A Phase 2 Randomized Single-Blind Study to Evaluate the Activity and Safety of Low Dose Oral Selinexor (KPT-330) in Patients With Severe COVID-19 Infection

    The main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo.

    NCT04349098
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Selinexor
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale

    Time: Baseline to Day 14

    Secondary Outcomes

    Measure: Time to Clinical Improvement (TTCI)

    Time: Up to Day 28

    Measure: Overall Death Rate

    Time: Day 14, Day 28

    Measure: Rate of Mechanical Ventilation

    Time: Up to Day 28

    Measure: Time to Mechanical Ventilation

    Time: Up to Day 28

    Measure: Overall Survival

    Time: Up to Day 28

    Measure: Time to Improvement (2 points) in Clinical Measures Using the Ordinal Scale

    Time: Baseline, Day 28

    Measure: Time to Intensive Care Unit (ICU) Admission

    Time: Up to Day 28

    Measure: Rate of Intensive Care Unit (ICU) Admission

    Time: Up to Day 28

    Measure: Length of Stay in Hospital

    Time: Up to Day 28

    Measure: Percentage of Participants Discharged from Hospital

    Time: Up to Day 28

    Measure: Length of Stay in Intensive Care Unit (ICU)

    Time: Up to Day 28

    Measure: Duration of Oxygen Supplementation

    Time: Up to Day 28

    Measure: Duration of Mechanical Ventilation

    Time: Up to Day 28

    Measure: Time to Clinical Improvement in Participants ≤ 70 Years Old

    Time: Up to Day 28

    Measure: Time to Clinical Improvement in Participants > 70 Years Old

    Time: Up to Day 28

    Measure: Time to Clinical Improvement in Participants with Pre-existing Diseases

    Time: Up to Day 28

    Measure: Change in Oxygenation Index

    Time: Up to Day 28

    Measure: Time to Improvement of One Point Using WHO Ordinal Scale Improvement

    Time: Up to Day 28

    Measure: Percentage of Participants Experiencing WHO Ordinal Scale Improvement of >1 point

    Time: Up to Day 28

    Measure: Change from Baseline in C-reactive protein (CRP) Levels

    Time: Up to Day 28

    Measure: Change from Baseline in Ferritin Levels

    Time: Up to Day 28

    Measure: Change from Baseline in Lactate Dehydrogenase (LDH) Levels

    Time: Up to Day 28

    Measure: Changes from Baseline in Blood Plasma Cytokines Levels

    Time: Up to Day 28

    Measure: Number of Participants with Adverse Events (AE)

    Time: From start of study drug administration up to Day 28
    127 Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

    As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.

    NCT04350580
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. COVID-19
    Interventions
    1. Drug: Human immunoglobulin
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero

    Measure: Ventilator-free days

    Time: 28 days

    Secondary Outcomes

    Description: Vital status at 28 and 90 days

    Measure: Mortality

    Time: 28 and 90 days

    Description: Used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing the higher the score

    Measure: Sequential Organ Failure Assessment Score

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)

    Measure: P/F ratio

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Measure of lung compliance

    Measure: Lung compliance

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Severity scoring of lung oedema on the chest radiograph

    Measure: Radiological score

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Concentration in mg/L

    Measure: Biological efficacy endpoints - C-reactive protein

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Concentration in microgram/L

    Measure: Biological efficacy endpoints - Procalcitonin

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

    Measure: Immunological profile

    Time: Up to 28 days

    Description: Use of corticosteroids, antiretroviral, chloroquine

    Measure: Number of patients using other treatments for COVID-19 related ARDS

    Time: Up to 28 days

    Description: Diagnosis of deep vein thrombosis or pulmonary embolism through imaging exam (eg ultrasound and CT scan)

    Measure: Occurrence of deep vein thrombosis or pulmonary embolism

    Time: 28 days

    Description: Total time of mechanical ventilation, weaning and use of neuromuscular blockade

    Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

    Time: 28 days

    Description: Divided in 3 stages, with higher severity of kidney injury in higher stages

    Measure: Kidney Disease: Improving Global Outcomes (KDIGO) score and need for dialysis

    Time: 28 days

    Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

    Measure: Occurrence of adverse event related to immunoglobulins

    Time: 28 days

    Description: Medical research council sum score on awakening

    Measure: Occurrence of critical illness neuromyopathy

    Time: Up to 28 days

    Description: Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling

    Measure: Occurrence of ventilator-acquired pneumonia

    Time: Up to 28 days
    128 An International, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Dapagliflozin in Respiratory Failure in Patients With COVID-19

    This is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with COVID-19 in the US and other countries with high prevalence of COVID-19. The study is evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily for 30 days in addition to background local standard of care therapy, in reducing disease progression, complications, and all-cause mortality.

    NCT04350593
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Dapagliflozin 10 MG
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: Respiratory decompensation (e.g., invasive or non-invasive mechanical ventilation) New or worsening congestive HF Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest Initiation of renal replacement therapy

    Measure: Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following:

    Time: Randomization through Day 30

    Secondary Outcomes

    Description: Time to death from any cause Time to new/worsened organ dysfunction (as defined in the primary outcome measure) Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction (using points 3 to 5 of a 7-point ordinal scale) Time to hospital discharge

    Measure: Hierarchical composite outcome measures including time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30 and time to hospital discharge

    Time: Randomization through Day 30

    Description: Time to hospital discharge

    Measure: Time to hospital discharge

    Time: Randomization through Day 30

    Description: Total number of days alive, out of hospital, and/or free from mechanical ventilation

    Measure: Total number of days alive, out of hospital, and/or free from mechanical ventilation

    Time: Randomization through Day 30

    Description: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)

    Measure: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)

    Time: Randomization through Day 30

    Description: Time to death from any cause

    Measure: Time to death from any cause

    Time: Randomization through Day 30

    Description: Time to new/worsened organ dysfunction

    Measure: Time to new/worsened organ dysfunction

    Time: Randomization through Day 30

    Description: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)

    Measure: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)

    Time: Randomization through Day 30
    129 A Phase 1, Double-blind, Randomized, Placebo-controlled, Sponsor-open, SAD and MAD Study in Healthy Subjects to Evaluate the Safety, Tolerability, and PK of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19

    This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.

    NCT04350736
    Conditions
    1. Acute Lung Injury (ALI) Associated With COVID-19
    2. Inflammatory Lung Conditions Associated With COVID-19
    Interventions
    1. Drug: TD-0903
    2. Drug: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

    Primary Outcomes

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of SAD of TD-0903: Adverse Events

    Time: Day 1 to Day 8

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events

    Time: Day 1 to Day 14

    Secondary Outcomes

    Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC

    Time: Day 1 through Day 4

    Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax

    Time: Day 1 through Day 4

    Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax

    Time: Day 1 through Day 4

    Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC

    Time: Day 1 through Day 9

    Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax

    Time: Day 1 through Day 9

    Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax

    Time: Day 1 through Day 9
    130 Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Symptomatic RT-PCR Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate

    To treat Pakistani patients with non-life threatening symptomatic SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different chloroquine and hydroxychloroquine dosing regimens in controlling SARS-CoV-2 infection.

    NCT04351191
    Conditions
    1. Sars-CoV2
    2. Symptomatic Condition
    3. Covid-19
    Interventions
    1. Drug: Hydroxychloroquine Sulfate Regular dose
    2. Drug: Hydroxychloroquine Sulfate Loading Dose
    3. Drug: Chloroquine
    4. Drug: Placebo

    Primary Outcomes

    Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7

    Measure: RT-PCR result

    Time: 6th and 7th day

    Secondary Outcomes

    Description: Time to progression to next stage of SARS-CoV-2 disease severity index

    Measure: Progression of symptoms

    Time: 7 days

    Description: Death

    Measure: Mortality

    Time: 30 days
    131 A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)

    Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

    NCT04351243
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Gimsilumab
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

    Primary Outcomes

    Measure: Incidence of mortality

    Time: Day 43

    Secondary Outcomes

    Measure: Incidence of subjects who are alive and not on mechanical ventilation

    Time: Day 29

    Description: Subjects who die will be assigned "0" ventilator-free days

    Measure: Number of ventilator-free days

    Time: Baseline to Day 29

    Measure: Time to hospital discharge

    Time: Baseline to Day 43
    132 Randomized Controlled Trial of Hydroxychloroquine Versus Placebo in Early Ambulatory Diagnosis and Treatment of Elderly COVID19 Patients

    Patients over equal or older than 65 yearswill be treated with a hydroxychloroquine versus placebo reduced loading dose of 600mg on the first day followed with 400mg/day divided in 2x200mg for 6 more days resulting in a total duration of therapy of 7 days. Measurement of Hydroxychloroquine-levels will be performed on day 7, . A follow-up by video or telephone conference will be performed to observe drug intake and collect adverse events during treatment phase on a daily base on working days and once during the weekend (i.e. 6 out of 7 days). After treatment phase follow-up by telephone calls will be done on day 10, 30, 60 (+/- 2 days).

    NCT04351516
    Conditions
    1. SARS-CoV 2
    2. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo

    Primary Outcomes

    Measure: ● Rate of hospitalization or death at day 7 after study inclusion

    Time: 7 days
    133 RAndomized Clinical Trial in COvid19 Patients to Assess the Efficacy of the Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor NAfamostat (RACONA Study)

    RACONA is a prospective trial that will test the hypothesis that nafamostat can lower lung function deterioration and need for intensive care admission in COVID-19 patients. Design: Adult hospitalized COVID-19 patients will be randomized in a prospective double-blind randomized placebo-controlled study to test the clinical efficacy of nafamostat mesylate (administered intravenously) on top of best standard of care. Primary outcome measures: the time-to-clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever comes first.

    NCT04352400
    Conditions
    1. COVID19
    Interventions
    1. Drug: Nafamostat Mesilate
    2. Drug: Placebo

    Primary Outcomes

    Description: Time-to-clinical improvement (time from randomization to an improvement of two points (from the status at randomization) on a 7 category ordinal scale or live discharge from the hospital, whichever came first.

    Measure: Time-to-clinical improvement

    Time: day 1 until day 28

    Secondary Outcomes

    Description: Rate of patients showing improvement of 2 points in 7 category ordinal scale (with 7 points the worst)(PubMed ID: 32187464)

    Measure: Responders

    Time: day 1 until day 28

    Description: Proportion of patients who will progress to critical illness/death

    Measure: Critical or dead patients

    Time: day 1 until day 28

    Description: Change in pO2/FiO2 ratio over time

    Measure: pO2/FiO2 ratio

    Time: day 1 until day 28

    Description: Change Sequential organ failure assessment score (SOFA score) over time. The Score ranges from 0 to 24 (with 24 the worst)(PubMed ID: 11594901)

    Measure: SOFA score over time

    Time: day 1 until day 28

    Description: Duration of hospitalization in survivors (days)

    Measure: Hospitalization

    Time: day 1 until day 28

    Description: Number of patients who require ventilation

    Measure: Mechanical ventilation

    Time: day 1 until day 28

    Description: Duration of ventilation (days)

    Measure: Mechanical ventilation duration

    Time: day 1 until day 28

    Description: Proportion of patients who develop arrhythmia, or myocardial infarction, or other cardiovascular disease not present at the baseline

    Measure: Cardiovascular disease

    Time: day 1 until day 28
    134 A Randomized Phase 2/3 Trial of Hydroxychloroquine In Covid-19 Kinetics

    To test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.

    NCT04353271
    Conditions
    1. Covid 19
    2. Corona Virus Infection
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs

    Measure: Percentage of virus free subjects

    Time: 7 days after initiation of trial

    Description: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .

    Measure: Disease severity

    Time: 6 days

    Secondary Outcomes

    Description: Number of subjects in each arm who are hospitalized for Covid 19 infection

    Measure: Incidence of hospitalization

    Time: 14 days

    Description: Number of subjects in each arm who die secondary to Covid-19 infection

    Measure: Incidence of Death

    Time: 70 Days (10 weeks)

    Description: Number of subjects in each arm who have confirmed Covid-19 infection

    Measure: Incidence of confirmed SARS-CoV-2 Detection

    Time: 14 days

    Description: Number of subjects in each arm who discontinue or withdraw medication use for any reason

    Measure: Incidence of all-cause study medication discontinuation or withdrawal

    Time: 14 days

    Description: Blood tests to determine level of immunity in each subject

    Measure: Immunity to Covid-19

    Time: 70 days (10 weeks)
    135 The Effect of Camostat Mesylate on COVID-19 Infection in Ambulatory Patients: An Investigator-Initiated Randomized, Placebo-Controlled, Phase IIa Trial

    The rationale of the present clinical trial is that an orally available drug given to outpatients that could reduce the viral burden in the upper respiratory tract could forestall complications of SARS-CoV-2 infection and reduce transmission from one infected individual to another.

    NCT04353284
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Camostat Mesilate
    2. Other: Placebo

    Primary Outcomes

    Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 4 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

    Measure: Change in SARS-COV-2 viral load

    Time: 5 days

    Secondary Outcomes

    Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 2 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

    Measure: Change in SARS-COV-2 viral load

    Time: 3 days

    Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 6 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

    Measure: Change in SARS-COV-2 viral load

    Time: 7 days

    Description: Change in risk for a positive COVID-19 test at day 6 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.

    Measure: Change in positive COVID-19 status

    Time: 7 days

    Description: Change of COVID-19 symptom severity from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom severity

    Time: 7 days

    Description: Change of COVID-19 symptom severity from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom severity

    Time: 14 days

    Description: Change of COVID-19 symptom score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom frequency

    Time: 7 days

    Description: Change of COVID-19 symptom score from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom frequency

    Time: 14 days

    Description: Change of COVID-19 symptom score from baseline to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in body temperature

    Time: 7 days

    Description: Change of COVID-19 symptom score from baseline to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in body temperature

    Time: 14 days
    136 A Randomized, Double-blind, Two Arm, Placebo Controlled Clinical Trial to Evaluate the Efficacy and Safety of Mycobacterium w in Preventing COVID-19 in Subjects at Risk of Getting Infected With COVID-19.

    This clinical trial is a randomized, blinded, two arms, placebo controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice to prevent COVID 19 in subjects at risk of getting infected with COVID 19.

    NCT04353518
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Suspension of heat killed (autoclaved) Mycobacterium w
    2. Other: Placebo
    MeSH:Mycobacterium Infections

    Primary Outcomes

    Description: To compare proportion of subjects acquiring COVID-19 infection between two arms over the time till 8 weeks from administration of 1st dose

    Measure: Number of subject acquiring COVID-19 infection

    Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing..

    Secondary Outcomes

    Description: Any AE / SAE observed during the study.

    Measure: Incidence of Adverse Event and Serious Adverse Event (safety and tolerability)

    Time: Till 8 weeks

    Description: Whether administration of Mw prevents development of Upper Respiratory Tract Infection (URTI) symptoms in close contacts of COVID-19 patients.

    Measure: Number of subject developing Upper Respiratory Tract Infection (URTI) symptoms

    Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing.

    Description: Whether administration of Mw prevents development of severe COVID-19 infection.

    Measure: Number of subject developing severe COVID-19 infection based on ordinal scale

    Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing
    137 DAS181 for COVID-19: A Phase II Multicenter, Randomized, Placebo-Controlled, Double-Blind Study

    It is a multicenter, randomized, placebo-controlled, double-blind study. The study population is defined as subjects diagnosed with lower respiratory tract COVID-19 who require supplemental oxygen ≥2 LPM at the time of randomization.

    NCT04354389
    Conditions
    1. COVID-19
    Interventions
    1. Drug: DAS181
    2. Drug: Placebo
    3. Drug: DAS181

    Primary Outcomes

    Measure: Percent of subjects return to room air (RTRA)

    Time: Day 14

    Secondary Outcomes

    Description: Percent of subjects who reach level 1 of COVID-19 Clinical Classification (discharged or return to normal activity)

    Measure: Percent of subjects who have recovered

    Time: Day 5, 10, 14, 21, 28

    Description: time to Improved COVID-19 Clinical Classification 1 to 6 (where higher score means worse outcome)

    Measure: Improved COVID-19 Clinical Classification

    Time: Day 28

    Description: Percent of subjects RTRA

    Measure: Return To Room Air (RTRA)

    Time: Day 10, 21, 28

    Measure: Percent of subjects who achieve clinical stability

    Time: Day 28

    Description: Time to

    Measure: SARS-CoV-2 RNA undetectable

    Time: Day 28

    Description: Time to

    Measure: Clinical Deterioration

    Time: Day 28

    Description: Percent of subjects discharge

    Measure: Percent of subjects discharged

    Time: Day 14, 21, 28

    Description: Time to

    Measure: Death (all cause)

    Time: Day 28
    138 Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia: a Randomized Controlled Double-blind Study From the Skip-icu Consortium

    The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.

    NCT04357457
    Conditions
    1. Covid 19
    2. Hypoxemic Respiratory Failure
    Interventions
    1. Drug: Almitrine
    2. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).

    Measure: Rate of endotracheal intubation

    Time: 7 days

    Secondary Outcomes

    Measure: 28-day mortality

    Time: 28 days

    Measure: In-hospital mortality

    Time: 28-day

    Measure: Number of ventilator-free days

    Time: 28 days

    Measure: Number of days in the ICU

    Time: 28 days

    Measure: Number of days in the hospital

    Time: 28 days

    Description: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.

    Measure: Discontinuation rate of the treatment

    Time: 28 days
    139 Use of a Medical Device, Viruxal Oral and Nasal Spray, for Treating the Symptoms of COVID-19 Via Application to the Naso- and Oropharyngeal Mucosa

    Viruxal Oral and Nasal Spray is a Class I CE marked medical device manufactured by Kerecis hf (the "Device"). A double blind clinical trial will be conducted to evaluate the Device against placebo in COVID-19 positive, symptomatic patients in Iceland. Immediate access to COVID-19 patients is available through a well-organized COVID-19 outpatient follow-up clinic. Up to 128 patients with mild to moderate symptoms of COVID-19 will be recruited (so called "higher end of the low risk group"). These patients will be positive for COVID-19, be symptomatic with upper respiratory symptoms, but without involvement of the entire respiratory system. The patients will be randomized to receive treatment with the Study Device or to receive placebo. 64 patients will be randomized into the Study Device group and 64 patients into the Control group. Patients will administer Study Device or Control for 14 days and will have their symptoms recorded until no further symptoms are reported, up to a maximum of 28 days follow-up.

    NCT04357990
    Conditions
    1. COVID-19
    Interventions
    1. Device: Viruxal Oral and Nasal Spray
    2. Other: Placebo

    Primary Outcomes

    Description: The number of days until participants report no symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.

    Measure: Number of days until complete resolution of symptoms per group

    Time: 28 days

    Description: The number of participants admitted to hospital due to deterioration of their condition due to COVID-19 will be compared between groups.

    Measure: Number of hospital admissions per group

    Time: 28 days

    Secondary Outcomes

    Description: The number of days until participants report a reduction in symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.

    Measure: Number of days until a reduction in symptoms per group

    Time: 28 days

    Description: The number of adverse events reported will be compared between groups.

    Measure: Number of adverse events per group

    Time: 28 days
    140 A Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease

    Two recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounce when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation. The purpose of the study is to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.

    NCT04358081
    Conditions
    1. Covid-19
    Interventions
    1. Drug: HCQ
    2. Drug: HCQ+AZT
    3. Drug: Placebo

    Primary Outcomes

    Description: To demonstrate in patients receiving standard of care that the percentage who achieve clinical response with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo at Day 15

    Measure: Percentage of participants who achieve clinical response

    Time: 15 days

    Secondary Outcomes

    Description: To demonstrate in patients receiving standard of care that the percentage with viral clearance at Day 15 with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo

    Measure: Percentage of Participants with Viral Clearance

    Time: 15 Days

    Description: To assess in patients receiving standard of care the safety of hydroxychloroquine or hydroxychloroquine and azithromycin compared to placebo

    Measure: Number of participants receiving hydroxychloroquine or hydroxychloroquine and azithromycin with adverse events of hydroxychloroquin or hydroxychloroquine and azithromycin compared to placebo

    Time: 40 days
    141 A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof-Of-Concept Study To Evaluate Efficacy And Safety Of Recombinant Human Plasma Gelsolin (Rhu-pGSN) Added To Standard Of Care In Subjects With Severe Covid-19 Pneumonia

    Study Objectives: Primary - To assess the efficacy (survival without organ failure on Day 14) of three doses of rhu-pGSN administered intravenously (IV) plus standard of care (SOC) to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5 or 6 on the World Health Organization (WHO) 9-point severity scale - To evaluate the safety and tolerability of three IV doses of rhu-pGSN administered to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5, or 6 on the WHO 9-point severity scale Secondary - To further assess the efficacy of IV administered rhu-pGSN - To assess changes in WHO 9-point severity score for SOC with or without rhu-pGSN - To evaluate the effect of administered rhu-pGSN on survival rates - To assess the relationship of pGSN levels (and other biomarkers) at baseline with clinical outcomes - [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN Immunogenicity • To investigate the development of antibodies against rhu-pGSN post-treatment

    NCT04358406
    Conditions
    1. Sars-CoV2
    Interventions
    1. Drug: Recombinant human plasma gelsolin (Rhu-pGSN)
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

    Measure: Efficacy: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

    Time: Day 14

    Description: Proportion of subjects with SAEs as judged by the investigator

    Measure: Safety and Tolerability: Proportion of subjects with serious adverse events (SAEs)

    Time: Continuous through Day 28

    Secondary Outcomes

    Description: Daily change in the 9-point Severity Score (ordinal scale) proposed by a special WHO committee for COVID-19 pneumonia where a score of 8 indicates death and 0 is no clinical or virological evidence of COVID-19 infection

    Measure: Efficacy: Daily change in the WHO 9-point severity score

    Time: Daily through at least Day 14

    Description: All cause mortality rate using Kaplan-Meier survival analysis

    Measure: Efficacy: All cause mortality rate at Days 28 and 90

    Time: At Days 28 and 90

    Description: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit, new ongoing need for dialysis/renal replacement therapy

    Measure: Efficacy: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for dialysis/renal replacement therapy

    Time: Days 7, 28, 60, and 90

    Description: Proportion of subjects discharged to home or immediate prior residence

    Measure: Efficacy: Proportion of subjects discharged to home or immediate prior residence

    Time: Continuous through Day 28

    Description: LOS of surviving subjects in the hospital and in ICU

    Measure: Efficacy: Length of stay (LOS) of surviving subjects in the hospital and in ICU

    Time: Continuous through day 28

    Description: Proportion of subjects readmitted to the hospital

    Measure: Efficacy: Proportion of subjects readmitted to the hospital

    Time: Up to 90 days

    Description: Proportion of subjects with adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measure: Safety and Tolerability: Proportion of subjects with adverse events (AEs)

    Time: Continuous through Day 28

    Description: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

    Measure: Safety and Tolerability: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

    Time: Continuous through Day 28

    Description: Proportion of subjects with rhu-pGSN antibodies

    Measure: Immunogenicity: Proportion of subjects with rhu-pGSN antibodies

    Time: Days 1, 28, and 90

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

    Measure: Pharmacokinetics: Maximum concentration (C max) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

    Measure: Pharmacokinetics: Time to maximum concentration (T max) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Half-life (T 1/2) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Area under the curve from time 0 to 8 hours (AUC 0-8) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Area under the curve from time 0 to infinity (AUC 0-inf) of added rhu-pGSN

    Time: Continuous through day 3
    142 A Randomized, Double-blind, Two Arm, Controlled Clinical Trial to Compare the Efficacy and Safety of Mycobacterium w (Mw) Administered Along With Standard of Care Versus Placebo Administered Along With Standard of Care, in Adult, COVID 19 Positive Patients Hospitalized But Not Critically Ill.

    This is a randomized, double blind, two arms, placebo controlled, clinical trial to study to evaluate the the safety and efficacy of Mycobacterium w in combination with standard of care versus placebo with standard of care for preventing the progression of COVID-19 disease and for reduction in transfer to ICU in COVID-19 infected patients admitted to the hospital.

    NCT04358809
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Suspension of heat killed (autoclaved) Mycobacterium w
    2. Other: Placebo
    MeSH:Mycobacterium Infections Critical Illness

    Primary Outcomes

    Description: To compare the difference in proportion of patients with increased disease severity

    Measure: Number of patients with increased disease severity

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Secondary Outcomes

    Description: To evaluate safety of Mw in COVID-19 patients admitted to hospital

    Measure: Incidence of adverse events and serious adverse events (Safety)

    Time: Till day 28

    Description: To compare the proportion of patients discharged from hospital

    Measure: Number of COVID-19 patients discharged from hospital

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Description: To compare the proportion of patients transfer to ICU

    Measure: Number of COVID-19 patients transfer to ICU

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Description: To compare the proportion of patients with reduction in disease severity by 1 ordinal scale

    Measure: Number of COVID-19 patients with reduction in disease severity by 1 ordinal scale

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Description: To compare the proportion of symptom free patients

    Measure: Number of of symptom free patients

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.
    143 Comparative Efficacy of Various Doses of Hydroxychloroquine in Pre-Exposure Prophylaxis for COVID 19 in Healthcare Personnel

    Hydroxychloroquine has been approved by FDA as one of the treatment options for COVID 19.Healthcare personnel are amongst those at highest risk to contract the disease. Several health authorities are now recommending the use of hydroxychloroquine as pre-exposure prophylaxis is in health care personnel. Several studies are on going in this context. However there is a controversy regarding the dosage regimen. This drug has a half life of 22.4 days. In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.

    NCT04359537
    Conditions
    1. COVID 19
    Interventions
    1. Drug: Hydroxychloroquine Sulfate 200 MG
    2. Other: Placebo

    Primary Outcomes

    Description: Outcome reported as the percentage of participants in each arm who are COVID-19-free at the end of study treatment

    Measure: COVID-19-free survival in experimental arms compared to placebo

    Time: 12 weeks

    Secondary Outcomes

    Description: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.

    Measure: Incidence of confirmed SARS-COV-2 detection

    Time: 12 weeks

    Description: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment

    Measure: Incidence of possible COVID-19 symptoms

    Time: 12 weeks

    Description: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.

    Measure: Incidence of all-cause study medicine discontinuation

    Time: 12 weeks

    Description: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), Hospitalization with ICU stay (score 4),Death from COVID 19(score=5) Possible scores range from 1-5 with higher scores indicating greater disease severity.

    Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end

    Time: 12 weeks

    Description: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.

    Measure: Incidence of Hospitalization for COVID-19 or death

    Time: 12 weeks

    Description: Outcome reported as the percent of participants experiencing any possible adverse events from Hydroxychloroquine

    Measure: Incidence of study medication-related adverse events

    Time: 12 weeks
    144 A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection

    Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection

    NCT04359680
    Conditions
    1. COVID-19
    2. Viral Respiratory Illnesses
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    3. Dietary Supplement: Vitamin Super B-Complex
    MeSH:Infection

    Primary Outcomes

    Measure: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the 6-week treatment period.

    Time: Up to 6 weeks

    Measure: The proportion of subjects with symptomatic laboratory-confirmed VRI identified after the start of treatment and before the end of the 6-week treatment period.

    Time: Up to 6 weeks
    145 Inhaled Aviptadil for the Treatment of Moderate and Severe COVID-19

    Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care. Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer. The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

    NCT04360096
    Conditions
    1. SARS-CoV 2
    2. COVID
    3. ARDS
    4. ALI
    5. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
    6. Dyspnea
    Interventions
    1. Drug: RLF-100 (aviptadil)
    2. Drug: Placebo
    3. Device: Nebulized administration of RLF-100 or Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury
    HPO:Dyspnea Respiratory distress

    Primary Outcomes

    Description: Progression to ARDS is defined as the need for mechanical ventilation

    Measure: Progression to ARDS

    Time: 28 days

    Secondary Outcomes

    Description: Blood PO2 as measured by pulse oximetry

    Measure: Blood oxygenation

    Time: 28 days

    Description: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity

    Measure: RDP Dsypnea Scale

    Time: 28 days

    Description: Distance walked in six minutes

    Measure: Distance walked in six minutes

    Time: 28 days
    146 Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial of the Safety and Efficacy of Telmisartan for the Mitigation of Pulmonary and Cardiac Complications in COVID-19 Patients

    This study will enroll 40 symptomatic outpatients tested positive for Coronavirus 2019 (COVID-19). Patients to be randomized 1:1 to Telmisartan (40 mg) vs placebo to be administered orally once daily x 21 days. Daily, the study patients will be asked to keep a record of the severity of their fever, dyspnea and fatigue and take their blood pressure (BP) and temperature. Study visits to occur on day 1 (entry), day 4, day 10 and day 21. Oro-pharyngeal swabs, and approximately 25 cc of blood will be collected at each study visit for safety labs and for the evaluation of the renin-angiotensin system (RAS) system and for various blood biomarkers of inflammation, coagulation and fibrosis.

    NCT04360551
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Telmisartan 40mg
    2. Drug: Placebo

    Primary Outcomes

    Description: Based on a modified World Health Organization (WHO) COVID-19 7-point ordinal scale

    Measure: Maximum clinical severity of disease

    Time: Over the 21 day period of study

    Secondary Outcomes

    Description: Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014

    Measure: Incidence of treatment emergent adverse events

    Time: Through study completion at day 21 of study

    Description: Angiotensin I (AngI), AngII, Ang1-9 and Ang1-7

    Measure: Renin angiotensin system peptides

    Time: At each study time point (day 4, day 10, day 21)

    Description: plasma biomarkers of organ function/coagulation, inflammation, leukocyte chemotaxis, tissue remodeling/fibrosis and immune exhaustion by Luminex multiplexing assays such as TNF-alpha, IL-6, CK-MB, Troponin I, Fractalkine, MCP-1, PD-1, TIMP-1

    Measure: Plasma biomarkers

    Time: At each study time point (day 4, day 10, day 21)
    147 Double-blind Randomized Controlled Clinical Trial of Low-dose Lenalidomide in the Treatment of COVID-19 Disease

    Double-blind randomized controlled clinical trial (RCT) of low-dose lenalidomide in the treatment of elderly patients (> 60 years of age) with mild to moderate clinical signs of COVID-19 disease from the Hospital Universitario of Getafe. The study will include patients of both sexes (> 60 years of age) with mild to moderate clinical presentation of COVID-19 (ROX index > 10). Subjects will be randomly assigned to the experimental arm with lenalidomide (5 mg/24h, day 1, 3 and 5) or to the controlled arm. Other concomitant medication for the treatment of COVID-19 will be also considered.

    NCT04361643
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5.
    2. Drug: Placebo

    Primary Outcomes

    Description: Days to clinical recovery or days until discharge

    Measure: Clinical improvement

    Time: 30 days

    Description: o Improvement of the neutrophil-to-lymphocyte ratio (NLR)

    Measure: Immune-inflammatory improvement

    Time: 30 days

    Secondary Outcomes

    Description: All-cause mortality at 30 days after enrollment

    Measure: Mortality

    Time: 30 days
    148 Double Blind, Placebo-controlled, Phase II Trial to Evaluate Safety and Efficacy of Allogenic Mesenchymal Stromal Cells MSV_allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (COVID_MSV)

    Novel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.

    NCT04361942
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: Mesenchymal Stromal Cells
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Index of therapy success to preserve Intensive Care Hospitalization space

    Measure: Proportion of patients who have achieved withdrawal of invasive mechanical ventilation

    Time: 0-7 days

    Description: To measure global success

    Measure: Rate of mortality

    Time: 28 days

    Secondary Outcomes

    Description: Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2

    Measure: Proportion of patients who have achieved clinical response

    Time: 0-7days

    Description: Evaluation of pneumonia changes

    Measure: Proportion of patients who have achieved radiological responses

    Time: 0-28 days

    Other Outcomes

    Description: Haemogram and cell subpopulations

    Measure: Blood white cell counts and their subpopulations.

    Time: 0-180 days

    Description: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs

    Measure: Cellular markers of inflammation

    Time: 0-180 days

    Description: IL-10, IL-6, IP-10, TNF-alpha

    Measure: Cytokines and chemokines in peripheral blood

    Time: 0-180 days
    149 Performance Evaluation of BCG Vaccination in Healthcare Personnel to Reduce the Severity of SARS-COV-2 Infection in Medellín, Colombia, 2020

    Until the first half of April, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases. Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view. Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question may be that there are differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe. This finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses. Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations, and currently there are no vaccines or proven preventive interventions available to protect them. For this reason, this research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death. In the future, and if these results are as expected, they may be the basis for undertaking a population vaccination campaign that improves clinical outcomes in the general population.

    NCT04362124
    Conditions
    1. COVID-19
    Interventions
    1. Biological: vaccine BCG
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Incidence of COVID-19 cases confirmed or probable in the study population

    Measure: Primary outcome

    Time: From date of randomization to 360 day of the study

    Secondary Outcomes

    Description: Incidence of severe or critical infection in COVID-19 cases

    Measure: Secondary outcome

    Time: From date to diagnosis to 1 month after

    Description: Lethality of the infection in both groups

    Measure: Secondary outcome

    Time: From date to diagnosis to 1 month after

    Description: Assess the safety (frequency, seriousness, and severity of adverse events) of BCG vaccination

    Measure: Secondary outcome

    Time: From date of randomization to 7 day of the study

    Description: Prevalence of SARS-Cov-2 infection

    Measure: Secondary outcome

    Time: At baseline evaluation
    150 Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)

    This is a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 pneumonia.

    NCT04362137
    Conditions
    1. Cytokine Storm (Covid-19)
    Interventions
    1. Drug: Ruxolitinib
    2. Drug: Placebo

    Primary Outcomes

    Description: Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19.

    Measure: Proportion of patients who die, develop respiratory failure [require mechanical ventilation] or require intensive care unit (ICU) care

    Time: 29 days

    Secondary Outcomes

    Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

    Measure: Clinical status

    Time: Day 15, Day 29

    Description: Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale.

    Measure: Percentage of patients with at least two-point improvement from baseline in clinical status

    Time: Baseline, Day 15, Day 29

    Description: Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale.

    Measure: Percentage of patients with at least one-point improvement from baseline in clinical status

    Time: Baseline, Day 15, Day 29

    Description: Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale.

    Measure: Percentage of patients with at least one-point deterioration from baseline in clinical status

    Time: Baseline, Day 15, Day 29

    Description: Time to improvement from baseline category to one less severe category of the 9-point ordinal scale.

    Measure: Time to improvement in clinical status

    Time: 29 days

    Description: Mean change from baseline in the 9-point ordinal scale.

    Measure: Mean change from baseline in the clinical status

    Time: Baseline, Day 15, Day 29

    Description: Mortality rate at Day 15 and at Day 29

    Measure: Mortality rate

    Time: Day 15, Day 29

    Description: Proportion of patients requiring mechanical ventilation

    Measure: Proportion of patients requiring mechanical ventilation

    Time: 29 days

    Description: Duration of hospitalization

    Measure: Duration of hospitalization

    Time: 29 days

    Description: The time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).

    Measure: Time to discharge or to a NEWS2 score of ≤2

    Time: 29 days

    Description: The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).

    Measure: Change from baseline in NEWS2 score

    Time: Baseline, Days 3, 5, 8, 11, 15, and 29

    Description: Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio)

    Measure: Change from baseline in SpO2/FiO2 ratio.

    Time: Baseline, Day 15, Day 29

    Description: No oxygen therapy is required if oxygen saturation is ≥ 94% on room air.

    Measure: Proportion of patients with no oxygen therapy

    Time: Day 15, Day 29
    151 A Randomized, Controlled Clinical Trial to Test the Safety and Efficacy of Convalescent Donor Plasma to Treat COVID-19 in Hospitalized Adults

    The purpose of this study is to test the safety and efficacy of convalescent donor plasma to treat COVID-19 in hospitalized adults in a randomized, placebo-controlled setting. The effect of convalescent plasma will be compared to placebo on clinical outcomes, measured using the COVID Ordinal Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.

    NCT04362176
    Conditions
    1. COVID-19
    2. Coronavirus
    3. SARS-CoV-2
    Interventions
    1. Biological: pathogen reduced SARS-CoV-2 convalescent plasma
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Death Hospitalized on invasive mechanical ventilation or ECMO Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)

    Measure: COVID Ordinal Outcomes Scale:Day 15

    Time: Study Day 15

    Secondary Outcomes

    Description: All-location, all-cause 14-day mortality

    Measure: All-location, all-cause 14-day mortality

    Time: Baseline to Study Day 14

    Description: All-location, all-cause 28-day mortality

    Measure: All-location, all-cause 28-day mortality

    Time: Baseline to Study Day 28

    Description: Death Hospitalized on invasive mechanical ventilation or ECMO Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)

    Measure: COVID Ordinal Outcomes Scale Day 3

    Time: Baseline to Study Day 3

    Description: Death Hospitalized on invasive mechanical ventilation or ECMO Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)

    Measure: COVID Ordinal Outcomes Scale Day 8

    Time: Study Day 8

    Description: Death Hospitalized on invasive mechanical ventilation or ECMO Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)

    Measure: COVID Ordinal Outcomes Scale Day 29

    Time: Study Day 29

    Description: Number of participants that died or received ECMO

    Measure: Composite of death or receipt of ECMO through Day 28

    Time: Baseline to Day 28

    Description: Number of days without use of oxygen

    Measure: Oxygen-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days without use of vasopressors

    Measure: Vasopressor-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days without use of a ventilator

    Measure: Ventilator-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days outside of ICU

    Measure: ICU-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days outside of the hospital

    Measure: Hospital-free days through Day 28

    Time: Baseline to Day 28

    Other Outcomes

    Description: Number of participants with Acute kidney injury

    Measure: Acute kidney injury

    Time: Baseline to Day 28

    Description: Number of participants requiring renal replacement therapy

    Measure: Renal replacement therapy

    Time: Baseline to Day 28

    Description: Number of participants with documented venous thromboembolic disease (DVT or PE)

    Measure: Documented venous thromboembolic disease (DVT or PE)

    Time: Baseline to Day 28

    Description: Number of Participants with myocardial infarction or ischemic stroke

    Measure: Documented cardiovascular event (myocardial infarction or ischemic stroke)

    Time: Baseline to Day 28

    Description: Number of participants with transfusion reaction (fever/rash)

    Measure: Transfusion reaction

    Time: Baseline to Day 28

    Description: Number of participants with transfusion related acute lung injury (TRALI)

    Measure: Transfusion related acute lung injury (TRALI)

    Time: Baseline to Day 28

    Description: Number of participants with transfusion associated circulatory overload (TACO)

    Measure: Transfusion associated circulatory overload (TACO)

    Time: Baseline to Day 28

    Description: Number of participants with transfusion related infection

    Measure: Transfusion related infection

    Time: Baseline to Day 28
    152 A Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19

    Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as treatment for patients suspected to have COVID-19. The study purpose is to evaluate the safety and efficacy of four IV infusions of either placebo or HB-adMSCs in subjects with COVID-19.

    NCT04362189
    Conditions
    1. COVID-19
    Interventions
    1. Drug: HB-adMSC
    2. Drug: Placebo

    Primary Outcomes

    Description: change from baseline in interleukin-6

    Measure: Interleukin-6

    Time: screening, day 0, 7, 10

    Description: Change from baseline in C Reactive protein

    Measure: C Reactive protein

    Time: screening, day 0, 7, 10

    Description: change from baseline oxygenation (%)

    Measure: Oxygenation

    Time: screening, day 0, 7, 10

    Description: change from baseline in TNF alpha

    Measure: TNF alpha

    Time: screening, day 0, 7, 10

    Description: change from baseline level of IL-10 in the blood (pg/mL)

    Measure: IL-10

    Time: screening, day 0, 7. 10

    Description: Time to return to room air

    Measure: Return to room air (RTRA)

    Time: Day 0, 3, 7, 10, 28

    Secondary Outcomes

    Description: Monitoring for changes in qt interval

    Measure: EKG qt interval

    Time: screening, day 0, 3, 7, 10

    Description: change from baseline in leukocyte differential

    Measure: Leukocyte differential

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of glucose in the blood (mg/dL)

    Measure: Glucose

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of calcium in the blood (mg/dL)

    Measure: Calcium

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of albumin in the blood (g/dL)

    Measure: Albumin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of total protein in the blood (g/dL)

    Measure: Total protein

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of sodium in the blood (mol/L)

    Measure: Sodium

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)

    Measure: Total carbon dioxide

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of potassium in the blood (mmol/L)

    Measure: Potassium

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of chloride in the blood (mmol/L)

    Measure: Chloride

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of BUN in the blood (mg/dL)

    Measure: BUN

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of creatinine in the blood (mg/dL)

    Measure: Creatinine

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)

    Measure: Alkaline phosphatase

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)

    Measure: Alanine aminotransferase

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of total bilirubin in the blood (mg/dL)

    Measure: Total bilirubin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of white blood cells in the blood (x10^3/uL)

    Measure: White blood cells

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of red blood cells in the blood (x10^6/uL)

    Measure: Red blood cells

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of hemoglobin in the blood (g/dL)

    Measure: Hemoglobin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of hematocrit in the blood (%)

    Measure: Hematocrit

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of mean corpuscular volume in the blood (fL)

    Measure: Mean corpuscular volume

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of mean corpuscular hemoglobin in the blood (pg)

    Measure: Mean corpuscular hemoglobin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of mean corpuscular hemoglobin concentration in the blood (g/dL)

    Measure: Mean corpuscular hemoglobin concentration

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of red cell distribution width in the blood (%)

    Measure: Red cell distribution width

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of neutrophils in the blood (%)

    Measure: Neutrophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of lymphocytes in the blood (%)

    Measure: Lymphs

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of monocytes in the blood (%)

    Measure: Monocytes

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of eosinophils in the blood (%)

    Measure: Eosinophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of basophils in the blood (%)

    Measure: Basophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute neutrophils in the blood (x10^3/uL)

    Measure: Absolute neutrophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute lymphocytes in the blood (x10^3/uL)

    Measure: Absolute lymphs

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute monocytes in the blood (x10^3/uL)

    Measure: Absolute monocytes

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute eosinophils in the blood (x10^3/uL)

    Measure: Absolute eosinophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute basophils in the blood (x10^3/uL)

    Measure: Absolute basophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of immature granulocytes in the blood (x10^3/uL)

    Measure: Immature granulocytes

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of platelets in the blood (x10^3/uL)

    Measure: Platelets

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of time for blood to coagulate (seconds)

    Measure: Prothrombin time

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of international normalized ratio of blood coagulation (no unit)

    Measure: INR

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of percentage of cells CD3- and CD54+ (%)

    Measure: NK cell surface antigen (CD3-CD54+)

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of ratio of CD4+ cells to CD8+ cells (no unit)

    Measure: CD4+/CD8+ ratio

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)

    Measure: Myoglobin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)

    Measure: Troponin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of creatinine kinase in the blood (U/L)

    Measure: Creatinine kinase MB

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of serum ferritin in the blood (ng/mL)

    Measure: Serum ferritin

    Time: screening, day 0, 7, 10

    Description: incidence of adverse events

    Measure: Adverse events

    Time: screening through day 28

    Description: change from baseline in ordinal scale score; scale of 1-7; a score of 1 indicates death and 7 indicates subject is not hospitalized and has no limitations on activities.

    Measure: 7-point ordinal scale

    Time: screening, day 0, 3, 7, 10, 28

    Description: change from baseline in D-dimer

    Measure: D-dimer

    Time: screening, day 0, 7, 10

    Description: change from baseline chest x-ray result

    Measure: Chest X-ray

    Time: Day 0, Day 28

    Description: change from baseline CT scan result

    Measure: CT scan

    Time: Day 0, Day 28

    Description: time to achieve negative PCR test results

    Measure: PCR test for SARS-CoV-2

    Time: day 0, 3, 7, 10
    153 Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)

    This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

    NCT04362813
    Conditions
    1. Pneumonia and Cytokine Release Syndrome (Covid-19)
    Interventions
    1. Drug: Canakinumab
    2. Drug: Placebo
    MeSH:Pneumonia Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.

    Measure: Number of patients with clinical response

    Time: Day 3 to Day 29

    Secondary Outcomes

    Description: COVID-19-related death during the 4-week period after study treatment.

    Measure: COVID-19-related death rate during the 4-week period after study treatment

    Time: 4 weeks

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the C-reactive protein (CRP)

    Time: Baseline, Day 29

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the serum ferritin

    Time: Baseline, Day 29

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the D-dimer

    Time: Baseline, Day 29

    Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).

    Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs

    Time: 127 days
    154 A Pilot, Multiple Dose Study to Evaluate the Efficacy and Safety of MRx-4DP0004 in Hospitalised Patients With Symptoms of COVID-19 (SARS-CoV-2 Infection)

    This is a randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of MRx-4DP0004 in patients with COVID-19. 90 hospitalised patients will be enrolled and randomised (2:1) to receive MRx-4DP0004 or placebo for up to 14 days. MRx-4DP0004 is an immunomodulating Live Biotherapeutic Product (LBP) which is expected to prevent or reduce the hyperinflammatory response to SARS-CoV-2 infection without impairing viral clearance.

    NCT04363372
    Conditions
    1. COVID-19
    Interventions
    1. Drug: MRx-4DP0004
    2. Drug: Placebo

    Primary Outcomes

    Description: Clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement where patients are scored on a scale of 0-8 with 0 being uninfected and 8 being dead

    Measure: Change in mean clinical status score in each treatment arm

    Time: Baseline to Day 42

    Secondary Outcomes

    Description: Safety and tolerability will be determined according to clinically relevant reported adverse events

    Measure: Number of adverse events in each treatment arm

    Time: Baseline to Day 42

    Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement

    Measure: Number of patients with an improvement in clinical status score in each treatment arm

    Time: Day 1 to Day 42

    Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement

    Measure: Number of patients with a deterioration in clinical status score in each treatment arm

    Time: Day 1 to Day 42

    Description: Oxygen saturation will be measured as per local standard procedures

    Measure: Number of patients with at least 95% oxygen saturation on room air in each treatment arm

    Time: Day 1 to Day 14

    Description: Oxygen saturation will be recorded daily during hospitalisation to determine the mean time for each arm to reach at least 95% saturation

    Measure: Time to patients with at least 95% oxygen saturation on room air in each treatment arm

    Time: Day 1 to Day 14

    Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature

    Measure: Number of patients with an improvement in the National Early Warning Score (NEWS) 2 in each treatment arm

    Time: Day 1 to Day 14

    Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature

    Measure: Number of patients with an deterioration in the National Early Warning Score (NEWS) 2 in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout hospitalisation

    Measure: Number of patients requiring Continuous Positive Airway Pressure in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout the treatment period

    Measure: Number of patients requiring Intermittent Positive Pressure Ventilation in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout the treatment period

    Measure: Time to patients requiring Continuous Positive Airway Pressure in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout the treatment period

    Measure: Time to patients requiring Intermittent Positive Pressure Ventilation in each treatment arm

    Time: Day 1 to Day 14

    Description: Length of hospital stay will be compared

    Measure: Time to discharge in each treatment arm

    Time: Day 1 to Day 42

    Description: All cause mortality will be compared

    Measure: Number of deaths in each treatment arm

    Time: Day 1 to Day 42
    155 Hydroxychloroquine as Primary Prophylaxis for COVID-19 in Healthcare Workers (HCQPreP)

    This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.

    NCT04363450
    Conditions
    1. COVID-19
    2. Corona Virus Infection
    3. Wuhan Coronavirus
    4. Prophylaxis
    5. Healthcare Worker
    6. Sars-CoV2
    7. Hydroxychloroquine
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay

    Measure: Incidence of symptomatic COVID-19 infection in healthcare workers

    Time: 12 weeks

    Secondary Outcomes

    Description: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection

    Measure: Absenteeism from work due to COVID-19

    Time: 12 weeks

    Description: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)

    Measure: Severity of COVID-19 infection

    Time: 12 weeks
    156 A Randomized Placebo-controlled Safety and Dose-finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

    In this study Investigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.

    NCT04363502
    Conditions
    1. Covid19
    Interventions
    1. Drug: Clazakizumab
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Serum CRP (measured in mg/dl) will be evaluated at baseline and on days 1 and 2 following clazakizumab or placebo administration to assess response

    Measure: Change in C-reactive protein (CRP) level

    Time: Up to 3 days
    157 A Randomized-Control Pilot Study to Assess Hydroxychloroquine in Patients Infected With SARS-CoV-2 (COVID-19)

    This is a prospective, randomized, double-blinded, placebo-controlled, pilot study to assess the preliminary efficacy and safety of hydroxychloroquine for the treatment of patients with lower respiratory tract SARS-CoV-2 infection.

    NCT04363866
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Description: A 6-point ordinal scale ranging from "Death" to "Not hospitalized with full resumption of normal activities" is used to evaluate differences in the clinical status between participants that receive placebo vs hydroxychloroquine

    Measure: Clinical Status at Day 5 Assessed by a 6-Point Ordinal Scale

    Time: Day 5

    Secondary Outcomes

    Description: Assess differences in SARS-CoV-2 viral shedding between participants that receive placebo vs hydroxychloroquine

    Measure: Number of Participants with Detectable SARS-CoV-2 Virus from Day 0 to Day 28 and at Day 5

    Time: Day 0 to Day 28 and at Day 5

    Description: Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)

    Measure: Toxicity of Study Drug Assessed by Incidence of Adverse Events

    Time: Day 0 to Day 28

    Other Outcomes

    Description: Assess length of hospitalization

    Measure: Duration of Initial Hospitalization

    Time: Day 0 to Day 28

    Description: Assess number of deaths during study follow-up

    Measure: Mortality During Follow-Up

    Time: Day 0 to Day 28

    Description: Assess number of deaths in the hospital during initial hospitalization

    Measure: Mortality During Initial Hospitalization

    Time: Day 0 to Day 28

    Description: Assessing utilization of hospital resources

    Measure: Incidence of New Hospital Resource Utilization

    Time: Day 0 to Day 28

    Description: Assessing duration of hospital resource utilization

    Measure: Duration of Hospital Resource Utilization

    Time: Day 0 to Day 28

    Description: Provide preliminary characterization of differences in inflammatory response between participants that receive placebo vs hydroxychloroquine

    Measure: Changes in Cytokine Profile

    Time: Day 0 to Day 28
    158 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

    Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.

    NCT04365985
    Conditions
    1. COVID-19
    2. Acute Respiratory Distress Syndrome
    3. Severe Acute Respiratory Syndrome (SARS)
    4. Coronavirus Infections
    Interventions
    1. Drug: Naltrexone
    2. Drug: Ketamine
    3. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)

    Measure: Progression of oxygenation needs

    Time: up to 1 month

    Secondary Outcomes

    Description: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.

    Measure: Renal failure

    Time: up to 1 month

    Description: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits

    Measure: Liver failure

    Time: up to 1 month

    Description: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)

    Measure: Cytokine Storm

    Time: up to 1 month

    Description: Count of participants who die from COVID-19

    Measure: Mortality

    Time: up to 1 month post hospital discharge

    Description: Length of hospital stay in days

    Measure: Length of hospital stay

    Time: up to 1 month

    Description: Count of patients admitted to the ICU at any time during index hospitalization

    Measure: Intensive Care Unit (ICU) admission

    Time: up to 1 month

    Description: Length of ICU stay in days

    Measure: Intensive Care Unit (ICU) duration

    Time: up to 1 month

    Description: Count of participants requiring intubation

    Measure: Intubation

    Time: up to 1 month

    Description: Length of intubation, measured in days

    Measure: Intubation duration

    Time: up to 1 month

    Description: Time measured in days from hospital admission to determination patient is stable for discharge

    Measure: Time until recovery

    Time: up to 1 month
    159 A Randomized, Double-Blind, Placebo-Controlled, Phase 1/2 Study Evaluating AVM0703 in Patients With COVID-19

    This is a randomized, double-blind, placebo-controlled, single-ascending dose study of AVM0703 administered as a single intravenous (IV) infusion to patients with COVID-19. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single-ascending dosing of AVM0703 in patients with COVID-19.

    NCT04366115
    Conditions
    1. Covid19
    2. Acute Respiratory Distress Syndrome
    Interventions
    1. Drug: AVM0703
    2. Drug: Placebo
    3. Drug: hydrocortisone
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: The primary endpoint of the Phase 1 portion of the study is to evaluate the safety of AVM0703 in subjects with severe or life-threatening COVID-19 infection, and to identify the RP2D.

    Measure: Dose-Limiting Toxicities

    Time: 0-12 months

    Description: The primary endpoint of the Phase 1/2 portion of the study is to evaluate the efficacy of AVM0703 in subjects with severe or life-threatening COVID-19 infection.

    Measure: 28 day all-cause mortality will be a primary end point for Phase 1 and 2

    Time: 0-12 months
    160 A Phase 2/3 Study to Assess the Safety and Efficacy of MultiStem® Therapy in Subjects With Acute Respiratory Distress Syndrome (ARDS) Due to Coronavirus Disease (COVID-19)

    Multicenter investigation featuring an open-label lead-in followed by a double blinded, randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy of MultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.

    NCT04367077
    Conditions
    1. ARDS
    Interventions
    1. Biological: MultiStem
    2. Biological: Placebo

    Primary Outcomes

    Measure: Ventilator-Free Days

    Time: Day 0 through Day 28.

    Measure: Safety and Tolerability as measured by the incidence of treatment-emergent adverse events as assessed by CTCAE v5.0.

    Time: Day 28

    Secondary Outcomes

    Measure: All-cause mortality

    Time: Day 60

    Measure: Ranked hierarchical composite outcome of alive and ventilator-free

    Time: Day 28

    Measure: Ventilator-free days

    Time: Day 0 through Day 60
    161 A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY INDIVIDUALS

    This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals. The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part. The study will evaluate the safety, tolerability, and immunogenicity of 2 different SARS CoV 2 RNA vaccine candidates against COVID 19 and the efficacy of 1 candidate: - As a 2-dose (separated by 21 days) schedule; - At various different dose levels in Phase 1; - In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: ≥12 years of age [stratified as 12-15, 16-55 or >55 years of age]). The candidate selected for evaluation in Phase 2/3 is BNT162b2 (mid-dose).

    NCT04368728
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: BNT162b1
    2. Biological: BNT162b2
    3. Other: Placebo

    Primary Outcomes

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: Percentage of participants in Phase 1 reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: Percentage of participants in Phase 1 reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 1 reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 1 reporting serious adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values

    Time: 1 day after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 2

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 1 day after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 7 days after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between before dose 2 and 7 days after dose 2

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting serious adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 2/3 reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 2/3 reporting serious adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: As elicited by investigational site staff

    Measure: Percentage of participants 12-15 years of age in Phase 3 reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants 12-15 years of age in Phase 3 reporting adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Secondary Outcomes

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, expressed as GMCs

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, GMFR in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels from before vaccination to each subsequent time point

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 (anti-S1 and anti-RBD) binding antibody levels

    Time: Through 2 years after the final dose

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: As measured at the central laboratory

    Measure: GMR of SARS CoV 2 neutralizing titers in the 2 age groups (12-15 years of age to 16-25 years of age)

    Time: 1 month after the second dose
    162 A Single-blinded, Randomized, Placebo Controlled Phase II Trial of Prophylactic Treatment With Oral Azithromycin Versus Placebo in Cancer Patients Undergoing Antineoplastic Treatment During the Corona Virus Disease 19 (COVID-19) Pandemic

    Prophylactic treatment in cancer patients undergoing antineoplastic therapy during the COVID-19 pandemic.

    NCT04369365
    Conditions
    1. COVID
    Interventions
    1. Drug: Azithromycin 500 milligram (mg) oral Tablet
    2. Drug: Placebo
    MeSH:Virus Diseases Coronavirus Infections

    Primary Outcomes

    Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)

    Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections

    Time: 12 weeks after initiation of therapy

    Secondary Outcomes

    Description: defined as combined endpoint of hospitalization rate or death

    Measure: Number of severe COVID-19 cases

    Time: 12 weeks after initiation of therapy

    Description: grading as outlined by the world health organization (WHO)

    Measure: Severity of COVID-19 cases

    Time: 12 weeks after initiation of therapy

    Description: significant clinical and laboratory abnormalities according to CTCAE criteria

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time: 12 weeks after initiation of therapy

    Description: other than COVID-19

    Measure: Number of viral and bacterial infections

    Time: 12 weeks after initiation of therapy

    Description: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test

    Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test

    Time: 12 weeks after initiation of therapy
    163 A Single Center, Double-blinded, ,Placebo-controlled Phase I Clinical Trial in Healthy Volunteer to Evaluate Tolerance and Pharmacokinetics of Meplazumab of Injection

    This is a single center, double-blinded, placebo-controlled phase I clinical trail in healthy volunteer of meplazumab for injection. The primary objective of this phase I trial is to evaluate the safety, tolerability, pharmacokinetic characteristics and occupancy characteristics of peripheral blood cell receptors of meplazumab in healthy volunteer, and provide a reference for the dosage of meplazumab in phase II clinical trial.

    NCT04369586
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: meplazumab for injection
    2. Drug: Placebo

    Primary Outcomes

    Description: Nature, incidence, and severity of AEs/SAEs, and the relationship to meplazumab treatment.

    Measure: Incidence rate of treatment-related adverse events as assessed by CTCAE v5.0

    Time: 0-28 days

    Secondary Outcomes

    Description: AUC0-tn

    Measure: Pharmacokinetic assessments of meplazumab- AUC0-tn

    Time: 0-28 days

    Description: AUC0-∞

    Measure: Pharmacokinetic assessments of meplazumab- AUC0-∞

    Time: 0-28 days

    Measure: Pharmacokinetic assessments of meplazumab-half life time

    Time: 0-28 days

    Description: Maximum observed plasma concentration of meplazumab (Cmax)

    Measure: Pharmacokinetic assessments of meplazumab-Cmax

    Time: 0-28 days
    164 COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement

    To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).

    NCT04369794
    Conditions
    1. COVID-19
    2. Therapeutic Vaccine
    3. BCG
    4. SARS-CoV 2
    5. Transmission
    Interventions
    1. Biological: BCG
    2. Biological: Placebo

    Primary Outcomes

    Description: Classified as mild, moderate and severe

    Measure: Clinical evolution of COVID-19

    Time: 45 days of symptoms onset or diagnosis

    Description: Virus detection by PCR

    Measure: SARS-CoV-2 elimination

    Time: 7 days of symptoms onset or diagnosis

    Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Measure: Seroconversion rate and titration

    Time: 7 days of symptoms onset or diagnosis

    Secondary Outcomes

    Description: Classified according to type and severity

    Measure: Local and systemic adverse events to BCG vaccination

    Time: 3 months

    Other Outcomes

    Description: Virus detection by PCR

    Measure: SARS-CoV-2 elimination

    Time: 21 days of symptoms onset or diagnosis

    Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Measure: Seroconversion rate

    Time: 21 days of symptoms onset or diagnosis

    Description: Virus detection by PCR

    Measure: SARS-CoV-2 elimination

    Time: 45 days of symptoms onset or diagnosis

    Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Measure: Seroconversion rate and titration

    Time: 45 days of symptoms onset or diagnosis
    165 A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of INB03 in the Treatment of Participants With Pulmonary Complications From Coronavirus Disease (COVID-19)

    The purpose of this study is to determine whether XPro1595 can prevent the progression of respiratory complications in COVID19 patients.

    NCT04370236
    Conditions
    1. COVID-19
    Interventions
    1. Drug: INB03
    2. Drug: Placebo

    Primary Outcomes

    Description: Disease progression is defined by the development of need for mechanical ventilation or death. Mechanical ventilation includes CPAP, BIPAP or mechanical ventilation requiring intubation.

    Measure: Proportion of participants with disease progression from randomization to 28 days post-randomization

    Time: 28 days

    Secondary Outcomes

    Measure: Proportion of participants with all-cause mortality

    Time: 28 days

    Measure: Proportion of participants who transfer to ICU level care by Day 28 (ICU level care is defined as a hospital setting where patient to nurse ratio is < 4);

    Time: 28 days

    Measure: Proportion of participants with a new onset of neurologic disease (requiring medical intervention), including stroke by Day 28;

    Time: 28 days

    Measure: Proportion of participants with evidence of new CHF or new MI requiring medical intervention by Day 28;

    Time: 28 days

    Measure: Proportion of participants with a new onset embolus or thrombus by Day 28;

    Time: 28 days

    Measure: Proportion of participants who develop a need for renal replacement therapy (defined as need for any type of dialysis including intermittent or continuous peritoneal or hemodialysis) by Day 28;

    Time: 28 days

    Measure: Proportion of participants with an increase in the WHO Ordinal Scale of Clinical Improvement score at any time during the study;

    Time: 28 days

    Measure: Length of hospital stay defined as the number of days in hospital from time of randomization to time of discharge or death, whichever occurs first;

    Time: 28 days

    Measure: Change from baseline in inflammation markers over time.

    Time: 28 days

    Other Outcomes

    Measure: Incidence of adverse events and serious adverse events not due to underlying disease

    Time: 28 days

    Measure: Incidence of abnormal findings in clinical safety laboratory parameters, vital signs, and ECGs.

    Time: 28 days
    166 A Double-blind, Randomized Study Versus Placebo of Avdoralimab (IPH5401), an Anti-C5aR Antibody, in Patients With COVID-19 Severe Pneumonia

    The primary objective of this trial is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by acute respiratory distress syndrome (ARDS).

    NCT04371367
    Conditions
    1. COVID
    Interventions
    1. Biological: avdoralimab
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: improvement of WHO ordinal scale

    Measure: Clinical improvement using WHO ordinal scale

    Time: day 28

    Description: Number of days without mechanical ventilation at Day 28 for COVID-19 related Acute Respiratory Distress Syndrome (ARDS) Patients hospitalized in ICU

    Measure: Number of ventilator-free days at Day 28 (VFD28)

    Time: day 28

    Secondary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: day 28
    167 Mesenchymal Stromal Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome

    The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

    NCT04371393
    Conditions
    1. Mesenchymal Stromal Cells
    2. Remestemcel-L
    3. Acute Respiratory Distress Syndrome
    4. COVID
    Interventions
    1. Biological: Remestemcel-L
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Number of all-cause mortality within 30 days of randomization.

    Measure: Number of all-cause mortality

    Time: 30 days

    Secondary Outcomes

    Description: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.

    Measure: Number of days alive off mechanical ventilatory support

    Time: 60 days

    Description: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.

    Measure: Number of adverse events

    Time: 30 days

    Measure: Number of participants alive at day 7

    Time: 7 days

    Measure: Number of participants alive at day 14

    Time: 14 days

    Measure: Number of participants alive at day 60

    Time: 60 days

    Measure: Number of participants alive at day 90

    Time: 90 days

    Measure: Number of participants alive at 12 Months

    Time: 12 Months

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 7

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 7 days

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 14

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 14 days

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 21

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 21 days

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 30

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 30 days

    Description: severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 7 days

    Description: severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 14 days

    Description: severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 21 days

    Description: severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 30 days

    Description: Hospital length of stay

    Measure: Length of stay

    Time: 12 months

    Description: number of readmission

    Measure: Readmissions

    Time: 12 months

    Measure: Length of Stay in Intensive Care Unit

    Time: 12 months

    Description: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 7 days

    Description: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 14 days

    Description: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 21 days

    Description: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 30 days

    Description: Changes from baseline in plasma hs-CRP concentration at days 7

    Measure: Change in plasma hs-CRP concentration

    Time: baseline and 7 days

    Description: Changes from baseline in plasma hs-CRP concentration at days 14

    Measure: Change in plasma hs-CRP concentration

    Time: baseline and 14 days

    Description: Changes from baseline in plasma hs-CRP concentration at days 21

    Measure: Change in plasma hs-CRP concentration

    Time: baseline and 21 days

    Description: Changes from baseline in serum hs-CRP concentration at days 30

    Measure: Change in serum hs-CRP concentration

    Time: baseline and 30 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 7 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 14 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 21 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 30 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 7 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 21 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 14 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 30 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 7 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 7 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 14 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 14 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 21 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 21 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 30 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 30 days

    Description: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization

    Measure: Pulmonary symptoms

    Time: 6 months

    Description: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization

    Measure: Pulmonary symptoms

    Time: 12 months
    168 A Randomized, Double-Blinded, Placebo-Controlled Trial Evaluating the Virological Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sirolimus Adjuvant Therapy in Patients With Coronavirus Disease (COVID-19)

    This is a double-blinded, two-arm, randomized, placebo controlled study comparing the virological efficacy of add-on sirolimus with standard care to placebo and standard care. Virological efficacy is defined as the change from baseline to day 7 in SARS-CoV-2 viral burden measured by quantitative real-time polymerase chain reaction.

    NCT04371640
    Conditions
    1. SARS-CoV-2
    2. Covid-19
    Interventions
    1. Drug: Sirolimus 1 MG/ML
    2. Drug: Placebo

    Primary Outcomes

    Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR

    Measure: Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment

    Time: Baseline, and days 1, 2, 3, 4, 5, 6, & 7 post-dose for all patients

    Secondary Outcomes

    Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR

    Measure: Change in SARS-CoV-2 viral burden at days 1-6

    Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patients

    Description: Safety and tolerability of sirolimus in patients with COVID-19

    Measure: Rate of treatment emergent adverse events

    Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patients
    169 Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study

    The aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of reducing or even abolishing the cytokine explosion and thus the evolution towards a serious form of the disease which can lead to death. Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival. Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may also be able to inhibit the replication of positive-polarity single-stranded RNA viruses, such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property used in the treatment of inflammatory skin diseases for many years. These modulating effects are noted on several targets of innate immunity: They can decrease the expression of NFKB, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and free radical release. Tetracyclines could therefore participate in limiting the cytokine release induced by COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to inhibit viral replication.

    NCT04371952
    Conditions
    1. COVID19
    Interventions
    1. Drug: Doxycycline
    2. Drug: Placebo

    Primary Outcomes

    Description: Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment

    Measure: Percentage of Patients with Clinical Respiratory Aggravation

    Time: after at least 48 hours of treatment

    Description: Percentage of patients hospitalized after at least 48 hours of experimental treatment

    Measure: Percentage of patients hospitalized

    Time: after at least 48 hours of experimental treatment

    Description: Percentage of patients requiring ventilatory assistance

    Measure: Percentage of patients requiring ventilatory assistance

    Time: Day 0 to Day 28

    Secondary Outcomes

    Description: Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)

    Measure: Positive SARS-CoV-2 PCR Test

    Time: Day -1 or day 0 AND Day 7

    Description: Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)

    Measure: Duration of symptoms

    Time: Day 0 to Day 28

    Description: Total duration of hospitalization

    Measure: Duration of hospitalization

    Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

    Description: Duration of hospitalization in intensive care or reanimation

    Measure: Hospitalization intensive care or reanimation

    Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

    Description: Duration of mechanical ventilatory assistance

    Measure: Duration of mechanical ventilatory assistance

    Time: to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0

    Description: Percentage of deaths related to SARS-CoV-2 infection

    Measure: Percentage of deaths related to SARS-CoV-2

    Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)

    Description: Number of AE / SAE in both arms

    Measure: AE / SAE in both arms

    Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)
    170 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia

    This study (EMPACTA) will a) evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia, and b) include an optional substudy to explore the long-term sequelae of resolved COVID-19 pneumonia.

    NCT04372186
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Placebo
    2. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28

    Time: Up to Day 28

    Secondary Outcomes

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

    Time: Up to Day 28

    Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

    Time: Up to Day 28

    Measure: Mortality Rate by Day 28

    Time: Up to Day 28

    Measure: Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen)

    Time: Up to Day 28

    Measure: Percentage of Participants with Adverse Events

    Time: Up to Day 60

    Measure: Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection

    Time: Up to Day 60

    Measure: Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline)

    Time: Up to Day 60
    171 A Pilot Study of Duvelisib to Combat COVID-19

    The exceedingly high mortality rates of severe and critical COVID-19 warrant the identification and evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. Based on preclinical data from this institution and others, the investigators hypothesize that PI3K inhibition with duvelisib could potentially quell aberrant hyperactivtation of the innate immune system, preferentially polarize macrophages, reduce pulmonary inflammation, and limit viral persistence, thereby improving patient outcomes.

    NCT04372602
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Duvelisib
    2. Procedure: Peripheral blood draw
    3. Drug: Placebo

    Primary Outcomes

    Measure: Overall survival

    Time: Through 28 days

    Secondary Outcomes

    Measure: Length of hospital stay

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Length of ICU stay

    Time: Through completion of follow-up (estimated to be 7 months)

    Description: -For those on a ventilator at the time of randomization

    Measure: Duration of ventilator use

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Duration of vasopressors use

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Duration on renal replacement therapy

    Time: Through completion of follow-up (estimated to be 7 months)

    Description: -Defined as increase in viral load of >0.5 log on two consecutive days, or >1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing

    Measure: Viral kinetics as measured by virologic failure

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Number of adverse events as measured by CTCAE v. 5.0

    Time: Through completion of follow-up (estimated to be 7 months)
    172 Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19

    Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19

    NCT04372628
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Lopinavir/Ritonavir 400 mg/100 mg
    2. Other: Placebo

    Primary Outcomes

    Description: Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial

    Measure: Modified COVID Ordinal Outcomes Scale: Study Day 15

    Time: Day 15

    Secondary Outcomes

    Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity

    Measure: Modified COVID Ordinal Outcome Scale: Study Day 8

    Time: Day 8

    Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale

    Measure: Modified COVID Ordinal Outcome Scale: Study Day 29

    Time: Day 29

    Description: Proportion hospitalized

    Measure: Proportion of patients hospitalized: Day 1 to 29

    Time: Day 1 to Day 29

    Description: Number of days from enrollment to hospitalization

    Measure: Time to hospitalization Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days from enrollment to resolution of COVID-19 symptoms

    Measure: Time to symptom resolution: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Survival status

    Measure: All-cause, all-location mortality: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of Days without oxygen

    Measure: Oxygen-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days without fever

    Measure: Fever-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days without ventilator use

    Measure: Ventilator-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days outside the ICU

    Measure: ICU-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days outside the hospital

    Measure: Hospital-free days: Day 1 to Day 29

    Time: Day 1 to Day 29
    173 RCT in Asymptomatic Volunteers With COVID-19 Comparing Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone vs Standard of Care Without Antibiotics

    The coronavirus disease-2019 (COVID-19) is spreading throughout the United States. While there are no known therapies to treat those who have become sick, there have been some reports that a medication currently used to treat rheumatoid arthritis, lupus, and malaria (Hydroxychloroquine sulfate, also known as Plaquenil) may help to lessen the chance or severity of illness, especially if combined with a medicine that treats other kinds of infections (Azithromycin, also known as Zithromax or Zmax or Zpak). There are some people who test positive for the virus but who are otherwise not ill. Current standard of care is to advise these people to self-monitor but no treatment is offered. It is not known how many of these individuals will remain symptom free, and how many will become sick or how severe those symptoms will be. This study will randomize those people who do not have symptoms into one of three treatment plans 1) Hydroxycholoquine and Azithromycin, or 2) no active medication (placebo). All participants will be followed for 2 months. The study will determine if there is any benefit to those who are asymptomatic to taking taking Hydroxychloroquine sulfate in combination with Azithromycin, or if there is no benefit from taking these medications.

    NCT04374552
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: Hydroxychloroquine sulfate &Azithromycin
    2. Drug: Placebo

    Primary Outcomes

    Description: Change in SARS-CoV-2 viral from baseline to day 6

    Measure: The primary outcome is the rate of decline in viral load over the 10 days after randomization

    Time: 10 days
    174 IbrutiNib in SARS CoV-2 Induced Pulmonary Injury and Respiratory Failure (iNSPIRE)

    Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection. Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States. Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care. There may be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

    NCT04375397
    Conditions
    1. CoronaVirus Induced Disease-2019 (COVID-19)
    Interventions
    1. Drug: Ibrutinib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Insufficiency Lung Injury

    Primary Outcomes

    Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

    Measure: Percentage of Participants Alive and Without Respiratory Failure

    Time: Day 28

    Secondary Outcomes

    Description: WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).

    Measure: Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline

    Time: Day 14

    Description: Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.

    Measure: Median Reduction in Days Spent on Supplemental Oxygen

    Time: Up to Day 28

    Description: Percentage of participants with mortality from any cause.

    Measure: All-Cause Mortality

    Time: Up to Day 28

    Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

    Measure: Percentage of Participants Experiencing Respiratory Failure or Death

    Time: Up to Day 28

    Description: Percentage of participants alive and not requiring mechanical ventilation.

    Measure: Mechanical Ventilation-Free Survival

    Time: Up to Day 56

    Description: Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.

    Measure: Days on Mechanical Ventilation

    Time: Up to Day 56

    Description: The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.

    Measure: Duration of hospitalization

    Time: Up to Day 56

    Description: Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.

    Measure: Time to Discharge

    Time: Up to Day 56

    Description: PaO2:FiO2 ratio is an index of respiratory distress.

    Measure: Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio

    Time: Up to Day 56

    Description: Oxygenation Index is a parameter of pulmonary function of participants.

    Measure: Oxygenation Index

    Time: Up to Day 56

    Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

    Measure: Number of Participants With Adverse Events

    Time: Up to Day 56

    Description: Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measure: Number of Participants With Abnormal Laboratory Findings

    Time: Up to Day 56
    175 A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease

    OSCAR (Otilimab in Severe COVID-19 Related Disease) is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. Otilimab is a human monoclonal anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of participants with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.

    NCT04376684
    Conditions
    1. Severe Acute Respiratory Syndrome
    Interventions
    1. Biological: Otilimab
    2. Biological: Placebo
    3. Drug: Standard of care
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections

    Primary Outcomes

    Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Proportion of participants alive and free of respiratory failure at Day 28

    Time: Day 28

    Secondary Outcomes

    Description: Number of deaths due to all causes will be assessed.

    Measure: Number of deaths due to all causes at Day 60

    Time: Day 60

    Description: Time to death due to all causes will be assessed.

    Measure: Time to number of deaths due to all causes up to Day 60

    Time: Up to Day 60

    Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Proportion of participants alive and free of respiratory failure at Days 7, 14, 42 and 60

    Time: Days 7, 14, 42, and 60

    Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Time to recovery from respiratory failure

    Time: Up to Day 28

    Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Proportion of participants alive and independent of supplementary oxygen at Days 7, 14, 28, 42, and 60

    Time: Days 7, 14, 28, 42, and 60

    Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Time to last dependence on supplementary oxygen

    Time: Up to Day 28

    Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.

    Measure: Proportion of participants admitted to Intensive Care Unit (ICU)

    Time: Up to Day 28

    Description: Defined as the time from dosing to when the participant is discharged from the ICU.

    Measure: Time to final ICU discharge

    Time: Up to Day 28

    Description: Time from dosing to when a participant is discharged from the hospital.

    Measure: Time to final hospital discharge

    Time: Up to Day 28

    Description: AEs and SAEs will be collected.

    Measure: Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)

    Time: Up to Day 60
    176 A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)

    The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.

    NCT04377620
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Placebo
    2. Drug: Ruxolitinib

    Primary Outcomes

    Description: To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.

    Measure: Proportion of participants who have died due to any cause

    Time: Up to Day 29

    Secondary Outcomes

    Description: Number of days participant did not require mechanical ventilation

    Measure: Number of Ventilator free days

    Time: Day 29

    Description: Number of days participant is out of the ICU

    Measure: Number of ICU free days

    Time: Day 29

    Description: Number of days participant did not receive supplemental oxygen

    Measure: Oxygen free days

    Time: Day 29

    Description: Number of days without use of vasopressor therapy

    Measure: Vasopressor free days

    Time: Day 29

    Description: Number of days Partcipant is out of the hospital

    Measure: Hospital free days

    Time: Day 29

    Description: Clinical status of participant at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

    Measure: Improvement in the COVID-19 ordinal scale

    Time: Day 15 and 29

    Description: SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems.

    Measure: Change in SOFA Score

    Time: from baseline to Days 3, 5, 8, 11, 15, and 29

    Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

    Measure: Number of treatment-related adverse events

    Time: Day 29
    177 A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Ciclesonide Metered-Dose Inhaler in Non-hospitalized Patients 12 Years of Age and Older With Symptomatic COVID-19 Infection

    The purpose of this study is to assess the safety and efficacy of Alvesco (ciclesonide) Inhalation Aerosol in non hospitalized patients with symptomatic COVID-19 infection in a multicenter, randomized, double-blind, placebo controlled study

    NCT04377711
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ciclesonide
    2. Drug: Placebo

    Primary Outcomes

    Measure: Percentage of patients hospital admission or death by day 30

    Time: Day 30

    Secondary Outcomes

    Measure: All-cause mortality by day 30

    Time: Day 30

    Measure: COVID-19-related mortality by day 30

    Time: Day 30

    Measure: Percentage of patients with subsequent emergency department visit or hospital admission for reasons attributable to COVID 19 by day 30

    Time: Day 30

    Measure: Time to hospital admission or death

    Time: Day 30

    Measure: Time to alleviation of COVID-19-related symptoms of cough, dyspnea, chills, and feeling feverish, defined as symptom-free for a continuous period of more than 24 hours (ie, > 3 AM/PM assessments)

    Time: Day 30

    Measure: Change from baseline in oxygen saturation levels

    Time: Day 30

    Measure: Change from baseline in COVID-19 viral load in nasopharyngel sample nasal secretions at day 30

    Time: Day 30

    Measure: Safety will be assessed based on adverse events.

    Time: Day 60
    178 A Prospective, Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19

    At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood. Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.

    NCT04379271
    Conditions
    1. COVID-19
    Interventions
    1. Drug: IMU-838
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Clinical

    Measure: Proportion of patients without any need* for INV until end-of-study (EoS)

    Time: Throughout the Study (Day 0 to Day 28)

    Secondary Outcomes

    Description: Key Secondary

    Measure: Duration of ICU treatment until EoS

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Key Secondary

    Measure: 28-day all-cause mortality

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy: defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9 category ordinal scale , or live discharge from hospital without oxygen supplementation, whichever comes first

    Measure: Time to clinical improvement

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy: Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)

    Measure: Duration of hospitalization

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients both for all patients and surviving patients free of renal-replacement therapy (RRT)* until EoS

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)* until EoS

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients free of INV until Days 6 and 14*

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients free of RRT until Days 6 and 14*

    Time: Day 0 to Days 6 and 14

    Description: Efficacy

    Measure: Proportion of patients free ECMO until Days 6 and 14*

    Time: Day 0 to Days 6 and 14

    Description: Efficacy

    Measure: Proportion of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Proportion of patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Proportion of patients with clinical recovery: Axillary temperature ≤36.6 ℃, or oral temperature ≤37.2 ℃, or rectal or tympanic temperature ≤37.8 ℃;

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients with clinical recovery: Respiratory frequency ≤24 times/min without oxygen inhalation; and

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients with clinical recovery: Oxygen saturation ≥98% without oxygen inhalation

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Duration of INV

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Duration of ECMO

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Duration of RRT

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Duration of auxiliary oxygen therapy (including all types of oxygen therapy)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Duration of hospitalization for survivors

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: The rate of ICU* admission on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Hospital-free days

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time from IMP treatment initiation to death

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of INV

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of RRT

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of ECMO

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of INV, RRT, and ECMO

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to ICU admission

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Cumulative dose of vasoactive therapies and days with vasoactive therapies (daily until Day 14)

    Time: Day 0 to day 14

    Description: Efficacy

    Measure: Time to clinical recovery

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Pharmacokinetics

    Measure: Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28

    Time: on Days 0, 1, 2, 3, 6, 14, and 28

    Description: Pharmacokinetics

    Measure: Correlation of trough levels (quartiles) to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

    Time: on Days 0, 1, 2, 3, 6, 14, and 28

    Description: Safety

    Measure: Adverse events (AEs) and serious AEs

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: height

    Time: only at Screening

    Description: Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: weight

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: body temperature (ºC)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Pulse must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: pulse rates,

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Blood pressure (systolic and diastolic) must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: systolic and diastolic blood pressures

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: Clinical laboratory parameters: blood chemistry

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: Clinical laboratory parameters: hematology

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: Clinical laboratory parameters: urinalysis

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: 12-lead electrocardiogram: heart rate

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: PQ-interval

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: QRS-interval

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: QT interval

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: the heart rate-corrected QTc interval (according to Bazett's formula)

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: Temperature

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: D-dimer

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Lactate dehydrogenase (LDH)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: C-reactive protein

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Troponin I

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Procalcitonin

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Correlation of disease markers to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Decrease of SARS-CoV-2 viral load

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Qualitative virologic clearance in spontaneous sputum and nasopharyngeal swab samples (= 2 consecutive negative SARS-CoV-2 reverse transcriptase polymerase chain reaction tests at least 24 hours apart)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Rate of conversion to a negative SARS-CoV-2 (qualitative) test on Days 6, 14 and 28

    Time: on Days 6, 14 and 28

    Description: Virologic markers

    Measure: Time to conversion to a negative SARS-CoV-2 (qualitative) test

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Biomarkers

    Measure: Interleukin (IL)-17

    Time: Day 0, 6, 14 and Day 28

    Description: Biomarkers

    Measure: Interleukin (IL)-1ß

    Time: Day 0, 6, 14 and Day 28

    Description: Biomarkers

    Measure: Interleukin (IL)-6

    Time: Day 0, 6, 14 and 28

    Description: Biomarkers

    Measure: interferon gamma (IFNγ)

    Time: Day 0, 6, 14 and 28

    Description: Biomarkers

    Measure: tumor necrosis factor alpha

    Time: Day 0, 6, 14 and 28

    Description: Serologic markers

    Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Time to appearance of IgA and/or IgG antibodies

    Time: Day 0, 6, 14 and 28

    Description: Serologic markers

    Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Proportion of patients with IgA and/or IgG antibodies on Days 6, 14, and 28

    Time: Day 0, 6, 14 and 28
    179 Single-center, Phase II, Randomized Double-blind, Placebo-controlled Study of Hydroxychloroquine Compared to Placebo as Treatment for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

    This study is being done to see if hydroxychloroquine is an effective treatment for COVID-19.

    NCT04379492
    Conditions
    1. COVID-19
    2. COVID19
    3. Sars-CoV2
    4. SARS-Cov-2
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo

    Primary Outcomes

    Description: Clinical improvement is defined as a composite endpoint of a two-point clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19

    Measure: Clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI)

    Time: 14 days

    Description: Clinical improvement is defined as no mechanical ventilation for respiratory failure attributed to SARS-CoV-2 within 14 days of randomization.

    Measure: Number of participants requiring mechanical ventilation for respiratory failure

    Time: 14 days
    180 An International, Multicenter, Randomized, Double-blind, Adaptive Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe SARS-CoV-2 Infection (COVID-19)

    The primary objective of the study is to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study

    NCT04380519
    Conditions
    1. COVID-19
    Interventions
    1. Biological: RPH-104 80 mg
    2. Drug: Olokizumab 64 mg
    3. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of patients, responded to the study therapy, in each of the treatment groups. The patient can be considered as the therapy responder, in case tocilizumab or sarilumab were not administered and there is an improvement of a clinical status at least by 1 point on a 6-points COVID-19 scale, where 1 point means most favorable outcome, 6 points means most undesirable outcome.

    Measure: Proportion of patients, responded to the study therapy, in each of the treatment groups

    Time: Day 15

    Secondary Outcomes

    Description: Changes of patients' clinical status on a 6 points ordinal scale over time

    Measure: Changes of patients' clinical status on a 6 points ordinal scale over time

    Time: from Day 2 until Day 15, Day 29

    Description: Mortality rate over the follow-up period

    Measure: Mortality rate over the follow-up period

    Time: from Day 1 until Day 29

    Description: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.

    Measure: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.

    Time: on screening and then from Day 1 until Day 29

    Description: Proportion of patients received tocilizumab or sarilumab due to COVID-19

    Measure: Proportion of patients received tocilizumab or sarilumab due to COVID-19

    Time: from Day 1 until the Day 29

    Other Outcomes

    Description: Proportion of patients having National Early Warning Score 2 (NEWS2) of ≤ 4 maintained for 2 consecutive days

    Measure: Proportion of patients having National Early Warning Score 2 of ≤ 4 maintained for 2 consecutive days

    Time: from day 3 until day 15

    Description: Time to a NEWS2 of ≤ 2 maintained for two consecutive days

    Measure: Time to a NEWS2 of ≤ 2 maintained for two consecutive days

    Time: from day 1 until day 15

    Description: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, CRP, ferritin (if applicable), D-dimer (if applicable)

    Measure: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable)

    Time: Day 2, Day 3, Day5, Day 7, Day 15

    Description: Mortality during an ICU stay, on days 7, 15, 29 of the study

    Measure: Mortality during an ICU stay, on days 7, 15, 29 of the study

    Time: On Day 7, Day 15, Day 29

    Description: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days

    Measure: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days

    Time: from Day 2 until Day 15

    Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period

    Measure: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period

    Time: On Day 1 and from Day 2 until Day 15

    Description: Duration of ICU stay measured in days

    Measure: Duration of ICU stay measured in days

    Time: from Day 2 until Day 15

    Description: Changes from baseline (if applicable) in severity of ARDS according to WHO criteria

    Measure: Changes from baseline (if applicable) in severity of Acute Respiratory Distress Syndrome (ARDS) according to World Health Organization (WHO) criteria

    Time: from Day 1 until Day 15

    Description: Duration of mechanical ventilation and EMO (if applicable) measured in days

    Measure: Duration of mechanical ventilation and Extracorporeal Membrane Oxygenation (EMO) (if applicable) measured in days

    Time: from Day 2 until Day 15

    Description: Duration of oxygen support (if applicable) measured in days

    Measure: Duration of oxygen support (if applicable) measured in days

    Time: from Day 1 until Day 15

    Description: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days

    Measure: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days

    Time: from day 3 until day 15

    Description: Time to a NEWS2 of ≤ 4 maintained for two consecutive days

    Measure: Time to a NEWS2 of ≤ 4 maintained for two consecutive days

    Time: from day 1 until day 15

    Description: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)

    Measure: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)

    Time: On Day 1 and from Day 2 until Day 15

    Description: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)

    Measure: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)

    Time: from day 1 until day 15

    Description: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale

    Measure: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale

    Time: from day 1 until day 29

    Description: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale

    Measure: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale

    Time: from day 1 until day 29

    Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study

    Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study

    Time: from Day 1 until Day 29

    Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable

    Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable

    Time: from Day 1 until Day 29

    Description: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)

    Measure: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)

    Time: from Day 1 until Day 29
    181 Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical COVID-19 Disease

    The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.

    NCT04380961
    Conditions
    1. Severe or Critical Confirmed Coronavirus Disease (COVID)-19
    Interventions
    1. Drug: Sirukumab
    2. Drug: Placebo
    3. Other: Standard of Care (SOC)
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Time to improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale. The 6-point ordinal clinical recovery scale provides 6 mutually exclusive conditions ordered from best to worst, and the score reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are : not hospitalized (category 1); Hospitalization; not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO (category 5); death (category 6).

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale

    Time: Up to Day 28

    Secondary Outcomes

    Description: Percentage of participants with an improvement of at Least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.

    Measure: Percentage of Participants with an Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28

    Time: Day 28

    Description: Percentage of participants with all-cause mortality will be reported.

    Measure: Percentage of Participants with All-cause Mortality

    Time: Up to Day 28

    Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.

    Measure: Percentage of Participants with Serious Adverse Events (SAEs)

    Time: Up to Day 28

    Description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Percentage of Participants with Related Adverse Events

    Time: Up to Day 28

    Description: Percentage of participants with severe or life-threatening, bacterial, invasive fungal, viral or opportunistic infections (other than severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) will be reported.

    Measure: Percentage of Participants with Severe or Life Threatening Bacterial, Invasive Fungal, Viral or Opportunistic Infections

    Time: Up to Day 28

    Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) neutropenia will be reported.

    Measure: Percentage of Participants with Grade 3 and 4 Neutropenia

    Time: Up to Day 28

    Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) lymphocytopenia will be reported.

    Measure: Percentage of Participants with Grade 3 and 4 Lymphocytopenia

    Time: Up to Day 28

    Description: Percentage of participants with increased ALT >=3 times ULN combined with increased bilirubin >2 times ULN (up to Day 28) will be reported.

    Measure: Percentage of Participants with Increased Alanine Aminotransferase (ALT) Greater than or equal to 3 Times Upper Limit of Normal (ULN) Combined with Increased Bilirubin > 2 Times ULN

    Time: Up to Day 28

    Description: Time to improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale will be reported.

    Measure: Time to Improvement of at least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale

    Time: Up to Day 28

    Description: Percentage of participants with an improvement of at Least 1 category relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.

    Measure: Percentage of Participants with an Improvement of at Least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28

    Time: Day 28

    Description: Time from study intervention to end of oxygen supplementation is defined as achieving category 1 or 2 on the 6-point ordinal clinical recovery scale.

    Measure: Time from Study Intervention to end of Oxygen Supplementation

    Time: Up to Day 28

    Description: Time from study intervention to hospital discharge among the surviving participants will be reported.

    Measure: Time from Study Intervention to Hospital Discharge Among the Surviving Participants

    Time: Up to Day 28

    Description: Total length of hospitalization (days from admission to hospital discharge) among the surviving participants will be reported.

    Measure: Total Length of Hospitalization

    Time: Up to Day 28

    Description: Number of Ventilation free Days will be reported.

    Measure: Number of Ventilation Free Days

    Time: Up to Day 28

    Description: Participant's clinical status at Day 7, 14, 21, 28 will be assessed by 6-point ordinal clinical recovery scale.

    Measure: Participant's Clinical Status at Day 7, 14, 21, 28 as Assessed by 6-Point Ordinal Clinical Recovery Scale

    Time: Day 7, 14, 21, 28

    Description: Total time on invasive mechanical ventilation will be reported.

    Measure: Total Time on Invasive Mechanical Ventilation

    Time: Up to Day 28

    Description: Percentage of participants with a worsening of at least 1 category on the 6-point ordinal clinical recovery scale over time (between Day 5 and Day 28) will be reported.

    Measure: Percentage of Participants with a Worse Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale over Time

    Time: From Day 5 up to Day 28

    Description: Percentage participants on ECMO over time will be reported.

    Measure: Percentage of Participants on Extracorporeal Membrane Oxygenation (ECMO) Over Time

    Time: Up to Day 28

    Description: Total time on ECMO will be reported.

    Measure: Total Time on ECMO

    Time: Up to Day 28

    Description: Percentage of alive participants at Day 28, Week 8 and Week 16 will be reported.

    Measure: Percentage of Alive Participants at Day 28, Week 8 and Week 16

    Time: Day 28, Week 8 and Week 16

    Description: Percentage of alive participants that required readmission (if previously discharged) at Week 8 and Week 16 will be reported.

    Measure: Percentage of Alive Participants that Required Readmission at Week 8 and Week 16

    Time: Week 8 and Week 16

    Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.

    Measure: Percentage of Participants with Serious Adverse Events (SAEs)

    Time: Up to Week 16
    182 A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

    In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.

    NCT04381052
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Clazakizumab
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Measure: Cumulative incidence of serious adverse events associated with clazakizumab or placebo

    Time: 60 days

    Secondary Outcomes

    Measure: Cumulative Incidence of Intubation

    Time: 14 days

    Measure: Time to Extubation

    Time: 14 days

    Measure: Length of Intensive Care Unit (ICU) stay

    Time: 14 days

    Measure: Number of Patients who Present a Decrease in C-reactive protein (CRP)

    Time: 14 days

    Measure: Number of Patients with Acute Kidney Injury (AKI)

    Time: 14 days

    Measure: Number of Patients with a Need for Renal Replacement Therapy (RRT)

    Time: 14 days

    Measure: Duration of Renal Replacement Therapy (RRT)

    Time: 60 days

    Description: Number of participants alive at day 28.

    Measure: Patient Survival

    Time: 28 days

    Description: Number of participants alive at day 60, end of study.

    Measure: Patient Survival

    Time: 60 days

    Measure: Number of Patients with Hemodialysis

    Time: 60 days

    Measure: Number of Patients with Continuous Renal Replacement Therapies (CRRT)

    Time: 60 days

    Measure: Number of Patients with Peritoneal Dialysis

    Time: 60 days
    183 A Multi-centre, Adaptive, Randomized, Double-blind, Placebo-controlled Comparative Clinical Study of the Safety and Efficacy of Polyoxidonium®, Lyophilizate for Solution for Injections and Topical Application, 6 mg (NPO Petrovax Pharm LLC, Russia) in Patients With Coronavirus Disease (COVID-19).

    The purpose of this study is to demonstrate the superiority of Polyoxidonium®, lyophilizate for solution for injections and topical application, 6 mg over placebo in hospitalized patients with coronavirus disease (COVID-19). This is a multicentre prospective, randomized, double-blind, placebo-controlled, parallel-group phase IIb\IIIa clinical trial.

    NCT04381377
    Conditions
    1. Infections, Coronavirus
    Interventions
    1. Drug: azoximer bromide
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: The primary efficacy outcome will be defined based on the blinded analysis of data of the first 100 patients in the 1st part of the study. There is uncertainty about the clinical course and potential different trajectories according to baseline disease severity, so the day of the primary endpoint may be modified based on a blinded evaluation of the primary efficacy outcome in various days.

    Measure: Clinical status of the patient (according to 7-point ordinal scale)

    Time: Day 15

    Secondary Outcomes

    Description: Time to improvement by one category from admission on the ordinal scale. Clinical status of the patient. Average change in the ordinal scale from baseline.

    Measure: Clinical status of the patient (according to 7-point ordinal scale)

    Time: Clinical status of the patient and the average change in the ordinal scale from baseline, both on days 3, 5, 8, 11, 29.

    Description: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Change in NEWS from baseline.

    Measure: NEWS

    Time: Change in NEWS from baseline on days 3, 5, 8, 11, 15, 29.

    Description: Oxygenation free days. Incidence and duration of new oxygen use.

    Measure: Oxygenation

    Time: Oxygenation free days in the first 28 days (to day 29). Incidence and duration of new oxygen use during the study.

    Description: Ventilator free days. Incidence and duration of new mechanical ventilation use.

    Measure: Mechanical Ventilation

    Time: Ventilator free days in the first 28 days (to day 29). Incidence and duration of new mechanical ventilation use during the trial.

    Measure: Mortality

    Time: 28-day mortality
    184 A Phase II Randomized Double-Blind Placebo-Controlled Clinical Trial Of Hydroxychloroquine For Prophylaxis Against Covid-19 In Patients Receiving Radiotherapy (COVID)

    The researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.

    NCT04381988
    Conditions
    1. COVID-19
    2. Cancer
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    3. Radiation: Radiation therapy

    Primary Outcomes

    Description: Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint.

    Measure: cumulative incidence of SARS-CoV-2 infection

    Time: within 9 weeks from randomization

    Secondary Outcomes

    Description: Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19.

    Measure: cumulative incidence of severe COVID-19 or death

    Time: within 12 weeks of randomization
    185 A Phase II, Controlled Clinical Study Designed to Evaluate the Effect of ArtemiC in Patients Diagnosed With COVID-19

    Agent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.

    NCT04382040
    Conditions
    1. COVID-19
    2. Corona Virus Infection
    3. SARS-CoV 2
    4. Coronavirus
    5. Coronavirus Infection
    Interventions
    1. Drug: ArtemiC
    2. Drug: Placebo
    MeSH:Infection Com Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: patient will be assessed using a scoring table for changes in clinical signs

    Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of Time: 24 hours

    Description: Adverse events caused by the study drug will be assessed

    Measure: Percentage of participants with definite or probable drug related adverse events

    Time: 14 days

    Secondary Outcomes

    Measure: Time to negative COVID-19 PCR

    Time: 14 days

    Measure: Proportion of participants with normalization of fever and oxygen saturation through day 14 since onset of symptoms

    Time: 14 days

    Measure: COVID-19 related survival

    Time: 14 days

    Measure: Incidence and duration of mechanical ventilation

    Time: 14 days

    Measure: Incidence of Intensive Care Init (ICU) stay

    Time: 14 days

    Measure: Duration of ICU stay

    Time: 14 days

    Measure: Duration of time on supplemental oxygen

    Time: 14 days
    186 A Phase 2, Randomized, Double Blind, Placebo-Controlled Study of Zanubrutinib Treatment in Patients Hospitalized for COVID-19 Infection and Pulmonary Distress

    The primary objective of this study is to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress.

    NCT04382586
    Conditions
    1. COVID-19 Pulmonary Complications
    2. COVID-19
    Interventions
    1. Drug: Zanubrutinib
    2. Drug: Supportive Care
    3. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Respiratory failure-free survival rate 28 is defined as the proportion of patients who have not had respiratory failure nor died <= 28 days from randomization.

    Measure: Respiratory failure-free survival rate at day 28

    Time: 28 Days

    Secondary Outcomes

    Measure: Median reduction in days spent on supplemental oxygen

    Time: Up to 28 Days

    Measure: All-cause mortality

    Time: Up to 28 Days

    Measure: Proportion of participants experiencing respiratory failure or death

    Time: Up to 28 Days

    Measure: Mechanical ventilation-free survival

    Time: Up to 28 Days

    Measure: Days on mechanical ventilation

    Time: Up to 28 Days

    Measure: Duration of hospitalization

    Time: Up to 28 Days

    Measure: Time to discharge

    Time: Up to 28 Days

    Measure: PaO2:FiO2 and/or oxygenation index

    Time: Up to 28 Days

    Description: This scale evaluates the safety and efficacy of investigational therapeutic agents in combination with care for the treatment of hospitalized participants suffering from COVID-19 infections on a scale of scores from 0 to 8, with higher scores indicating higher level of severity of the disease. (0 = No clinical or virological evidence of disease, and 8 = Death)

    Measure: Change from Baseline to Day 14 in WHO - 8 Point Ordinal Scale

    Time: Up to 28 Days
    187 A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Complement C5 Inhibition With Zilucoplan® in Improving Oxygenation and short-and Long-term Outcome of COVID-19 Patients With Acute Hypoxic Respiratory Failure

    The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury. Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.

    NCT04382755
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Zilucoplan®
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

    Measure: Mean change in oxygenation

    Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)

    Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

    Measure: Median change in oxygenation

    Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)

    Secondary Outcomes

    Measure: number of AE's (Adverse Events)

    Time: during hospital admission (up to 28 days)

    Measure: number of SAE's (Serious Adverse Events)

    Time: during hospital admission (up to 28 days)]

    Description: 6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: mean change in 6-point ordinal scale change

    Time: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).

    Description: defined as independence from supplemental oxygen

    Measure: Time since randomization until improvement in oxygenation

    Time: during hospital admission (up to 28 days)

    Description: defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen

    Measure: Number of days with hypoxia

    Time: during hospital admission (up to 28 days)

    Measure: Number of days of supplemental oxygen use

    Time: during hospital admission (up to 28 days)

    Measure: Time to absence of fever (defined as 37.1°C or more) for more than 48h without antipyretic

    Time: during hospital admission (up to 28 days)

    Description: defined as 37.1°C or more

    Measure: Number of days with fever

    Time: during hospital admission (up to 28 days)

    Measure: Mean change in CRP levels between day 1 and day 6

    Time: day 1, day 6

    Measure: Mean change in CRP levels between day 1 and day 15 (or discharge whichever comes first)

    Time: day 1, day 15

    Measure: Mean change in ferritin levels between day 1 and day 6

    Time: day 1, day 6

    Measure: Mean change in ferritin levels between day 1 and day 15 (or discharge, whichever comes first)

    Time: day 1, day 15

    Measure: Incidence of AE's

    Time: during hospital admission (up to 28 days)

    Measure: Incidence of SAE's

    Time: at 10-20 weeks follow-up

    Measure: Incidence of SUSAR's (Suspected Unexpected Serious Adverse Reaction)

    Time: during hospital admission (up to 28 days)

    Measure: Incidence of SAR's (Serious Adverse Reaction)

    Time: during hospital admission (up to 28 days)

    Measure: Duration of hospital stay

    Time: during hospital admission (up to 28 days)

    Measure: Duration of hospital stay in survivors

    Time: during hospital admission (up to 28 days)

    Description: SOFA score: 0 (best) - 24 (worse)

    Measure: Mean change of SOFA score between day 1 and day 6 (or on discharge, whichever is first)

    Time: day 1, day 6 or on discharge, whichever is first

    Description: SOFA score: 0 (best) - 24 (worse)

    Measure: Mean change of SOFA score between day 1 and day 15 or on discharge, whichever is first)

    Time: day 1, day 15 or on discharge, whichever is first

    Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale at randomization, day 6 and 15 (or discharge, whichever comes first) and day 28 (phone call)

    Time: day 1, day 6, day 15 (or discharge, whichever comes first)

    Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: 6-point Ordinal Scale at 6 and 15 days (or discharge whichever comes first) and day 28 (phone call), in relation to serum D-dimers and complement C5a levels at randomization

    Time: day 1, day 6, day 15 (or discharge, whichever comes first)

    Measure: Incidence of nosocomial bacterial or invasive fungal infection for 28 days (phone call) after enrolment in trial

    Time: day 28

    Measure: Time since randomization until first use of high-flow oxygen devices in non-ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Time since randomization until first use of non-invasive mechanical ventilation in non-ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Time since randomization until first use of invasive mechanical ventilation in non-ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Number of ventilator-free days

    Time: day 1, day 28 or discharge whichever comes first

    Measure: Duration of invasive and non-invasive mechanical ventilation in ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Duration of ICU stay in patients that enrolled in trial on invasive or non-invasive mechanical ventilation for less than 24h prior to or after randomization

    Time: during hospital admission (up to 28 days)

    Description: criteria-defined ARDS criteria-defined ARDS according to the adapted Berlin criteria as follow: within 1 week of a known Clinical insult or new or worsening respiratory symptoms bilateral infiltrates not supposed to be of cardiac origin or fluid overload PaO2/FiO2 < 300 mmHg

    Measure: Time since randomization to progression to ARDS (Acute Respiratory Distress Syndrome)

    Time: during hospital admission (up to 28 days)

    Measure: Time to progression to ARDS in ventilated patients according to D-dimers at randomization

    Time: during hospital admission (up to 28 days)

    Measure: Time to progression to ARDS in ventilated patients according to complement C5a at randomization

    Time: during hospital admission (up to 28 days)

    Measure: All-cause mortality rate (excluding group that entered during ventilation)

    Time: at day 28

    Measure: All-cause mortality rate (including group that entered during ventilation)

    Time: at day 28

    Measure: Percentage of patients in clinical status on 6-point Ordinal Scale

    Time: at 12-22 weeks follow-up

    Measure: Incidence of lung function abnormalities at follow up

    Time: at 12-22 weeks follow-up

    Measure: Incidence of lung fibrosis on chest CT scan at follow up

    Time: at 12-22 weeks follow-up

    Measure: All cause mortality for the entire study population

    Time: at follow up 12-22 weeks
    188 Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria

    A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

    NCT04383535
    Conditions
    1. SARS Virus
    2. SARS-CoV-2
    3. COVID-19
    Interventions
    1. Other: Convalescent SARS COVID-19 plasma
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 30th day

    Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Secondary Outcomes

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 7th day

    Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 14th day

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Hospital discharge or intrahospital death

    Measure: Time until hospital discharge (days).

    Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission

    Description: ICU discharge or ICU death

    Measure: Time until discharge from ICU (days)

    Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission

    Description: Death and time to death

    Measure: Time to death

    Time: In a 30 days follow up period

    Description: Time until complete functional recovery (according to basal status).

    Measure: Time until complete functional recovery

    Time: Whenever the patient returns to basal functional status until 1 month from discharge

    Description: Percentage of participants with adverse events / serious adverse events

    Measure: Percentage of participants with adverse events / serious adverse events

    Time: In a 30 days follow up period

    Description: Percentage of patients with negative SARS-CoV-3 PCR

    Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: D Dimer plasma concentration

    Measure: D Dimer plasma concentration at Day 14th

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Ferritin plasma concentration

    Measure: Ferritin plasma concentration at Day 13th

    Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Plasma concentration of neutralizing antibodies

    Measure: Plasma concentration of neutralizing antibodies at Day 2nd

    Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Plasma concentration of neutralizing antibodies

    Measure: Plasma concentration of neutralizing antibodies at Day 7th

    Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Post-transfusion adverse reactions between study groups

    Measure: Post-transfusion adverse reactions

    Time: In a 30 days follow up period
    189 A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Zofin for the Treatment of Moderate to SARS Related to COVID-19 Infection vs Placebo

    The purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Zofin for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.

    NCT04384445
    Conditions
    1. Corona Virus Infection
    2. COVID-19
    3. SARS
    4. Acute Respiratory Distress Syndrome
    Interventions
    1. Biological: Zofin
    2. Other: Placebo
    MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician

    Measure: Incidence of any infusion associated adverse events

    Time: 60 Days

    Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician

    Measure: Incidence of Severe Adverse Events

    Time: 60 Days

    Secondary Outcomes

    Description: Measured at day 60 or at hospital discharge, whichever comes first.

    Measure: All Cause Mortality

    Time: 60 Days

    Description: Number of participants that are alive at 60 days post first infusion follow up

    Measure: Survival Rate

    Time: 60 Days

    Description: Measure IL-6, TNF-alpha from serum of blood samples

    Measure: Cytokine Levels

    Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

    Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab

    Measure: D-dimer Levels

    Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

    Description: CRP from serum of blood samples

    Measure: C-reactive protein Levels

    Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

    Description: Viral load by real time RT methodology using blood samples or nose / throat swab

    Measure: Quantification of the COVID-19

    Time: Day 0, Day 4, Day 8

    Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.

    Measure: Improved Organ Failure

    Time: Day 30

    Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.

    Measure: Chest Imaging Changes

    Time: Day o, Day 30
    190 A Randomised Double-blind Placebo-controlled Trial to Determine the Safety and Efficacy of Inhaled SNG001 (IFN-β1a for Nebulisation) for the Treatment of Patients With Confirmed SARS-CoV-2 Infection

    SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. The study will start as a Pilot phase where 100 patients will be randomised in the hospital setting and a 120 patients randomised in the home setting. Once each of the Pilot phases are complete, a Pivotal phase will be conducted. It is estimated that the size of each of the Pivotal phases (hospital and home) will be around 100 to 300 patients per arm. The actual number will be determined after the data review at the end of each of the Pilot phases. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.

    NCT04385095
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Drug: SNG001
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)

    Measure: Ordinal Scale for Clinical Improvement

    Time: Day 1 to Days 15 and 28

    Secondary Outcomes

    Description: Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment

    Measure: Progression to pneumonia (hospital setting only)

    Time: Day 2 to Day 28

    Description: Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment

    Measure: Progression to pneumonia (hospital setting only)

    Time: Day 1 to Day 28

    Description: Time to clinical improvement

    Measure: Time to clinical improvement (hospital setting only)

    Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hours

    Description: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)

    Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity (hospital setting only)

    Time: Day 1 to Day 28

    Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)

    Measure: Changes in daily breathlessness, cough and sputum scale (BCSS)

    Time: Day 1 to Day 28

    Description: Looking at blood pressure measured in mmHg

    Measure: Safety and tolerability - blood pressure II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at heart rate measured in beats per minute

    Measure: Safety and tolerability - heart rate II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at temperature measured in degrees Celsius

    Measure: Safety and tolerability - temperature II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at respiratory rate measure in breaths per minute

    Measure: Safety and tolerability - respiratory rate II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at oxygen levels measured in a %

    Measure: Safety and tolerability - oxygen saturation II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at adverse events (numbers and terms)

    Measure: Safety and tolerability - adverse events II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at concomitant medications given during treatment

    Measure: Safety and tolerability - concomitant medications II. Viral load

    Time: Day 1 to Day 28

    Description: Temperature ≤37.8 °C AND COVID-19 symptoms (breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and taste, rhinorrhoea and anorexia) all rated as absent or mild

    Measure: Time to clinical improvement (home setting only)

    Time: Day 1 to Day 28

    Description: Time to improvement of COVID-19 symptoms (fever, breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and/or taste, rhinorrhoea and anorexia)

    Measure: Time to improvement of COVID-19 symptoms (home setting only).

    Time: Day 1 to Day 28

    Description: Time to self-reported recover

    Measure: Time to self-reported recovery (home setting only)

    Time: Day 2 to Day 16

    Description: Self-reported daily rating of overall feeling of wellness

    Measure: Self-reported daily rating of overall feeling of wellness (home setting only).

    Time: Day 1 to Day 28

    Description: Quality of life measured using EQ-5D-5L

    Measure: Quality of life measured using EQ-5D-5L (home setting only).

    Time: Day 1 to Day 28

    Description: Time to virus clearance and viral load

    Measure: Virus clearance/load (if samples are available)

    Time: Day 1 to Day 28

    Description: Blood and sputum biomarkers

    Measure: Blood and sputum biomarkers (if samples are available).

    Time: Day 1 to Day 28

    Description: Contact with health services

    Measure: Contact with health services (home setting only

    Time: Day 1 to Day 28

    Description: Consumption of antibiotics

    Measure: Consumption of antibiotics (home setting only

    Time: Day 1 to Day 28
    191 A Phase III, Double-blind, Randomized, Placebo-controlled Multicentre Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Healthcare Professionals' Absenteeism in the SARS-CoV-2 Pandemic by Modulating the Immune System

    The aim of this study is to investigate whether vaccination of healthcare professionals with VPM1002 could reduce the number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection). VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the new corona virus "SARS-CoV 2". A total of 1200 health care professionals (doctors, nurses and paramedical staff) with high expected exposure to SARSCoV-2 infected patients will receive a single dose of either VPM1002 or Placebo. All subjects will be requested to enter data regarding absenteeism, adverse events / serious adverse events, hospitalizations, intensive care unit admissions into an online questionnaire.

    NCT04387409
    Conditions
    1. Infection, Respiratory Tract
    Interventions
    1. Biological: VPM1002
    2. Biological: Placebo
    MeSH:Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Measure: Number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection)

    Time: From day 0 to day 240

    Secondary Outcomes

    Measure: Cumulative incidence of documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days absent from work due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days absent from work due to exposure to person with documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days absent from work due to symptoms of respiratory disease, documented SARS-CoV-2 infection, or fever (≥ 38 °C)

    Time: From day 0 to day 240

    Measure: Number of days of self-reported fever (≥ 38 °C)

    Time: From day 0 to day 240

    Measure: Number of days of self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of hospital admission for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of hospital admission due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240
    192 A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase II Study to Evaluate the Efficacy and Safety of Intramuscular Injections of PLX PAD for the Treatment of Severe COVID-19

    This clinical trial will examine if a new treatment of Mesenchymal-like Adherent stromal Cells (called PLX-PAD) can help patients intubated and mechanically ventilated due to COVID-19 to recover more quickly with less complications.

    NCT04389450
    Conditions
    1. COVID
    2. ARDS
    Interventions
    1. Biological: PLX-PAD
    2. Biological: Placebo

    Primary Outcomes

    Measure: Number of ventilator free days

    Time: 28 days

    Secondary Outcomes

    Measure: All-cause mortality

    Time: 28 days

    Measure: Duration of mechanical ventilation

    Time: 8 weeks
    193 A Phase 2/3 Study to Evaluate the Safety and Efficacy of Dociparstat Sodium for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure

    A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.

    NCT04389840
    Conditions
    1. COVID-19
    2. Acute Lung Injury
    3. SARS-CoV-2
    Interventions
    1. Drug: Dociparastat sodium
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

    Primary Outcomes

    Description: Alive and free of invasive mechanical ventilation

    Measure: Proportion of participants who are alive and free of invasive mechanical ventilation

    Time: Through Day 28

    Secondary Outcomes

    Description: Time to all-cause mortality

    Measure: All-cause mortality

    Time: Through Day 28
    194 Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission

    SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.

    NCT04390022
    Conditions
    1. Covid-19
    2. Coronavirus Infection
    3. SARS-CoV-2 In
    4. SARS-CoV-2 Infection
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment

    Measure: Proportion of patients with a positive SARS-CoV-2 PCR

    Time: 7 days post-treatment

    Secondary Outcomes

    Description: Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab

    Measure: Mean viral load

    Time: Baseline and on days 4, 7, 14 and 21

    Description: Proportion of patients with fever and cough at days 4, 7, 14 and 21 as well as proportion of patients progressing to severe disease or death during the trial

    Measure: Fever and cough progression

    Time: Up to and including day 21

    Description: Proportion of participants with positive IgG at day 21

    Measure: Seroconversion at day 21

    Time: Up to and including day 21

    Description: Proportion of drug-related adverse events

    Measure: Proportion of drug-related adverse events

    Time: 7 days post treatment

    Description: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay

    Measure: Levels of IgG, IgM and IgA

    Time: Up to and including day 28

    Description: Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry

    Measure: Frequency of innate immune cells

    Time: Up to and including day 7

    Description: Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry

    Measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells

    Time: Up to and including day 7

    Description: Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher)

    Measure: Results from cytokine Human Magnetic 30-Plex Panel

    Time: Up to and including day 28
    195 A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19

    Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

    NCT04390139
    Conditions
    1. COVID-19
    2. SARS-CoV 2
    3. Adult Respiratory Distress Syndrome
    Interventions
    1. Drug: XCEL-UMC-BETA
    2. Other: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Number of patients who died, by treatment group

    Measure: All-cause mortality at day 28

    Time: Day 28

    Secondary Outcomes

    Description: Number of patients with treatment-emergent adverse events, by treatment group

    Measure: Safety of WJ-MSC

    Time: Day 28

    Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group

    Measure: Need for treatment with rescue medication

    Time: Day 28

    Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group

    Measure: Need and duration of mechanical ventilation

    Time: Day 28

    Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.

    Measure: Ventilator free days

    Time: Day 28

    Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.

    Measure: Evolution of PaO2 / FiO2 ratio

    Time: Day 28

    Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.

    Measure: Evolution of the SOFA index

    Time: Day 28

    Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.

    Measure: Evolution of the APACHE II score

    Time: Day 28

    Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.

    Measure: Duration of hospitalization

    Time: Day 28

    Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.

    Measure: Evolution of markers of immune response (leucocyte count, neutrophils)

    Time: Day 28

    Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date

    Measure: Feasibility of WJ-MSC administration

    Time: Day 28

    Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.

    Measure: Feasibility of WJ-MSC administration

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR)

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH)

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: D-dimer

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: Ferritin

    Time: Day 28

    Other Outcomes

    Description: Blood sample analysis

    Measure: Analysis of subpopulations of lymphocytes and immunoglobulins

    Time: Day 28

    Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)

    Measure: Evaluation of the in vitro response of the receptor lymphocytes

    Time: Day 28

    Description: Reactivity will be assessed using ELISPOT

    Measure: Study of reactivity against SARS-CoV-2 peptides

    Time: Day 28

    Description: Blood sample analysis

    Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides

    Time: Day 28

    Description: Blood sample analysis for the patient's genomic sequencing

    Measure: Genetic variability of patient's genotype in response to treatment

    Time: Day 28

    Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample

    Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment

    Time: Day 28
    196 A Phase 2 Study to Evaluate LB1148 for the Treatment of Pulmonary Dysfunction Associated With COVID-19 Pneumonia

    This is a Phase 2, proof of concept, randomized, placebo-controlled, multicenter study to evaluate the ability of LB1148 to attenuate pulmonary dysfunction associated with COVID-19 pneumonia. The primary objective of this study is to determine if enteral administration of LB1148 will effect disease progression in hospitalized patients with moderate to severe COVID-19 via measurement of the proportion of subjects alive and free of respiratory failure at Day 28.

    NCT04390217
    Conditions
    1. COVID-19
    2. Coronavirus Disease 2019
    3. Covid19
    4. COVID-19 Pneumonia
    Interventions
    1. Drug: LB1148
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The proportion of subjects alive and free of respiratory failure at Day 28.

    Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure.

    Time: 28 Days

    Secondary Outcomes

    Description: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)

    Measure: Clinical status at fixed time points

    Time: Measured at 3, 5, 7, 8, 10, 14 and 28 Days

    Description: Length of hospital stay (live discharge)

    Measure: Duration of hospital stay

    Time: 28 Days

    Description: Number and proportion of patients requiring admission to the intensive care unit

    Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization

    Time: 28 Days

    Description: Length of ICU stay

    Measure: Duration of ICU stay

    Time: 28 Days

    Description: Number and proportion of patients requiring invasive mechanical ventilation

    Measure: Invasive mechanical ventilation requirements

    Time: 28 Days

    Description: Length of time patients require invasive mechanical ventilation

    Measure: Duration of invasive mechanical ventilation

    Time: 28 Days

    Description: The number and proportion of patients deceased at Day 28

    Measure: All-cause 28-day mortality

    Time: 28 Days

    Description: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Measure: Safety and tolerability of LB1148

    Time: 28 Days
    197 Efficacy and Safety of Hydroxychloroquine and Ivermectin in Hospitalized no Critical Patients Secondary to COVID-19 Infection: Randomized Controlled Trial

    Background: In December 2019, patients with pneumonia secondary to a new subtype of Coronavirus (COVID-19) were identified in China. In a few weeks the virus spread and cases started practically all over the world. In February 2020, the WHO declared a pandemic. Severe symptoms have been found in patients mainly with comorbidities and over 50 years of age. At this time there is no proven therapeutic alternative. In vitro studies and observational experiences showed that antimalarial drugs (Chloroquine and hydroxychloroquine) had antiviral activity and increased viral clearance. Ivermectin, on the other hand, has been shown in vitro to reduce viral replication and in an observational cohort, greater viral clearance with promising clinical results. So far there is no standard of treatment and clinical trials are needed to find effective treatment alternatives. Objective: To evaluate the safety and efficacy of treatment with hydroxychloroquine and ivermectin for serious COVID-19 infections in no critical hospitalized patients. Material and methods: Randomized controlled trial of patients diagnosed with respiratory infection by COVID-19, who present criteria for hospitalization. Randomization will be performed to receive hydroxychloroquine at a dose of 400 mg every 12 hours for one day and then 200 mg every 12 hours, to complete a 5-day treatment schedule. Group 2: Ivermectin 12 mg every 24 hours for one day (less than 80 kg) or Ivermectin 18 mg every 24 hours for one day (greater than 80 kg) + placebo until the fifth day. Group 3: Placebo. Prior to randomization, the risk of cardiovascular complications determined by corrected QT interval, related to hydroxychloroquine intake will be assessed. If the patient is at high risk, the allocation will be to ivermectin only or to placebo in an independent randomization, if the risk is low, any of the three groups could be assigned. Outcomes: The primary outcome will be discharge from hospital for improvement. The safety outcomes will be requirement of mechanical intubation, septic shock or death. Viral clearance will also be evaluated by means of PCR, which will be taken on the 5th day after admission, day 14 and 21.

    NCT04391127
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Ivermectin
    3. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Days from admission as a suspected case of COVID with hospitalization criteria until discharge

    Measure: Mean days of hospital stay

    Time: Three months

    Description: Respiratory deterioration defined by respiratory rate > 25 per minute, requirement of high oxygen supply (FiO2 > 80% ) to maintain oxygen saturation > 90 %, invasive mechanical ventilation or dead.

    Measure: Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead

    Time: Three months

    Description: Daily delta of oxygenation index during the hospitalization

    Measure: Mean of oxygenation index delta

    Time: Three months

    Secondary Outcomes

    Description: Mean time to viral negativization of RT-qPCR SARS-CoV-2. Pre Specified time: 5, 14, 21 and 28 days after the first positive PCR.

    Measure: Mean time to viral PCR negativization

    Time: 5, 14, 21 and 28 days after the first positive PCR
    198 Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)

    This is a multicenter, randomized, double-blind, placebo-controlled phase 2 study of IC14, an antibody to CD14, in reducing the severity of respiratory disease in hospitalized COVID-19 patients.

    NCT04391309
    Conditions
    1. SARS-CoV2
    Interventions
    1. Biological: IC14
    2. Other: Placebo

    Primary Outcomes

    Description: Days alive and free of any episodes of acute respiratory failure through Day 22 defined by need for high-flow nasal cannula, noninvasive positive-pressure ventilation, endotracheal intubation and mechanical ventilation, and extracorporeal membrane oxygenation

    Measure: Acute respiratory failure

    Time: Day 1-22

    Secondary Outcomes

    Description: Defined as time to the first day that a subject is in categories 6, 7, or 8 on the Eight-Point Ordinal Scale. The Eight-Point Ordinal Scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen-requiring ongoing medical care (COVID-19-related or otherwise); 6) Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to clinical improvement

    Time: Day 1-29

    Description: Proportion of patients alive and free of any episode of acute respiratory failure through Days 8, 15, 22, and 29

    Measure: Acute respiratory failure

    Time: Days 1-8, 1-15, 1-22, 1-29

    Description: Proportion of patients alive and free of invasive mechanical ventilation through Days 8, 15, 22, and 29

    Measure: Invasive mechanical ventilation

    Time: Days 1-8, 1-15, 1-22, 1-29

    Description: Days alive and free of acute respiratory failure through Days 15 and 29

    Measure: Acute respiratory failure

    Time: Days 1-15 and 1-29

    Description: Days alive and free of invasive mechanical ventilation through Days 15, 22, and 29

    Measure: Invasive mechanical ventilation

    Time: Days 1-15, 1-22, 1-29

    Description: Days alive and hospitalized through Day 29

    Measure: Hospitalization

    Time: Days 1-29

    Description: Change in Sequential Organ Failure Assessment (SOFA) score (range 0 [best] to 24 [worst]) from baseline to Day 8, Day 15, and Day 22

    Measure: Sequential Organ Failure Assessment

    Time: Days 1-8, 1-15, 1-22

    Description: Worst SOFA score from baseline to Day 22

    Measure: Sequential Organ Failure Assessment

    Time: Days 1-22

    Description: Proportion of patients alive and discharged from the hospital at Days 15 and 29.

    Measure: Hospitalization

    Time: Days 1-15, 1-29

    Description: Mean change in the eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29

    Measure: Ordinal Scale

    Time: Days 1-29

    Description: Time to improvement in one category from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.

    Measure: Time to clinical improvement

    Time: Days 1-29

    Description: Time to improvement in two categories from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.

    Measure: Time to clinical improvment

    Time: Days 1-29

    Description: Time to recovery through Day 29. Day of recovery is defined as the first day on which the subject satisfies one of categories 6-8 from the ordinal scale.

    Measure: Time to recovery

    Time: Days 1-29

    Description: Change in C-reactive protein in blood on Days 4 and 8 compared to baseline (from normal < 10 mg/L [normal] to >10 mg/L [worse])

    Measure: Change in C-reactive protein

    Time: Day 4 compared to baseline; Day 8 compared to baseline

    Description: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events

    Measure: Adverse events

    Time: Days 1-60

    Description: Cumulative incidence of serious adverse events

    Measure: Serious adverse events

    Time: Days 1-60
    199 A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of EIDD-2801 Following Oral Administration to Healthy Volunteers

    This is a First In Human study designed to assess the safety, tolerability and pharmacokinetics of EIDD-2801 in healthy human volunteers.

    NCT04392219
    Conditions
    1. Coronavirus
    Interventions
    1. Drug: EIDD-2801
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of Single Ascending Dose (SAD) of EIDD-2801 (Part 1): Adverse Events

    Time: From screening through study completion, up to 15 days

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of Multiple Ascending Dose (MAD) of EIDD-2801 (Part 3): Adverse Events

    Time: From screening through study completion, up to 20 days

    Description: Multiple pharmacokinetic variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

    Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Doses (Part 2): Maximum observed concentration Cmax

    Time: Day 1 through Day 18

    Secondary Outcomes

    Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

    Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Ascending Dose (SAD) (Part 1): Maximum observed concentration Cmax

    Time: Day 1 up to Day 4

    Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

    Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Multiple Ascending Dose (MAD) (Part 3): Maximum observed concentration Cmax

    Time: Day 1 up to Day 14

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of Single Doses of EIDD-2801 (Part 2): Adverse Events

    Time: From screening through study completion, up to 30 days
    200 A Phase 2/3, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ABX464 in Treating Inflammation and Preventing COVID-19 Associated Acute Respiratory Failure in Patients Aged ≥ 65 and Patients Aged ≥18 With at Least One Additional Risk Factor Who Are Infected With SARS-CoV-2.

    A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).

    NCT04393038
    Conditions
    1. COVID-19
    Interventions
    1. Drug: ABX464
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency Inflammation

    Primary Outcomes

    Measure: Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive

    Time: at the end of the 28-day treatment period

    Secondary Outcomes

    Measure: Rate of patients hospitalized

    Time: 28-day treatment period

    Description: 7-point ordinal scale is defined as Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death

    Measure: Percentage of patients reporting each severity rating on a 7-point ordinal scale

    Time: 28-day treatment period

    Measure: Change from enrolment in inflammatory markers in plasma and in immune phenotype and assessment of cell-activation markers in PBMCs

    Time: at each study visit during the 28-day treatment period

    Measure: Rate of patients requiring oxygen supplementation

    Time: 28-day treatment period

    Measure: Time to hospitalization

    Time: 28-day treatment period

    Measure: Time to assisted ventilation and oxygen supplementation

    Time: 28-day treatment period

    Measure: Change from baseline in microRNA-124 levels

    Time: at each study visit during the 28-day treatment period

    Measure: Change from baseline in CRP, Troponin I & T and D-dimer

    Time: at each study visit during the 28-day treatment period

    Description: Nasopharyngeal sample and/or in blood

    Measure: SARS-CoV-2 viral load

    Time: at each study visit during the 28-day treatment period

    Measure: Number and rates of participants with Treatment Emergent Adverse Event

    Time: 28-day treatment period
    201 A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Ulinastatin for the Treatment of COVID-19 in Hospitalized Patients

    The primary objective of this study is to evaluate the safety and efficacy of intravenous (IV) infusion of ulinastatin compared to placebo with respect to time to recovery, disease severity, need for ventilator support, and mortality in patients with COVID 19.

    NCT04393311
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ulinastatin
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities

    Measure: Time to recovery

    Time: Up to 29 days

    Secondary Outcomes

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 8

    Time: Day 8

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 15

    Time: Day 15

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 22

    Time: Day 22

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 29

    Time: Day 29

    Measure: Incidence of mortality at Day 29

    Time: 29 days

    Measure: Incidence of in-hospital mortality

    Time: Up to 29 days

    Measure: Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose

    Time: Up to 29 days

    Measure: Number of patients with resolution of symptoms defined as score of 8 on the 8-point ordinal scale at Day 29

    Time: Day 29

    Measure: Number of patients alive and free of respiratory failure defined as score of 4, 5, 6, 7, or 8 on the 8-point ordinal scale at Day 29

    Time: Day 29

    Description: For patients requiring mechanical ventilation.

    Measure: Duration of mechanical ventilation

    Time: Up to 29 days

    Description: For patients requiring mechanical ECMO.

    Measure: Duration of ECMO

    Time: Up to 29 days

    Description: For patients requiring non-invasive ventilation

    Measure: Duration of noninvasive ventilation

    Time: Up to 29 days

    Description: For patients admitted to ICU

    Measure: Duration of ICU stay

    Time: Up to 29 days

    Measure: Duration of hospital stay

    Time: Up to 29 days

    Measure: Change in oxygen saturation

    Time: Between screening and 24 hours after last dose (up to 6 days)
    202 Trial of Silymarin in Adults With COVID-19 Pneumonia

    A randomized placebo controlled trial to assess the clinical outcome in COVID-19 Pneumonia following administration of Silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and anti-oxidant effects

    NCT04394208
    Conditions
    1. COVID-19
    2. Viral Pneumonia Human Coronavirus
    Interventions
    1. Drug: Silymarin
    2. Drug: Placebo
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.

    Measure: Time to clinical improvement

    Time: 7-28 days

    Secondary Outcomes

    Description: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14

    Measure: Clinical outcome

    Time: 7-14 days

    Description: Time in days patient was intubated

    Measure: Duration of Mechanical Ventilation

    Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

    Description: Total days of hospitalization

    Measure: Hospitalization

    Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

    Description: number of days patient remained with positive RT-PCR SARS-CoV-2 swab

    Measure: Virologic Response

    Time: Randomization till discharge, up to 28 days

    Description: Any adverse events whether related to medication or not

    Measure: Adverse events

    Time: Randomization till hospital discharge, up to 28 days
    203 Aerosol Combination Therapy of All-trans Retinoic Acid and Isotretinoin as A Novel Treatment for Inducing Neutralizing Antibodies in COVID -19 Infected Patients Better Than Vaccine : An Innovative Treatment

    Aerosol Combination therapy of All-trans retinoic acid and Isotretinoin as A novel Treatment for Inducing Neutralizing Antibodies in COVID -19 Infected Patients better than vaccine : An innovative Treatment Mahmoud ELkazzaz(1),Tamer Haydara(2), Mohamed Abdelaal(3), Ahmed M. Kabel(4), Abedelaziz Elsayed(5) ,Yousry Abo-amer(6) ,Hesham Attia(7) 1. Department of chemistry and biochemistry, Faculty of Science, Damietta University,Egypt. 2. Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt 3. Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt 4. Department of Clinical Pharmacy, Faculty of Medicine , Tanta University,Egypt. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy,Tanta University,Egypt. 6. Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital,Egypt 7. Department of Immunology and Parasitology, Faculty of Science, Cairo University, Egypt. - Study Chair ((( Dr.Tamer Hydara))), Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt Contact: Dr.Tamer Hydara-Tel: 00201142233340 Mail: tamerhydara@yahoo.com - Principal Investigator ((( Mahmoud Elkazzaz))), Faculty of Science, Damietta University,GOEIC,Egypt Contact:Tel: 00201090302015 Mail: mahmoudramadan2051@yahoo.com - Study coordinator ((Prof/Dr Mohamed Abdelaal)), Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt Contact:Tel: 00201001422577 Mail: Malaal2@hotmail.com Abstract The pandemic of COVID-19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has infected over 20,000,000 people causing over 700,000 deaths .It has no currently approved treatments. In this clinical study we confirm that combination of isotretinoin and All trans retinoic acid can be used in the treatment of SARS-COV-2 better than vaccine according to the findings of previous studies and researches. Retenoic acid can induce neutralizing antibodies in case of corona virus (COVID-19) by restoring inhebited and exhausted T cells via inhebiting both CD13 and Angiotensin-converting enzyme-2 (ACE2). CD13 amyloid receptor which abundantly overexpressed on cell surface of lymphocyte, Dentritic cell, Macrophage, granulocytes and monocytes and is ubiquitous in respiratory tract epithelial cells, smooth muscle cells, fibroblasts, epithelial cells in the kidneys and small intestine, activated endothelial cells, and platelets In addition inhibing of Angiotensin-converting enzyme-2 (ACE2) , Angiotensin T1 protein and Angiotensin II-mediated intracellular calcium release pathway which is responsible for COVID-19 cell fusion and entry.ACE2-expressing cells are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. A study demonestrated that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously suggested to increase ACE2 expression.Butisotretinoin was found to be the strongest down-regulator of ACE 2 receptors.and this will give hope for diabetic patients or patients with hypertension infected with COVID-19.Therefore we suggest that Retinoic Acid will help in inhabiting factors which may enhance antibody dependent enhancement (ADE), A phenomenon caused by covid-19 which expected to lead to failure of vaccination specially in case of corona virus (covid-19) as a hyper mutatated COVID-19 antigens can lead to (ADE) phenomenon in which IgG antibodies facilitate viral entry and fusion with infected cell through uptake of the virus-IgG complex via the Fc receptors and later viral fusion with antigen presenting cells like Dentric cells, macrophages and B cells via FcR , through the neonatal FcR instead of antibodies induced viral agglutination and this is known as antibody dependent enhancement (ADE)(2) ADE can hamper vaccine development, as a vaccine may cause the production of antibodies which, via ADE, worsen the disease the vaccine is designed to protect against. ADE in COVID-19 infection can be caused by high mutation rate of the gene that encodes spike (S) protein. In this clinical study we suggest that Hyper mutated spike protein ,lymphopenia, and impaired dentreic cells all these factors can help in and lead to delayed antibodies response and appearing after a period of covid -19 symptoms onset and this may be responsible for antibody dependent enhancement (ADE) Keywords: COVID 2019 , Retinoic acid, Lymphopenia ,T Cells, Dentric cells , ADE, Vaccine

    NCT04396067
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Aerosolized 13 cis retinoic acid
    2. Drug: Aerosolized All trans retinoic acid
    3. Other: Placebo

    Primary Outcomes

    Description: Proportion of lung injury score decreased or increased after treatment

    Measure: lung injury score

    Time: at 7 days

    Secondary Outcomes

    Description: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

    Measure: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

    Time: at day 7 and 14 after randimization

    Description: Serum level of COVID19 RNA

    Measure: Serum level of COVID19 RNA

    Time: at day 7 and 14

    Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample

    Measure: d-dimers

    Time: within 14 days

    Description: lymphocyte counts

    Measure: Absolute lymphocyte counts

    Time: at day 7 and 14 after randimization

    Description: To determine the immune correlates of viral clearance (Antibody Titres sufficient for viral clearance and neutralizing ) against future exposure to SARS-CoV-2

    Measure: The immune correlates of protection against future exposure to SARS-CoV-2

    Time: within 14 days

    Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

    Measure: Immunological profile

    Time: within 14 days

    Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

    Time: at day 7 and 14

    Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

    Measure: Occurrence of adverse event related to immunoglobulins

    Time: at day 14

    Description: serum levels of IgG and IgM against COVID-19

    Measure: IgG, IgA and IgM against COVID-19

    Time: at day 7 and 14

    Description: ACE2 expression in patients with COVID-19 infection

    Measure: ACE2 expression in patients with COVID-19 infection

    Time: at day 7 and 14

    Measure: All cause mortality rate [

    Time: at day 7 and 14

    Measure: Ventilation free days

    Time: at 14 days

    Measure: ICU free days

    Time: at 14 days
    204 A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-527 in Subjects With Moderate COVID-19

    The objectives of this study are to evaluate the safety, tolerability and efficacy of AT-527 in older subjects (ages 45-80 years) with moderate COVID-19 and risk factors for poor outcomes (such as obesity (BMI>30), hypertension, diabetes or asthma). Eligible subjects will be randomized to blinded AT-527 (nucleotide analog) tablets or matching placebo tablets to be administered orally for 5 days. Local supportive standard of care (SOC) will be allowed for all subjects. Efficacy and safety observations will be compared for treatment with active AT-527 tablets + SOC vs. placebo tablets + SOC.

    NCT04396106
    Conditions
    1. COVID-19
    Interventions
    1. Drug: AT-527
    2. Other: Placebo

    Primary Outcomes

    Description: Progressive respiratory insufficiency defined as a ≥ 2-tier increase in respiratory support methods required to maintain satisfactory oxygenation (SpO2 ≥ 93%), using the 6-tier hierarchical scale of respiratory support methods

    Measure: Proportions (active vs. placebo) of subjects with progressive respiratory insufficiency.

    Time: Day 14

    Measure: Proportions (active vs. placebo) of subjects experiencing treatment-emergent adverse events

    Time: Day 14

    Secondary Outcomes

    Description: Clinical recovery defined as time from randomization to disease resolution status on an 8 point Clinical Status scale

    Measure: Time to clinical recovery

    Time: Day 14

    Measure: Proportions (active vs. placebo) of subjects with respiratory failure or death

    Time: Day 28
    205 Safety and Efficacy of Post-exposure Prophylaxis With Hydroxychloroquine (HCQ) for the Prevention of COVID-19 in High-risk Older Individuals in Long-term and Specialized Care: A Double-blind Randomized Control Trial

    Older adults are at the highest risk of complications and severe illness for 2019-nCoV infections. Hydroxychloroquine (HCQ), an emerging chemoprophylaxis, which holds clinical and mechanistic plausibility, will help to reduce disease incidence and mitigate disease severity across in-patient settings. This study is designed to assess the safety and efficacy of post-exposure prophylaxis with hydroxychloroquine (HCQ) for the prevention of Coronavirus Infectious Disease-19 (COVID-19) in high-risk older individuals in long-term and specialized care.

    NCT04397328
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of symptomatic fever >37.8, dry cough, or shortness of breath (resident/patient report or nurse observation) respiratory infection with confirmed PCR+ result for SARS-CoV-2.

    Time: baseline through day 90

    Secondary Outcomes

    Measure: Requirement for admission to acute care hospital and/or ICU admission or death

    Time: baseline through day 90

    Measure: Asymptomatic PCR+ SARS-CoV-2 test result

    Time: baseline, days 2, 5, 12, and 19

    Measure: Time to clinical recovery (TTCR).

    Time: baseline through day 90
    206 Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration

    Ranitidine is an over-the-counter and prescription drug, which decreases the amount of acid secreted by the stomach. Some ranitidine medicines contain an impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. The US Food and Drug Administration (FDA) has found levels of NDMA in some ranitidine products similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats. The ranitidine that will be used in this study has been tested twice (months apart) and shown to have stable NDMA levels well below the acceptable daily limit. Of note, the risk of NDMA with ranitidine is only relevant with prolonged chronic administration as at the acceptable limit, there is approximately a 1 in 100,000 chance of cancer after 70 years of exposure to that level. FDA has also conducted tests that simulate the potential formation of NDMA from ranitidine after it has been exposed to acid in the stomach with a normal diet. Results of these tests indicate that NDMA is not formed in typical stomach conditions. Similarly, if ranitidine is exposed to a simulated small intestinal fluid, NDMA is not formed. Other laboratory experiments suggest a combination of nitrites, such as found in processed meats, and an acidic environment may increase NDMA formation, however the levels of nitrites tested were very high. Separately, a previous study in 10 healthy volunteers showed that volunteers who received ranitidine had an increase in urinary NDMA excreted over 24 h. The level of increase was greater than would be expected from laboratory testing. This clinical study is being performed to determine if and how much NDMA is produced from ranitidine in the human body and whether nitrite-containing foods may increase formation of NDMA. The study will use a prescription dose of ranitidine (300 mg) to test whether there is increased urinary NDMA excretion levels over 24-hours after ranitidine administration in comparison to placebo when participants are administered low nitrite/NDMA meals and when subjects are administered high nitrite/NDMA meals. On 4 different days, each participant will receive ranitidine or placebo with high nitrite/NDMA meals and ranitidine or placebo with low nitrite/NDMA meals.

    NCT04397445
    Conditions
    1. Ranitidine Adverse Reaction
    2. Pharmacokinetics
    3. Food-drug Interaction
    Interventions
    1. Drug: Ranitidine
    2. Other: Low nitrite/NDMA meals
    3. Drug: Placebo
    4. Other: High nitrite/NDMA meals

    Primary Outcomes

    Description: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.

    Measure: 24-hour Urinary NDMA Excretion

    Time: 24 hours

    Other Outcomes

    Description: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.

    Measure: Area under the curve from time zero to infinity (AUC(0-inf)) of plasma ranitidine

    Time: 24 hours

    Description: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.

    Measure: AUC(0-inf) of plasma NDMA

    Time: 24 hours

    Description: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.

    Measure: AUC(0-inf) of plasma dimethylamine (DMA)

    Time: 24 hours

    Description: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.

    Measure: Cumulative ranitidine amount excreted in urine over 24 hours after drug administration

    Time: 24 hours

    Description: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.

    Measure: Cumulative DMA amount excreted in urine over 24 hours after drug administration

    Time: 24 hours
    207 A Randomized, Double Blind, Placebo-controlled Trial of Mavrilimumab for Acute Respiratory Failure Due to COVID-19 Pneumonia With Hyper-inflammation (the COMBAT-19 Trial)

    This study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.

    NCT04397497
    Conditions
    1. Covid-19
    2. Acute Respiratory Failure
    3. ARDS, Human
    4. Sars-CoV2
    5. Viral Pneumonia
    Interventions
    1. Drug: Mavrilimumab
    2. Drug: Placebo
    MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm

    Measure: Reduction in the dependency on oxygen supplementation

    Time: within day 14 of treatment

    Secondary Outcomes

    Description: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

    Measure: Proportion of responders (using the WHO 7-point ordinal scale)

    Time: Day 7, 14, and 28

    Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

    Measure: Time to response (using the WHO 7-point ordinal scale)

    Time: Within day 28 of intervention

    Description: Proportion of patients with at least two-point improvement in clinical status

    Measure: Proportion of improving patients (using the WHO 7-point ordinal scale)

    Time: At day 7, 14, and 28

    Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner

    Measure: Time to resolution of fever

    Time: Within day 28 of intervention

    Description: COVID-19-related death

    Measure: Reduction in case fatality

    Time: Within day 28 of intervention

    Description: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)

    Measure: Proportion of patient requiring mechanical ventilation/deaths

    Time: Within day 14 of intervention

    Description: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)

    Measure: Change in biochemical markers

    Time: Within day 28 of intervention or discharge -whatever comes first

    Description: Median changes of NEWS2 score from baseline

    Measure: Median changes in the National Early Warning Score 2 (NEWS2)

    Time: At day 7, 14, and 28

    Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)

    Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2)

    Time: Within day 28 of intervention or discharge -whatever comes first

    Description: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.

    Measure: Variations in radiological findings

    Time: Within day 28 of intervention or discharge -whatever comes first

    Description: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time: By day 84

    Other Outcomes

    Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg

    Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity

    Time: Within day 28 of intervention

    Description: Median changes in serum IL-6

    Measure: Changes in serum IL-6 (exploratory biomarker)

    Time: By day 84

    Description: Median changes in serum IL-1 receptor antagonist

    Measure: Changes in serum IL-1RA (exploratory biomarker)

    Time: By day 84

    Description: Median changes in serum TNF-alpha

    Measure: Changes in serum TNF-alpha (exploratory biomarker)

    Time: By day 84

    Description: Median variations in haemoglobin and leucocyte counts

    Measure: Changes in CBC + differential (exploratory biomarker)

    Time: By day 84

    Description: Median titres od anti-SARS-CoV2 antibodies

    Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker)

    Time: By day 84

    Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR

    Measure: Virus eradication (exploratory biomarker)

    Time: By day 84

    Description: Proportion of patients who developed anti-drug antibodies

    Measure: Anti-drug antibodies (exploratory biomarker)

    Time: By day 84
    208 A Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptively Designed Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19

    The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.

    NCT04397562
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Levilimab
    2. Drug: Placebo

    Primary Outcomes

    Description: The proportion of deaths in each group

    Measure: Mortality rate

    Time: Day 60

    Secondary Outcomes

    Description: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care; 6. Hospitalized, not requiring supplemental oxygen; 7. Not hospitalized / discharged

    Measure: 7-point Ordinal Scale

    Time: Day 60

    Measure: Duration of hospital stay

    Time: Day 60

    Measure: Rate of subjects required ICU stay

    Time: Day 60

    Measure: Duration of ICU Stay

    Time: Day 60

    Measure: Rate of subjects with COVID-19 progression to critical (respiratory failure required invasive ventilation or septic shock or multiple organ failures

    Time: Day 60

    Measure: Rate of subjects requiring the rescue therapy

    Time: Day 60

    Measure: Duration of oxygen supplementation

    Time: Day 60

    Measure: Rate of subjects requiring the invasive ventilation

    Time: Day 60

    Measure: Duration of invasive ventilation

    Time: Day 60
    209 Phase 1b Randomized, Double-Blind, Placebo-Controlled Study Of The Safety Of Therapeutic Treatment With Immunomodulatory Mesenchymal Stem Cells In Adults With COVID-19 Infection Requiring Mechanical Ventilation

    This is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with Coronavirus Disease 2019 (COVID-19). This clinical trial will evaluate the preliminary safety and efficacy of BM-Allo.MSC vs placebo in treating subjects with severe disease requiring ventilator support during COVID 19 infection.

    NCT04397796
    Conditions
    1. COVID
    Interventions
    1. Biological: BM-Allo.MSC
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Incidence of AEs within 30 days of randomization.

    Measure: Incidence of AEs

    Time: 30 days

    Description: Mortality within 30 days of randomization.

    Measure: Mortality

    Time: 30 days

    Description: Cause of death within 30 days of randomization

    Measure: Death

    Time: 30 days

    Description: Number of ventilator-free days within 60 days of randomization.

    Measure: Number of ventilator-free days

    Time: 60 days

    Secondary Outcomes

    Description: Time from randomization to an improvement of one category using the ordinal scale. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities

    Measure: Improvement of one category

    Time: 30 days

    Description: Change in the 7-point ordinal scale from baseline. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities

    Measure: 7-point ordinal scale

    Time: 30 days

    Description: Change in NEWS from baseline. The following 7 clinical parameters will be assessed: Respiration rate Oxygen saturation Any supplemental oxygen Temperature Systolic blood pressure Heart rate Level of consciousness Measurements within normal ranges are assigned a 0. If the measurement in each category is substantially above or below the normal range, it is given a +1, +2, or +3. The more far off than normal, the bigger the number (in each category). A higher number indicates worse outcome. Each category can be 0-3, except for supplemental oxygen which is only 0-2. The highest value a patient can get is 20.

    Measure: NEWS

    Time: 30 days

    Description: Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.

    Measure: NEWS of ≤ 2

    Time: 30 days

    Description: Change from baseline in Sequential Organ Failure Assessment (SOFA) score on days 8, 15, 22, and 29. System Score for each category is 0-4 with 28 is the maximum score for worst outcome. The following categories are: Respiration Coagulation Liver Cardiovascular Central Nervous System Renal

    Measure: Sequential Organ Failure Assessment (SOFA)

    Time: days 8, 15, 22, and 29

    Description: Number of days requiring oxygen.

    Measure: Oxygen

    Time: 30 days

    Description: Duration of hospitalization from randomization.

    Measure: Hospitalization

    Time: 30 days

    Description: Incidence of SAEs within 30 days of randomization

    Measure: Incidence of SAEs

    Time: 30 days
    210 A Randomized, Observer-Blind, Dose-escalation Phase I/II Clinical Trial of Ad5-nCoV Vaccine in Healthy Adults From 18 to <85 Years of Age in Canada

    This study is a phase I /II adaptive clinical trial to evaluate the safety, tolerability and the Immunogenicity of Ad5-nCoV in healthy adults from 18 to <55 and 65 to <85 years of age，with the randomized, observer-blind, dose-escalation design

    NCT04398147
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
    2. Biological: Placebo

    Primary Outcomes

    Description: The occurrence of Solicited AE in all groups within 0-6 days after each vaccination;

    Measure: Incidence of the Solicited AE in all groups

    Time: 0-6 days after each vaccination

    Description: The occurrence of Unsolicited AE in all groups within 0-28 days after each vaccination.

    Measure: Incidence of Unsolicited AE in all groups

    Time: 0-28 days after each vaccination

    Description: The occurrence of Serious adverse events (SAE) in all groups within 6 months after the final vaccination.

    Measure: Incidence of Serious adverse events (SAE) in all groups

    Time: 6 months after the final vaccination

    Secondary Outcomes

    Description: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);

    Measure: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 (ELISA method);

    Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Seroconversion rate (%of subjects with 4-fold or greater increase in antibody level) of the IgG antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method );

    Measure: Seroconversion rate of the IgG antibody against SARS-CoV-2(ELISA method )

    Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);

    Measure: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2(ELISA method);

    Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)

    Measure: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)

    Time: Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Seroconversion rate of the neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group(Pseudo-viral neutralization assay);

    Measure: Seroconversion rate of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)

    Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)

    Measure: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 (Pseudo-viral neutralization assay)

    Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group;

    Measure: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector

    Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Measure: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector

    Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: The positive rate of IFN-γ stimulated by S protein overlapping peptide library detected by ELISpot

    Measure: cellular immune response by ELISpot

    Time: on Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: The positive rate of IFN-γ, TNF-α, and IL-2 expressed by CD4+ and CD8+ T lymphocytes stimulated by S protein overlapping peptide library detected by Intracellular Cytokine Staining (ICS);

    Measure: cellular immune response by ICS

    Time: Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group
    211 A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia

    The primary objective of this study is determine the safety and efficacy of ACT-20-MSC (allogenic human umbilical derived mesenchymal stem cells) and ACT-20-CM (allogenic human umbilical derived mesenchymal stem cells in conditioned media) in patients with moderate to severe COVID-19 pneumonia.

    NCT04398303
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: ACT-20-MSC
    2. Biological: ACT-20-CM
    3. Biological: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Mortality at day 30

    Time: 30 days post treatment

    Secondary Outcomes

    Description: Number of ventilator-free days

    Measure: Ventilated Subjects - Ventilator Free Days

    Time: 28 days post treatment

    Description: Improvement in ventilator settings: Minute ventilation, PEEP, FiO2

    Measure: Ventilated Subjects - Improvement in Ventilator Settings

    Time: 28 days post treatment, or until off of ventilator

    Description: Days of step-down O2 therapy as evidenced by: improvement in required volume, change to nasal cannula or face mask delivery or improvement in required concentration.

    Measure: High-Flow O2 Support Subjects - Step-Down O2 Therapy

    Time: 30 days post treatment, or until off of high-flow O2 support

    Description: Respiration Rate < 30 for > 24 hours.

    Measure: High Flow O2 Support Subjects - Respiration Rate

    Time: 30 days post treatment, or until off of high-flow O2 support

    Description: Number of ICU-free days

    Measure: Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

    Description: Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation

    Measure: Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

    Description: Increased Berlin Criteria score > 24 hours

    Measure: Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support
    212 Niclosamide for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

    This study will evaluate the antihelmintic drug, Niclosamide, as a potential treatment for mild to moderate coronavirus disease 2019 (COVID-19).

    NCT04399356
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Niclosamide
    2. Drug: Placebo
    3. Other: Telehealth monitoring

    Primary Outcomes

    Description: Oropharangeal swabs

    Measure: Change in respiratory viral clearance (by PCR)

    Time: Days 3 and 10

    Secondary Outcomes

    Description: Fecal swabs

    Measure: Fecal viral clearance (by PCR)

    Time: Day 14

    Description: Oropharngeal swabs

    Measure: Reduction (change) in respiratory viral shedding (by PCR)

    Time: Days 1,3,7,10,14

    Description: Fecal swabs

    Measure: Reduction (change) in GI viral shedding (by PCR)

    Time: Days 1,3,7,10,14, 21

    Description: Defined as 1) O2 saturation <92% on room air (in two consecutive measurements at least 2 hours apart) OR 2) requirement of hospitalization OR 3) need for artificial ventilation OR 4) death.

    Measure: Progression to severe COVID-19 Disease

    Time: Enrollment through final day of participation

    Description: Days

    Measure: Time to resolution of a fever

    Time: Enrollment through final day of participation

    Other Outcomes

    Description: Composite counts by Adverse Events and Serious Adverse Events

    Measure: Incidence of Adverse Events (AEs)

    Time: Enrollment through 30 days after final day of participation
    213 Efficacy and Safety of Octagam 10% Therapy in COVID-19 Patients With Severe Disease Progression

    This is a randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to evaluate if high-dose Octagam 10% therapy can stabilize or improve clinical status in patients with severe Coronavirus disease

    NCT04400058
    Conditions
    1. Covid-19
    Interventions
    1. Biological: Octagam 10%
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: Proportion of subjects with stabilized or improved clinical status at Day 7 on at least one category on a 6-point clinical status scale. Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.

    Measure: Stabilization or Improvement in Clinical Status

    Time: 7 days

    Description: Change from Baseline (Day 1) at Day 7 in terms of the 6-point clinical status scale (descriptive analysis). Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.

    Measure: Descriptive Clinical Status Analysis

    Time: 7 days

    Secondary Outcomes

    Description: Proportion of subjects with maintenance or improvement by at least one category on the 6-point clinical status scale on Day 14. (This endpoint will go into formal hypothesis testing procedure) Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.

    Measure: Clinical Status Assessment

    Time: 14 days

    Description: Time to death

    Measure: Time to death

    Time: Up to 33 days

    Description: Proportion of subjects requiring invasive mechanical ventilation by Day 33.

    Measure: Mechanical Ventilation Initiation

    Time: Up to 33 days

    Description: Duration of invasive mechanical ventilation

    Measure: Mechanical Ventilation Duration

    Time: Up to 33 days

    Description: Results of RT-PCR for SARS-CoV-2 from nares/throat swab and/or sputum and/or lower respiratory tract sample on Day 7.

    Measure: SARS-CoV-2 Test Result

    Time: 7 days

    Description: Incidence of all AEs

    Measure: Incidence of all AEs

    Time: Up to 33 days

    Description: Incidence of AEs considered related to the IMP

    Measure: Incidence of AEs considered related to the IMP

    Time: Up to 33 days

    Description: Incidence of serious adverse events (SAEs)

    Measure: Incidence of serious adverse events (SAEs)

    Time: Up to 33 days

    Description: Radiological findings (chest CT/chest X-ray)

    Measure: Radiological findings (chest CT/chest X-ray)

    Time: Up to 7 days

    Description: Change from baseline in blood glucose

    Measure: Blood glucose

    Time: Up to 33 daya

    Description: Change from baseline in blood calcium

    Measure: Blood calcium

    Time: Up to 33 days

    Description: Change from baseline in sodium

    Measure: Sodium

    Time: Up to 33 days

    Description: Change from baseline in potassium

    Measure: Potassium

    Time: Up to 33 days

    Description: Change from baseline in carbon dioxide

    Measure: Carbon dioxide

    Time: Up to 33 days

    Description: Change from baseline in chloride

    Measure: Chloride

    Time: Up to 33 days

    Description: Change from baseline in albumin

    Measure: Albumin

    Time: Up to 33 days

    Description: Change from baseline in total protein

    Measure: Total protein

    Time: Up to 33 days

    Description: Change from baseline in alkaline phosphatase

    Measure: Alkaline phosphatase

    Time: Up to 33 days

    Description: Change from baseline in alanine transaminase

    Measure: Alanine transaminase

    Time: Up to 33 days

    Description: Change from baseline in aspartate aminotransferase

    Measure: Aspartate aminotransferase

    Time: Up to 33 days

    Description: Change from baseline in bilirubin

    Measure: Bilirubin

    Time: Up to 33 days

    Description: Change from baseline in blood urea nitrogen

    Measure: Blood urea nitrogen

    Time: Up to 33 days

    Description: Change from baseline in D-dimer

    Measure: D-dimer

    Time: Up to 33 days

    Description: Change from baseline in fibrinogen

    Measure: Fibrinogen

    Time: Up to 33 days

    Description: Change from baseline in PT

    Measure: PT

    Time: Up to 33 days

    Description: Change from baseline in PTT

    Measure: PTT

    Time: Up to 33 days

    Description: Change from baseline in INR

    Measure: INR

    Time: Up to 33 days

    Description: Change from baseline in hsCRP

    Measure: hsCRP

    Time: Up to 33 days

    Description: Change from baseline in ferritin

    Measure: Ferritin

    Time: Up to 33 days

    Description: Change from baseline in LDH

    Measure: LDH

    Time: Up to 33 days

    Description: Change from baseline in IgG

    Measure: IgG

    Time: Up to 33 days

    Description: Change from baseline in IgM

    Measure: IgM

    Time: Up to 33 days

    Description: Change from baseline in IgA

    Measure: IgA

    Time: Up to 33 days

    Description: Change from baseline in IFE

    Measure: IFE

    Time: Up to 33 days

    Description: Change from baseline in troponin

    Measure: Troponin

    Time: Up to 33 days

    Description: Change from baseline in red blood cell count

    Measure: Red blood cell count

    Time: Up to 33 days

    Description: Change from baseline in hemoglobjn

    Measure: Hemoglobin

    Time: Up to 33 days

    Description: Change from baseline in hematocrit

    Measure: Hematocrit

    Time: Up to 33 days

    Description: Change from baseline in mean corpuscular volume

    Measure: Mean corpuscular volume

    Time: Up to 33 days

    Description: Change from baseline in mean corpuscular hemoglobin

    Measure: Mean corpuscular hemoglobin

    Time: Up to 33 days

    Description: Change from baseline in mean corpuscular hemoglobin concentration

    Measure: Mean corpuscular hemoglobin concentration

    Time: Up to 33 days

    Description: Change from baseline in red cell distribution width

    Measure: Red cell distribution width

    Time: Up to 33 days

    Description: Change from baseline in white blood cell count

    Measure: White blood cell count

    Time: Up to 33 days

    Description: Change from baseline in white blood cell differential

    Measure: White blood cell differential

    Time: Up to 33 days

    Description: Change from baseline in platelet count

    Measure: Platelet count

    Time: Up to 33 days

    Description: Change from baseline in mean platelet volume

    Measure: Mean platelet volume

    Time: Up to 33 days

    Description: Change from baseline in platelet distribution width

    Measure: Platelet distribution width

    Time: Up to 33 days

    Description: Change from baseline in SpO2

    Measure: SpO2

    Time: Up to 33 days

    Description: Change from baseline in A-a gradient

    Measure: A-a gradient

    Time: Up to 33 days

    Description: Change from baseline in blood pressure

    Measure: Blood Pressure

    Time: Up to 33 days

    Description: Change from baseline in pulse

    Measure: Pulse

    Time: Up to 33 days

    Description: Change from baseline in respiration rate

    Measure: Respiration Rate

    Time: Up to 33 days

    Description: Change from baseline in body temperature

    Measure: Body Temperature

    Time: Up to 33 days
    214 Randomized Controlled Trial of Angiotensin 1-7 (TXA127) for the Treatment of Severe COVID-19

    The purpose of this study is to determine if administration of angiotensin-(1-7) (TXA127) prevents acute kidney injury and deterioration into multi-organ failure in patients with severe COVID-19. Participants will undergo a 10-day treatment with either placebo or study drug. The drug will be administered intravenously for 3 hours once each day for 10 days consecutively.

    NCT04401423
    Conditions
    1. COVID-19
    Interventions
    1. Drug: TXA127
    2. Drug: Placebo

    Primary Outcomes

    Description: Calculated from baseline (at enrollment) to end of study

    Measure: Change of serum creatinine

    Time: Day 1 and Day 10

    Measure: Number of participants requiring intubation and ventilatory support

    Time: Up to Day 10

    Secondary Outcomes

    Measure: Change in number of deceased participants

    Time: Day 1 and Day 10

    Measure: Number of participants requiring dialysis

    Time: Up to Day 10

    Measure: Number of participants requiring a vasopressors

    Time: Up to Day 10

    Measure: Change in blood inflammatory markers

    Time: Day 1 and Day 10

    Measure: Percent change in supplemental oxygen requirements

    Time: Day 1 and Day 10
    215 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-2)

    ACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.

    NCT04401579
    Conditions
    1. COVID-19
    Interventions
    1. Other: Placebo
    2. Drug: Remdesivir
    3. Drug: Baricitinib

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.

    Measure: Time to recovery

    Time: Day 1 through Day 29

    Secondary Outcomes

    Measure: Change from baseline in alanine transaminase (ALT)

    Time: Day 1 through Day 29

    Measure: Change from baseline in aspartate transaminase (AST)

    Time: Day 1 through Day 29

    Measure: Change from baseline in creatinine

    Time: Day 1 through Day 29

    Measure: Change from baseline in glucose

    Time: Day 1 through Day 29

    Measure: Change from baseline in hemoglobin

    Time: Day 1 through Day 29

    Measure: Change from baseline in platelets

    Time: Day 1 through Day 29

    Description: PT reported as international normalized ratio (INR).

    Measure: Change from baseline in prothrombin time (PT)

    Time: Day 1 through Day 29

    Measure: Change from baseline in total bilirubin

    Time: Day 1 through Day 29

    Measure: Change from baseline in white blood cell count (WBC) with differential

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 29

    Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days

    Measure: Duration of oxygen use

    Time: Day 1 through Day 29

    Description: For any reason.

    Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics

    Time: Day 1 through Day 10

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Mean change in the ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Participant's clinical status at Day 15 by ordinal scale

    Time: Day 15

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale

    Time: Days 3, 5, 8, 11, 22, and 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 28-day mortality

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29

    Measure: Change from baseline in C-reactive protein (CRP)

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29
    216 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19

    This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.

    NCT04402866
    Conditions
    1. Acute Lung Injury (ALI) Associated With COVID-19
    2. Lung Inflammation Associated With COVID-19
    Interventions
    1. Drug: TD-0903
    2. Drug: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of Respiratory Failure-Free Days (RFDs) from randomization through Day 28

    Measure: Part 2: Respiratory Failure-Free Days (RFDs)

    Time: Baseline through Day 28

    Secondary Outcomes

    Description: Proportion of subjects in each category of the 8-point Clinical Status scale. The Clinical Status scale contains 8 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized, no limitations on activities') to 8 (representing 'Death'). The various measures describe hospitalization status and the various limitations and requirements for oxygen support.

    Measure: Part 2: Clinical Status Scale

    Time: Day 7, 14, 21 and 28

    Description: Proportion of subjects alive and respiratory failure-free on Day 28

    Measure: Part 2: Subjects alive and respiratory failure-free

    Time: Day 28

    Description: Change from baseline in SaO2/FiO2 ratio on Day 7

    Measure: Part 2: SaO2/FiO2 ratio

    Time: Baseline, Day 7
    217 Pulmozyme to Improve COVID-19 ARDS Outcomes

    This is a randomized double-blind placebo-controlled Phase II trial of recombinant human deoxyribonuclease I (rhDNase I) - Pulmozyme - in mechanically ventilated patients with COVID-19 pneumonia. Patients admitted to the ICU with severe COVID-19 pneumonia who require mechanical ventilation will be invited to participate in this study. Potential subjects will be identified from medical record review or from direct contact with physicians. Investigators will check medical history and confirm eligibility. Informed consent will be obtained from either the patient or designated healthcare proxy. 60 subjects will be enrolled. After obtaining informed consent, patients will be randomized 2:1 to Pulmozyme 2.5 mg BID for up to 28 days or until they are no longer receiving mechanical ventilation, whichever is sooner plus standard of care vs. placebo normal saline 2.5 ml plus standard of care.

    NCT04402944
    Conditions
    1. COVID
    Interventions
    1. Drug: Pulmozyme
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary outcome

    Measure: Ventilator-free days at 28 days

    Time: 28 days

    Secondary Outcomes

    Description: change in airway resistance

    Measure: change in airway resistance

    Time: 28 days

    Description: Change in lung compliance

    Measure: change in lung compliance

    Time: 28 days

    Description: oxygenation

    Measure: oxygenation (PaO2/FiO2 ratio)

    Time: 28 days

    Description: length of stay

    Measure: length of stay (ICU and hospital)

    Time: 28 days

    Description: rate of batotrauma

    Measure: rate of barotrauma

    Time: 28 days

    Description: mortality

    Measure: mortality.

    Time: 28 days
    218 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)

    To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 <10 mL/min/1.73 m2.

    NCT04402957
    Conditions
    1. COVID
    2. Severe Acute Respiratory Syndrome
    3. Sars-CoV2
    4. Acute Kidney Injury
    Interventions
    1. Drug: LSALT peptide
    2. Drug: Placebo
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Acute Kidney Injury Syndrome Wounds and Injuries
    HPO:Acute kidney injury

    Primary Outcomes

    Description: To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.

    Measure: Development of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries

    Time: 28 days

    Secondary Outcomes

    Description: High-frequency oscillatory ventilation, with its rapid delivery of low tidal volumes and a respiratory rate in the range of 60 to 900 breaths/minute, has also been utilized in ARDS patients.

    Measure: Ventilation-free days

    Time: 28 days

    Description: Oxygen therapy provided as non-invasive therapy for ARDS patients.

    Measure: Time on nasal cannula or oxygen masks

    Time: 28 days

    Description: 28 day mortality - all cause and attributable

    Measure: 28 day mortality - all cause and attributable

    Time: 28 days

    Description: ICU and hospitalization length of stay (days)

    Measure: ICU and hospitalization length of stay (days)

    Time: 28 days

    Description: Swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication → virologic clearance rate

    Measure: SARS-CoV2 testing

    Time: 28 days

    Description: Extracorporeal membrane oxygenation (ECMO) is often used for severe ARDS to allow lung healing/repair and reverse respiratory failure.

    Measure: Need and duration for extracorporeal membrane oxygenation (ECMO)

    Time: 28 days

    Description: Vasopressor free days

    Measure: Vasopressor free days

    Time: 28 days

    Description: Chest X-rays performed at Baseline, Day 3, at clinical improvement, and end-of-treatment (EOT) and study (EOS) to determine presence of bilateral opacities.

    Measure: Radiographic pulmonary assessments

    Time: 28 days

    Description: Change in daily mMRC dyspnea and SOFA scores (0 to 4) with 4 being the most severe outcome

    Measure: Change in modified Medical Research Council (mMRC) dyspnea and Sequential Organ Failure Assessment (SOFA) scores

    Time: 28 days

    Description: Incidence of other organ (non-lung) disorders

    Measure: Incidence of non-lung disorders

    Time: 28 days

    Description: Change in liver function tests (ALT, AST, and total bilirubin levels) from baseline

    Measure: Measures of liver dysfunction

    Time: 28 days

    Description: Change in SCr and eGFR from baseline

    Measure: Measures of kidney dysfunction

    Time: 28 days

    Description: Change in highly-sensitive troponin (hs-troponin) from baseline

    Measure: Measures of cardiac dysfunction

    Time: 28 days

    Description: Change from baseline ACT, aPTT, and/or PT/INR levels

    Measure: Measures of coagulopathies

    Time: 28 days

    Description: Change in baseline antiviral immunoglobulins (IgG, IgM) at EOS.

    Measure: Changes in immunogenic responses

    Time: 28 days

    Description: Changes in total healthcare costs from admission to discharge between treatment groups.

    Measure: Healthcare outcomes

    Time: 28 days

    Description: Change in serum cytokines including IL-1α, IL-1ß, IL-1ra, IL-5, IL-6, IL-8, IL-12, TNFα, CXCL10/IP10, MCP-3, and ferritin drawn at the same time as LSALT peptide levels

    Measure: Molecular changes in pro-inflammatory pathways

    Time: 28 days

    Description: Pharmacokinetics of LSALT peptide over the study period.

    Measure: Pharmacokinetics of LSALT peptide

    Time: 28 days
    219 Hydroxychloroquine and Lopinavir/ Ritonavir for Hospitalization and Mortality Reduction in Patients With COVID-19 and Mild Disease Symptoms: "The Hope Coalition"

    The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in certain subgroups of patients. To date, no treatment has been shown to be effective in controlling this disease in hospitalized patients with moderate and / or severe cases of this disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV viral replication in experimental severe acute respiratory symptoms models and have similar activity against SARS-CoV2. Although widely used in studies of critically ill patients, to date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed patients with COVID-19 and mild symptoms.

    NCT04403100
    Conditions
    1. COVID-19
    2. Coronavirus Infection
    3. Virus Disease
    4. Acute Respiratory Infection
    5. SARS-CoV Infection
    Interventions
    1. Drug: Hydroxychloroquine Sulfate Tablets
    2. Drug: Lopinavir/ Ritonavir Oral Tablet
    3. Drug: Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets
    4. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Virus Diseases Severe Acute Respiratory Syndrome
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)

    Measure: Proportion of participants who were hospitalized for progression of COVID-19 disease

    Time: Measuring during 28-day period since randomization (Intention to treat analysis)

    Measure: Proportion of participants who died due to COVID-19 progression and/ or complications

    Time: Measuring during 28-day period since randomization (Intention to treat analysis)

    Secondary Outcomes

    Description: Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)

    Measure: Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization

    Time: Measuring during 14-day period since randomization

    Description: Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.

    Measure: Time to clinical improvement

    Time: Measuring during 28-day period since randomization

    Description: Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;

    Measure: Time to clinical failure

    Time: Measuring during 28-day period since randomization

    Description: Proportion of participants with hospitalization for any cause

    Measure: Hospitalization for any cause

    Time: Measuring during 28-day period since randomization

    Measure: Proportion of participants who died due to pulmonary complications

    Time: Measuring during 28-day period since randomization

    Measure: Proportion of participants who died due to cardiovascular complications

    Time: Measuring during 28-day period since randomization

    Description: Evaluation of adverse events evaluated as associated to any of study arms

    Measure: Proportion of participants who presented with adverse events

    Time: Measuring during 28-day period since randomization

    Description: Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.

    Measure: Time to improvement on respiratory scale symptoms

    Time: Measuring during 28-day period since randomization

    Measure: proportion of non-adherent participants to any of study drugs

    Time: Measuring during 10-day period since randomization
    220 Randomized Clinical Trial of Açaí Palm Berry Extract as an Intervention in Patients Diagnosed With COVID-19

    The Açaí trial will be testing if the açaí berry extract, a safe natural product with anti-inflammatory properties, can be used as a treatment option in adult patients with COVID-19 in the community.

    NCT04404218
    Conditions
    1. COVID
    Interventions
    1. Dietary Supplement: Açaí palm berry extract - natural product
    2. Other: Placebo

    Primary Outcomes

    Description: Symptom comparison between patients from the treatment vs control group, using an ordinal symptom scale based on the WHO scale. Patients who were hospitalized will be classified according to their worst score over 30 days and non-hospitalized patients according to their score at 30 days.

    Measure: 7-point ordinal symptom scale

    Time: 30 days

    Secondary Outcomes

    Description: First occurrence of all-cause mortality or need for mechanical ventilation

    Measure: The composite of all-cause mortality and need for mechanical ventilation

    Time: 30 days

    Description: First occurrence of all-cause mortality or hospitalization

    Measure: The composite of all-cause mortality and hospitalization

    Time: 30 days

    Description: All-cause mortality

    Measure: All-cause mortality

    Time: 30 days

    Description: Need for mechanical ventilation

    Measure: Need for mechanical ventilation

    Time: 30 days

    Description: Need for hospitalization

    Measure: Need for hospitalization

    Time: 30 days
    221 A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Pacritinib Plus Standard of Care Versus Placebo and Standard of Care in Hospitalized Patients With Severe COVID-19 With or Without Cancer

    This is a Phase 3 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer.

    NCT04404361
    Conditions
    1. COVID
    Interventions
    1. Drug: Pacritinib
    2. Drug: Placebo

    Primary Outcomes

    Description: The proportion is calculated as the number of patients who progress divided by the total number of patients in the ITT population.

    Measure: Proportion of patients who progress to IMV and/or ECMO or death during the 28 days following randomization

    Time: 28 days
    222 CACOLAC : Randomized Trial of Citrulline Administration in the Hospital Patient in Intensive Care for COVID-19 Acute Respiratory Distress Syndrome

    Respiratory involvement of SARS-CoV2 leads to acute respiratory distress syndrome (ARDS) and significant immunosuppression (lymphopenia) exposing patients to long ventilation duration and late mortality linked to the acquisition of nosocomial infections. Lymphopenia characteristic of severe forms of ARDS secondary to SARS-CoV2 infection may be linked to expansion of MDSCs and arginine depletion of lymphocytes. Severe forms of COVID-19 pneumonitis are marked by persistent ARDS with acquisition of nosocomial infections as well as by prolonged lymphocytic dysfunction associated with the emergence of MDSC. It has been found in intensive care patients hypoargininaemia, associated with the persistence of organ dysfunction (evaluated by the SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, the enteral administration of ARG was not deleterious and increased the synthesis of ornithine, suggesting a preferential use of ARG by the arginase route, without significant increase in argininaemia nor effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, is an interesting alternative to increase the availability of ARG. Recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. The hypothesis is therefore that CIT supplementation is more effective than the administration of ARG to correct hypoargininaemia, decrease lymphocyte dysfunction, correct immunosuppression and organ dysfunction in septic patients admitted to intensive care. The main objective is to show that, in patients hospitalized in intensive care for ARDS secondary to COVID-19 pneumonia, the group of patients receiving L-citrulline for 7 days, compared to the group receiving placebo, has a score of organ failure decreased on D7 (evaluated by the SOFA score) or by the last known SOFA score if the patient has died or been resuscitated.

    NCT04404426
    Conditions
    1. ARDS Secondary to COVID-19 Pneumonia
    Interventions
    1. Dietary Supplement: L-citrulline
    2. Other: Placebo
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
    HPO:Pneumonia

    Primary Outcomes

    Description: SOFA score for organ failures on D7 or last known SOFA score if the patient has died or been resuscitated

    Measure: SOFA

    Time: Day 7

    Secondary Outcomes

    Description: Number and phenotype of lymphocytes on days 1, 3, 7, 10 and 14

    Measure: Number and phenotype of lymphocytes

    Time: Days 1, 3, 7, 10 and 14

    Description: Monocytic expression HLA-DR (Flow cytometry) on days 1, 3, 7, 10 and 14

    Measure: HLA-DR

    Time: Days 1, 3, 7, 10 and 14

    Description: Number of Myeloid-derived suppressor cells (Flow cytometry) on days 1, 3, 7, 10 and 14

    Measure: Number of Myeloid-derived suppressor cells

    Time: Days 1, 3, 7, 10 and 14

    Description: Plasma cytokines / chemokines (IL-6, IL-8, IL-10, IL-7, CXCL10, G-CSF, TNF-alpha, IFN-β) at days 1, 3, 7, 10 and 14

    Measure: Plasma cytokines / chemokines

    Time: Days 1, 3, 7, 10 and 14

    Description: Diversity of the repertoire T at days 1, 3, 7, 10 and 14

    Measure: Repertoire T

    Time: Days 1, 3, 7, 10 and 14

    Description: T lymphocyte exhaustion: measurement of lymphocyte apoptosis and lymphocyte proliferation on days 1, 3, 7, 10 and 14

    Measure: Lymphocyte T exhaustion

    Time: Days 1, 3, 7, 10 and 14

    Description: Measurement of mitochondrial activity (measurement of the number of mitochondria and their membrane potential, measurement of the expression of Beclin1) on days 1, 3, 7, 10 and 14

    Measure: Mitochondrial activity

    Time: Days 1, 3, 7, 10 and 14

    Description: Plasma amino acids (arginine and its metabolites (ornithine, glutamate, glutamine, citrulline, proline) and tryptophan / kynurenine) on days 1, 3, 7, 10 and 14

    Measure: Plasma amino acids

    Time: Days 1, 3, 7, 10 and 14

    Description: SOFA score of organ failures on days 3, 7, 10 and 14

    Measure: SOFA

    Time: Days 3, 7, 10 and 14

    Description: Duration of hospitalization in intensive care (days), up to day 28 maximum

    Measure: Duration of hospitalization in intensive care

    Time: Day 28

    Description: Duration of hospital stay in hospital (days), up to day 28 maximum

    Measure: Duration of hospital stay in hospital

    Time: Day 28

    Description: Duration of mechanical ventilation (days), up to day 28 maximum

    Measure: Duration of mechanical ventilation

    Time: Day 28

    Description: Mortality in intensive care on day 28

    Measure: Mortality in intensive care on day 28

    Time: Day 28

    Description: Hospital mortality on day 28

    Measure: Hospital mortality on day 28

    Time: Day 28

    Description: Measurement of the presence of SARS-CoV2 in the tracheal aspiration by PCR on days 1, 3, 7, 10 and 14

    Measure: Measurement of the presence of SARS-CoV2

    Time: Days 1, 3, 7, 10 and 14

    Description: Incidence of nosocomial infections during the intensive care unit (maximum D28). The diagnosis of nosocomial infections will be made according to the definitions of nosocomial infections of the CDC. An independent committee of experts will validate or not the infections

    Measure: Nosocomial infections

    Time: D28

    Description: Number of days of exposure to each antibiotic per 1000 days of hospitalization (maximum day 28).

    Measure: Number of days of exposure to each antibiotic per 1000 days of hospitalization

    Time: Day 28
    223 A Phase 2a, Randomized, Observer-Blind, Placebo Controlled, Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-COV-2 Vaccine in Adults Aged 18 Years and Older

    This clinical study will assess the safety, reactogenicity, and immunogenicity of 2 dose levels of mRNA-1273 SARS-COV-2 vaccine in adults 18 years of age or older.

    NCT04405076
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: Biological: mRNA-1273: 50 mcg
    2. Other: Placebo
    3. Biological: Biological: mRNA-1273: 100 mcg

    Primary Outcomes

    Measure: Solicited local and systemic adverse reactions (ARs)

    Time: 7 days post-vaccination

    Measure: Unsolicited adverse events (AEs)

    Time: 28 days post-vaccination

    Measure: Medically-attended adverse events (MAAEs)

    Time: Month 0 through Month 13

    Measure: Serious adverse events (SAEs)

    Time: Month 0 through Month 13

    Measure: Change in the measure of clinical safety laboratory values in Cohort 2 from baseline

    Time: Through 1 month after last vaccination

    Measure: The number and percentage of participants with abnormalities in blood pressure, temperature, HR or respiratory rate will be assessed.

    Time: Through 1 year after last vaccination

    Measure: The number and percentage of participants with abnormalities in physical examinations will be assessed

    Time: Through 1 year after last vaccination

    Measure: Evaluate immunogenicity of mRNA-1273 by titer of SARS-CoV-2-specific binding antibody (bAb) measured by enzyme-linked immunosorbent assay (ELISA)

    Time: Through 1 year after the final dose

    Secondary Outcomes

    Measure: Titer of SARS-CoV-2-specific neutralizing antibody (nAb)

    Time: Through 1 year post last vaccination

    Description: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer either from below the limit of detection (LOD) or lower limit of quantification (LLOQ) to equal to or above LOD or LLOQ, or a 4-times higher titer in participants with pre-existing nAb titers.

    Measure: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer

    Time: Through 1 year post last vaccination
    224 Randomized, Double-blind, Placebo-controlled Trial of TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study)

    A randomized parallel double-blinded placebo-controlled clinical trial to evaluate the effect of Emtricitabine/Tenofovir alafenamide (FTC/TAF) compared with placebo on the risk of developing SARS-CoV-2 disease (COVID-19) in healthcare workers with high transmission risk in addition to currently recommended control measures.

    NCT04405271
    Conditions
    1. Healthcare Workers
    2. COVID-19
    3. SARS-CoV 2
    Interventions
    1. Drug: Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Description: SARS-CoV-2 disease (COVID-19) with or without symptoms at week 12 of treatment as defined by the presence of specific antibodies against the virus. Positive cases will be confirmed by PCR

    Measure: COVID-19 incident cases

    Time: During treatment (12 weeks)

    Secondary Outcomes

    Description: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology

    Measure: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology

    Time: During treatment (12 weeks)

    Description: Severity of symptomatic SARS-CoV-2 (Covid-19) infections as defined by the following categories: Mild symptoms: malaise, fever, cough, arthralgia myalgias, Moderate symptoms: same as above plus shortness of breath Severe symptoms: clinical status requiring admission in Intensive care unit

    Measure: Severity of symptomatic COVID-19

    Time: During treatment (12 weeks)

    Description: Respiratory symptom duration in days

    Measure: Respiratory symptom duration in days

    Time: During treatment (12 weeks)

    Description: Relation between treatments and symptoms duration

    Measure: Relation between treatments and symptoms duration

    Time: During treatment (12 weeks)

    Description: Time course of specific IgM/IgG seroconversion

    Measure: Time course of specific IgM/IgG seroconversion

    Time: During treatment (12 weeks)
    225 Randomized, Placebo Controlled, Double Blind Clinical Trial to Evaluate the Efficacy of Molecule D11AX22 in Adults Patients From Valle Del Cauca, Colombia With Early Stages of SARS COV2 / COVID-19

    Double blind, placebo controlled, randomized clinical trial to evaluate the efficacy of ivermectin in preventing progression of disease in adult patients with early stages of COVID-19

    NCT04405843
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ivermectin Oral Product
    2. Drug: Placebo

    Primary Outcomes

    Description: Time until resolution of symptoms

    Measure: Time to event

    Time: 21 days

    Secondary Outcomes

    Description: Clinical condition in an ordinal scale of 7 points, on day 2. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 2

    Time: On day 2 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 5. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 5

    Time: On day 5 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 8. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 8

    Time: On day 8 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 11. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 11

    Time: On day 11 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 15. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 15

    Time: On day 15 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 21. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 21

    Time: On day 21 (± 1 day) after randomization

    Description: Proportion of subjects who require hospitalization, use of supplementary oxygen for >24 hours or ICU admission

    Measure: Proportion of subjects with additional care

    Time: 21 days

    Description: Proportion of subjects who die

    Measure: Proportion of subjects who die

    Time: From randomization up to 21 days

    Description: Duration of supplementary oxygen, hospitalization, ICU stay

    Measure: Duration of additional care

    Time: 21 days

    Description: Proportion of subjects who develop solicited adverse events

    Measure: Adverse events

    Time: 21 days

    Description: Proportion of subjects who required discontinuation of the trial due to adverse events

    Measure: Proportion of subjects who discontinue intervention

    Time: 21 days

    Description: Time until deterioration of 2 or more points in an ordinal 7 points scale.

    Measure: Time to event

    Time: 21 days
    226 Ivermectin and Doxycycline in Combination or Ivermectin Alone for the Treatment of Adult Bangladeshi Patients Hospitalized for COVID-19: a Randomised, Double-blind, Placebo-controlled Trial.

    Burden: Initial outbreak of corona virus disease 2019 (COVID-19) was reported from Wuhan, China in early December 2019.Presently known to be caused by a novel beta-corona virus, named as Severe acute respiratory syndrome corona virus 2 ( SARS-CoV-2). World Health Organization (WHO) declared a pandemic on March. The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnoea and pneumonia Infected individuals exhibit: 1. Mostly mild illness (80% +) recover without any treatment (~80%) 2. Moderate illness that needs hospitalization and recovers after standard 3. supportive treatment (~14%) 4. Critical illness (~5%) needs ICU support 5. Death (1-2% ) COVID-19 has now spread >210 countries and territories globally. SARS-CoV-2 is a respiratory virus which spreads primarily through droplets generalized when an infected person coughs or sneezes or through droplets of saliva or discharge from the nose. Symptomatic management remains the mainstay of treatment strategy. Mortality appears to be more common in older individuals and those with co-morbidities, such as chronic lung disease, cardiovascular disease and diabetes. Young people with no comorbidities also appear to be at risk for critical illness including multi-organ failure and death. Seen more in Bangladesh between 21-40 yrs of age. Knowledge Gap: There is no specific treatment against this new virus that WHO has officially declared until now.There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. National Guidelines on Clinical Management of Corona virus Disease 2019 (Covid-19): V 5.0 date 9th April 2020) CDC, DGHS, GoB Thus an RCT is urgently needed in Bangladesh: Based on recent literatures on Rx studies in COVID-19 patients from other countries as well as its availability & affordability of those repurposed medicines

    NCT04407130
    Conditions
    1. COVID-19 Patients
    Interventions
    1. Drug: Ivermectin + Doxycycline + Placebo
    2. Drug: Ivermectin + Placebo
    3. Drug: Placebo

    Primary Outcomes

    Description: • Presence of virus will be negative on Day 7 detected by RT PCR

    Measure: Virological clearance

    Time: within 7 days after enrollment

    Description: • Body temperature will be between 36.1 to 37.2 C by day 7 detected by Infrared thermometer

    Measure: Remission of fever

    Time: within 7 days after enrollment

    Description: • Remission of cough: No signs of cough showing respiratory rate within 12-20/ min, on day7

    Measure: Remission of cough

    Time: within 7 days after enrollment

    Secondary Outcomes

    Description: Detected SPO2 level <94% on Day 7or before by pulse oxymeter

    Measure: Patients requiring oxygen

    Time: within 7 days after enrollment

    Description: Patients who fail to maintain pulse oxymeter detected SpO2 level>88% despite O2 supplementation of 2-6L/min, on Day 7 or before

    Measure: Patients failing to maintain SpO2 >88% despite oxygenation

    Time: within 7 days after enrollment

    Description: Any number of days on oxygen support on Day 7 or before recorded in CRF

    Measure: Number of days on oxygen support

    Time: within 7 days after enrollment

    Description: CXR showing decreases lung opacity or consolidation on day 7 compared with enrollment day

    Measure: Chest X-ray improvement

    Time: within 7 days after enrollment

    Description: Hospital stay ≥7days to ≤14 days as per CRF records

    Measure: Duration of hospitalization

    Time: within 14 days after enrollment

    Description: Death any time during 14 days of study period from any cause recorded in CRF and Hospital death certificate

    Measure: All causes of mortality

    Time: within 14 days after enrollment
    227 Effects of Nicotinamide Riboside on the Clinical Outcome of Covid-19 in the Elderly. A Randomized Double-blind, Placebo-controlled Trial of Nicotinamide Riboside NR-COVID19

    The purpose of this study is to investigate whether nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections in elderly patients. A major event in aging is the loss of the central metabolite nicotinamide adenine dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur during aging. Notably, recent work from our and other groups suggest that aging can be ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside. Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger state even after short term treatment. This vitamin B3- analog is naturally occurring, is readily taken up through oral administration and has been tested in human trials with few side effects. In this randomized double blinded case-control trial, the investigators will treat elderly (>70 year old) COVID19 patients with 1 g of nicotinamide riboside (NR-E) or placebo for 2 weeks and investigate if this affects the clinical course of the disease.

    NCT04407390
    Conditions
    1. COVID
    Interventions
    1. Dietary Supplement: Nicotinamide riboside
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 1

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 7

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 14

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 90

    Secondary Outcomes

    Description: Overall mortality

    Measure: Mortality

    Time: Day 1

    Description: Overall mortality

    Measure: Mortality

    Time: Day 7

    Description: Overall mortality

    Measure: Mortality

    Time: Day 14

    Description: Overall mortality

    Measure: Mortality

    Time: Day 90

    Description: Sepsis

    Measure: Sepsis

    Time: Day 1

    Description: Sepsis

    Measure: Sepsis

    Time: Day 7

    Description: Sepsis

    Measure: Sepsis

    Time: Day 14

    Description: Sepsis

    Measure: Sepsis

    Time: Day 90

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 1

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 7

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 14

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 90

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 1

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 7

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 14

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 90

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 1

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 7

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 14

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 90
    228 Multicenter, Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of Ivermectin in Mild Virus-positive Subjects (SARS-CoV)-2 With or Without Symptoms

    This study aims to evaluate the efficacy, safety and tolerability of Ivermectin in patients with mild SARS-CoV-2 infection, in the rate of progression to severe 2019 novel coronavirus disease (COVID-19). The primary efficacy endpoint is the proportion of participants with a disease control status defined as no progression of severe disease Hypothesis (H0): There is no difference between group A (ivermectin + paracetamol) and group B (ivermectin + paracetamol) in terms of the primary endpoint on day 14.

    NCT04407507
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo

    Primary Outcomes

    Description: The subject is considered to have progressed to severe illness when one or more of the following criteria are present: Breathing difficulty (≥30 breaths per minute); Resting oxygen saturation ≤93%; Severe complications such as: respiratory failure, need for mechanical ventilation, septic shock, non-respiratory organic failure.

    Measure: Participants with a disease control status defined as no disease progression to severe.

    Time: 14 days
    229 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection in France and Belgium

    Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/ kg twice a week for two weeks on immune reconstitution of lymphopenic COVID-19 patients.

    NCT04407689
    Conditions
    1. COVID-19
    2. Lymphocytopenia
    Interventions
    1. Drug: Interleukin-7
    2. Drug: Placebo
    MeSH:Lymphopenia
    HPO:Lymphopenia

    Primary Outcomes

    Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge

    Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first

    Time: 1 month

    Secondary Outcomes

    Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score

    Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD.

    Time: 1 month

    Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

    Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD

    Time: 1 month or HD (whichever occurs first)

    Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

    Measure: frequency of secondary infections through day 45 compared tp placebo arm

    Time: 45 days

    Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

    Measure: length of hospitalization compared to placebo arm

    Time: 45 days

    Description: Number of days in ICU during index hospitalization

    Measure: length of stay in ICU compared to placebo arm

    Time: 45 days

    Description: Readmissions to ICU through Day 45

    Measure: number of readmissions to ICU compared to placebo arm

    Time: 45 days

    Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

    Measure: organ support free days compared to placebo arm

    Time: 45 days

    Description: Number of readmissions to the hospital through Day 45

    Measure: Frequency of re-hospitalization through day 45 compared to placebo arm

    Time: 45 days

    Description: All-cause mortality through Day 45

    Measure: All-cause mortality through day 45 compared to placebo arm

    Time: 45 days

    Description: Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD

    Measure: CD4+ and CD8+ T cell counts compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

    Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm

    Time: 30 days

    Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

    Measure: Physiological status through NEWS2 evaluation compared to Placebo arm

    Time: 30 days

    Other Outcomes

    Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)

    Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events

    Time: 45 days
    230 Efficacy, Safety, and Tolerability of GLS-1200 Topical Nasal Spray in the Prevention of Incident Confirmed, Symptomatic SARS-CoV-2 Infection in Healthcare Personnel

    This clinical trial will evaluate the safety, tolerability and effectiveness of topical GLS-1200 nasal spray to reduce the incidence of confirmed, symptomatic SARS-CoV-2 infection.

    NCT04408183
    Conditions
    1. SARS-CoV 2
    2. Infection
    Interventions
    1. Drug: GLS-1200
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Measure: Evaluate the number of GLS-1200 topical nasal spray adverse events as assessed by CTCAE v5.0

    Time: 4 weeks of treatment

    Measure: Incidence of SARS-CoV-2 infection, confirmed by PCR relative to treatment group

    Time: 4 weeks of treatment

    Secondary Outcomes

    Measure: Symptom score of documented SARS-CoV-2 infection relative to treatment group with a higher score being a worse outcome.

    Time: 4 weeks of treatment
    231 A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia

    This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

    NCT04409262
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Remdesivir
    2. Drug: Tocilizumab
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Time from Randomization to Hospital Discharge (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or Time: Up to Day 28

    Secondary Outcomes

    Measure: Time to Clinical Improvement (TTCI) Defined as Time from Randomization to National Early Warning Score 2 (NEWS2) Score of Time: Up to Day 60

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

    Time: Up to Day 60

    Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Days 7, 14, 21, and 28

    Time: Days 7, 14, 21, and 28

    Measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline

    Time: Up to Day 60

    Measure: Ventilator-Free Days from Randomization to Day 28

    Time: Up to Day 28

    Measure: Proportion of Participants Requiring Initiation of Intensive Care Unit (ICU) Care Post-baseline

    Time: Up to Day 60

    Measure: Duration of ICU Stay in Days

    Time: Up to Day 60

    Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.

    Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

    Time: Up to Day 60

    Measure: Mortality up to Day 28 and Day 60

    Time: Days 28 and 60

    Measure: Mortality Rate on Days 7, 14, 21, 28, and 60

    Time: Days 7, 14, 21, 28, and 60

    Measure: Time to Recovery, Defined as Time from Randomization to the Time when a Category of 2, Non-ICU Hospital Ward (or "Ready for Hospital Ward") not Requiring Supplemental Oxygen, or Better is Observed

    Time: Up to Day 28

    Measure: Duration of Supplemental Oxygen Use

    Time: Up to Day 60

    Other Outcomes

    Measure: Percentage of Participants with Adverse Events (AEs)

    Time: Up to 60 days

    Measure: Proportion of Participants with any Post-Treatment Infection

    Time: Up to 60 days

    Measure: Plasma Concentration of Remdesivir

    Time: Days 4 and 7
    232 Randomized Double Blind Placebo-Controlled Study to Determine if Prophylaxis With RTB101 Compared to Placebo Reduces Severity of Lab Confirmed COVID19 in Adults ≥65 Years in a Nursing Home in Which ≥1 Person(s) Have Lab Confirmed COVID19

    The purpose of this study is to determine if prophylaxis with RTB101 decreases the severity of laboratory-confirmed COVID-19 among adults ≥ 65 years who reside in a nursing homes in which one or more residents or staff have laboratory-confirmed COVID-19

    NCT04409327
    Conditions
    1. COVID19
    Interventions
    1. Drug: RTB101
    2. Drug: Placebo

    Primary Outcomes

    Measure: The percentage of subjects who develop laboratory-confirmed COVID-19: - with protocol-defined progressive symptoms OR - are hospitalized OR - die

    Time: Through Week 4

    Secondary Outcomes

    Measure: The percentage of subjects who develop symptomatic laboratory-confirmed COVID-19 infection

    Time: Through Week 4

    Measure: Mortality rate in subjects who develop laboratory-confirmed COVID19

    Time: Through Week 8

    Measure: Percent of subjects who are hospitalized due to having one or more predefined COVID-19 symptoms and laboratory-confirmed SARS-CoV-2

    Time: Through Week 4

    Measure: Percent of subjects who require mechanical ventilation, noninvasive ventilation, high flow nasal canula oxygen delivery or ICU admission during the hospitalization for COVID19

    Time: Through Week 8

    Measure: Safety and tolerability will be assessed by report of AE/SAEs

    Time: Through Week 5 and 8
    233 A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)

    This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled, parallel group study to assess the safety and efficacy of CSL312 administered intravenously, in combination with standard of care (SOC) treatment, in patients with Coronavirus disease 2019 (COVID 19)

    NCT04409509
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: The incidence of tracheal intubation or death prior to tracheal intubation

    Time: From randomization to Day 28

    Secondary Outcomes

    Measure: Proportion of subjects with death from all causes

    Time: From randomization to Day 28

    Measure: Proportion of subjects intubated

    Time: From randomization to Day 28

    Measure: Number and proportion of subjects with ≥ 2-point improvement on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal scale

    Time: From randomization to Day 28

    Measure: Number and proportion of subjects within each of the categories of the NIAID

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring continuous positive airway pressure (CPAP)

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring bilevel positive airway pressure (BiPAP)

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring high-flow nasal cannula (HFNC)

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring extracorporeal membrane oxygenation (ECMO)

    Time: From randomization to Day 28

    Measure: Maximum change from baseline in Sequential Organ Failure Assessment (SOFA) score

    Time: From randomization to Day 28

    Measure: Change from Baseline in SOFA score and in the individual components of SOFA score

    Time: From randomization to Day 28

    Measure: Length of hospital stay

    Time: From randomization to Day 28

    Measure: Number and proportion of subjects experiencing Adverse Events (AEs)

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Number and proportion of subjects experiencing serious adverse events (SAEs)

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Number and proportion of subjects with adverse events of special interest (AESIs)

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Number and proportion of subjects with CSL312 induced anti-CSL312 antibodies

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Maximum plasma concentration (Cmax) of CSL312

    Time: Up to 28 days after CSL312 administration

    Measure: Time to maximum plasma concentration (Tmax) of CSL312

    Time: Up to 28 days after CSL312 administration

    Measure: Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last) of CSL312

    Time: Up to 28 days after CSL312 administration

    Measure: Terminal half-life (T1/2) of CSL312

    Time: Up to 28 days after CSL312 administration
    234 Study of the P2Et Extract Obtained From Caesalpinia Spinosa in the Symptomatic Treatment of Subjects With COVID-19 at the Hospital Universitario San Ignacio, Colombia.

    Antioxidants, and particularly polyphenols, have shown protection in respiratory pathologies, which is related to the decrease in the severity of the clinical picture and suppression of inflammation. This suppression of inflammation may be related to the inhibition of NF-kB polyphenols, where its activation is related to the stimulation of 150 stimuli including cytokines (IL-1β, IL-6, THF-α, GM-CSF, MCP-1), TLRs, among others. There may be other additional mechanisms that can help control virus-induced respiratory pathologies, among which are the regulation of reactive oxygen species (ROS) associated with tissue destruction caused by the virus and a selective antiviral action can be reported. direct. The standardized P2Et extract obtained from C. spinosa, by the Immunobiology Group of the Pontificia Universidad Javeriana, is highly antioxidant, decreases lipid peroxidation and tissue damage and induces complete autophagy in stressed or tumor cells. The induction of a full autophagic flow could inhibit the replication of beta-coronaviruses like SARS-CoV-2. Furthermore, P2Et can decrease the factors involved in tissue damage by reducing IL-6 and decrease ILC2 cells of the lung in animals with lung metastases (unpublished data). These antecedents suggest that the supplementation of patients with COVID-19 with the extract P2Et, could improve their general condition and decrease the inflammatory mediators and the viral load.

    NCT04410510
    Conditions
    1. COVID
    2. Coronavirus Infection
    3. SARS-CoV 2
    4. COVID19
    Interventions
    1. Drug: P2Et (Caesalpinia spinosa extract)
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of patients who reduce the time in the hospital

    Measure: Evaluate the efficacy of P2Et in reducing the length of hospital stay of patients with clinical suspicion or confirmed case of COVID-19

    Time: 30 days

    Secondary Outcomes

    Description: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19

    Measure: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19

    Time: 30 days

    Description: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment

    Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment

    Time: 30 days

    Description: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment

    Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment

    Time: 30 days

    Description: Assess the efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.

    Measure: Efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.

    Time: 30 days

    Description: Evaluate the efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.

    Measure: Efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.

    Time: 30 days

    Description: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19

    Measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19

    Time: 30 days
    235 Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy

    It still unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes, including the timing of maternal viral exposure by gestational age, the effects of parity, age, host immune responses, coexisting medical and obstetrical conditions and the effects of treatment regimens. While further information is gathered, based on the existing evidence from other infections causing pneumonia, pregnant women should be considered to be at high risk for developing severe infection during the current COVID-19 epidemic. Results from clinical trials with HCQ in nonpregnant adults may not be directly extrapolated to pregnant women given the special features of the pregnancy status. Thus, clinical research is urgently needed to improve the care and reduce the risk of poor pregnancy outcomes of women in this and in future epidemics.

    NCT04410562
    Conditions
    1. Pregnancy Related
    2. COVID
    3. Covid-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start

    Measure: Number of PCR confirmed cases among pregnant women

    Time: 21 days after intervention

    Secondary Outcomes

    Measure: Incidence of COVID-19 disease during pregnancy

    Time: through study completion, an average of 1 year

    Measure: Incidence of COVID-19-related admissions

    Time: through study completion, an average of 1 year

    Measure: Incidence of all-cause admissions

    Time: through study completion, an average of 1 year

    Measure: Incidence of all-cause outpatient attendances

    Time: through study completion, an average of 1 year

    Measure: Mean duration of symptoms-signs of COVID-19

    Time: through study completion, an average of 1 year

    Measure: Frequency and severity of adverse events

    Time: through study completion, an average of 1 year

    Measure: Incidence of preeclampsia

    Time: through study completion, an average of 1 year

    Measure: Incidence of gestational diabetes

    Time: through study completion, an average of 1 year

    Measure: Incidence of SARS-CoV-2 infections during pregnancy

    Time: through study completion, an average of 1 year

    Measure: Prevalence of intrauterine growth restriction

    Time: through study completion, an average of 1 year

    Measure: Maternal mortality rate

    Time: through study completion, an average of 1 year

    Measure: Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate.

    Time: through study completion, an average of 1 year

    Measure: Proportion of neonates with clinical signs/symptoms of COVID-19

    Time: through study completion, an average of 1 year

    Measure: Prevalence of low birth weight (<10th centile according to local standards)

    Time: through study completion, an average of 1 year

    Measure: Prevalence of preterm birth (<37 weeks of gestational age)

    Time: through study completion, an average of 1 year

    Measure: Prevalence of embryo and foetal losses (miscarriages and stillbirths)

    Time: through study completion, an average of 1 year

    Measure: Frequency of congenital malformations

    Time: through study completion, an average of 1 year

    Measure: Proportion of adverse perinatal outcome

    Time: through study completion, an average of 1 year

    Measure: Neonatal morbidity

    Time: through study completion, an average of 1 year

    Measure: Neonatal mortality rate

    Time: through study completion, an average of 1 year
    236 Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients

    The recent inception of the coronavirus SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused thousands of deaths globally. The most frequently reported complications among COVID-19 patients are from respiratory involvement. Vitamin D has immunomodulatory effects that could protect against COVID-19 infection. Indeed, there is good evidence from randomized clinical trials suggesting that high doses of vitamin D administered during cold seasons prevent viral respiratory infections in at risk individual, and more recently, observational studies suggested that the mortality rate from COVID-19 is inversely correlated with levels of serum 25(OH)vitamin D. The hypothesis of the study is that a high dose of vitamin D given orally to patients admitted to the hospital for COVID-19 will prevent the occurrence of respiratory deragement and other adverse clinical events. To evaluate the aforementioned hypothesis, a randomized, controlled, double-blind, clinical trial comparing a 500.000 UI dose of vitamin D versus placebo among COVID-19 patients at moderate risk, requiring hospitalization but without requirements of critical care at admission was designed. The intervention will be one dose of 500.000 UI given orally or matching placebo. The trial has a sequential design with two steps: - The first step, projected to include 200 patients, will assess the effects of the intervention on the respiratory SOFA; and - If there is a detectable effects, the second step, projected to include 1265 patients, will assess the effects on a combined event that includes need of high dose of oxygen or mechanical ventilation. All study outcomes will be measured during the index hospitalization.

    NCT04411446
    Conditions
    1. COVID
    Interventions
    1. Drug: Vitamin D
    2. Drug: Placebo

    Primary Outcomes

    Description: Is the respiratory component of the sequential organ failure assessment score (SOFA score). It is a 4 points scale, each point indicate a deeper respiratory impairment. The score is based on the relationship between the arterial pressure of oxygen (PaO2) and inspired fraction of oxygen (FiO2), as the ratio of both (PaFi). In the cases were arterial blood gas are not measured, the pulse oximetry will be used instead. The respiratory SOFA is as follows: 1: PaO2/FiO2 >=300; 2: PaO2/FiO2 >=200 and <300; 3: PaO2/FiO2 >=100 and <200; 4: PaO2/FiO2 <300. The minimum respiratory SOFA score will be record on daily basis during first week or to death or discharge, whichever occur first. This outcome is the primary outcome of the first study phase.

    Measure: Respiratory SOFA.

    Time: One week

    Description: The start of oxygen supplementation at FiO2 >40% or the initiation of invasive through orotracheal intubation) or non-invasive ventilation (Continuous positive airway pressure or Bilevel positive airway ventilation). This outcome will be recorded during hospitalization to 30 days, the death or discharge, whichever occur first. This is the primary outcome of the second study phase.

    Measure: Need of a high dose of oxygen or mechanical ventilation.

    Time: 30 days

    Secondary Outcomes

    Description: Difference between the oxygen saturation at study entry and the lowest oxygen saturation measured during the first week, the death or discharge, whichever occur first. The oxygen saturation will be measured by pulse oximetry using commercially available devices.

    Measure: Change in oxygen saturation.

    Time: One week

    Description: Oxygen saturation equal or less than 90% in any moment during the hospitalization. This outcome will be measured by pulse oximetry using commercially available devices. The outcome will be measured during the first week, the death or hospital discharge, whichever occur first.

    Measure: Oxygen desaturation.

    Time: One week

    Description: The difference between the Quick SOFA score at study entry and the highest value recorded during the hospitalization. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Change in Quick SOFA score.

    Time: 30 days.

    Description: Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Myocardial infarction.

    Time: 30 days

    Description: Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Stroke.

    Time: 30 days

    Description: Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Acute kidney injury.

    Time: 30 days

    Description: Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Pulmonary thromboembolism.

    Time: 30 days

    Description: Combined outcome of the aforementioned events, Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism.

    Time: 30 days

    Description: Admission to Intensive Care Unit due to clinical deterioration as judged by the treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Admission to ICU.

    Time: 30 days

    Description: The start of mechanical ventilation invasive during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Invasive Mechanical Ventilation.

    Time: 30 days

    Description: Total duration of initial hospital stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with hospital stays longer than 30 days, it will considered as 30 days.

    Measure: Hospital Length of Stay.

    Time: 30 days.

    Description: Total duration of initial ICU stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with ICU stays longer than 30 days, it will considered as 30 days.

    Measure: ICU length of stay.

    Time: 30 days

    Description: Death of any cause during the hospitalization until 30 days or discharge whichever occur first.

    Measure: Death

    Time: 30 days.
    237 A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI

    Clinical phase 3 study to investigate the effect of recAP on 28 day mortality in patients admitted to the ICU with acute kidney injury that is caused by sepsis. The study has three distinct SA-AKI trial populations: 1. The main trial population: Patients with a pre-AKI reference eGFR ≥45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization. 2. A 'moderate' CKD population: Patients with a pre-AKI reference eGFR ≥25 and <45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization. 3. A COVID-19 population: Patients with proven or suspected SARS-CoV-2 at time of randomization with or without 'moderate' CKD. In the main study population approximately 1400 patients will be enrolled and in the two cohorts with moderate CKD and COVID-19 each up to 100 patients. There are two arms in the study, one with active treatment and one with an inactive compound (placebo). Treatment is by 1 hour intravenous infusion, for three days. Patients are followed up for 28 days to see if there is an improvement on mortality, and followed for 90 and 180 days for mortality and other outcomes e.g. long-term kidney function and quality of life.

    NCT04411472
    Conditions
    1. Acute Kidney Injury Due to Sepsis
    Interventions
    1. Biological: Recombinant human alkaline phosphatase
    2. Other: Placebo
    MeSH:Sepsis Acute Kidney Injury
    HPO:Acute kidney injury Sepsis

    Primary Outcomes

    Description: To demonstrate an effect of recAP on 28 day all cause mortality

    Measure: 28-day all-cause mortality

    Time: 28 days

    Secondary Outcomes

    Description: MAKE 90: dead or on RRT or ≥25% decline in estimated glomerular filtration rate (eGFR) on Day 90 relative to the known or assumed pre-AKI reference level.

    Measure: To investigate the effect of recAP on long-term Major Adverse Kidney Events (MAKE).

    Time: 90 Days

    Description: Days alive and free of organ support through Day 28, i.e., days alive with no MV, RRT, vasopressors or inotropes (with death within 28 days counting as zero days).

    Measure: To investigate the effect of recAP on use of organ support, i.e., mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors or inotropes.

    Time: 28 days

    Description: Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).

    Measure: To investigate the effect of recAP on length of stay (LOS) in ICU.

    Time: 28 days

    Description: Time to death through Day 90.

    Measure: To investigate the effect of recAP on 90-day allcause mortality

    Time: 90 days
    238 A Randomized, Placebo-Controlled, Double-Blind, Sponsor Unblinded, Single Ascending Dose, Phase 1 First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous LY3819253 in Participants Hospitalized for COVID-19

    The purpose of this study is to test the safety and tolerability of LY3819253 when it is given by injection into a vein to participants hospitalized with COVID-19. Blood tests will be done to check how much LY3819253 is in the bloodstream and how long the body takes to eliminate it. Participation could last about 8 weeks and may include up to 15 visits in the hospital or the home.

    NCT04411628
    Conditions
    1. COVID-19
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo

    Primary Outcomes

    Description: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

    Measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

    Time: Baseline through Day 60

    Secondary Outcomes

    Description: PK: AUC of LY3819253

    Measure: Pharmacokinetics (PK): Area Under the Concentration-time Curve (AUC) of LY3819253

    Time: Baseline through Day 29

    Description: PD: Change from Baseline in Viral Load

    Measure: Pharmacodynamics (PD): Change from Baseline to Day 29 in Viral Load

    Time: Baseline, Day 29
    239 A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-002 in Adults With COVID 19 Pneumonia and Acute Lung Injury

    The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT, for the treatment of patients with COVID-19 pneumonia who have mild to moderate ARDS. LIGHT is a cytokine in the TNF super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.

    NCT04412057
    Conditions
    1. COVID-19 Pneumonia
    2. Acute Lung Injury
    3. ARDS
    Interventions
    1. Drug: CERC-002
    2. Drug: Placebo
    MeSH:Pneumonia Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
    HPO:Pneumonia

    Primary Outcomes

    Description: Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation, Extracorporeal membrane oxygenation

    Measure: Proportion of patient alive and free of respiratory failure

    Time: Baseline to Day 28

    Secondary Outcomes

    Description: 1-month mortality

    Measure: Proportion of subjects who are alive

    Time: Baseline to Day 28
    240 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE SAFETY AND EFFICACY OF TOFACITINIB IN HOSPITALIZED PARTICIPANTS WITH COVID-19 PNEUMONIA WHO ARE RECEIVING STANDARD OF CARE THERAPY

    The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1. Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60. An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.

    NCT04412252
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tofacitinib
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using ordinal scale

    Time: Day 28

    Secondary Outcomes

    Description: Ordinal scale of disease severity. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using ordinal scale

    Time: Day 14

    Description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

    Time: Day 14 and Day 28

    Description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Status of discharged or not requiring supplemental oxygen

    Time: Day 28

    Description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

    Measure: Mortality

    Time: Day 60
    241 A Randomized Double-blind Placebo-controlled Study to Evaluate the Safety and Efficacy of ATYR1923 In Adult Patients With Severe Pneumonia Related to SARS-CoV-2 Infection (COVID-19)

    A Phase 2 study to evaluate the safety and preliminary efficacy of ATYR1923, compared to placebo, in hospitalized patients with SARS-CoV-2 (COVID-19) severe pneumonia not requiring mechanical ventilation

    NCT04412668
    Conditions
    1. SARS-CoV-2 (COVID-19) Severe Pneumonia
    Interventions
    1. Drug: ATYR1923 1 mg/kg
    2. Drug: ATYR1923 3 mg/kg
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Incidence of treatment-emergent adverse events (TEAEs)

    Time: Baseline through Day 60

    Secondary Outcomes

    Measure: Time to normalization of oxygen saturation (SpO2) (>93% on room air sustained for at least 24 hours)

    Time: Baseline through Day 14 or discharge

    Measure: Duration of supplemental oxygen (O2) requirement

    Time: Baseline through Day 14 or discharge

    Measure: Number of days with fever (temperature >100.4ºF [38.0ºC])

    Time: Baseline through Day 14 or discharge

    Measure: Time to normalization of temperature (≤100.4ºF [38.0ºC])

    Time: Baseline through Day 14 or discharge

    Measure: Change from baseline in World Health Organization (WHO) Ordinal Scale score on Days 5, 7, 14, 28, and 60

    Time: Baseline through Day 60

    Measure: Time to improvement from inpatient hospital admission based on at least a 1 point reduction in WHO Ordinal Scale score

    Time: Baseline through Day 60
    242 A Randomized, Controlled Clinical Trial of the Safety and Efficacy of Tocilizumab for the Treatment of Severe COVID-19

    The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g. increase in oxygen requirements). Participants will be followed for 28 days.

    NCT04412772
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tocilizumab
    2. Drug: Placebo

    Primary Outcomes

    Description: Clinical Status 7-point ordinal scale: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death

    Measure: Clinical status (on a 7-point ordinal scale) at day 28

    Time: up to day 28

    Secondary Outcomes

    Description: ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of < 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status

    Measure: Clinical improvement

    Time: up to day 28

    Description: iv. Incidence of mechanical ventilation v. Ventilator-free days

    Measure: Mechanical Ventilation

    Time: up to day 28

    Description: vi. Duration of time on supplemental oxygen

    Measure: Oxygenation

    Time: up to day 28
    243 A Randomized Clinical Trial for Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination to Prevent Infections by COVID-19: The ACTIVATE II Trial

    Based on findings of the interim analysis of the ACTIVATE study showing 53% decrease of the incidence of all new infections with BCG vaccination, a new trial is designed aiming to validate if BCG can protect against COVID-19 (Corona Virus Disease-19).The aim of the study is to demonstrate in a double-blind, placebo-controlled approach if vaccination of participants susceptible to COVID-19 with BCG vaccine may modulate their disease susceptibility for COVID-19. This will be validated using both clinical and immunological criteria. At the same time, a sub-study will be conducted and the mechanism of benefit from BCG vaccination by assessing its effect on vascular endothelial function and mononuclear blood cells will be studied

    NCT04414267
    Conditions
    1. COVID-19
    2. Virus Diseases
    3. Corona Virus Infection
    4. Coronary Heart Disease
    5. Chronic Obstructive Pulmonary Disease
    Interventions
    1. Biological: BCG vaccine
    2. Biological: Placebo
    MeSH:Infection Virus Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Heart Diseases Coronary Disease
    HPO:Chronic pulmonary obstruction Pulmonary obstruction

    Primary Outcomes

    Description: This is set on visit 3 (90 ± 5 days from the date of visit 1). The two groups of vaccination are compared for the primary endpoints which is composite. Patients who meet any of the following will be considered to meet the primary endpoint: Positive for the respiratory questionnaire endpoint when at least one of the following combination is met either at visit 2 and/or at visit 3: One situation definitively related to COVID-19 All four questions of symptoms possibly related to COVID-19 At least two questions of symptoms possibly related to COVID-19 as well as need for admission at the emergency department of any hospital and/or need for intake of antibiotics At least four questions of symptoms probably related to COVID-19 one of which is "need for admission at the emergency department of any hospital and/or need for intake of antibiotics" Positive IgG or IgM antibodies against SARS-CoV-2

    Measure: Positive for the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 3.

    Time: Visit 3 (90 +/- 5 days)

    Secondary Outcomes

    Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint on visit 4

    Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 4

    Time: Visit 4 (135 +/- 5 days)

    Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint (as defined at primary study endpoint) on visit 5

    Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 5

    Time: Visit 5 (180 +/- 5 days)

    Description: Prevalence of IgG/IgM against SARS-CoV-2 will be measured among the patients who failed the eligibility procedure and the patients that were eligible and were enrolled

    Measure: Prevalence of IgG/IgM against SARS-CoV-2

    Time: Screening Visit and Visit 3 (90 +/- 5 days)

    Description: Itemized analysis of each of the components of the respiratory questionnaire on each study visit

    Measure: Analysis of each of the components of the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19.

    Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: The impact of new cardiovascular events between the two study groups (placebo and BCG) will be analyzed, though the collection of any cardiovascular events occured to the enrolled patients.

    Measure: The impact of new cardiovascular events between the two study groups

    Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of arterial stiffness in visit 3 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.

    Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 3 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.

    Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of endothelial function in visit 3 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 3 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of arterial stiffness in visit 5 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.

    Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 5 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.

    Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 5 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of endothelial function in visit 5 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in cardiac ultrasound at visit 5 between the two sub-study groups (placebo or BCG) will be assessed using standard measurements from 2-D and Doppler echocardiography.

    Measure: Differences in cardiac ultrasound at visit 5 between the two sub-study groups

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups (placebo or BCG) will be analyzed

    Measure: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)
    244 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia

    Opaganib, a sphingosine kinase-2 (SphK2) inhibitor, has been broadly tested in Phase I/II studies. Extensive nonclinical data indicates both anti-viral and anti-inflammatory activity via selective SphK2 inhibition which may prove beneficial for treating COVID-19 infection and resulting pneumonia. This proof of concept study will take place in the US and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. Half of the patients, i.e. 20 patients, will receive opaganib in addition to standard of care for 14 days. The other 20 will receive matching placebo (capsules that do not contain the medication) in addition to standard of care. Study drug will be administered every day for 14 days, twice each day, unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.

    NCT04414618
    Conditions
    1. Coronavirus Infections
    Interventions
    1. Drug: Opaganib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Measurement of the oxygen requirement

    Measure: Evaluation of the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days

    Time: Every day from day 1 to day 14 of treatment

    Secondary Outcomes

    Description: Measurement of the oxygen requirement

    Measure: Evaluation of the time to 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min

    Time: Every day from day 1 to day 14 of treatment

    Measure: Evaluation of the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Measurement of temperature

    Measure: Evaluation of the proportion of afebrile patients at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

    Measure: Evaluation of the time to negative swabs for SARS-CoV-2 by PCR

    Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

    Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

    Measure: Evaluation of the proportion of patients with negative swabs for SARS-CoV-2 by PCR at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

    Measure: The percentage of patients who require intubation and mechanical ventilation by Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Measure: Evaluation of the time to mechanical ventilation

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Evaluation the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C[100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14

    Measure: Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Measure: Evaluation of mortality 30 days post-baseline

    Time: 30 days after day 1 of treatment

    Other Outcomes

    Measure: To determine the incidence rate of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Time: Every day from day 1 to day 14 of treatment and at end of the 4 weeks follow-up after the end of treatment
    245 A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Axatilimab for the Treatment of Hospitalized Patients With Respiratory Signs and Symptoms Secondary to Novel Coronavirus Disease (COVID-19)

    This is a randomized, double-blind, placebo-controlled, 29-day study to assess the efficacy and safety of axatilimab plus standard of care, compared with placebo plus standard of care, in patients with respiratory signs and symptoms secondary to novel coronavirus disease (COVID-19).

    NCT04415073
    Conditions
    1. Coronavirus
    2. COVID
    3. ARDS
    4. Cytokine Storm
    5. Cytokine Release Syndrome
    Interventions
    1. Drug: SNDX-6352
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Respiratory failure as defined by need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation >6L oxygen/minute, or clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making is driven solely by resource limitation

    Measure: Proportion of subjects alive and free of respiratory failure

    Time: 29 Days

    Secondary Outcomes

    Description: Proportion of subjects achieving a ≥ 2 category improvement on 7-point ordinal score relative to the baseline on Day 28 as collected on Day 29

    Measure: Secondary clinical improvement outcomes

    Time: 29 Days

    Description: National early warning score (NEWS) of ≤2 maintained for 24 hours

    Measure: Time to clinical improvement (TTCI)

    Time: 29 Days

    Description: Change from baseline to Day 29 or hospital discharge or death, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen (SpO2/FiO2)

    Measure: To evaluate improvement in oxygenation in hospitalized adults with respiratory signs and symptoms secondary to COVID 19 treated with axatilimab

    Time: 29 Days

    Description: Serum concentrations of IL 6 and c-reactive protein (CRP) change from baseline to Day 15 or hospital discharge or death

    Measure: To evaluate changes in biomarkers following treatment with axatilimab

    Time: 15 Days

    Description: Frequency and severity of AEs and SAEs

    Measure: To evaluate the safety and tolerability of axatilimab in the same population

    Time: 29 Days

    Description: Proportion of subjects who require initiation of mechanical ventilation after study entry

    Measure: Ventilation outcomes

    Time: 29 Days

    Description: Proportion of subjects who are SARS CoV-2 virus free by Day 15 or hospital discharge, whichever is sooner

    Measure: To evaluate antiviral effect of axatilimab in hospitalized adults with recently diagnosed SARS CoV-2 infection

    Time: Day 15

    Description: Serum concentration of axatilimab and presence of anti-drug antibody

    Measure: To characterize exposure to axatilimab

    Time: 29 Day
    246 Investigation of Tofacitinib to Mitigate the Impact of COVID-19 (I-TOMIC) in Moderate SARS-CoV-2 (MODERATE I-TOMIC)

    The purpose of this randomized, double blinded, placebo controlled study is to assess the efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have serologic markers of inflammation but do not need mechanical ventilation.

    NCT04415151
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tofacitinib 10 mg
    2. Drug: Placebo

    Primary Outcomes

    Description: The primary objective of this study is to determine whether tofacitinib improves the clinical outcomes of patients with moderate SARS-CoV-2 infection as determined by the primary outcome measure: Proportion of subjects alive and not needing any form of mechanical ventilation, high flow oxygen, or ECMO by day 14.

    Measure: Disease Severity

    Time: 14 days

    Secondary Outcomes

    Description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) at day 14. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical improvement

    Time: 14 days

    Description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) (days 3 through day 14): The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical improvement

    Time: Up to 14 days

    Description: Time to recovery [ Time Frame: Day 1 through Day 14] (Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities)

    Measure: Time to recovery

    Time: Up to 14 days

    Description: Time to clinical improvement (defined as a 2-point increase on the NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities). The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Time to clinical improvement

    Time: 30 days

    Description: Clinical status on the NIAID 8-point ordinal scale at day 30 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical status

    Time: 30 Days

    Description: Clinical status on the NIAID 8-point ordinal scale at day 60 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical status

    Time: 60 Days

    Description: Clinical status on the NIAID 8-point ordinal scale at day 90 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical status

    Time: 90 Days

    Description: Mortality rate at day 30

    Measure: Mortality

    Time: 30 Days

    Description: Mortality rate at day 60

    Measure: Mortality

    Time: 60 Days

    Description: Mortality rate at day 90

    Measure: Mortality

    Time: 90 Days

    Description: Proportion of patients requiring mechanical ventilatory support.

    Measure: Mechanical Ventilatory Support

    Time: Up to 14 Days

    Description: Duration of invasive mechanical ventilation (days).

    Measure: Mechanical Ventilatory Support Duration

    Time: Up to 14 Days

    Description: Invasive mechanical ventilation free days.

    Measure: Freedom from mechanical ventilation

    Time: Up to 14 Days

    Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

    Measure: Adverse events

    Time: Up to 14 days

    Description: Did the patient receive an intervention with additional immunomodulatory agent (i.e. IL-6 targeting therapy)? (y/n)

    Measure: Additional intervention

    Time: Up to 14 days

    Description: Change in SARS-CoV-2 viral titers during intervention.

    Measure: Viral titer

    Time: Up to 14 days
    247 Reducing Hospital Admission of Elderly in SARS-CoV-2 Pandemic Via the Induction of Trained Immunity by Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial

    Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also been shown to induce protection against various infections with a viral aetiology, leading to significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease severity in elderly people, who are known to be at increased risk of illness and death from SARS-CoV-2 infection. Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).

    NCT04417335
    Conditions
    1. COVID-19
    Interventions
    1. Biological: BCG vaccine
    2. Biological: Placebo

    Primary Outcomes

    Measure: SARS-CoV-2 related hospital admission

    Time: Maximum of 1 year

    Secondary Outcomes

    Measure: the duration of hospital admission due to documented COVID-19

    Time: Maximum of 1 year

    Measure: the cumulative incidence of documented SARS-CoV-2 infection

    Time: Maximum of 1 year

    Measure: the cumulative incidence of self-reported acute respiratory symptoms or fever

    Time: Maximum of 1 year

    Measure: the cumulative incidence of death due to documented SARS-CoV-2 infection

    Time: 1 year

    Measure: the cumulative incidence of hospital admission for any reason

    Time: Maximum of 1 year

    Measure: the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection

    Time: Maximum of 1 year
    248 A Randomised, Double-blind, Placebo-controlled Parallel Group Study in IPF Patients Over 12 Weeks Evaluating Efficacy, Safety and Tolerability of BI 1015550 Taken Orally

    To investigate the efficacy of BI 1015550 compared to placebo based on the change from baseline in Forced Vital Capacity (FVC). To investigate safety and tolerability of BI 1015550 in the overall trial population.

    NCT04419506
    Conditions
    1. Idiopathic Pulmonary Fibrosis
    Interventions
    1. Drug: BI 1015550
    2. Drug: Placebo
    MeSH:Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Measure: change from baseline in Forced Vital Capacity (FVC)

    Time: up to 12 weeks

    Secondary Outcomes

    Measure: percentage of patients with Treatment Emergent Adverse Events (TEAE)

    Time: up to 13 weeks
    249 Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection: A Randomized, Double-blind, Placebo Controlled, Telemedicine Study (SynCov Study)

    The investigators hypothesize that the intake of Omni-Biotic® 10 AAD can reduce the duration of diarrhea in Covid-19 disease. The investigators further hypothesize that Omni-Biotic® 10 AAD can reduce stool frequency, improve stool consistency, improve other gastrointestinal symptoms of Covid-19, reduce disease duration and severity, reduce intestinal inflammation and can improve dysbiosis. The investigators aim to perform a randomized, double blind, placebo-controlled study using telemedicine in patients with Covid-19 disease.

    NCT04420676
    Conditions
    1. COVID
    Interventions
    1. Dietary Supplement: Omnibiotic AAD
    2. Dietary Supplement: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Duration of diarrhea (defined as days with 3 or more loose stools)

    Measure: Diarrhea

    Time: 30 days

    Secondary Outcomes

    Description: stool evacuations per days

    Measure: Stool frequency

    Time: 30 days

    Description: Stool consistency according to Bristol stool scale for each evacuation, score 1-7, a higher score means a lower stool consistancy

    Measure: Stool consistency

    Time: 30 days

    Description: presence of anorexia, nausea, vomiting, abdominal pain, bloating (yes/no)

    Measure: Gastrointestinal symptoms

    Time: 30 days

    Description: days patients feel sick, are not able to work or are on sick leave

    Measure: Duration of Covid-19 disease

    Time: 30 days

    Description: mild/moderate/severe

    Measure: Severity of Covid-19 disease

    Time: 30 days

    Description: measured by ELISA

    Measure: Stool Calprotectin

    Time: 30 days

    Description: measured by ELISA

    Measure: Stool Zonulin

    Time: 30 days

    Description: 16S RNA sequencing

    Measure: Microbiome composition

    Time: 30 days
    250 A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection

    The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.

    NCT04421027
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Baricitinib
    2. Drug: Placebo

    Primary Outcomes

    Description: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including ECMO)

    Measure: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including extracorporeal membrane oxygenation [ECMO])

    Time: Day 1 to Day 28

    Secondary Outcomes

    Description: The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants with at Least 1-Point Improvement on NIAID-OS or Live Discharge from Hospital

    Time: Day 10

    Description: Number of Ventilator-Free Days

    Measure: Number of Ventilator-Free Days

    Time: Day 1 to Day 28

    Description: Recovery assessed by the NIAID-OS.

    Measure: Time to Recovery

    Time: Day 1 to Day 28

    Description: Overall Improvement on the NIAID-OS

    Measure: Overall Improvement on the NIAID-OS

    Time: Day 1 to Day 28

    Description: Duration of Hospitalization

    Measure: Duration of Hospitalization

    Time: Day 1 to Day 28

    Description: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline

    Measure: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline

    Time: Day 10

    Description: Mortality

    Measure: Mortality

    Time: Day 1 to Day 28

    Description: Duration of Stay in the ICU in Days

    Measure: Duration of Stay in the Intensive Care Unit (ICU) in Days

    Time: Day 1 to Day 28

    Description: Time to Clinical Deterioration (one-category increase on the NIAID-OS)

    Measure: Time to Clinical Deterioration (one-category increase on the NIAID-OS)

    Time: Day 1 to Day 28

    Description: Time to Resolution of Fever, in Participants with Fever at Baseline

    Measure: Time to Resolution of Fever, in Participants with Fever at Baseline

    Time: Day 1 to Day 28

    Description: The NEWS is used to detect and report changes in illness severity in participants with acute illness. The score is determined from six physiological parameters readily measured over time in hospitalized participants: Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness

    Measure: Mean Change from Baseline on the National Early Warning Score (NEWS)

    Time: Baseline, Day 1 to Day 28

    Description: Time to Definitive Extubation

    Measure: Time to Definitive Extubation

    Time: Day 1 to Day 28

    Description: Time to Independence from Non-Invasive Mechanical Ventilation

    Measure: Time to Independence from Non-Invasive Mechanical Ventilation

    Time: Day 1 to Day 28

    Description: Time to Independence from Oxygen Therapy in Days

    Measure: Time to Independence from Oxygen Therapy in Days

    Time: Day 1 to Day 28

    Description: Number of Days with Supplemental Oxygen Use

    Measure: Number of Days with Supplemental Oxygen Use

    Time: Day 1 to Day 28

    Description: Number of Days of Resting Respiratory Rate <24 Breaths per Minute

    Measure: Number of Days of Resting Respiratory Rate <24 Breaths per Minute

    Time: Day 1 to Day 28
    251 A Randomized Controlled Adaptive Study Comparing COVID-19 Convalescent Plasma (CCP) to Non-immune Plasma to Limit Coronavirus-associated Complications in Hospitalized Patients

    The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset of initial symptoms.

    NCT04421404
    Conditions
    1. COVID-19
    2. Sars-CoV2
    Interventions
    1. Biological: COVID-19 Convalescent Plasma (CCP)
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Progression to mechanical ventilation or death within the first 14 days of enrollment.

    Measure: Mechanical Ventilation or Death Endpoint

    Time: Day 14

    Secondary Outcomes

    Description: Progression to mechanical ventilation or death within the first 28 days of enrollment.

    Measure: Mechanical Ventilation or Death Endpoint

    Time: Day 28

    Description: Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.

    Measure: 8-Point Ordinal Scale Endpoint

    Time: Day 29
    252 A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Subjects With Mild or Moderate Coronavirus (COVID-19)

    A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed inhaled iNO compared to placebo in subjects with COVID-19.

    NCT04421508
    Conditions
    1. COVID-19
    2. Coronavirus
    3. Coronavirus Infection
    Interventions
    1. Combination Product: INOpulse
    2. Combination Product: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: The proportion of subjects who died or had respiratory failure

    Time: Through Day 28

    Secondary Outcomes

    Description: The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale

    Time: Day 7, 14, 28 and day of discharge

    Measure: Proportion of subject to recover, defined as return to room air or baseline O2, or discharged alive

    Time: Through Day 28

    Measure: Proportion of subjects discharged alive from hospital

    Time: Through Day 28

    Measure: Duration of Hospitalization

    Time: Through Day 28

    Measure: Mortality - all cause and cardiopulmonary

    Time: Through Day 28

    Measure: Proportion of subjects with a negative conversion of reverse transcription polymerase chain reaction (RT-PCR) from a nasopharyngeal swab

    Time: Through Day 28

    Other Outcomes

    Measure: Proportion of subjects with adverse events leading to study drug discontinuation

    Time: Through Day 28
    253 Coronavirus Smell Therapy for Anosmia Recovery

    As the COVID-19 pandemic spread around the world, anosmia and dysgeusia were quickly recognized as two of the key presenting symptoms. The probability of return of smell is related to severity of smell loss at presentation, but it appears that the loss of sense of smell and taste seems to persist in approximately 10% of the affected patients after 6 months. As a result of COVID-19, it is estimated that within the next 12 months > 150,000 Americans will suffer permanent loss of smell. The magnitude of this impairment on the health, safety, and quality of life is truly unprecedented and makes post-COVID olfactory disorder a major public health problem. Thus, there is a pressing need to identify effective treatments. The research questions are to determine the effects of steroid nasal saline lavage and olfactory training among adults with post-COVID olfactory dysfunction and identify confounders and modifiers of any observed effects. To answer the research question, the investigators propose a 2 x 2 factorial design blinded randomized clinical trial whereby 220 subjects with documented COVID-19 with anosmia/hyposmia of 12 weeks duration or longer from Missouri, Illinois, and Indiana will be recruited electronically from COVID patient advocacy sites, social media sites, and other internet sources. Enrolled subjects will be randomized to nasal saline lavage with topical budesonide or placebo to address the presumed role of inflammation in the olfactory cleft and each subject will also be randomized to olfactory training with patient-specific, high- or low-concentration essential oil scent to assess the role of olfactory training. Data will be analyzed in a blinded fashion to allow estimation of observed effect size for both anti-inflammatory and olfactory training. This innovative study will exploit the unique opportunities presented by COVID-19. The study will use a high-tech virtual "contactless" research strategy, including eConsent and digital mHealth techniques to obtain rapid answers to the research questions. The interventions are low-cost, readily available, and results of this study can be directly disseminated to the care of COVID-19 patients with anosmia.

    NCT04422275
    Conditions
    1. Anosmia
    Interventions
    1. Drug: Budesonide
    2. Behavioral: High-Concentration Essential Oil
    3. Drug: Placebo
    4. Behavioral: Low-Concentration Essential Oil
    MeSH:Olfaction Disorders
    HPO:Anosmia

    Primary Outcomes

    Description: The University of Pennsylvania Smell Identification Test (UPSIT) (Sensonics, New Jersey)7 is the most widely accepted olfactory identification test in North America. The UPSIT consists of four 10-page booklets, with a total of 40 items. Subjects are asked to scratch each strip with a pencil to release the scents, detect the smell, and identify the smell from the four choice options. The UPSIT comes from a scoring rubric that identifies the normalcy benchmark based on age and gender. Normosmia is defined as ≥34 for males and ≥35 for females, and an increase of 4 points or more from baseline indicates a clinically meaningful improvement. UPSIT has high internal reliability across a wide range of populations.

    Measure: University of Pennsylvania Smell Identification Test (UPSIT)

    Time: The within subject change in UPSIT between baseline and 12- and 24-week assessment time frame.

    Secondary Outcomes

    Description: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) was adapted from the original 52-item Questionnaire of Olfactory Disorders. This short-modified version is a validated 17-item questionnaire about quality of life and impairments related to olfactory dysfunction. The maximum score is 51, and higher values indicate worse quality of life or higher degree of impairment of normal daily activity. Mean scores in anosmics is 19; hyposmics is 8; and normosmics is 0. Prior studies used a cutoff score of 12.5 to reflect normal vs. abnormal scores.The minimum clinically important difference is 5.2.

    Measure: Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS).

    Time: The within subject change in QOD-NS between baseline and assessment time frame.

    Description: The Global Rating of Smell is a single-item, global rating that asks: "Overall, please rate your current sense of smell? Excellent, Very Good, Good, Fair, Poor, Absent."

    Measure: Global Rating of Smell.

    Time: 12 weeks - End of nasal lavage & olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)

    Description: The Global Rating of Smell Change is a single-item, global rating that asks: "Compared to your sense of smell # weeks ago, how would you rate your change in smell since then? Much better, Somewhat better, Slightly better, Neither better nor worse, Slightly worse, Somewhat worse, or Much worse." The time frame ("#") will be changed to reflect the correct time since enrollment (i.e., 12, or 24 weeks).

    Measure: Global Rating of Smell Change.

    Time: 12 weeks - End of olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
    254 Randomized, Single-blind, Double-dummy, 4-fold Cross-over, Placebo- and Active-controlled Study to Investigate the Influence of BAY 1817080 on the QTc Interval in Healthy Male and Female Participants (TQT Study)

    In this study, researchers want to find whether the study drug BAY1817080 has an effect on the electrocardiogram (ECG). 40 healthy male or female participants with the age of 18 to 65 years will be enrolled into this study. The ECG of the participants will be monitored closely by the researchers to detect any change after intake of the study medication.

    NCT04423744
    Conditions
    1. Cough
    2. Endometriosis
    3. Overactive Bladder
    Interventions
    1. Drug: BAY1817080
    2. Drug: Moxifloxacin
    3. Drug: Placebo
    MeSH:Urinary Bladder, Overactive Endometriosis
    HPO:Endometriosis

    Primary Outcomes

    Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 therapeutic dose

    Time: Baseline and Day 3

    Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 supra-therapeutic dose

    Time: Baseline and Day 3

    Secondary Outcomes

    Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after a single oral dose of moxifloxacin

    Time: Baseline and Day 3

    Measure: Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose

    Time: Baseline and Day 3

    Measure: Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after a single oral dose of moxifloxacin

    Time: Baseline and Day 3

    Description: Area under the concentration vs. time curve from zero to 24 hours after multiple doses

    Measure: AUC(0-24)md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose

    Time: Predose and up to 24 hours after last dose of BAY1817080 at Day 3

    Description: Area under the concentration vs. time curve from zero to infinity after single dose

    Measure: AUC after a single oral dose of moxifloxacin

    Time: Predose and up to 24 hours after single dose of moxifloxacin at Day 3

    Description: Maximum observed drug concentration in measured matrix after multiple doses

    Measure: Cmax,md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose

    Time: Up to 24 hours after last dose of BAY1817080 at Day 3

    Description: Maximum observed drug concentration in measured matrix after single dose

    Measure: Cmax after a single oral dose of moxifloxacin

    Time: Up to 24 hours after single dose of moxifloxacin at Day 3

    Measure: Incidences of treatment-emergent adverse events (TEAEs) after BAY1817080 therapeutic or supra-therapeutic dose

    Time: From the start of BAY1817080 administration until 7 days after last dose, assessed up to 10 days
    255 A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of PRV-015 in Adult Patients With Non-Responsive Celiac Disease as an Adjunct to a Gluten-free Diet

    This study will evaluate the efficacy and safety of PRV-015 in adult patients with non-responsive celiac disease (NRCD) who are on a gluten-free diet (GFD).

    NCT04424927
    Conditions
    1. Celiac Disease
    Interventions
    1. Biological: PRV-015
    2. Other: Placebo
    MeSH:Celiac Disease
    HPO:Celiac disease Gluten intolerance

    Primary Outcomes

    Description: Celiac Disease Patient-Reported Outcome (CeD PRO)

    Measure: Efficacy of PRV-015 in attenuating the symptoms of celiac disease in adult patients with NRCD as measured by the Celiac Disease Patient-Reported Outcome (CeD PRO) questionnaire

    Time: 24 weeks

    Secondary Outcomes

    Description: Intraepithelial lymphocyte (IEL) density

    Measure: Effect of treatment with PRV-015 on other measures of disease activity

    Time: 24 weeks

    Description: Safety endpoint

    Measure: Incidence of treatment-emergent adverse events (TEAEs)

    Time: 28 weeks

    Description: Characterize the pharmacokinetics (PK) of PRV-015

    Measure: Serum trough concentrations of PRV-015 at scheduled visits

    Time: 28 weeks

    Description: Immunogenicity endpoint

    Measure: Incidence of anti-PRV-015 antibodies

    Time: 28 weeks
    256 A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Adult Patients With COVID-19-Moderate Type

    This is a multi-center, randomized, double-blind, placebo-controlled, phase III clinical study to evaluate the efficacy of Favipiravir combined with supportive care for adult patients with COVID-19-Moderate type.

    NCT04425460
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Other: Placebo

    Primary Outcomes

    Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72h. Criteria for normalization or relief: Pyrexia (body temperature): axillary ≤37℃，or oral≤37.5℃，or rectal or tympanic ≤38℃; Respiratory rate: ≤24/min without oxygen inhalation; SPO2: >94% without oxygen inhalation; Cough: Subject-perceived improvement or resolution of cough.

    Measure: Time from randomization to clinical recovery

    Time: 28 days

    Secondary Outcomes

    Description: Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;

    Measure: Negativity in RT-PCR nucleic acid test

    Time: 28 days

    Description: Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;

    Measure: Time from randomization to resolution of pyrexia

    Time: 28 days

    Description: Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization; It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0: Mild: Requires non-prescription treatment; Moderate: Requires medication treatment; limits instrumental activities of daily living; Severe: Limits self-care activities of daily living;

    Measure: Time from randomization to relief of cough

    Time: 28 days

    Description: Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;

    Measure: Incidence of deterioration/aggravation of pneumonia

    Time: 28 days

    Description: Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;

    Measure: Time from randomization to relief of dyspnoea

    Time: 28 days

    Description: Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization;

    Measure: Rate of auxiliary oxygen therapy or non-invasive ventilation

    Time: 28 days

    Description: ICU admission rate within 28 days of randomization (except patients already enrolled in ICU which respect eligibility criteria);

    Measure: ICU admission rate within 28 days of randomization

    Time: 28 days

    Description: All-cause mortality within 28 days of randomization.

    Measure: All-cause mortality within 28 days of randomization.

    Time: 28 days
    257 A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19

    The primary objectives are: Phase 1 - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 2 • To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 3 • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo

    NCT04425629
    Conditions
    1. COVID-19
    Interventions
    1. Drug: REGN10933+REGN10987 combination therapy
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary: Phase 1 Secondary: Phase 2, Phase 3

    Measure: Proportion of patients with treatment-emergent serious adverse events (SAEs)

    Time: Through Day 29

    Description: Primary: Phase 1 Secondary: Phase 2, Phase 3

    Measure: Proportion of patients with infusion-related reactions

    Time: Through Day 4

    Description: Primary: Phase 1 Secondary: Phase 2, Phase 3

    Measure: Proportion of patients with hypersensitivity reactions

    Time: Through Day 29

    Description: Primary: Phase 1, Phase 2 Secondary: Phase 3

    Measure: Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples

    Time: Baseline up to Day 22

    Description: Primary: Phase 3 Secondary: Phase 1, Phase 2

    Measure: Proportion of patients with at least one COVID-19 related medically attended visit

    Time: Through Day 29

    Secondary Outcomes

    Description: Phase 1 Only

    Measure: Time-weighted average change from baseline in viral shedding measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 22

    Description: Phase 1 Only

    Measure: Time-weighted average change from baseline in viral shedding measured by RT-qPCR in nasal swab samples

    Time: Baseline up to Day 22

    Description: Phase 1 Only

    Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples

    Time: Through Day 29

    Description: Phase 2, Phase 3

    Measure: Time to negative RT-qPCR in NP swabs with no subsequent positive RT-qPCR

    Time: Through Day 29

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in NP swabs

    Time: Baseline up to Day 29

    Description: Phase 1 Only

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 29

    Description: Phase 1 Only

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in nasal swabs

    Time: Baseline up to Day 29

    Description: Phase 1 Only

    Measure: Correlation of RT-qPCR results over time between different sample types (NP, nasal, and saliva)

    Time: Up to Day 29

    Description: Phase 1 Only

    Measure: Concordance of RT-qPCR results over time between different sample types (NP, nasal, and saliva)

    Time: Up to Day 29

    Measure: Time-weighted average change from baseline in viral shedding

    Time: Baseline up to Day 29

    Description: Phase 1 Phase 2

    Measure: Proportion of patients with at least two COVID-19 related medically attended visits

    Time: Through Day 29

    Measure: Total number of COVID-19 related medically-attended visits

    Time: Through Day 29

    Measure: Proportion of patients admitted to a hospital due to COVID-19

    Time: Through Day 29

    Description: Phase 2, Phase 3

    Measure: Proportion of patients admitted to an intensive care unit (ICU) due to COVID-19

    Time: Through Day 29

    Measure: Proportion of patients at least 1 outpatient or telemedicine visit due to COVID-19

    Time: Through Day 29

    Description: Phase 2, Phase 3

    Measure: Proportion of patients requiring mechanical ventilation due to COVID-19

    Time: Through Day 29

    Description: Phase 2, Phase 3

    Measure: Number of days of hospitalization due to COVID-19

    Time: Through Day 29

    Description: Phase 2, Phase 3

    Measure: Number of deaths due to any cause (All-Cause Mortality)

    Time: Through Day 29

    Description: Phase 2

    Measure: Time to first onset of symptoms consistent with COVID-19 (asymptomatic cohort only)

    Time: Up to Day 29

    Description: Phase 2

    Measure: Duration of symptoms consistent with COVID-19

    Time: Up to Day 29

    Measure: Serum concentration of REGN10933 over time

    Time: Through Day 29

    Measure: Serum concentration of REGN10987 over time

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10987

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933

    Time: Through Day 29

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987

    Time: Through Day 29

    Measure: Incidence of anti-drug antibodies (ADA) to REGN10933

    Time: Through Day 29

    Measure: Incidence of anti-drug antibodies (ADA) to REGN10987

    Time: Through Day 29
    258 A Study to Assess the Safety, Tolerability, and Pharmacodynamics of Multiple Dose MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia

    The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of MK-5475 after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that MK-5475 when administered to participants with COVID-19 pneumonia and hypoxemia improves arterial oxygenation as measured by the ratio of blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio) compared to placebo.

    NCT04425733
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    2. Pneumonia
    3. Hypoxemia
    Interventions
    1. Drug: MK-5475
    2. Drug: Placebo
    MeSH:Pneumonia Hypoxia
    HPO:Hypoxemia Pneumonia

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.

    Measure: Number of Participants Who Experience an Adverse Event (AE)

    Time: Up to ~Day 21

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study drug due to an AE will be reported.

    Measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

    Time: Up to ~Day 7

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours post-dose on Day 1 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 1 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 1.

    Measure: Change From Baseline to Day 1 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 2 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 2 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 2.

    Measure: Change From Baseline to Day 2 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 3 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 3 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 3.

    Measure: Change From Baseline to Day 3 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 4 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 4 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 4.

    Measure: Change From Baseline to Day 4 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 5 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 5 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 5.

    Measure: Change From Baseline to Day 5 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 6 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 6 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 6.

    Measure: Change From Baseline to Day 6 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 7 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 7 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 7.

    Measure: Change From Baseline to Day 7 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
    259 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Oncology Cohort

    Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

    NCT04426201
    Conditions
    1. COVID-19
    2. Lymphocytopenia
    Interventions
    1. Drug: CYT107
    2. Drug: Placebo
    MeSH:Lymphopenia
    HPO:Lymphopenia

    Primary Outcomes

    Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or HospitalDischarge

    Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first

    Time: one month

    Secondary Outcomes

    Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score

    Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD.

    Time: one month

    Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

    Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD

    Time: 1 month or HD (whichever occurs first)

    Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

    Measure: frequency of secondary infections through day 45 compared to placebo arm

    Time: 45 days

    Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

    Measure: length of hospitalization compared to placebo arm

    Time: 45 days

    Description: Number of days in ICU during index hospitalization

    Measure: length of stay in ICU compared to placebo arm

    Time: 45 days

    Description: Readmissions to ICU through Day 45

    Measure: number of readmissions to ICU compared to placebo arm

    Time: 45 days

    Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

    Measure: organ support free days compared to placebo arm

    Time: 45 days

    Description: Number of readmissions to the hospital through Day 45

    Measure: Frequency of re-hospitalization through day 45 compared to placebo arm

    Time: 45 days

    Description: All-cause mortality through Day 45

    Measure: All-cause mortality through day 45 compared to placebo arm

    Time: 45 days

    Description: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA) through Day 30 or HD

    Measure: CD4+ and CD8+ T cell counts compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

    Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm

    Time: 30 days

    Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

    Measure: Physiological status through NEWS2 evaluation compared to Placebo arm

    Time: 30 days

    Other Outcomes

    Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety

    Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events

    Time: 45 days
    260 A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19

    The primary objectives are: Phase 1 - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 2 - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 - To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status Phase 3 - To evaluate and confirm the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status

    NCT04426695
    Conditions
    1. COVID-19
    Interventions
    1. Drug: REGN10933+REGN10987 combination therapy
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary: Up to Day 169: Phase 1: C1 Secondary: Up to Day 29: Phase 1: C1, Phase 2: C1A, C1, C2, C3 Up to Day 57: Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients with treatment-emergent Serious Adverse Events (SAEs)

    Time: Through Day 169

    Description: Primary: Phase 1:C1 Secondary: Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients with infusion-related reactions

    Time: Through Day 4

    Description: Primary: Phase 1:C1 Secondary: Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients with hypersensitivity reactions

    Time: Through Day 29

    Description: Phase 1:C1 Phase 2: C1A, C1, C2, C3

    Measure: Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples

    Time: Baseline up to Day 22

    Description: Primary: Day 8: Phase 2: C1A, C1, Phase 3:C1 Day 22: Phase 2:C2, C3, Phase 3:C2, C3 Secondary: Day 8: Phase 1:C1 Day 29: Phase 1:C1, Phase 2: C1A, C1, C2, C3 7-point Ordinal Scale: Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized

    Measure: Proportion of patients with at least 1-point improvement on a 7-Point Ordinal Scale in clinical status

    Time: From Day 1 up to Day 29

    Secondary Outcomes

    Description: Phase 1: C1

    Measure: Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 22

    Description: Phase 1: C1

    Measure: Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in nasal samples

    Time: Baseline up to Day 22

    Description: Phase 1: C1

    Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples

    Time: Through Day 29

    Description: Phase 2: C1A, C1, C2, C3

    Measure: Time to negative RT-qPCR in NP swabs with no subsequent positive RT-qPCR

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in NP swabs

    Time: Baseline up to Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Time-weighted average change in viral shedding

    Time: Baseline up to Day 29

    Description: Phase 1: C1

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 29

    Description: Phase 1: C1

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in nasal swabs

    Time: Baseline up to Day 29

    Description: Phase 1: C1

    Measure: Correlation of RT-qPCR results over time between different sample types

    Time: Up to Day 29

    Description: Phase 1: C1

    Measure: Concordance of RT-qPCR results over time between different sample types

    Time: Up to Day 29

    Description: Phase 1: C1, Phase 2: C1A, C1 Day 8 Phase 2: C2, C3 Day 22 Phase 1: C1, Phase 2: C1A, C1, C2, C3 Day 29

    Measure: Proportion of patients with at least 2-point improvement on a 7-Point Ordinal Scale in clinical status

    Time: From Day 1 up to Day 29

    Description: Phase 1: C1 Phase 2: C1, C2, C3

    Measure: Time to no longer requiring oxygen supplementation

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of supplemental oxygen use

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients initiating high-intensity oxygen therapy

    Time: Up to Day 29 or hospital discharge

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of high-intensity oxygen therapy

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients initiating mechanical ventilation

    Time: Up to Day 29 or hospital discharge

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of mechanical ventilation

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of Ventilator-free days

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of hospitalization

    Time: Through Day 29

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 57

    Measure: Proportion of patients re-admitted to hospital after discharge through the end of study

    Time: Through Day 169

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients admitted into an intensive care unit (ICU)

    Time: Up to Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Days of ICU stay

    Time: Up to Day 29

    Description: Phase 1: C1 Through Day 29 and Day 169 Phase 2: C1A, C1, C2, C3 Through Day 29 and Day 57

    Measure: Number of deaths due to any cause (All-Cause Mortality)

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 57

    Measure: Overall Survival

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Serum concentration of REGN10933 over time

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Serum concentration of REGN10987 over time

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Incidence of anti-drug antibodies (ADA) to REGN10933

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Incidence of anti-drug antibodies (ADA) to REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933

    Time: Through day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987

    Time: Through day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Observed terminal half-life [t1/2] for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Observed terminal half-life [t1/2] of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Clearance (CL) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Clearance (CL) of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Mean residence time (MRT) of REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Mean residence time (MRT) of REGN10987

    Time: Through Day 169
    261 A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of LY3819253 and LY3832479 in Participants With Mild to Moderate COVID-19 Illness

    The purpose of this study is to measure how well LY3819253 and LY3832479 work against the virus that causes COVID-19. LY3819253 and LY3832479 will be given to participants with early symptoms of COVID-19, via an injection into a vein. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 weeks and includes one required visit to the study site, with the remainder of assessments performed in the home or by phone.

    NCT04427501
    Conditions
    1. COVID-19
    Interventions
    1. Drug: LY3819253
    2. Drug: LY3832479
    3. Drug: Placebo

    Primary Outcomes

    Description: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load

    Measure: Change from Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load

    Time: Baseline, Day 11

    Description: Percentage of Participants with SARS-CoV-2 Viral Load Greater than a Prespecified Threshold

    Measure: Percentage of Participants with SARS-CoV-2 Viral Load Greater than a Prespecified Threshold

    Time: Day 7

    Secondary Outcomes

    Description: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization

    Measure: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization

    Time: Baseline, Day 11

    Description: Percentage of Participants Demonstrating Symptom Resolution

    Measure: Percentage of Participants Demonstrating Symptom Resolution

    Time: Day 11

    Description: Percentage of Participants Demonstrating Symptom Improvement

    Measure: Percentage of Participants Demonstrating Symptom Improvement

    Time: Day 11

    Description: PK: Mean Concentration of LY3819253 and LY3819253 in the Presence of LY3832479

    Measure: Pharmacokinetics (PK): Mean Concentration of LY3819253 and LY3819253 in the Presence of LY3832479

    Time: Day 29

    Description: PK: Mean Concentration of LY3832479 in the Presence of LY3819253

    Measure: PK: Mean Concentration of LY3832479 in the Presence of LY3819253

    Time: Day 29

    Description: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related ER Visit, or Death

    Measure: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death

    Time: Baseline through Day 85

    Description: Change from Baseline to Day 7 in SARS-CoV-2 Viral Load

    Measure: Change from Baseline to Day 7 in SARS-CoV-2 Viral Load

    Time: Baseline, Day 7

    Description: Percentage of Participants Enrolled with Recent Symptoms Prior to Randomization Who Experience COVID-Related Hospitalization, COVID-Related ER Visit, or Death

    Measure: Percentage of Participants Enrolled with Recent Symptoms Prior to Randomization Who Experience COVID-Related Hospitalization, COVID-Related ER Visit, or Death

    Time: Baseline through Day 29
    262 A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, Tolerability, Biomarkers and Pharmacokinetics of Ibudilast (MN-166) in COVID-19 Subjects at Risk for Developing Acute Respiratory Distress Syndrome

    The study aims to evaluate MN-166 (ibudilast) in patients with COVID-19 who are at risk of developing acute respiratory distress syndrome. Subjects will be screened, randomly assigned to MN-166 or placebo groups, receive study drug on Days 1-7, and followed up on Day 14 and Day 28.

    NCT04429555
    Conditions
    1. Pneumonia, Viral
    Interventions
    1. Drug: Ibudilast
    2. Drug: Placebo
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirements (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 7

    Measure: Proportion of subjects free from respiratory failure

    Time: 7 days

    Description: Mean change from baseline in clinical status based on the NIAID 8-point scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.

    Measure: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 7

    Time: 7 days

    Description: Percentage of patients with at least a one-point improvement in clinical status using the NIAID 8-point ordinal scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.

    Measure: Percentage of patients with improvement in clinical status

    Time: 7 days

    Description: Mean change from baseline (baseline = 1-fold; any value above 1.0 indicates elevation in cytokine levels; any value below 1.0 indicates reduction in cytokine levels) in migration inhibitory factor (MIF), (interleukin 1-beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) at Day 7.

    Measure: Change in cytokine levels from baseline

    Time: 7 days

    Secondary Outcomes

    Description: Incidence, frequency, and severity of adverse events at Day 7 and Day 14

    Measure: Adverse event Incidence, severity, relationship to study drug, and study discontinuations

    Time: Days 7, 14

    Description: Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.

    Measure: Changes in laboratory values from baseline

    Time: 7 days

    Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14

    Measure: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14

    Time: 14 days

    Description: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 14 and Day 28

    Measure: Mean change from baseline in clinical status

    Time: Days 14, 28

    Description: Proportion of subjects receiving mechanical ventilation or intubation.

    Measure: Incidence of mechanical ventilation or intubation

    Time: Days 7, 14

    Description: Proportion of subjects requiring submission to the intensive care unit

    Measure: Intensive care unit admission

    Time: 7 days

    Description: Blood sample collection to determine plasma concentrations of ibudilast.

    Measure: Plasma concentrations of Ibudilast

    Time: 7 days

    Description: Number of deaths from any cause

    Measure: All cause mortality

    Time: Days 7, 14, 28
    263 Safety and Efficacy of Mesenchymal Stem Cells in the Management of Severe COVID-19

    The disease caused by the new coronavirus, SARS-CoV-2, called COVID-19, it has considered a worldwide pandemia by the WHO. Suddently, it produces a lot of patients severe ill, in a little geographic area, that could surpase the resourses of the any health system in the world. There is no documentation of an effective alternative for the treatment of the severe ill patients, that can reduce the mortality or the adverse events suffered by these people. It is has suggested the usefulness of the Mesenchymal Stem cells (MSC) for the management of these patients, thanks to their direct and indirect antiviral capacity, and its potency as immunomodulator, that could ameliorate the lung disease and the severity of COVID-19.

    NCT04429763
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Umbilical cord derived mesenchymal stem cells
    2. Biological: Placebo

    Primary Outcomes

    Description: Change in two or more degrees in the NEWS scale

    Measure: Clinical deterioration or death

    Time: 4 weeks
    264 Hydroxychloroquine Use in Hospitalized Patients With COVID-19: Impact on Progression to Severe or Critical Disease

    The primary objective is to assess the impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.

    NCT04429867
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: The impact will be evaluated by comparing rates of a composite primary outcome in patients randomized to hydroxychloroquine versus those randomized to placebo. The composite outcome includes progression to severe/critical disease or death (including withdrawal of care/hospice transfer). Progression to severe/critical disease is defined by requiring oxygen delivery via high flow nasal cannula, non-rebreather mask, bipap, or transfer to intensive care (ICU) or intermediate care units (IMCU) due to COVID-19-related complications.

    Measure: Impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.

    Time: 30 Days

    Secondary Outcomes

    Measure: Hospital length of stay

    Time: 30 Days

    Measure: 30-Day Mortality

    Time: 30 Days

    Description: Resolution of symptoms will be assessed using standard medical interview procedures with the subject and review of the medical records.

    Measure: Resolution of Symptoms

    Time: 14 Days

    Measure: Incidence of QTc >500ms after initiation of therapy

    Time: 30 Days

    Measure: Incidence of discontinuation of therapy

    Time: 30 Days
    265 A Phase I Open Label Followed by a Phase II Randomized, Controlled Study to Assess the Efficacy and Safety of ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic

    A Phase I open label followed by a Phase II randomized, controlled study to assess the efficacy and safety of ABTL0812 in combination with FOLFIRINOX for first-line treatment of metastatic pancreatic

    NCT04431258
    Conditions
    1. Pancreatic Cancer
    Interventions
    1. Drug: ABTL0812
    2. Drug: Folfirinox
    3. Drug: Placebo

    Primary Outcomes

    Description: Recommended Phase II Dose (RP2D) of ABTL0812 in combination with FOLFIRINOX

    Measure: RP2D

    Time: 6 months

    Description: PFS using RECIST v1.1 by investigator analysis

    Measure: PFS

    Time: 1 year

    Description: Objective response rate (ORR)

    Measure: ORR

    Time: 1 year
    266 Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Efficacy and Safety of Intravenous Pamrevlumab, a Monoclonal Antibody Against Connective Tissue Growth Factor (CTGF), in Hospitalized Patients With Acute COVID-19 Disease

    This is a Phase 2 trial to evaluate the efficacy and safety of intravenous (IV) infusions of pamrevlumab as compared to placebo in hospitalized subjects with acute COVID-19 disease.

    NCT04432298
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Pamrevlumab
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of subjects who never received mechanical ventilation and/or ECMO and alive

    Time: Baseline to Day 28

    Secondary Outcomes

    Measure: Proportion of subjects alive, discharged home, and not on supplemental oxygen

    Time: Baseline to Day 28

    Measure: Time to recovery based on a Modified 8-Point Ordinal Scale

    Time: Baseline to Day 28

    Measure: Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO)

    Time: Baseline to Day 28

    Measure: Days on mechanical ventilation and/or ECMO

    Time: Baseline to Day 28

    Measure: Time to death from any cause

    Time: Baseline to Day 28

    Measure: Changes in PaO2/FiO2 ratio, both as categorical and continuous variable

    Time: Baseline to Day 28

    Measure: Change in (non-invasive) oxygen supplementation requirements

    Time: Baseline to Day 28
    267 A Randomized Controlled Trial Assessing the Efficacy of Lianhua Qingwen as an Adjuvant Treatment in Patients With Mild Symptoms of COVID-19

    COVID-19 virus remains in infected patients for extended periods of time. A great resource burden is placed on the healthcare system and society at large to isolate COVID-19 patients for prolonged periods. Thus, being able to increase the rate of viral clearance, thus reducing the duration of COVID-19 infection, would allow patients to be discharged earlier to free up resources for those who require it. The investigators designed a randomized controlled trial, investigating the use of Lianhua Qingwen, a TCM treatment, in COVID-19 infected patients with mild symptoms. The investigators hypothesize that the use of Lianhua Qingwen will increase the proportion of patients who test negative for COVID-19 after 8 days of TCM treatment when compared to the group of patients provided with standard care and placebo. Patients will be recruited from community isolation facilities, and have onset of symptoms within 5 days prior to admission to the isolation facility. The trial also evaluates the time taken for relief of clinical symptoms associated with COVID-19 and assesses the safety of the TCM treatment given to patients.

    NCT04433013
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Lianhua Qingwen
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of participants who test negative for COVID-19

    Time: after 8 days of treatment

    Secondary Outcomes

    Measure: Time taken in days for relief of clinical symptoms

    Time: during the 8-day course of treatment

    Measure: Proportion of participants with mild symptoms of COVID-19 progressing to moderate or severe illness

    Time: after 8 days of treatment and at the end of the trial

    Measure: Proportion of participants who test positive for COVID-19 with Ct value>30

    Time: after 8 days of treatment
    268 RepurpoSing Old Drugs TO SuppRess a Modern Threat: The STORM Trial

    The primary aim of this study is to test whether Doxycycline can benefit patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by inhibiting the replication of the virus while at the same time blocking the development of cytokine storms or inhibiting cytokine-associated coagulopathy respectively. The investigators hypothesize that Doxycycline will will improve survival and reduce morbidity in SARS-CoV-2 infected patients. A secondary aim is to identify genetic variants that predict either an unusually mild disease or an unusually severe disease - knowledge that can be used to design new and precise medications and to be able to predict patients who might get into early trouble and to therefore hospitalize them.

    NCT04433078
    Conditions
    1. Cytokine Storm
    2. SARS-CoV-2
    Interventions
    1. Drug: Doxycycline
    2. Drug: Placebo

    Primary Outcomes

    Description: Days Alive and Out of Hospital (Composite Endpoint)

    Measure: Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death

    Time: 21 days

    Secondary Outcomes

    Description: Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative)

    Measure: NP SARS-CoV-2 PCR

    Time: 21 days

    Description: Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load

    Measure: SARS-CoV-2 Serum Quantitative Viral Load

    Time: 21 days

    Description: Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative)

    Measure: SARS-CoV-2 IgM/IgG Antibodies

    Time: 21 days

    Description: Change From Baseline of White Blood Count (CBC) K/mm3

    Measure: White Blood Cell Count (WBC)

    Time: 21 days

    Description: Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3

    Measure: Absolute Lymphocyte Count (ALC)

    Time: 21 days

    Description: Change From Baseline of C-Reactive Protein (CRP) mg/dL

    Measure: C-Reactive Protein (CRP)

    Time: 21 days

    Description: Change From Baseline of N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) pg/mL

    Measure: N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP)

    Time: 21 days

    Description: Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL

    Measure: High Sensitivity Troponin I (hsTnT)

    Time: 21 days

    Description: Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a)

    Measure: Tumor Necrosis Factor Alpha (TNF-a)

    Time: 21 days

    Description: Change From Baseline of IL-1

    Measure: IL-1

    Time: 21 days

    Description: Change From Baseline of IL-1B

    Measure: IL-1B

    Time: 21 days

    Description: Change From Baseline of IL-6

    Measure: IL-6

    Time: 21 days
    269 Efficacy of Pentoxifylline as Add on Therapy in COVID19 Patients

    With potential antiviral effects on severe acute respiratory syndrome (SARS) and as a methyl-xanthine derived inhibitor of phosphodiesterase-4, pentoxifylline basically functions as a hemorrheologic agent for a better circulation and oxygenation and exerts unique effects on immune modulation, inflammation and oxidative stress. As the main regulator of cAMP metabolism, posphodiesterase-4 plays a key role in proinflammatory and immune cells. Pentoxifylline plays its anti-inflammatory role by reducing the production of proinflammatory cytokines such as TNF-a, IL-1 and IL-6. Given its unique impacts on immune modulation, homeostasis and fibrinolysis and its supportive effects on oxidative stress and organ failure, pentoxifylline can constitute a multipurpose and generally-safe adjuvant therapy for COVID-19 patients.

    NCT04433988
    Conditions
    1. COVID
    Interventions
    1. Drug: Pentoxifylline
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of Participants need hospitalization

    Measure: Primary Outcome

    Time: 7 days

    Secondary Outcomes

    Description: Incidence of any acute respiratory infection

    Measure: Respiratory infection

    Time: 7 days

    Description: Absolute and relative frequencies of Serious Adverse Events

    Measure: Serious Adverse Events

    Time: 7 days
    270 Prospective, Randomized, Double-blind, Parallel, Placebo Controlled Study to Evaluate the Safety and Efficacy of Nitazoxanide 600 mg Three Times a Day for Post Exposure Prophylaxis of COVID-19 in Subjects From Vulnerable Communities

    The primary objective of this study is to evaluate the efficacy of the drug nitazoxanide 600 mg, administered three times a day, in relation to placebo in preventing the development of COVID-19 in subjects from vulnerable communities that had direct contact with patients diagnosed with the disease.

    NCT04435314
    Conditions
    1. covid19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo

    Primary Outcomes

    Description: PCR will be done to evaluate infection

    Measure: The proportion of subjects with laboratory-confirmed COVID-19 identified after start of treatment and before the end of the study

    Time: 28 days

    Secondary Outcomes

    Description: Number of participants with treatment-related adverse events

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: 28 days

    Description: Symptomatic PCR positive subjects

    Measure: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the study

    Time: 28 days

    Description: Asymptomatic PCR will be done to evaluate infection

    Measure: The proportion of subjects with asymptomatic laboratory-confirmed COVID identified after the start of treatment and before the end of the study

    Time: 28 days

    Description: Subject adherence to treatment will be assessed through study diary record

    Measure: Treatment adherence

    Time: 7 days

    Description: Proportion of patients with severe condition

    Measure: Disease complication

    Time: 28 days

    Description: Proportion of patient that needed undergo an unscheduled visit

    Measure: Incidence of subjects that underwent unscheduled visit

    Time: 28 days
    271 A Phase III, Randomized, Double-blind, Placebo-controlled, Multicentre, Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in the SARS-CoV-2 Pandemic by Modulating the Immune System

    The aim of this study is to investigate whether vaccination of elderly with VPM1002 could reduce hospital admissions and/or severe respiratory infectious diseases in the SARS-CoV-2 pandemic . VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the "new corona virus" SARS-CoV 2.

    NCT04435379
    Conditions
    1. Infection, Respiratory Tract
    Interventions
    1. Biological: VPM1002
    2. Biological: Placebo
    MeSH:Communicable Diseases Infection Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Measure: Number of days with severe respiratory disease at hospital and/or at home

    Time: From day 0 to day 240

    Secondary Outcomes

    Measure: Cumulative incidence of hospital admissions

    Time: From day 0 to day 240

    Measure: Cumulative incidence of documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days with self-reported fever (≥ 38 ºC)

    Time: From day 0 to day 240

    Measure: Number of days with self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection

    Time: From day 0 to day 240
    272 A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older

    The purpose of the study is to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S at 2 dose levels, administered intramuscularly (IM) as a single-dose or 2-dose schedule, with a single booster vaccination administered in one cohort, in healthy adults aged greater than or equal to 18 to less than or equal to 55 years and in adults aged greater than or equal to 65 years in good health with or without stable underlying conditions.

    NCT04436276
    Conditions
    1. Healthy
    Interventions
    1. Biological: Ad26.COV2.S
    2. Biological: Placebo

    Primary Outcomes

    Description: Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after first vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after First Vaccination

    Time: Day 8 (7 Days after first vaccination on Day 1)

    Description: Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after second vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after Second Vaccination

    Time: Day 64 (7 Days after second vaccination on Day 57)

    Description: Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after first vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after First Vaccination

    Time: Day 8 (7 Days after first vaccination on Day 1)

    Description: Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after second vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after Second Vaccination

    Time: Day 64 (7 Days after second vaccination on Day 57)

    Description: Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after First Vaccination

    Time: Day 29 (28 Days after first vaccination on Day1)

    Description: Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after Second Vaccination

    Time: Day 85 (28 Days after second vaccination)

    Description: SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

    Measure: Cohort 1 and 3: Number of Participants with Serious Adverse Events (SAEs) from the First Vaccination until 1 Year after the Second Vaccination

    Time: From Day 57 (vaccination 2) up to 1 year

    Description: SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

    Measure: Cohort 2: Number of Participants with SAEs from the First Vaccination until 6 Months after the First Vaccination

    Time: Day 1 (vaccination 1) up to 6 Months

    Secondary Outcomes

    Description: Number of participants with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported.

    Measure: Cohorts 1, 2, and 3: Number of Participants With SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA)

    Time: Up to 38 Months

    Description: Number of participants with SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.

    Measure: Cohorts 1, 2, and 3: Number of Participants with SARS-CoV-2 Binding Antibodies Assessed by ELISA

    Time: Up to 38 Months

    Description: Number of participants with Th-1 and Th-2 immune responses will be reported. Th1 and Th2 immune responses will be assessed by flow cytometry after SARS-CoV-2 S protein peptide stimulation of peripheral blood mononuclear cells (PBMCs) and intracellular staining [ICS] including cluster of differentiation (CD)-4+/CD-8+, Interferons (INF)-gamma, interleukin [IL] 2, Tumor Necrosis Factor (TNF)-alpha, IL-4, IL-5, IL-13, and/or other Th-1/Th-2 markers.

    Measure: Cohorts 1, 2, and 3: Number of Participants with T-helper (Th)-1 and Th-2 Immune Responses as Assessed by Flow Cytometry

    Time: Up to 38 Months
    273 Phase 2, Multicentre, Randomized, Double Blind, 2 Arms Placebo-controlled Study in Adults With Moderate COVID-19 With Gastrointestinal Signs and Symptoms

    This is a Phase 2, multicentre, randomized, double blind, 2 arm placebo-controlled study in adults with moderate COVID-19 with gastrointestinal signs and symptoms.

    NCT04436458
    Conditions
    1. COVID
    Interventions
    1. Drug: Niclosamide Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Measure: The primary endpoint is the rate of faecal SARS-CoV-2 virus clearance (rectal swab or stool sample) assessed by RT-PCR in the niclosamide group, compared to the placebo group

    Time: From Day 1 to 42
    274 Randomized, Double-blind, Multi Centre Phase II, Proof of Concept, Dose Finding Clinical Trial on Ivermectin for the Early Treatment of COVID-19

    Prospective, multi-centre, randomized, double-blind trial to assess efficacy and safety of ivermectin for the treatment of initial infection with SARS-CoV2 infection. Study arms: A) placebo B) ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo. C) ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days (I_1200). Patients will be randomized at emergency room of hospitals as well as at outpatient ambulatory care as well as at home, according to routine procedures of recruiting centres. In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C.

    NCT04438850
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin
    2. Other: Placebo

    Primary Outcomes

    Description: Number of serious adverse drug reaction

    Measure: SADR

    Time: 14 days

    Description: Quantitative viral load as measured by quantitative, digital droplet PCR.

    Measure: Viral load

    Time: Assessed at day 7

    Secondary Outcomes

    Description: 1. Trend over time of quantitative viral load at Day 7 and 14 as measured by quantitative, digital droplet PCR.

    Measure: Trend viral load

    Time: Days 7 and 14 from baseline

    Description: Time to clinical resolution (for symptomatic patients).

    Measure: Clinical resolution

    Time: Assessed on Day 30

    Description: Time from diagnosis to documented viral clearance

    Measure: Viral clearance

    Time: assessed on days 14 and 30

    Description: Proportion of patients with virological clearance

    Measure: Virological clearance

    Time: Assessed at day 14 and 30

    Description: rate of hospitalization

    Measure: hospitalization rate

    Time: Day 30

    Description: COVID-19 Severity Score (Coronavirus Diseases 19 Severity Score) - min value 1 ("no limitation of activities), max value 8 ("death"). Higher scores mean worse outcome

    Measure: Severity score

    Time: Assessed at Day 14 and Day 30
    275 Treatment of COVID-19 Pneumonia With Glucocorticoids. A Randomized Controlled Trial

    Around 30% of admitted patients with COVID-19 pneumonia develop a hyper-inflammatory state whose progression to an acute respiratory distress syndrome (ARSD) could be prevented by the early initiation of immune-modulatory agents. The role of glucocorticoids (GC) in this setting remains controversial. This study aims to assess the safety and effectiveness of GC pulses to improve the clinical outcomes of patients with COVID-19 pneumonia with risen inflammatory biomarkers.

    NCT04438980
    Conditions
    1. Covid-19 Pneumonia
    Interventions
    1. Drug: Methylprednisolone
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: • Death

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Description: • Need for admission in an intensive care unit (ICU)

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Description: • Need for mechanical ventilation

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Description: • Decrease in SpO2 <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, associated with radiological impairment

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Secondary Outcomes

    Measure: Mortality at day 28

    Time: At 28 days after randomization

    Measure: Proportion of patients requiring ICU admission

    Time: At 28 days after randomization

    Measure: Proportion of patients requiring rescue-therapy with tocilizumab

    Time: At 14 days after randomization

    Description: Time in days from randomization until the date of hospital discharge.

    Measure: Length of hospital stay

    Time: At 28 days after randomization

    Description: Any undesirable experience related to the use of the studied drugs, which causes patient's death, life-threatening risk, hospitalization or extension of a previous hospitalization, disability or permanent damage, requires intervention to prevent permanent impairment or damage, or is considered medically relevant

    Measure: Proportion of severe adverse events

    Time: At 28 days after randomization

    Measure: Proportion of bacterial, fungal or opportunistic infections

    Time: At 28 days after randomization

    Description: Change in plasma levels of C-reactive protein (CRP)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of ferritin

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of interleukin-6 (IL-6)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of lactate dehydrogenase (LDH)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of D-dimer (DD)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Negativization of RT-PCR for SARS-CoV-2 on nasopharyngeal swab or sputum

    Measure: Proportion of SARS-CoV-2 clearance.

    Time: At 7 days after randomization
    276 A Randomized, Double-blind, Placebo-controlled Phase 3 Study: Efficacy and Safety of VPM1002 in Reducing SARS-CoV-2 Infection Rate and COVID-19 Severity

    Bacille Calmette-Guerin (BCG) is a live attenuated vaccine administered for prevention of tuberculosis. Recently, several groups have hypothesized that BCG may "train" the immune system to respond to a variety of unrelated infections, including viruses and in particular the coronavirus responsible for COVID-19. Trials are currently being conducted in Australia, Netherlands, Germany and the United Kingdom to evaluate its effectiveness. Front line workers includes members of municipal and provincial police services, emergency medical personnel, firefighters, public transport employees, health service workers and food manufacturing employees. They are at high risk of infection from COVID-19, with potentially high infection rate. The investigators propose an interventional trial to evaluate the effectiveness of BCG vaccination to prevent COVID-19 infection and reduce its severity in front-line employees in Ontario.

    NCT04439045
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Biological: VPM1002
    2. Other: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Description: To compare the self-reported incidence of SARS-CoV-2 infection (confirmed by positive test) following vaccination with either VPM1002 or placebo.

    Measure: COVID-19 infection

    Time: 7 months

    Secondary Outcomes

    Description: Compare the incidence of hospitalization in participants with positive COVID-19 test treated with either VPM1002 or placebo

    Measure: Incidence of hospitalization for COVID-19

    Time: 7 months

    Description: Compare the incidence of hospitalization requiring intensive care (ICU admission) in participants with positive COVID-19 test treated with either VPM1002 or placebo

    Measure: Incidence of ICU admission for COVID-19

    Time: 7 months

    Description: Compare the incidence of acute respiratory distress syndrome (ARDS) in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Incidence of ARDS

    Time: 7 months

    Description: Compare the incidence of the need for mechanical ventilation in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Mechanical ventilation for COVID-19

    Time: 7 months

    Description: To compare the incidence of secondary infection in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Secondary infection in COVID-19

    Time: 7 months

    Description: To compare the mortality in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: COVID-19-related Mortality

    Time: 7 months

    Description: Compare the incidence of deep vein thrombosis, pulmonary embolism, or stroke in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Incidence of DVT

    Time: 7 months

    Other Outcomes

    Description: Compare the incidence of COVID-19 in participants who have received BCG vaccination previously.

    Measure: Incidence of COVID-19 in Participants with Past BCG Vaccination

    Time: 7 months

    Description: To measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin identified as potential biomarkers of COVID-19 infection using blood samples collected prior to the vaccination and at the end of the 7-month follow-up.

    Measure: Measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin as biomarkers of COVID-19

    Time: 7 months

    Description: Adverse events following administration of VPM1002 when used for prevention of COVID-19.

    Measure: Adverse events following BCG vaccine

    Time: 7 months

    Description: Compare the priming of the innate trained immunity (i.e. induction of Th1 and Th17 responses to unrelated stimuli) to participants administered placebo.

    Measure: Innate Trained Immunity

    Time: 7 months
    277 Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects With COVID-19 (FITE19)

    This is a randomized, double-blind, placebo-controlled, multicenter, 28-day study of adult participants hospitalized with COVID-19, with a safety follow-up telephone call at Day 60.

    NCT04439071
    Conditions
    1. Pneumonia
    2. COVID-19
    3. Coronavirus
    Interventions
    1. Drug: PTC299
    2. Other: SOC
    3. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Respiratory improvement is defined as sustained peripheral oxygen saturation (SpO2) ≥94% on room air.

    Measure: Time from Randomization to Respiratory Improvement

    Time: up to Day 28

    Secondary Outcomes

    Measure: Percentage of Participants Requiring Invasive Ventilation

    Time: up to Day 28

    Measure: Percentage of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants who did not Require Supplemental Oxygen at Baseline

    Time: up to Day 28

    Measure: Time from Randomization to Defervescence

    Time: up to Day 28

    Measure: Time from Randomization to Respiratory Rate ≤ 24 Breaths per Minute on Room Air

    Time: up to Day 28

    Measure: Time from Randomization to Cough Reported as Mild or Absent

    Time: up to Day 28

    Measure: Time from Randomization to Dyspnea Reported as Mild or Absent

    Time: up to Day 28

    Measure: Reduction of Immune Responses

    Time: up to Day 28

    Measure: Reduction in Viral Load

    Time: up to Day 28

    Measure: Duration of Hospitalization

    Time: up to Day 28

    Measure: Number of Fatalities

    Time: up to Day 28

    Measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    Time: up to Day 28
    278 Prospective, Randomized, Double-blind, Parallel, Placebo Controlled Study to Evaluate the Safety and Efficacy of Nitazoxanide 600 mg Three Times a Day to Treat Ambulatory Adult Subjects Diagnosed With COVID-19 With Mild Symptoms Assisted in the Public Health System of the City of Mesquita -RJ

    The aim is to demonstrate a decrease in complications among ambulatory patients who are diagnosed with mild COVID-19 by treating them with nitazoxanide for 7 to 14 days on top of standard care compared to patients who receive standard care and placebo only.

    NCT04441398
    Conditions
    1. covid19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo

    Primary Outcomes

    Description: Symptoms will be assessed using a 5 point scale (1- excellent, 2- good, 3- fair, 4 - poor 5 - very poor).

    Measure: Change in signs and symptoms scale

    Time: 21 days

    Secondary Outcomes

    Description: Number of participants with treatment-related adverse events

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: 21 days

    Description: Change in clinical condition - WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)

    Measure: The proportion of subjects hospitalized after start of treatment and before the end of the study

    Time: 21 days

    Description: Change in clinical condition - WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)

    Measure: The proportion of subjects that need mechanical ventilation after start of treatment and before the end of the study

    Time: 21 days

    Description: Time required (days) to full symptom recovery

    Measure: Duration of symptoms

    Time: 21 days

    Description: Evaluation of change in acute respiratory syndrome

    Measure: Rate of mortality within 21-days

    Time: 21 days
    279 A Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate COPD With Chronic Bronchitis

    The purpose of this study is to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in patients with mild to moderate COPD with CB.

    NCT04441788
    Conditions
    1. Chronic Bronchitis
    2. Chronic Obstructive Pulmonary Disease
    Interventions
    1. Drug: ION-827359
    2. Drug: Placebo
    MeSH:Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Bronchitis Bronchitis, Chronic Acute Disease
    HPO:Abnormal lung morphology Bronchitis Chronic bronchitis Chronic pulmonary obstruction Pulmonary obstruction

    Primary Outcomes

    Measure: Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo

    Time: From Baseline up to average of Weeks 13 and 14

    Secondary Outcomes

    Description: The EXACT (E-RS) scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with COPD. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms. The E-RS will be collected on the daily e-diary, which will include all 14 items from the EXACT questionnaire.

    Measure: Change From Baseline in the EXACT Respiratory Symptoms (E-RS) Daily Symptom Diary to the Primary Time Point

    Time: One week prior to first dose through one week after the last dose.

    Description: The CAT is an eight-item questionnaire that will be completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. The CAT provides a score of 0-40 to indicate the impact of the disease.

    Measure: Change From Baseline in the COPD Assessment Test (CAT) to the Week 14 Time Point

    Time: From Baseline up to Week 14

    Description: The SGRQ is a participant completed, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. Scores of the SGRQ-C range from 0 to 100, with higher scores indicating more limitations.

    Measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) to the Week 14 Time Point

    Time: From Baseline up to Week 14

    Measure: Change from Baseline in Post-Bronchodilator FEV1

    Time: From Baseline up to average of Weeks 13 and 14

    Measure: Cmax: Maximum Observed Plasma Concentration for ION-827359

    Time: Up to Week 24

    Measure: Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359

    Time: Up to Week 24

    Measure: AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Time Zero to t for ION-827359

    Time: Up to Week 24

    Measure: Incidence of Participants With at Least One Treatment-Emergent Adverse Event (TEAE), Graded by Severity

    Time: Up to Week 24

    Measure: Number of Participants With Abnormal Laboratory Values

    Time: Up to Week 24

    Measure: Number of Participants With Abnormal Vital Signs Measurements

    Time: Up to Week 24
    280 A Phase 1, Randomized, Placebo-Controlled Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Immunogenicity of LY3832479 Given as a Single Intravenous Dose in Healthy Participants

    The main purpose of this study is to learn more about the safety of LY3832479 and any side effects that might be associated with it. Blood tests will be done to measure how much LY3832479 is in the bloodstream and how long it takes the body to eliminate it. Participation could last up to 16 weeks and may include up to 10 visits to the study center.

    NCT04441931
    Conditions
    1. Healthy
    Interventions
    1. Drug: LY3832479
    2. Drug: Placebo

    Primary Outcomes

    Description: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

    Measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug

    Time: Baseline through Follow-up (Week 12)

    Secondary Outcomes

    Description: PK: AUC of LY3832479

    Measure: 2. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3832479

    Time: Day 1: Pre-dose through Day 85

    Description: PK: Cmax of LY3832479

    Measure: PK: Maximum Concentration (Cmax) of LY3832479

    Time: Day 1: Pre-dose through Day 85
    281 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Infectious Cohort

    Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

    NCT04442178
    Conditions
    1. COVID-19
    2. Lymphocytopenia
    Interventions
    1. Drug: CYT107
    2. Drug: Placebo
    MeSH:Lymphopenia
    HPO:Lymphopenia

    Primary Outcomes

    Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge

    Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first

    Time: one month

    Secondary Outcomes

    Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score

    Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD.

    Time: one month

    Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

    Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD

    Time: one month

    Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

    Measure: frequency of secondary infections through day 45 compared to placebo arm

    Time: 45 days

    Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

    Measure: length of hospitalization compared to placebo arm

    Time: 45 days

    Description: Number of days in ICU during index hospitalization

    Measure: Length of stay in ICU compared to placebo arm

    Time: 45 days

    Description: Readmissions to ICU through Day 45

    Measure: number of readmissions to ICU compared to placebo arm

    Time: 45 days

    Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

    Measure: organ support free days compared to placebo arm

    Time: 45 days

    Description: Number of readmissions to the hospital through Day 45

    Measure: Frequency of re-hospitalization through day 45 compared to placebo arm

    Time: 45 days

    Description: All-cause mortality through Day 45

    Measure: All-cause mortality through day 45 compared to placebo arm

    Time: 45 days

    Description: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD

    Measure: CD4+ and CD8+ T cell counts compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

    Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo a

    Time: 30 days

    Description: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm

    Time: 30 days

    Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

    Measure: Physiological status through NEWS2 evaluation compared to Placebo arm

    Time: 30 days

    Other Outcomes

    Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety

    Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events

    Time: 45 days
    282 Infusion of Convalescent Plasma for the Treatment of Patients Infected With Severe Acute Respiratory Syndrome-Coronavirus-2 (COVID-19): A Double-blinded, Placebo-controlled, Proof-of-concept Study

    Patients who are ill with COVID-19 may benefit from receiving convalescent plasma infusions containing antibodies from donors who have recovered from the disease and are proven to no longer be infected. Given the current public health emergency due to COVID-19, the FDA has recently fast-tracked the use of convalescent plasma. The purpose for this study is to assess if convalescent plasma collected from donors previously infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can provide clinical benefit to those acutely ill with the virus and to evaluate if such treatment is safe. There will be two arms in the interventional study, where subjects will either be treated with convalescent plasma or fresh frozen plasma in a randomized and blinded manner. As an additional comparison, the clinical course of subjects enrolled during the period of the study who do not receive an alternative treatment for COVID-19 will be assessed.

    NCT04442191
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Convalescent plasma
    2. Biological: Placebo

    Primary Outcomes

    Description: The primary endpoint will be clinical response at 8 days, defined as no need for oxygen supplementation for the previous 24 hours.

    Measure: Oxygen supplementation

    Time: 8 days

    Secondary Outcomes

    Description: Mortality rate during the 28 days of follow-up and during the subjects' initial hospital stays

    Measure: 28-day and in-hospital mortality rate

    Time: 28 days

    Description: Transfer to an ICU bed during the 28 days following study enrollment

    Measure: Number of participants transferred to the Intensive Care Unit (ICU)

    Time: 28 days

    Description: Intubation within the 28 days following study enrollment

    Measure: Number of participants intubated

    Time: 28 days

    Description: Number of days admitted to the hospital during the 28-day follow-up period

    Measure: Length of hospital stay in days

    Time: 28 days

    Description: Type of respiratory support required during the 28-day follow-up period: intubation, high-flow oxygen by nasal canula, nasal canula

    Measure: Type of respiratory support

    Time: 28 days

    Description: Change in CRP following treatment

    Measure: C-reactive Protein (CRP)

    Time: 28 days

    Description: Change in lymphocyte count following treatment

    Measure: Lymphocyte count

    Time: 28 days

    Description: Number of days respiratory support is required

    Measure: Length or respiratory support required, in days

    Time: 28 days

    Description: Change in LDH following treatment

    Measure: Lactate dehydrogenase (LDH)

    Time: 28 days

    Description: Change in Ferritin level following treatment

    Measure: Ferritin

    Time: 28 days

    Description: Change in D-Dimer level following treatment

    Measure: D-Dimer

    Time: 28 days

    Description: Change in WBC count following treatment

    Measure: White Blood Cell (WBC) Count

    Time: 28 days

    Other Outcomes

    Description: Severe transfusion reaction will be defined as having any of the following occur within 6 hours of the infusion of blood product and not attributable to the underlying disease: 1) an increase of 2 L/minutes or more in supplemental oxygen requirement compared to the baseline requirement before transfusion, 2) oxygen saturations <93% despite oxygen via nasal canula, or 3) need for transfer to the ICU.

    Measure: Safety endpoint: Severe transfusion reaction

    Time: 6 hours following transfusion

    Description: Cumulative incidence of adverse events during the study period: transfusion reaction (fever, rash), transfusion related acute lung injury (TRALI), transfusion associated circulatory overload (TACO), transfusion related infection.

    Measure: Safety endpoint two: adverse events

    Time: 24 hours following transfusion
    283 Phase 2, Double-blind, Randomized, Placebo-controlled Study of NasoVAX in the Prevention of Clinical Worsening in Patients With Early Coronavirus Infectious Disease 2019 (COVID-19)

    The purpose of this study is to evaluate the safety and effectiveness of NasoVAX in preventing worsening of symptoms and hospitalization in patients with early COVID-19.

    NCT04442230
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Biological: NasoVAX
    2. Other: Placebo
    MeSH:Communicable Diseases Infection Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Decrease from baseline in mean resting SpO2

    Measure: Proportion of patients with clinical worsening

    Time: Day 1 to Day 14

    Secondary Outcomes

    Description: Proportion of patients requiring hospitalization

    Measure: Maximal severity of COVID-19 after treatment

    Time: Day 1 to Day 42

    Measure: All-cause mortality

    Time: Day 1 to Day 42
    284 Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)

    Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have carried out/published clinical trials on treatment based on Western medicine, traditional Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small (median sample size 100) and the bulk of potential therapeutic strategies remain in the experimental phase and currently there is no effective specific antiviral with high-level evidence.The aim of this study is assess the efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with moderate/severe COVID-19.

    NCT04444271
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Mesenchymal stem cells
    2. Other: Placebo

    Primary Outcomes

    Description: Assessment of Overall survival at 30 days post intervention

    Measure: Overall survival

    Time: 30 days post intervention

    Secondary Outcomes

    Description: days required for oxygen support independence after intervention

    Measure: Clinical improvement

    Time: 30 days

    Description: PCR testing to check PCR negativity

    Measure: Time of COVID19 PCR negativity

    Time: day 1,3,7,10, 14

    Description: Computed tomography Chest assesment will be done to assess improvment in radiological findings of COVID-19

    Measure: Radiological improvement (day 15 and day 30 assessment)

    Time: day 15 and day30

    Description: number of days required for discharge from hospital

    Measure: days required to discharge from hospital

    Time: 30 days post admission
    285 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 1569912 in Healthy Male Subjects (Single-blind, Partially Randomized Within Dose Groups, Placebo-controlled, Parallel-group Design) With an Additional Relative Bioavailability/ Food Effect Part (Open-label, Randomized, Three-way Crossover Design)

    SRD-Part: To investigate safety, tolerability, pharmacokinetics and pharmacodynamics following single rising doses (SRD) of BI 1569912 BA/FE-Part: To investigate (a) the relative bioavailability (BA) of BI 1569912 and (b) the influence of food (FE) on the relative bioavailability of BI 1569912

    NCT04445090
    Conditions
    1. Healthy
    Interventions
    1. Drug: BI 1569912
    2. Drug: Placebo

    Primary Outcomes

    Measure: SRD-part: % of subjects with drug-related adverse events

    Time: up to 14 days

    Measure: BA/FE-part: AUC0-tz (area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 to the last quantifiable data point)

    Time: up to 4 days

    Measure: BA/FE-part: Cmax (maximum measured concentration of BI 1569912 in plasma)

    Time: up to 4 days

    Secondary Outcomes

    Measure: SRD-Part: AUC0-∞ (area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 extrapolated to infinity)

    Time: up to 4 days

    Measure: SRD-Part: Cmax (maximum measured concentration of BI 1569912 in plasma)

    Time: up to 4 days

    Measure: BA/FE-Part: AUC0-∞ (area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 extrapolated to infinity)

    Time: up to 4 days
    286 Prasugrel in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients

    Inflammatory diseases favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended if concomitant inflammatory disease. In severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pneumonia an inflammation-dependent thrombotic process occurs and platelet activation may promote thrombosis and amplify inflammation, as indicated by previous experimental evidence , and the similarities with atherothrombosis and thrombotic microangiopathies. Antiplatelet agents represent the cornerstone in the prevention and treatment of atherosclerotic arterial thromboembolism, with limited efficacy in the context of venous thromboembolism. The use of purinergic receptor P2Y12 inhibitors in pneumococcal pneumonia may improve inflammation and respiratory function in humans. There are no validated protocols for thrombosis prevention in Covid-19. There is scientific rationale to consider a P2Y12 inhibitor for the prevention of thrombosis in the pulmonary circulation and attenuation of inflammation. This is supported by numerous demonstrations of the anti-inflammatory activity of P2Y12 inhibitors and the evidence of improvement in respiratory function both in human and experimental pathology. Prasugrel could be considered as an ideal candidate drug for Covid-19 patients because of higher efficacy and limited Interactions with drugs used in the treatment of Sars-CoV2. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs through an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients could reduce the incidence of pulmonary thrombosis and respiratory and multi-organ failure improving clinical outcome in patients with SARS-CoV2 pneumonia. The prevention of thrombogenic platelet activity with a P2Y12 inhibitor could be superior to fixed dose enoxaparin alone. The proposed treatment is feasible in all coronavirus disease 2019 (COVID-19) patients, regardless of the treatment regimen (antivirals, anti-inflammatory drugs, antibiotics), except for specific contraindications.

    NCT04445623
    Conditions
    1. COVID19
    2. Thrombosis
    Interventions
    1. Drug: Prasugrel Hydrochloride 10 MG Oral Tablet
    2. Drug: Placebo
    MeSH:Pneumonia Thrombosis
    HPO:Pneumonia

    Primary Outcomes

    Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected after 7 days of treatment

    Measure: P/F ratio at day 7

    Time: day 7

    Secondary Outcomes

    Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected daily for 15 days

    Measure: Daily P/F ratio

    Time: 15 days

    Description: daily need for oxygen supply for 15 days

    Measure: Daily need for oxygen supply

    Time: 15 days

    Description: Number of patients requiring transfer to the intensive care unit (ICU) by treatment arm

    Measure: Need for ICU

    Time: day 15 and day 30

    Description: death by day 15 and day 30 by treatment arm

    Measure: Death

    Time: 15 day and day 30

    Description: Multi-organ failure (MOF) by day 15 and day 30 assessed using sequential organ failure assessment score (SOFA) score (Units 0-4 better outcome, over 30 worse outcome) by treatment arm

    Measure: MOF

    Time: day 15 and day 30

    Description: Number of patients discharged after improvement by day 15 and day 30 by treatment arm

    Measure: Discharge

    Time: day 15 and day 30

    Description: Clinical progression of the disease evaluated by SOFA score (Units 0-6 better outcome, 15-24 worse outcome) by day 15 and day 30

    Measure: Clinical progression of the disease SOFA score

    Time: day 15 and day 30

    Description: Clinical progression of the disease evaluated by Acute Physiology And Chronic Health Evaluation (APACHE II) score (Units 1-5 better outcome, over 30 worse outcome) by day 15 and day 30

    Measure: Clinical progression of the disease APACHE II

    Time: day 15 and day 30

    Description: Number of patients with venous thrombosis/ pulmonary embolism/thrombosis by day 15 and day 30

    Measure: Venous thrombosis/ pulmonary embolism/thrombosis

    Time: day 15 and day 30

    Description: Number of patients requiring computerized tomography (CT) imaging due to worsening of respiratory function by treatment arm

    Measure: Need for CT imaging

    Time: day 15

    Description: Body temperature measured twice daily for 15 days, C°

    Measure: Daily Temperature

    Time: 15 days

    Description: Blood pressure measured twice daily for 15 days, mmHg

    Measure: Daily blood pressure

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, Hemoglobin, g/L (cell/mcL

    Measure: Daily total blood count Hemoglobin

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, Red Blood cells (cell/mcL)

    Measure: Daily total blood count Red Blood Cells

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, Leukocytes (cell/mcL)

    Measure: Daily total blood count Leukocytes

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, platelets (cell/mcL)

    Measure: Daily total blood count Platelets

    Time: 15 days

    Description: ALT U/L in venous blood

    Measure: Daily indices of organ damage Liver

    Time: 15 days

    Description: C-reactive protein microg/L in venous blood

    Measure: Indices of inflammation C-reactive protein

    Time: day 1, 2, 7, 15

    Description: PT ratio in venous blood by treatment arm

    Measure: Indices of haemostasis PT

    Time: day 1, 2, 7,15

    Description: progression of lung infiltrates as detected by chest-X-ray by treatment arm

    Measure: Daily progression at imaging (chest-X-ray)

    Time: 15 days

    Description: Major and/or clinically relevant bleeding according to International Society of Thrombosis and Haemostasis (ISTH) bleeding scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.

    Measure: Major bleeding

    Time: day 1, 2, 7, 15, 30

    Description: Total bleeding according to International Society of Thrombosis and Haemostasis (ISTH bleeding) scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.

    Measure: Total bleeding

    Time: day 1, 2, 7, 15, 30

    Description: Number of unexpected changes in clinical or laboratory findings not included in the predefined list of outcomes during treatment. .

    Measure: Unexpected clinical or laboratory findings

    Time: day 1, 2, 7, 15

    Description: D-dimer microg/L in venous blood

    Measure: Indices of inflammation D-dimer

    Time: day 1, 2, 7, 15

    Description: Fibrinogen g/L in venous blood

    Measure: Indices of inflammation Fibrinogen

    Time: day 1, 2, 7, 15

    Description: Interleukin (IL)-6 pg/mL in venous blood by treatment arm

    Measure: Indices of inflammation IL-6

    Time: day 1, 2, 7, 15

    Description: Interleukin (IL)-1 pg/mL in venous blood by treatment arm

    Measure: Indices of inflammation IL-1

    Time: day 1, 2, 7, 15

    Description: serum creatinine micromol/L by treatment arm

    Measure: Daily indices of organ damage kidney

    Time: 15 days

    Description: troponin t ng/L by treatment arm

    Measure: Daily indices of organ damage heart

    Time: 15 days

    Description: aPTT ratio by treatment arm

    Measure: Haemostasis aPTT

    Time: day 1, 2, 7,15

    Description: Vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) % by treatment arm

    Measure: Haemostasis VASP PRI

    Time: day 1, 2, 7,15

    Description: Platelet-leukocytes aggregates % in peripheral by treatment arm

    Measure: Haemostasis platelet-leukocytes aggregates

    Time: day 1, 2, 7,15
    287 A Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Trial to Protect Health Workers Against COVID-19 by Using Previfenon® as Chemoprophylaxis During a SARS-CoV-2 Outbreak. The HERD Study

    The purpose of this clinical trial is to determine the efficacy of Previfenon® (EGCG) to prevent COVID-19, enhance systemic immunity, and decrease the frequency and intensity of selected symptoms when used as pre-exposure chemoprophylaxis to SARS-CoV-2.

    NCT04446065
    Conditions
    1. COVID-19
    2. SARS-CoV2
    Interventions
    1. Drug: Previfenon®
    2. Drug: Placebo

    Primary Outcomes

    Description: A positive case or event of COVID-19 is defined as a patient with acute respiratory illness presenting fever (37.8º C); at least one of the following symptoms: odynophagia, cough, myalgia, or dyspnea; and a specific positive rtPCR test for SARS-CoV-2.

    Measure: Event of clinical acute respiratory disease with a diagnosis of COVID-19 confirmed with rtPCR

    Time: The date for censoring a case will be defined as that date when the rtPCR test results positive minus 4 days, with the aim to calculate the time free of clinically defined COVID-19 infection over 40 to 70 days of intervention

    Secondary Outcomes

    Description: Rate of positive cases for IgM and IgG anti-SARS-CoV-2 measured by immunochromatographic test in treatment and placebo group at the end of the study

    Measure: Rate of positive cases for IgM and IgG anti-SARS-CoV-2

    Time: Positive cases in each two-week examination and to the end of the study over 40 to 70 days of intervention

    Description: Rate of asymptomatic cases defined as a positive rtPCR for SARS-CoV-2 viral RNA but with no symptoms of COVID-19 in treatment and placebo group at the end of the study, and a composite outcome considering symptomatic and asymptomatic cases (i.e. all cases with positive rtPCR test)

    Measure: Composite outcome considering symptomatic and asymptomatic cases with positive rtPCR test

    Time: Positive cases in each two-weeks examination and to the end of the study over 40 to 70 days of intervention

    Description: Rate of hospitalizations due to any acute respiratory infection at the end of the study

    Measure: Hospitalization due to any acute respiratory infection

    Time: Positive cases in each two-week examination visit and to the end of the study over 40 to 70 days of intervention

    Description: Global frequency of events of upper and lower airway respiratory infections

    Measure: Event of upper and lower airway respiratory infection

    Time: Positive cases in each two-week examination and to the end of the study over 40 to 70 days of intervention

    Other Outcomes

    Description: Registry of Visual Analogue Scale (VAS) in the log diary of every healthcare worker for the following selected symptoms: cough, muscle pain (myalgia); difficulty breathing (dyspnea); loss of smell (anosmia); loss of taste (ageusia); pain when swallowing (odynophagia, sore throat); and finally headache

    Measure: Exploratory outcome: Frequency and intensity of selected symptoms for COVID-19

    Time: Different VAS scores calculated each two-week examination visit over 40 to 70 days of intervention

    Description: Elevation of liver enzymes over 5 times the normal value

    Measure: Primary safety outcome: event of major hepatic harm

    Time: Cases accounted by liver profile lab test in each two-week examination visit over 40 to 70 days of intervention.

    Description: Elevation of liver enzymes over 5 times the normal value

    Measure: Event of liver enzymes over 3 times the normal value

    Time: Cases accounted by liver profile lab test in each two-week examination visit over 40 to 70 days of intervention

    Description: Any adverse event reported over the intervention period

    Measure: Frequency of adverse events

    Time: Records of self-reported adverse effects on log dairy accounted in each examination visit over 40 to 70 days of intervention
    288 A Phase II Randomized, Double-Blind, Placebo-Controlled Study of LAM-002A for the Prevention of Progression of COVID-19

    This is a clinical trial to evaluate the efficacy of LAM-002A compared to placebo treatment in adults with a confirmed SARS-CoV-2 infection who are receiving standards supportive care in an outpatient setting.

    NCT04446377
    Conditions
    1. COVID-19 Disease
    Interventions
    1. Drug: Apilimod Dimesylate Capsule
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: The primary efficacy outcome measure evaluates change in SARS-CoV-2 viral load at Day 4 from Day 1, of LAM-002A or placebo-treated participants. SARS-CoV-2 viral load will be measured by a qRT-PCR test of nasopharyngeal samples. Analysis will focus on log10 viral load on Day 4 compared to baseline viral load at Day 1 in participants with baseline viral load >100,000 copies/mL

    Measure: Viral Load Change

    Time: 4 Days

    Secondary Outcomes

    Description: The proportion of LAM 002A-treated participants who develop TEAEs compared to placebo

    Measure: Safety and Tolerability

    Time: 28 Days

    Description: The proportion of participants treated with LAM-002A compared to placebo, who have disease progression by Day 28 as defined by the occurrence of: Hospitalization Death

    Measure: Clinical Efficacy

    Time: 28 Days

    Description: To evaluate change in COVID-19 clinical status, as defined by the ordinal scale, of participants treated with LAM-002A compared to placebo at Day 28, in participants who become hospitalized and continue LAM-002A/placebo treatment, based on the following scores: Not in the hospital Hospitalized, requiring low flow supplemental oxygen (such as nasal cannula) Hospitalized, not on invasive ventilation (such as 100% non-rebreather, BIPAP), (pre-ICU) Hospitalized, in the ICU, on invasive ventilation or ECMO Dead

    Measure: Change in COVID-19 Clinical Status

    Time: 28 Days

    Description: To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo treatment groups as measured on Days 1, 4, and 11.

    Measure: Oxygen Saturation

    Time: 11 Days

    Other Outcomes

    Description: To potentially evaluate the change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples on Day 4, compared between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL

    Measure: Viral Clearance

    Time: 4 Days

    Description: To potentially evaluate the change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples on Day 11, compared between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL

    Measure: Viral Clearance

    Time: 11 Days

    Description: To potentially evaluate the change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples on Day 28, compared between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL

    Measure: Viral Clearance

    Time: 28 Days

    Description: To potentially evaluate the difference in SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples based on AUC(Day1-Day11), between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL.

    Measure: Viral Clearance AUC

    Time: 11 Days

    Description: To potentially evaluate the difference in SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples based on AUC(Day1-Day28), between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL.

    Measure: Viral Clearance AUC

    Time: 28 Days

    Description: To potentially evaluate the difference in proportion of participants with a SARS-CoV-2 viral load less than Measure: Proportion of participants with viral load < lower limit of detection

    Time: 4 Days
    289 Randomized, Doubled-blind Phase II Trial Evaluating the Use of Ivermectin Plus Losartan for Prophylaxis of Severe Events in Cancer Patients With Recent Diagnosis of COVID-19

    Ivermectin plus losartan as prophilaxy to severe events in patients with cancer with recent diagnosis of COVID-19

    NCT04447235
    Conditions
    1. Cancer
    2. COVID
    3. Coronavirus Infection
    Interventions
    1. Drug: Placebo
    2. Drug: Ivermectin
    3. Drug: Losartan
    MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Incidence of severe complications due COVID-19 infection defined as need for ICU admission, need for mechanical ventilation, or death

    Measure: Incidence of severe complications due COVID-19 infection

    Time: 28 days

    Secondary Outcomes

    Description: Severe Acute Respiratory Syndrome defined as oxygen saturation less than 93%

    Measure: Incidence of Severe Acute Respiratory Syndrome

    Time: 28 days

    Description: Severe Acute Respiratory Syndrome defined as respiratory rate higher than 24 incursion per minute

    Measure: Incidence of Severe Acute Respiratory Syndrome

    Time: 28 days

    Description: Incidence of hepatic toxicity (elevation of ALT, AST above the upper limit of normal, measured by U/L)

    Measure: Adverse events

    Time: 28 days

    Description: Incidence of hepatic toxicity (elevation of bilirubin above the upper limit of normal, measured by mg/dL)

    Measure: Adverse events

    Time: 28 days

    Description: Incidence of renal toxicity (elevation of serum creatinine levels above the upper limit of normal, measured by mg/dL)

    Measure: Adverse events

    Time: 28 days

    Description: Incidence of symptomatic postural hypotension, diagnosed by clinical assessment of reduction of > 20 mmHG of arterial systolic pressure after measurement in prone position and orthostatic position.

    Measure: Adverse events

    Time: 28 days

    Description: Death of any cause since protocol enrollment

    Measure: Overall survival

    Time: 28 days
    290 A Randomized, Double-Blind, Placebo Controlled Study to Evaluate Safety and Efficacy of DUR-928 in Subjects Infected With SARS-CoV-2 With Acute Liver or Kidney Injury

    Evaluate safety and efficacy of DUR-928 in treatment of acute organ failure in subjects infected with SARS-CoV-2

    NCT04447404
    Conditions
    1. SARS-CoV 2
    Interventions
    1. Drug: DUR-928
    2. Drug: Placebo

    Primary Outcomes

    Description: Free of mechanical ventilation, free of renal replacement therapy and free of acute liver failure

    Measure: Composite endpoint of alive and free of organ failure

    Time: Day 28

    Measure: Occurrence of serious adverse events following treatment

    Time: Day 1 to Day 60

    Secondary Outcomes

    Measure: Alive at days 28 and 60

    Time: Days 28 and 60

    Measure: Alive and out of ICU

    Time: Day 28

    Measure: Alive and out of hospital

    Time: Day 28 and Day 60
    291 A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation

    Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).

    NCT04447469
    Conditions
    1. COVID
    Interventions
    1. Drug: mavrilimumab
    2. Other: Placebo
    MeSH:Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).

    Measure: Cohort 1: Proportion of Participants Alive and Without Respiratory Failure at Day 15

    Time: Day 15

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 2: Mortality Rate at Day 15

    Time: Day 15

    Secondary Outcomes

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (National Institute of Allergy and Infectious Diseases [NIAID] scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Time to Return to Room Air by Day 15

    Time: up to Day 15

    Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Time to 2-point Clinical Improvement by Day 15

    Time: up to Day 15

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 1: Mortality Rate at Day 29

    Time: Day 29

    Description: Clinical improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Time to 1-Point Clinical Improvement by Day 15

    Time: up to Day 15

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 2: Mortality Rate at Day 29

    Time: Day 29

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.

    Measure: Cohort 2: Proportion of Participants Alive and Without Respiratory Failure at Day 15

    Time: Day 15

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO

    Measure: Cohorts 1 and 2: Proportion of Participants Alive and Without Respiratory Failure At Day 29

    Time: Day 29

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Time to Return to Room Air by Day 29

    Time: up to Day 29

    Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 2: Time to 2-point Clinical Improvement by Day 15

    Time: up to Day 15

    Description: Clinical Improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Time to 1-point Clinical Improvement by Day 29

    Time: up to Day 29

    Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Time to 2-point Clinical Improvement by Day 29

    Time: up to Day 29

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.

    Measure: Cohort 1: Respiratory Failure-Free Survival by Day 15

    Time: up to Day 15

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO

    Measure: Cohort 1: Respiratory Failure-Free Survival by Day 29

    Time: up to Day 29

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Proportion of Participants Who Return to Room Air by Day 15

    Time: up to Day 15

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Proportion of Participants Who Return to Room Air by Day 29

    Time: up to Day 29

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 1: Mortality Rate at Day 15

    Time: Day 15

    Description: Overall survival is defined as time from date of randomization to the date of death.

    Measure: Cohorts 1 and 2: Overall Survival by Day 29

    Time: up to Day 29

    Description: Clinical status, based on the NIAID 8-point ordinal scale. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Clinical Status Over Time

    Time: Days 4, 8, 15, 22, and 29

    Measure: Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90

    Time: through Day 90
    292 Stop of Proton-pump Inhibitor Treatment in Patients With Liver Cirrhosis - a Double-blind, Placebo-controlled Trial

    Proton-pump inhibitors (PPI) are commonly prescribed in an uncritical manner to patients with liver cirrhosis without a clear evidence-based indication. Observational studies suggests that PPI use in cirrhotic patients may be a risk factor for the development of infections, especially spontaneous bacterial peritonitis (SBP). A possible explanation are PPI-associated microbiotic shifts leading to small intestinal bacterial overgrowth with subsequently increased bacterial translocation. Furthermore, PPI therapy in cirrhotic patients may lead to an increased risk for pneumonia and Clostridium difficile-infections. However, the evidence is ambiguous, as other published studies found no evidence for an association of PPI use with an increased risk for SBP or pneumonia. Moreover, an association between episodes of hepatic encephalopathy and PPI use has been reported. Infections and hepatic encephalopathy may often lead to a hospitalization of cirrhotic patients and PPI use at discharge has also been associated to early re-hospitalization. While some studies found an association of PPI and increased mortality in cirrhotic patients, other studies could not observe this association. Thus, some of the current evidence suggests an unfavourable risk profile of PPIs in patients with liver cirrhosis. However, this patient population is considered to be at a high risk of gastrointestinal haemorrhage from peptic ulcers. Importantly, patients with liver cirrhosis have an increased mortality after peptic ulcer bleeding as compared to patients without cirrhosis. Therefore, generous PPI use may also have a yet unproven preventive effect against upper gastrointestinal bleeding. The STOPPIT trial is the first prospective, randomized, controlled, double-blind trial investigating the effect of discontinuation of long-term PPI therapy on hospitalized patients with complicated liver cirrhosis with a pre-existing long-term PPI therapy. Importantly, patients with an evidence-based indication for PPI therapy are excluded from the trial. All study participants (n=476) stop their previous PPI treatment and are then randomized (1:1) to receive either placebo (intervention group) or esomeprazole 20mg/day (control group) for 360 days. The primary hypothesis anticipates a delay of re-hospitalisation and/or death (composite endpoint) in patients who discontinue PPI treatment as compared to patients who continue PPI therapy. Secondary objectives include the assessment of mortality, re-hospitalisation rates, infection rates, rate of acute hepatic decompensation and ACLF, as well as rates of upper and lower gastrointestinal bleeding events in both groups. Impact of prolonged or discontinued PPI therapy on the intestinal microbiota and pharmacoeconomics will be studied as a secondary assessment.

    NCT04448028
    Conditions
    1. Liver Cirrhosis
    Interventions
    1. Drug: Placebo
    2. Drug: Esomeprazole 20mg
    MeSH:Liver Cirrhosis Fibrosis
    HPO:Cirrhosis Hepatic fibrosis

    Primary Outcomes

    Measure: Timepoint of first unplanned re-hospitalization or death (whichever occurs first)

    Time: Within 12 months (360 days) after randomization

    Secondary Outcomes

    Measure: Timepoint of death

    Time: Within 12 months (360 days) after randomization

    Measure: Mortality rate

    Time: 360 days after randomization

    Measure: Timepoint of first unplanned re-hospitalization

    Time: Within 12 months (360 days) after randomization

    Measure: Rate of unplanned re-hospitalizations

    Time: 360 days after randomization

    Measure: Overall infection rate

    Time: 360 days after randomization

    Description: Infection rates by site of infection (SBP, pneumonia, urinary tract infection, blood stream infection, Clostridium difficile-associated enterocolitis, Norovirus-infection, Sars-CoV-2-infection)

    Measure: Infection rates differentiated by site

    Time: 360 days after randomization

    Measure: Rate of acute decompensation of liver cirrhosis

    Time: 360 days after randomization

    Measure: Rate of acute-on-chronic liver failure (ACLF)

    Time: 360 days after randomization

    Measure: Rate of upper gastrointestinal bleeding events

    Time: 360 days after randomization

    Measure: Rate of lower gastrointestinal bleeding events

    Time: 360 days after randomization

    Description: The gut microbiota composition will be analyzed by PCR

    Measure: Changes of intestinal microbiota between baseline and day 90

    Time: 90 days after randomization

    Other Outcomes

    Measure: Rate of occurence of the safety endpoint (evidence-based indication for open-label re-therapy with PPIs)

    Time: 360 days after randomization

    Measure: Rate of any (serious) adverse events

    Time: 360 days after randomization
    293 A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of M5049 in Hospitalized Participants With COVID-19 Pneumonia

    The study will evaluate the safety and efficacy of orally-administered M5049 in COVID-19 pneumonia participants who are hospitalized but not on mechanical ventilation.

    NCT04448756
    Conditions
    1. Coronavirus Disease 2019
    Interventions
    1. Drug: M5049
    2. Drug: M5049
    3. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation

    Time: Day 14

    Measure: Occurrence of Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious AEs (SAEs)

    Time: Day 1 through Day 60

    Measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters and Electrocardiogram Findings

    Time: Day 1 through Day 28

    Secondary Outcomes

    Description: A nine point ordinal scale - 0: Uninfected No limitation of activities Limitation of activities Hospitalized, mild disease on, no oxygen therapy Hospitalized, with oxygen by mask or nasal prongs Hospitalized, severe disease: noninvasive ventilation or high flow oxygen Hospitalized, severe disease: intubation and mechanical ventilation Hospitalized, severe disease: ventilation plus additional organ support - example, vasopressors, Extracorporeal membrane oxygenation (ECMO) Death.

    Measure: Clinical Status of Participants on a 9-Point Ordinal Scale

    Time: Day 1 through Day 60

    Description: Normal oxygen exchange in room air.

    Measure: Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours on Room Air

    Time: Day 1 through Day 28

    Description: Percentage of Participants who die for any reason.

    Measure: Percentage of Participants With All-Cause Mortality

    Time: Day 1 through Day 28

    Description: Clinical Deterioration

    Measure: Clinical Deterioration: Time to Intensive Care Unit (ICU) Admission

    Time: Day 1 through Day 28

    Description: Clinical Deterioration

    Measure: Clinical Deterioration: Time to Invasive Mechanical Ventilation

    Time: Day 1 through Day 28

    Description: Clinical Deterioration

    Measure: Clinical Deterioration: Time to Non-Invasive Mechanical Ventilation

    Time: Day 1 through Day 28

    Measure: Total Length of Stay in Intensive Care Unit (ICU)

    Time: Day 1 through Day 60

    Measure: Total Length of Hospitalization Stay

    Time: Day 1 through Day 60

    Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation

    Time: Day 1 through Day 28

    Measure: Percentage Change From Baseline in Inflammatory Biomarkers

    Time: Day 1 through Day 28

    Measure: Percentage Change From Baseline in Cytokine Biomarkers

    Time: Day 1 through Day 28

    Description: Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.

    Measure: Percentage of Participants With Relapse

    Time: Day 5 through Day 60

    Description: Percentage or participants who are re-hospitalized for any reason.

    Measure: Percentage of Participants who are Re-Hospitalized

    Time: Day 5 through Day 60

    Description: Only the first 15 participants will be evaluated for Pharmacokinetic parameters.

    Measure: Maximum Observed Concentration (Cmax) of M5049

    Time: Day 1 and Day 7

    Measure: Time to Reach the Maximum Observed Concentration (tmax) of M5049

    Time: Day 1 and Day 7

    Measure: Terminal Rate Constant (Lambda z) of M5049

    Time: Day 1 and Day 7

    Measure: Apparent Elimination Half-Life (t1/2) of M5049

    Time: Day 1 and Day 7

    Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t) of M5049

    Time: Day 1 and Day 7

    Measure: Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h) of M5049

    Time: Day 1 and Day 7

    Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity) of M5049

    Time: Day 1 and Day 7

    Measure: Apparent Total Body Clearance (CL/F) of M5049

    Time: Day 1 and Day 7

    Measure: Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Maximum Observed Concentration (Cmax/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Accumulation Ratio for Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose [Racc(AUC0- 12h)] of M5049

    Time: Day 1 and Day 7

    Measure: Accumulation Ratio for Maximum Observed Concentration [Racc(Cmax)] of M5049

    Time: Day 1 and Day 7
    294 COVID-19: A Phase 1, Partially Blind, Placebo-controlled, Dose-escalation, First-in-human, Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity After 1 and 2 Doses of the Investigational SARS-CoV-2 mRNA Vaccine CVnCoV Administered Intramuscularly in Healthy Adults

    This study aims to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of CVnCoV at different dose levels.

    NCT04449276
    Conditions
    1. Severe Acute Respiratory Syndrome
    2. Coronavirus
    3. SARS-CoV-2
    4. COVID-19
    Interventions
    1. Biological: CVnCoV Vaccine
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: This data will be collected for decisions on subsequent vaccination of an additional open-label sentinel group with the same dose level.

    Measure: Number of Participants With Grade 3 Adverse Reactions or any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 24 Hours After the First Vaccination

    Time: Up to 24 hours after vaccination on Day 1

    Description: This data will be collected for decisions on dose escalation as well as continuation of enrollment at the same dose level in the observer-blind placebo-controlled part of the trial.

    Measure: Number of Participants With Grade 3 Adverse Reactions or any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 60 Hours After the First Vaccination

    Time: Up to 60 hours after vaccination on Day 1

    Measure: Number of Participants with Solicited Local Adverse Events

    Time: 7 days after vaccination

    Measure: Intensity of Solicited Local Adverse Events per the FDA Toxicity Grading Scale

    Time: 7 days after vaccination

    Measure: Duration of Solicited Local Adverse Events

    Time: 7 days after vaccination

    Measure: Number of Participants with Solicited Systemic Adverse Events

    Time: 7 days after vaccination

    Measure: Intensity of Solicited Systemic Adverse Events per the FDA Toxicity Grading Scale

    Time: 7 days after vaccination

    Measure: Duration of Solicited Systemic Adverse Events

    Time: 7 days after vaccination

    Measure: Number of Participants with Solicited Systemic Adverse Events Considered Related to Trial Vaccine

    Time: 7 days after vaccination

    Measure: Number of Participants with Unsolicited Adverse Events

    Time: 28 days after vaccination

    Measure: Intensity of Unsolicited Adverse Events Assessed by the Investigator

    Time: 28 days after vaccination

    Measure: Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine

    Time: 28 days after vaccination

    Measure: Number of Participants with One or More Serious Adverse events (SAEs)

    Time: Baseline to Day 393

    Measure: Number of Participants with One or More Serious Adverse events (SAEs) Considered Related to Trial Vaccine

    Time: Baseline to Day 393

    Measure: Number of Participants with One or More Adverse Events of Special Interest (AESIs)

    Time: Baseline to Day 393

    Measure: Number of Participants with One or More Adverse Events of Special Interest (AESIs) Considered Related to Trial Vaccine

    Time: Baseline to Day 393

    Secondary Outcomes

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).

    Measure: Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies

    Time: Baseline and on Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).

    Measure: Individual SARS-CoV-2 Spike Protein-Specific Antibody Levels in Serum

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).

    Measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using an activity assay.

    Measure: Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies

    Time: Baseline and on Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using an activity assay.

    Measure: Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using an activity assay.

    Measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393
    295 Vitamin D Supplementation in Patients With COVID-19: A Randomized, Double-blind, Placebo-controlled Trial

    Coronavirus disease 2019 (COVID-19) was declared an emergency public health problem by the World Health Organization (WHO) in March 2020. Since then, several initiatives by the medical and scientific community have sought alternatives to treat infected individuals, as well as identifying risk or protective factors for the contamination and prognosis of patients. In this perspective, vitamin D supplementation can improve some important outcomes in critically ill patients, being considered a potent immunomodulatory agent. Vitamin D deficiency is a common outcome in critically ill patients, thus making it a modifiable risk factor with great potential for reducing hospital stay and intensive care and mortality. The investigators speculate that vitamin D supplementation could have therapeutic effects in patients with COVID-19.

    NCT04449718
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: Vitamin D
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Description: total number of days that patient remained hospitalized

    Measure: Length of hospitalization

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Secondary Outcomes

    Description: number of patients that died

    Measure: Mortality

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Description: total number of days that patient remained in ICU

    Measure: Number of cases admitted to Intensive Care Unit (ICU)

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Description: total number of days that patient remained in mechanic ventilator

    Measure: Length of use of mechanic ventilator

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Measure: Number and severity of symptoms

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Description: C-reactive protein, IL-1alpha (pg/ml), IL-1beta (pg/ml), IL-6 (pg/ml), TNF-alpha (pg/ml), IL-1ra (pg/ml), IL-10 (pg/ml) concentration in the serum

    Measure: Inflammatory markers

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: C-reactive protein

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: Vitamin D

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: Creatinine

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: Calcium

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: Baecke questionnaire (higher scores mean a higher physical activity level)

    Measure: Physical activity

    Time: Baseline
    296 The Efficacy of Topical Povidone-Iodine Rinses in the Management of the Coronavirus Disease 2019 (COVID-19)

    The aim of this study is to determine if Povidone iodine (PVP-I) rinses and throat gargles or a PVP-I gel forming nasal spray compared to a placebo (a treatment that has no physical effect to a person) is an effective treatment for patients diagnosed with COVID-19. These patients have been diagnosed with mild/moderate COVID-19 symptoms and sent home for self-isolation. Patients will be instructed to take either of the two treatments or placebo twice daily for two weeks and have follow up visits 2 and 4 weeks after. The participants will also complete study related procedures such as saliva sample collection, and two questionnaires throughout the study period. The investigators hypothesize that COVID 19 positive participants who use either of the Povidone - Iodine treatment will have a reduction in their viral load, develop a negative oral mucosa sample and improve their clinical symptoms.

    NCT04449965
    Conditions
    1. Covid19
    Interventions
    1. Drug: Povidone-iodine
    2. Drug: Placebo

    Primary Outcomes

    Description: A saliva sample will be analyzed to monitor the duration of positivity and when test becomes negative for SARS-CoV-2.

    Measure: Change in SARS-CoV-2 positivity in the saliva

    Time: A saliva sample will be taken every 2 days for 2 weeks, and again at 4 and 6 weeks

    Description: Quantify the amount of SAR-CoV-2 viral load present in the saliva.

    Measure: Change in the SAR-CoV-2 viral load in the saliva

    Time: A saliva sample will be taken every 2 days for 2 weeks, and again at 4 and 6 weeks

    Secondary Outcomes

    Description: This is a 44 question, quality of life survey designed to measure different aspects affected by the common cold.

    Measure: Change in Wisconsin Upper Respiratory Symptom Survey (WURSS-44)

    Time: daily for 2 weeks, 4 weeks, and 6 weeks

    Description: That includes 22 questions about symptoms and social/emotional consequences of your nasal disorder.

    Measure: Change Sino nasal Outcome Test (SNOT-22)

    Time: baseline, 2 weeks, 4 weeks, 6 weeks

    Description: We will record and worsening of clinical condition such as, need for hospitalization/oxygen support.

    Measure: Change in clinical condition

    Time: daily for 2 weeks, 4 weeks, and 6 weeks
    297 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-CoV-2 Infection in Household Contacts of Individuals Infected With SARS-CoV-2

    Primary Objective: - To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing symptomatic SARS-CoV-2 infection (strict-term) confirmed by RT-qPCR - To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing asymptomatic or symptomatic SARS-CoV-2 infection confirmed by RT-qPCR - To evaluate the safety and tolerability of REGN10933+REGN10987 following subcutaneous (SC) administration compared to placebo

    NCT04452318
    Conditions
    1. Healthy Participants
    Interventions
    1. Drug: REGN10933 + REGN10987
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR (based on central lab test) and signs and symptoms (strict-term) of SARS-CoV-2 infection during the Efficacy assessment period (EAP)

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a RT-qPCR confirmed SARS-CoV-2 infection (either symptomatic or asymptomatic) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants with treatment-emergent adverse events (TEAEs) and severity of TEAEs

    Time: Up to 8 months

    Secondary Outcomes

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad term) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (strict term) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (broad term) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days of symptomatic SARS-CoV-2 infection (strict-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days of symptomatic SARS-CoV-2 infection (broad-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Time-weighted average of viral shedding (log10 copies/mL) from the first positive SARS CoV-2 RT-qPCR Nasopharyngeal (NP) swab sample (with an onset during the EAP) until the visit within the window including 22 days after the positive test during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in Nasopharyngeal (NP) swab samples among individuals with ≥1 RT-qPCR positive that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Area under the curve (AUC) in viral shedding (log10 copies/mL) from the first positive SARS-CoV-2 RT-qPCR NP swab sample until the first confirmed negative test, that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Daily responsibilities including work (employed adults) or school (matriculating students), or family obligations/responsibilities (childcare or eldercare) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Incidence of symptomatic SARS-CoV-2 infection in seronegative and seropositive participants (based on central lab test) in both the EAP and follow-up periods

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Severity of symptomatic SARS-CoV-2 infection in seronegative and seropositive participants (based on central lab test) in both the EAP and follow-up periods

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of baseline seropositive subjects (based on central lab test) with TEAEs and severity of TEAEs

    Time: Up to 8 months

    Description: Pharmacokinetic (PK) parameters may include, but are not limited to: - Maximum observed plasma concentration (Cmax) - Cmax/Dose - Time of maximum observed plasma concentration (tmax) - Time of Clast (tlast) - Last measurable plasma concentration (Clast) - Area under plasma concentration-time curve from time 0 to infinity (AUCinf) - AUCinf/Dose - Elimination half-life (t1/2) - Concentration in serum 28 days (C28) after dosing) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Concentrations of REGN10933 in serum over time and selected PK parameters

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Concentrations of REGN10987 in serum over time and selected PK parameters

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933 over time

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987 over time

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants who subsequently develop signs and symptoms (strict-term) of symptomatic SARS-CoV-2 infection during EAP

    Time: Within 14 and 28 days of a positive RT-qPCR

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants who subsequently develop signs and symptoms (broad-term) of symptomatic SARS-CoV-2 infection during EAP

    Time: Within 14 and 28 days of a positive RT-qPCR

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days of symptomatic SARS CoV-2 infection (strict-term)

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days of symptomatic SARS CoV-2 infection (broad-term)

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Time-weighted average change from baseline in viral shedding in NP swab samples until the visit within the window including day 23

    Time: Until day 23

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Area under the curve (AUC) in viral shedding (log10 copies/mL) in NP swab samples until the first confirmed negative test

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in NP swab samples

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of medically attended visits in emergency rooms or urgent care centers related to RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Daily responsibilities including work (employed adults) or school (matriculating students), or family obligations/responsibilities (childcare or eldercare) Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants with TEAEs and severity of TEAEs

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Incidence of symptomatic SARS-CoV-2 infection in both the EAP and follow-up periods

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Severity of symptomatic SARS-CoV-2 infection in both the EAP and follow-up periods

    Time: Up to 8 months
    298 A Randomised, Double-blind, Placebo-controlled, Phase 2 Trial Investigating the Safety and Efficacy of C21 in Hospitalised Subjects With COVID-19 Infection Not Requiring Mechanical Ventilation

    This is a randomised, double-blind, placebo-controlled phase 2 trial investigating the safety and efficacy of C21 in subjects who are hospitalised with COVID-19 infection, but not in need of mechanical invasive or non-invasive ventilation. In total, approximately 100 subjects will be enrolled and randomised to receive twice daily oral administration of either standard of care (SoC) + placebo (N=50) or SoC + C21 (N=50). Subjects will be treated for 7 days.

    NCT04452435
    Conditions
    1. COVID-19
    Interventions
    1. Drug: C21
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary endpoint

    Measure: Change from baseline in C-reactive protein (CRP) after treatment with C21 200 mg daily dose (100 mg b.i.d.)

    Time: Treatment period of 7 days
    299 A Multicenter, Randomized, Double-blind, Adaptive, Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab vs. Placebo in Addition to Standard Treatment in Patients With Severe SARS-CoV-2 Infection (COVID-19)

    The primary objective of the study is to evaluate the efficacy of a single dose of OKZ (64 mg) vs placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 29.

    NCT04452474
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Olokizumab 64 mg
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Difference between OKZ and placebo groups in the percentage of subjects with an improvement of at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category. The points of the scale are: 1. Not hospitalized; 2.Hospitalized, not requiring supplemental oxygen; 3.Hospitalized, supplemental oxygen, spontaneous breathing;4. Hospitalized, mechanical ventilation (invasive/non-invasive) or extracorporeal membrane oxygenation (ECMO); 5. Death

    Measure: Percentage of subjects achieving a change in their clinical status defined as improvement for at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category

    Time: at Day 29

    Secondary Outcomes

    Description: Subjects' clinical status distribution based on 5-point clinical status scale during the study

    Measure: Subjects' clinical status distribution based on 5-point clinical status scale during the study

    Time: from Day 2 tо Day 15, Day 29, Day 60

    Description: 28-day case fatality rates

    Measure: 28-day case fatality rates

    Time: from Day 1 to Day 29

    Other Outcomes

    Description: Case fatality rates during the intensive care unit (ICU) stay at Days 7, 15, and 60

    Measure: Case fatality rates during the intensive care unit (ICU) stay, at Days 7, 15, and 60

    Time: from Day 1 to Day 60

    Description: Duration of oxygen support (if applicable)

    Measure: Duration of oxygen support

    Time: From Day 1 to Day 60

    Description: The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached

    Measure: The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached

    Time: from Day 2 to Day 60

    Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable)

    Measure: Changes of oxygenation index PaO2/FiO2 from baseline

    Time: from Day 2 to Day 60

    Description: Duration of oxygen support (if applicable), in days

    Measure: Duration of oxygen support (if applicable)

    Time: from Day 1 to Day 60

    Description: Duration of mechanical ventilation and/or ECMO (if applicable), in days

    Measure: Duration of mechanical ventilation and/or ECMO (if applicable)

    Time: from Day 1 to Day 60

    Description: Duration of ICU stay (if applicable)

    Measure: Duration of ICU stay (if applicable)

    Time: from Day 1 to Day 60

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte counts

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte count

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached

    Measure: The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached

    Time: from Day 1 and until the end of hospitalization, Day 29 as a maximum

    Description: The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached

    Measure: The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached

    Time: from Day 1 and until the end of hospitalization, Day 29 as a maximum
    300 Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial on the Efficacy of BACMUNE (MV130) in the Prevention of Disease Due to SARS-CoV-2 Infection in Healthcare Personnel

    The purpose of this trial is to assess the effect of immunotherapy with the bacterial preparation MV130 on the spread and course of SARS-CoV-2 infection in highly exposed subjets, as is the case with healthcare personnel.

    NCT04452643
    Conditions
    1. Covid19
    Interventions
    1. Biological: BACMUNE (MV130)
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Incidence of subjects with COVID-19, defined by the presence of: Fever Any of the respiratory signs and/or symptoms: cough, dyspnea, respiratory failure, runny nose/nasal obstruction. Positive test for SARS-COV-2 (PCR o serology)

    Measure: Incidence of subjects with COVID-19

    Time: 60 days

    Description: Incidence of severe COVID-19, defined by CURB > 2 and/or death

    Measure: Severity of COVID-19

    Time: 60 days

    Secondary Outcomes

    Description: Rate of subjects with seroconversion to SARS-CoV-2 (negative serology at the beginning of the study and positive at the end of the study

    Measure: Seroconversion to SARS-CoV-2

    Time: 60 days

    Description: Rate of subjects with any symptoms, whether confirmed, probable or suspected, according to the WHO definition

    Measure: Subjects with symptoms

    Time: 60 days

    Description: The effect of the treatment on the severity of the disease will be measured based on the rate of subjects requiring hospital admission for COVID-19

    Measure: Hospital admission due to COVID-19

    Time: 60 days

    Description: The effect of the treatment on the severity of the disease will be measured based on the rate of subjects who require admission to an intensive care unit for COVID-19 • Time from confirmation of SARS-CoV-2 infection to the appearance of symptoms.

    Measure: Admission to an intensive care unit due to COVID-19

    Time: 60 days

    Description: Elapsed time until the first symptoms of COVID-19 appears to hospitalization due to COVID-19.

    Measure: Elapsed time until hospitalization

    Time: 60 days

    Description: Elapsed time until the first symptoms of COVID-19 appears to admission into an intensive care unit pro COVID-19.

    Measure: Elapsed time until admission into an care unit for COVID-19

    Time: 60 days

    Description: Elapsed time until the first symptoms of COVID-19 appears to death from any cause not related to COVID-19.

    Measure: Elapsed time until death not related to COVID-19

    Time: 60 days
    301 Double-blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of the Manremyc® Food Supplement to Prevent SARS-CoV-2 Infection

    The purpose of this study is to assess the efficacy of Manremyc® food supplement for reduce the incidence of SARS-CoV-2 infection in a high risk population, as healthcare workers.

    NCT04452773
    Conditions
    1. COVID19
    Interventions
    1. Dietary Supplement: Manremyc
    2. Dietary Supplement: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: % of positive serology at the end of the study or positive PCR test in the course of routine clinical practice

    Measure: Documented cumulative incidence of SARS-CoV-2 infection

    Time: up to 4 months

    Secondary Outcomes

    Description: Number of days Documented as sick leave for SARS-CoV-2

    Measure: Documented sick leave for SARS-CoV-2

    Time: up to 4 months (cumulative)

    Description: Number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2

    Measure: days off work due to the quarantine

    Time: up to 4 months

    Description: Number of days in quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Measure: Quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Time: up to 4 months

    Description: Number of days of self-reported fever (≥38 ºC)

    Measure: Fever

    Time: Up to 4 months

    Description: Cumulative incidence of self-reported acute respiratory symptoms

    Measure: Cumulative incidence of self-reported acute respiratory symptoms

    Time: up to 4 months

    Description: Number of days of self-reported acute respiratory symptoms

    Measure: Number of days of self-reported acute respiratory symptoms

    Time: up to 4 months

    Description: Number of participants with pneumonia confirmed by X-ray

    Measure: Incidence of pneumonia

    Time: up to 4 months

    Description: Cumulative incidence of death from documented SARS-CoV-2 infection

    Measure: Cumulative incidence of death from documented SARS-CoV-2 infection

    Time: Up to 4 months

    Description: Cumulative incidence of admissions to intensive care unit for documented SARS-CoV-2 infection

    Measure: Incidence of admission to ICU

    Time: Up to 4 months

    Description: Number of days admitted to the ICU for documented SARS-CoV-2 infection

    Measure: Days in IUC

    Time: Up to 4 months

    Description: Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection

    Measure: Incidence of mechanical ventilation

    Time: Up to 4 months

    Description: Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection

    Measure: Incidence of hospital admissions

    Time: Up to 4 months

    Description: Number of days of hospitalization for documented SARS-CoV-2 infection

    Measure: Days of hospitalization

    Time: Up to 4 months

    Description: Levels of IgG

    Measure: Levels of IgG

    Time: Up to 4 months

    Description: Levels of IgM

    Measure: Levels of IgM

    Time: Up to 4 months

    Description: Levels of SARS-CoV-2 antibodies at the end of the study period

    Measure: Levels of SARS-CoV-2 antibodies at the end of the study period

    Time: Up to 4 months

    Other Outcomes

    Description: All adverse events reported by the subjects, both serious and non-serious, will be collected. All events related to a SARS-CoV-2 infection will be exempted from collection, as they will be collected as part of the associated symptoms

    Measure: AEs

    Time: Up to 4 months

    Description: All thoseAdverse Events that lead to hospitalization of the patient, that endanger his life or cause or may cause death.

    Measure: SAEs

    Time: Up to 4 moths
    302 A Randomized, Double-blind, Placebo-controlled Phase 2 (2a and 2b) Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia

    Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunt an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions1-3. Because a suboptimal endogenous early antibody response with regard to SARS-CoV-2 replication in severe cases is observed, neutralising antibody treatment can be very interesting for patient with COVID-19 induced moderate pneumonia4,5. Convalescent plasma to treat infected patients is therefore an interesting therapeutic option currently under evaluation. However, the difficulties of collecting plasma and its safety aspects are not adapted to many patients. A new polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) is being developed by Xenothera, which can be administered as intravenous treatment. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, inhibiting infection of ACE-2 positive human cells with SARS-CoV-2. Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates and a First In Human study with another fully representative GH-pAb from Xenothera is ongoing in volunteer patients recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objective of this 2-steps phase 2 randomized double-blind, placebo-controlled study is 1) to define the optimal and safety XAV-19 dose to administrate in patients with COVID-19 induced moderate pneumonia ; 2) to show the clinical benefit of selected dose of XAV-19 when administered to patients with COVID-19 induced moderate pneumonia.

    NCT04453384
    Conditions
    1. SARS Virus
    Interventions
    1. Drug: XAV-19
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8

    Measure: Phase 2a: XAV-19 antibody titers

    Time: Day 8

    Description: Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days

    Measure: Phase 2a: Adverse events of XAV-19

    Time: Day 29

    Description: If patient is still on oxygen at Day 15 or if the patient is weaned but put back on oxygen then the delay will be censored at 15 days.

    Measure: Phase 2b: Time to weaning of supplemental oxygen.

    Time: Day 15

    Secondary Outcomes

    Description: XAV-19 Antibody titer over the time

    Measure: Phase 2a: Pharmacokinetic analysis

    Time: Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29

    Description: b) The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients

    Measure: Phase 2a: Antibody titer between the two groups

    Time: day 15

    Description: Duration of supplemental oxygen

    Measure: Phase 2a: Supplemental oxygen

    Time: Day 1 to Day 29

    Description: Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen

    Measure: Phase 2a: Evaluation of Transfer to intensive care

    Time: Day 1 to Day 29

    Description: Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1

    Measure: Phase 2a: Normalization of Fever

    Time: Day 1 to Day 29

    Description: Biomarkers : CRP, Ferritin

    Measure: Phase 2a: Biomarkers

    Time: Day 1 to Day 29

    Description: Evaluation of Hospital length of stay

    Measure: Phase 2a: Hospital length of stay

    Time: Day 1 to Day 29

    Description: Evaluation of the National Early Warning Score at Day 15 and difference in NEWS between Day1 and Day15. The NEWS is graded from to 23 with an aggregated score between 0-4 being a low clinical risk and an aggregated score >7 being a hich clinical risk

    Measure: Phase 2b: National Early Warning Score (NEWS)

    Time: Day 1 and Day 15

    Description: Clinical status using the 7-point ordinal scale assessed

    Measure: Phase 2b: clinical status

    Time: Day 3, Day 5, Day 8, Day 11, Day15, and Day 29

    Description: Time to improvement of one category from admission using the 7-point ordinal scale. This scale is rated 0 to 7 with score 0 being the better score (no clinical impact) and 7 being the worst score (death)

    Measure: Phase 2b: Time to improvement

    Time: 29 Days

    Description: d) Time to first fever normalization (criteria for normalization: temperature < 36.6°C armpit, < 37.2°C oral, < 37.8°C rectal or tympanic)

    Measure: Phase 2b: fever normalization

    Time: 29 Days

    Description: Duration of oxygen therapy

    Measure: Phase 2b: Oxygen therapy

    Time: 29 Days

    Description: Comparison of oxygen requirement between the two groups

    Measure: Phase 2b: oxygen requirement

    Time: 29 Days

    Description: g) Time to weaning in supplemental oxygen and proportion without O2 requirement at D15, according to baseline (D1) oxygen requirement (≤ 4 L/min or 4 L/min)

    Measure: Phase 2b: Time to weaning

    Time: Day 15

    Description: h) Incidence and duration of non-invasive ventilation or high flow oxygen devices, of invasive mechanical ventilation during the study

    Measure: Phase 2b: Ventilation

    Time: 29 Days

    Description: Evaluation of hospital length of stay

    Measure: Phase 2b: Hospital length of stay

    Time: 29 Days

    Description: All cause mortality

    Measure: Phase 2b: mortality

    Time: 29 Days

    Description: Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events Proportion of participants with treatment emergent adverse events leading to study drug discontinuation Incidence of major or opportunistic bacterial or fungal infections Incidence of hypersensitivity reactions and infusion reactions White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D11, D15 and D29 SARS-CoV-2 viral load over time (D1-D29), as collected by nasopharyngeal swab samples Time to RT-PCR virus negativity in nasopharyngeal swab samples

    Measure: Phase 2b: safety

    Time: 29 Days
    303 Double-blind, Randomized, Placebo-controlled Clinical Trial to Evaluate the Efficacy of the RUTI® Vaccine to Prevent SARS-CoV-2 Infection

    The purpose of this study is to assess the efficacy of RUTI® vaccine preventing SARS-CoV-2 infection (COVID-19) in healthcare workers.

    NCT04453488
    Conditions
    1. Covid-19
    2. Sars-CoV2
    Interventions
    1. Biological: RUTI® vaccine
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: % positive serology at the end of the study or positive PCR test in the course of routine clinical practice

    Measure: Documented cumulative incidence of SARS-CoV-2 infection

    Time: Up to 4 months

    Secondary Outcomes

    Description: Number of days of documented sick leave for SARS-CoV-2

    Measure: Sick leave for SARS-CoV-2

    Time: Up to 4 months

    Description: The number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2

    Measure: Days off work due to the quarantine

    Time: Up to 4 months

    Description: Number of days of quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Measure: Quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Time: Up to 4 months

    Description: Number of MD, nursing, personnel management and services, etc.

    Measure: Professional category

    Time: Up to 4 months

    Description: Number of days of self-reported fever (≥38 ºC)

    Measure: Fever

    Time: Up to 4 months

    Description: Cumulative incidence of self-reported acute respiratory symptoms

    Measure: Incidence of self-reported acute respiratory symptoms

    Time: Up to 4 months

    Description: Number of days of self-reported acute respiratory symptoms

    Measure: Days of self-reported acute respiratory symptoms

    Time: Up to 4 months

    Description: Number of participants with pneumonia confirmed by X-ray

    Measure: Incidence of pneumonia

    Time: Up to 4 months

    Description: Cumulative incidence of death from documented SARS-CoV-2 infection

    Measure: Incidence of death from SARS-CoV-2 infection

    Time: Up to 4 months

    Description: Cumulative incidence of admissions to intensive care unit for documented SARS-CoV-2 infection

    Measure: Incidence of admissions to Intensive Care Unit (ICU)

    Time: Up to 4 months

    Description: Number of days admitted to the ICU for documented SARS-CoV-2 infection

    Measure: Days in ICU

    Time: Up to 4 months

    Description: Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection

    Measure: Incidence of mechanical ventilation

    Time: Up to 4 months

    Description: Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection

    Measure: Incidence of hospital admissions

    Time: Up to 4 months

    Description: Number of days of hospitalization for documented SARS-CoV-2 infection

    Measure: Days of hospitalization

    Time: Up to 4 months

    Description: Incidence of SARS-CoV-2 antibodies at the end of the study period

    Measure: Incidence of SARS-CoV-2 antibodies

    Time: Final visit

    Description: Frequency and levels of immunoglobulin IgG and immunoglobulin IgM

    Measure: Types of antibodies detected

    Time: Final visit

    Description: Levels of SARS-CoV-2 antibodies at the end of the study period

    Measure: Levels of SARS-CoV-2 antibodies

    Time: Final visit

    Other Outcomes

    Description: All adverse events reported by the subjects, both serious and non-serious, will be collected. All events related to a SARS-CoV-2 infection will be exempted from collection as part of the associated symptoms.

    Measure: AEs

    Time: Up to 4 months

    Description: All those Adverse Events that lead to hospitalization of the patient, that endanger his life or cause or may cause death.

    Measure: SAEs

    Time: Up to 4 months
    304 A Randomized, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Efficacy of a Single Dose of STI-1499 (COVI-GUARD™) in Hospitalized Patients With Moderate COVID-19

    Randomized, placebo-controlled study to evaluate the safety, pharmacokinetics and efficacy of a single dose of STI-1499 (COVI-GUARD™) in hospitalized patients with moderate COVID-19

    NCT04454398
    Conditions
    1. Covid-19
    Interventions
    1. Biological: COVI-GUARD
    2. Other: Standard of Care
    3. Drug: Placebo

    Primary Outcomes

    Description: Types, frequencies, and severities of adverse events and their relationships to COVI-GUARD

    Measure: Incidence of adverse events (safety)

    Time: Randomization through study completion through Day 60

    Description: Types, frequencies, and severities of treatment-emergent adverse events and their relationships to COVI-GUARD

    Measure: Incidence of treatment-emergent adverse events (safety)

    Time: Randomization through study completion through Day 60

    Description: Types, frequencies, and severities of serious adverse events and their relationships to COVI-GUARD

    Measure: Incidence of serious adverse events (safety)

    Time: Randomization through study completion through Day 60

    Description: All-cause mortality at 29 and 60 days

    Measure: All-cause mortality at 29 and 60 days

    Time: Randomization through Day 29 and Day 60

    Description: Dose-limiting toxicities, particularly presence of acute or delayed hypersensitivity reactions

    Measure: Incidence of dose-limiting toxicities (safety)

    Time: Randomization through study completion through Day 60

    Description: Clinically meaningful laboratory abnormalities

    Measure: Incidence of laboratory abnormalities (safety)

    Time: Randomization through study completion through Day 60

    Description: Plasma samples and salivary samples are taken to correlate viral load with nasopharyngeal testing at various timepoints; stool or rectal swab samples are taken if possible for additional virologic assessments

    Measure: SARS-CoV-2 viral load as assessed using various sample types

    Time: Randomization through study completion through Day 60

    Description: Time from onset of COVID-19 symptoms to hospitalization and to treatment on Day 1, and if applicable, time to ICU admission, discharge from ICU and discharge from hospital

    Measure: Time to hospitalization, treatment, ICU admission, and discharge from ICU and/or hospital

    Time: Randomization up to study completion through Day 60

    Description: Presence and levels of anti-drug antibodies (ADA) directed to COVI-GUARD

    Measure: Anti-drug antibodies

    Time: Randomization through study completion through Day 60

    Description: Levels of cytokines including EGF, IFNγ, IL-1β, IL-6, IL-8, IL-10, and TNFα

    Measure: Cytokine levels

    Time: Randomization through study completion through Day 60

    Secondary Outcomes

    Description: Area under the serum concentration-time curve (AUC) of COVI-GUARD

    Measure: AUC of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60

    Description: Maximum observed serum concentration (Cmax) of COVI-GUARD

    Measure: Cmax of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60

    Description: Apparent serum terminal elimination half life (t½) of COVI-GUARD

    Measure: t½ of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60

    Description: Time to Cmax (Tmax) of COVI-GUARD

    Measure: Tmax of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60
    305 Pilot Double Blinded Randomized Placebo Controlled Multi Central Clinical Trial on Inflammatory Regulation Effect of NAC on COVID-19

    Study times to evaluate the efficacy of N-Acetylcysteine therapy in the management of adult admitted patients with COVID-19.

    NCT04455243
    Conditions
    1. COVID-19
    Interventions
    1. Drug: N-Acetyl cysteine
    2. Drug: Placebo

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which of the following three categories from The Ordinal Scale on Covid-19 Clinical Improvement Not-Hospitalized, No limitation on activity. Not Hospitalized, with limitation on activity. Hospitalized, Not requiring supplemental Oxygen

    Measure: Time to Recovery

    Time: 28 days
    306 Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate Efficacy and Safety in Healthcare Professionals of the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac

    This is a phase III clinical trial to assess efficacy and safety of the Adsorbed COVID-19 (inactivated) vaccine manufactured by Sinovac in health care professionals

    NCT04456595
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Adsorbed COVID-19 (inactivated) Vaccine
    2. Biological: Placebo

    Primary Outcomes

    Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine

    Measure: Incidence of COVID-19 cases after two-doses immunization schedule

    Time: Two weeks after second dose up to one year after first dose

    Description: Frequency of adverse reaction in the seven days following each immunization per age group

    Measure: Frequency of adverse events up to seven days after immunization

    Time: Seven days after each immunization

    Secondary Outcomes

    Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine according to previous exposure to SARS-CoV-2

    Measure: Incidence of COVID-19 cases after two-doses immunization schedule according to previous exposure

    Time: Two weeks after first dose up to one year after first dose

    Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after first dose of vaccine, regardless the vaccination schedule was completed

    Measure: Incidence of COVID-19 cases after 14-days of first immunization

    Time: Two weeks after last dose uup to one year after first dose

    Description: Number of virologically-confirmed and or serologically-confirmed SARS-CoV-2 infections two weeks after first dose of vaccine

    Measure: Combined incidence of SARS-CoV-2 infection

    Time: Two weeks after second dose up to one year after first dose

    Description: Number of virologically-confirmed severe COVID-19 two weeks after second dose of vaccine

    Measure: Incidence of severe COVID-19 cases after two-doses immunization schedule

    Time: Two weeks after second dose up to one year after first dose

    Description: Frequency of adverse reaction in the 28 days following each immunization per age group

    Measure: Frequency of adverse events up to 28 days after immunization

    Time: 28 days after each immunization

    Description: Frequency of virologically-confirmed severe COVID-19 cases after receiving, at least, one dose of the vaccine

    Measure: Frequency of severe COVID-19 cases

    Time: From first vaccination up to one year after first dose

    Description: Frequency of adverse events of special interest after receiving, at least, one dose of the vaccine

    Measure: Frequency of adverse events of special interest after immunization

    Time: From first vaccination up to one year after first dose

    Description: Number of seroconversion responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants

    Measure: Seroconversion rate

    Time: Two weeks after each vaccination

    Description: Number of cell-mediated immune response against SARS-CoV-2 in the week two and four after the second vaccination per age group in a subset of participants

    Measure: Cell-mediated immune profile

    Time: Two and four weeks afer each vaccination

    Description: Number of seropositive responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants

    Measure: Seropositivity rate

    Time: Two weeks after second vaccination
    307 A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study in Healthy Participants and Multiple Dose Study in Participants With Ulcerative Colitis to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-66525433

    The purpose of this study is to evaluate safety and tolerability of JNJ 66525433 compared with placebo after administration of: 1) single ascending oral doses of JNJ 66525433 administered to healthy participants (Part 1), 2) multiple, ascending oral doses of JNJ 66525433, administered to healthy participants once daily over 14 consecutive days (Part 2), and 3) multiple oral doses of JNJ 66525433, administered once daily over 14 consecutive and once daily over 42 consecutive days in participants with ulcerative colitis (UC) (Part 3).

    NCT04457960
    Conditions
    1. Healthy
    2. Colitis, Ulcerative
    Interventions
    1. Drug: JNJ-66525433
    2. Drug: Placebo
    MeSH:Colitis Colitis, Ulcerative Ulcer
    HPO:Colitis Ulcerative colitis

    Primary Outcomes

    Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days will be considered as TEAE.

    Measure: Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability

    Time: Up to 224 Days

    Description: Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.

    Measure: Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities

    Time: Up to 224 Days

    Description: Number of participants with physical examination abnormalities will be reported.

    Measure: Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities

    Time: Up to 224 Days

    Description: Number of participants with clinical laboratory abnormalities (serum chemistry, hematology and urinalysis) will be reported.

    Measure: Part 1, 2 and 3: Number of Participants with Clinical Laboratory Abnormalities

    Time: Up to 224 Days

    Description: Number of participants with ECG abnormalities will be reported.

    Measure: Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities

    Time: Up to 224 Days

    Secondary Outcomes

    Description: Plasma concentrations of JNJ-66525433 will be reported.

    Measure: Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433

    Time: Up to 224 Days

    Description: Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.

    Measure: Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing

    Time: Up to Day 14

    Description: Mayo scoring system is used for assessment of ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each ranges from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12, where higher score indicates severe disease.

    Measure: Part 3: Mayo Score

    Time: Up to Day 84

    Description: Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease.

    Measure: Part 3: Partial Mayo Score

    Time: Up to Day 70

    Description: Endoscopy sub-score ranges from 0 to 3 where; 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = severe disease (spontaneous bleeding, ulceration).

    Measure: Part 3: Endoscopic Subscore

    Time: Up to Day 84

    Description: IBDQ18 is a validated, 32-item, self-reported questionnaire for participants with inflammatory bowel disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.

    Measure: Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

    Time: Days 1, 7, 14, 28, 43, 70 and 84

    Description: Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.

    Measure: Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels

    Time: Up to 182 Days

    Description: Tissue biopsy concentrations of JNJ-66525433 will be reported.

    Measure: Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations

    Time: Up to 182 Days
    308 A Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of OP-101 (Dendrimer N-acetyl-cysteine) in Patients With Severe COVID-19

    The primary purpose is to evaluate the safety and tolerability of OP-101 and secondary purpose is to determine the effect of OP-101 reducing proinflammatory cytokines after a single dose in severe COVID-19 Patients.

    NCT04458298
    Conditions
    1. COVID-19
    Interventions
    1. Drug: OP-101
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of participants with treatment emergent adverse events will be evaluated as a measure of safety and tolerability of OP-101 by monitoring and documenting all adverse events, which include laboratory test variables.

    Measure: Number of Participants with Treatment Emergent Adverse Events Graded as Assessed by CTCAE Version 4.0

    Time: Up to Day 60

    Secondary Outcomes

    Description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.

    Measure: Time to Improvement (2 points) in Clinical Status Assessment Using the World Health Organization 7-Point Ordinal Scale (WHO 7OS)

    Time: Up to Day 30

    Measure: Time to Resolution of Fever for at least 48 hours Without Antipyretics for Patients with Documented Fever (>=37.2 degree celsius [oral], or >=37.8 degree celsius [rectal], or >=38.0 degree celsius [tympanic])

    Time: Up to Day 30

    Description: Improvement in oxygenation is defined by increase in pulse oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) of >=50 compared with nadir SpO2/FiO2.

    Measure: Time to Improvement in Oxygenation for at least 48 hours

    Time: Up to Day 30

    Description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.

    Measure: Change from Baseline in the World Health Organization (WHO)-7 Point Ordinal Scale

    Time: Baseline up to Day 30

    Description: NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C).

    Measure: Time to Discharge from Clinic or Hospital or to National Early Warning Score 2 (NEWS2) of <=2 and maintained for 24 hours

    Time: Up to Day 30

    Measure: Percentage of Patients Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 30

    Time: Up to Day 30

    Measure: Number of Days of Resting Respiratory Rate of more than 24 breath/min

    Time: Up to Day 30

    Description: Hypoxemia is defined by Saturation of Peripheral Oxygen (SpO2) of less than (<) 95 percent (%) on room air or acute respiratory distress syndrome (ARDS).

    Measure: Number of Days with Hypoxemia

    Time: Up to Day 30

    Measure: Number of Days of Supplemental Oxygen use

    Time: Up to Day 30

    Measure: Number of Ventilator-free Days

    Time: Up to Day 28

    Measure: Number of Days in Intensive Care Unit (ICU)

    Time: Up to Day 30

    Measure: Number of Days of Hospitalization for Survivors

    Time: Up to Day 30

    Measure: Number of Participants with all cause deaths

    Time: Up to Day 30

    Description: Percent change from baseline in proinflammatory cytokines (C-reactive protein [CRP], ferritin, and interleukin-6 [IL-6]) will be reported.

    Measure: Percent change from baseline in Proinflammatory Cytokines

    Time: Baseline up to Day 30

    Measure: Incidence of Drug-related Serious Adverse Events (SAEs)

    Time: Up to Day 60
    309 A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 Pneumonia

    The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in adults hospitalized with COVID-19 pneumonia.

    NCT04460105
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Lanadelumab
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.

    Measure: Number of Participants with Treatment emergent adverse events (TEAEs)

    Time: From start of study drug administration to follow-up (up to Day 29)

    Secondary Outcomes

    Description: Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.

    Measure: Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours post-dose

    Description: Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.

    Measure: Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose

    Description: Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.

    Measure: Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose

    Description: Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.

    Measure: Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose
    310 PREPARE-IT. Prevention of COVID19 With EPA in Healthcare Providers at Risk - Intervention Trial

    The PREPARE-IT trial is a simple, pragmatic and universally applicable strategy with icosapent ethyl (IPE) at high doses intended to reduce infection rate and subsequent morbidity and mortality among subjects at high risk of infection due to COVID-19.

    NCT04460651
    Conditions
    1. COVID19
    Interventions
    1. Drug: Icosapent ethyl (IPE)
    2. Drug: Placebo

    Primary Outcomes

    Description: SARS-CoV-2 positive subjects are defined as subjects with positive tests for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies after developing COVID-19 disease at any stage within the follow-up period (including those subjects with or without symptomatic COVID-19 evaluated before the final visit) or those individuals who test positive for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies at the final visit (day 60).

    Measure: Percentage of SARS-CoV-2 positive subjects

    Time: 60 days

    Measure: Highest mean WHO descriptive score of COVID-19 in the active treatment group compared to the placebo group.

    Time: 60 days

    Secondary Outcomes

    Measure: Highest mean WHO score up to day 60 for the active treatment group as compared to placebo among subjects with a positive test received at any moment during the study after the first visit

    Time: 60 days

    Description: Mean change from baseline will be computed

    Measure: Total cholesterol, LDL, HDL, triglycerides (mg/dL) at baseline and at day 60

    Time: baseline, 60 days

    Description: Mean change from baseline will be computed

    Measure: Ultrasensitive C-reactive Protein (mg/dL) at baseline and at day 60

    Time: baseline, 60 days

    Measure: Difference in hospital length of stay between groups

    Time: 60 days

    Measure: Difference in duration of mechanical ventilation in both groups

    Time: 60 days

    Measure: Rate of hospital admissions due to SARS (Severe Acute Respiratory Syndrome) in patients who were negative for SARS CoV-2 upon admission

    Time: 60 days

    Measure: Mean highest WHO descriptive score in active treatment versus placebo groups up to day 60 among hospitalized patients (WHO grades 3 or more) without serum evidence / PCR detecting SARS-CoV-2 infection

    Time: 60 days

    Measure: Rate of total events, non-fatal myocardial infarction or non-fatal stroke or death (initial and subsequent), up to day 60

    Time: 60 days
    311 A Phase 1 Randomized Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers

    This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary objectives are as follows: - To assess the safety and tolerability of AHCQ administered as a single dose by oral inhalation in healthy individuals at escalating doses until either the maximum tolerated dose (MTD) is identified or 1 mL of a 50 mg/mL solution is administered. - To determine the recommended Phase 2a dose (RP2D). Secondary objectives: • To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.

    NCT04461353
    Conditions
    1. Severe Acute Respiratory Syndrome Coronavirus 2
    Interventions
    1. Drug: Aerolized Hydroxychloroquine Sulfate
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: TEAEs (defined as AEs with onset after study drug administration or existing AEs that worsen in severity after study drug administration)

    Measure: Incidences of treatment-emergent adverse events (TEAEs) as assessed by TGSHAAV (September 2007) or CTCAE version 5.0

    Time: after treatment (Day 1) through to Day 30

    Description: Blood sample collected for CBC with differential will be assessed from baseline (at screening)

    Measure: Change from baseline in clinical laboratory test results for CBC with differential

    Time: Screening and Day 8

    Description: Screening blood sample collected for CBC with differential, counting the number of abnormal clinical tests

    Measure: Incidence of abnormal laboratory test results for CBC with differential at Screening

    Time: Screening

    Description: Day 8 blood sample collected for CBC with differential

    Measure: Incidence of abnormal laboratory test results for CBC with differential - Day 8

    Time: Day 8

    Description: Blood sample collected for blood glucose and measured with a glucometer

    Measure: Changes from baseline for blood glucose

    Time: Screening and Day 1

    Description: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)

    Measure: Incidence of abnormal laboratory test results for chemistry -Screening

    Time: Screening

    Description: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)

    Measure: Incidence of abnormal laboratory tests results for chemistry - Day 8

    Time: Day 8

    Description: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood

    Measure: Incidence of abnormal laboratory tests results for urinalysis - Screening

    Time: Screening

    Description: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood

    Measure: Incidence of abnormal laboratory tests results for urinalysis- Day 8

    Time: Day 8

    Description: The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (September 2007) (TGSHAAV) will be used as the primary criteria for assessment of clinical abnormalities. Mild (17-20 breaths per minute) to Potentially Life Threatening (intubation)

    Measure: Changes in vital signs from baseline (pre-dose) - respiratory rate

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Oral temperature

    Measure: Changes in vital signs from baseline (pre-dose)- temperature

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Systolic and diastolic blood pressure

    Measure: Changes in vital signs from baseline (pre-dose) - seated blood pressure

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Heart rate measure by radial pulse rate (beats/min)

    Measure: Changes in vital signs from baseline (pre-dose) - pulse

    Time: Screening, Day 1, Day 2 and Day 8

    Description: O2 saturation (%), measured by pulse oximeter. Graded as per TGSHAAV (September 2007) from Moderate (pulse oximeter <92%) to Potentially Life Threatening (Life-threatening airway compromise; urgent intervention indicated)

    Measure: Changes in vital signs from baseline (pre-dose) - O2 saturation

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- general appearance

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - general appearance

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- general appearance

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- general appearance

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- neurological

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1- neurological

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- neurological

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- neurological

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening - heart/cardiovascular

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - heart/cardiovascular

    Time: Day 1 (pre-dose, within 3 hours of dose)

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - heart/cardiovascular

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8 - heart/cardiovascular

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening - lungs

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - lungs

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - lungs

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8 - lungs

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- abdomen

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - abdomen

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- abdomen

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- abdomen

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during screening- endocrine

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - endocrine

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- endocrine

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- endocrine

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- extremities

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1- extremities

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- extremities

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- extremities

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- lymphatic

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1- lymphatic

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - lymphatic

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- lymphatic

    Time: Day 8

    Description: A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during screening - skin

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - skin

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - skin

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8 - skin

    Time: Day 8

    Description: Pulmonary function testing and recording of FEV1, both actual and percent predicted

    Measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1

    Time: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.

    Description: Pulmonary function testing and recording of FVC, , both actual and percent predicted

    Measure: Changes from baseline for pulmonary function tests (PFTs) - FVC

    Time: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.

    Description: Pulmonary function testing and recording of FEV1/FVC

    Measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1/FVC

    Time: creening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - QT interval

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QTcB interval (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - QTcB Interval

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QRS duration (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - QRS duration

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG PR interval (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - PR interval

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG heart rate (beats/min) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - heart rate

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG - Screening

    Time: Screening

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG- Day 1

    Time: Day 1 pre-dose (within 3 hours of dose) and +2 and +6 hours

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG - Day 2

    Time: Days 2

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG - Day 8

    Time: Days 8.

    Secondary Outcomes

    Description: Blood samples for PK analysis will be collected via indwelling catheter or via direct venipuncture.

    Measure: HCQ concentration in whole blood versus time profiles

    Time: Day 1 pre-dose (time 0) and +2, +3, +5, and +15 minutes after dose, and also +1, +2, +4 and +6 hours post-dose completion. Day 2 (+24±4 hours post dose) and Day 8.
    312 Prevention, Efficacy and Safety of BCG Vaccine in COVID-19- Randomized Clinical Trial

    In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19.

    NCT04461379
    Conditions
    1. BCG
    2. COVID-19
    3. SARS-CoV2
    4. Corona Virus Infection
    Interventions
    1. Biological: BCG vaccine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Cumulative incidence of infection in 6 months: disease defined as positive SARS-Cov-2 test (serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)

    Measure: Demonstrate COVID- 19 disease incidence among Health care workers:

    Time: During the 6 months study period

    Description: Cumulative incidence of hospitalization for COVID-19

    Measure: Demonstrate cumulative incidence of hospitalization for COVID-19 among Health care workers:

    Time: During the 6 months study period

    Description: Incidence of specific Antibodies (IgG and IgM) against SARS-CoV-2 will be measured at 3 and 6 months

    Measure: Demonstrate the Incidence of specific Antibodies against SARS-CoV-2 at 3 and 6 months in health care workers

    Time: During the 6 months study period

    Description: Number of participants who needed hospitalization

    Measure: Hospitalization of severe disease COVID-19

    Time: During the 6 months study period

    Description: Number of participants who Need for oxygen supplementation (nasal cannulas, masks, high flow oxygen) in hospitalized patients

    Measure: Oxygen supplementation in severe disease COVID-19

    Time: During the 6 months study period

    Description: Number of participants who Need for intubation or non-invasive ventilation in hospitalized patients

    Measure: Need for intubation or non-invasive ventilation for the patient.

    Time: During the 6 months study period

    Description: Number of participants in Critical care admission with SARS-CoV2 in hospitalized patients

    Measure: Critical care admission with SARS-CoV2

    Time: During the 6 months study period

    Description: Mortality associated to progressive pulmonary disease in hospitalized patients

    Measure: Mortality associated to progressive pulmonary disease

    Time: During the 6 months study period

    Secondary Outcomes

    Measure: Evaluate the safety of the vaccine by measuring the incidence rates of local and systemic adverse effects that occur after one month its application.

    Time: 1 month after vaccine/placebo application

    Measure: Calculate the incidence of COVID-19 complications

    Time: During the 6 months study period

    Measure: Determine the mean days of hospitalization and days in intensive care unit by COIVD-19

    Time: During the 6 months study period

    Measure: Calculate the cost associated with in-hospital medical care

    Time: During the 6 months study period

    Description: SOFA score: PaO2/FIO2 (mm Hg), SaO2/FIO2, Platelets (×10³/µL), Bilirubin (mg/dL), Hypotension, Glasgow Coma Score and Creatinine (mg/dL) or urine output (mL/d).

    Measure: Determine the scores of the Clinical Prediction Rules associated with mortality using Sequential Organ Failure Assessment (SOFA score) at the patient's hospital admission:

    Time: During the 6 months study period

    Description: APACHE: History of severe organ failure or immunocompromise Heart Failure Class IV, cirrhosis, chronic lung disease, or dialysis-dependent, Age, Temperature (C°), Mean arterial pressure (mmHg), pH, Sodium (mEq/L), Potassium (mEq/L), Creatinine (mg/dL), Hematocrit (%), WBC (x 109/L)

    Measure: Determine the scores of the Clinical Prediction Rules associated with mortality using Acute Physiology and Chronic Health disease Classification System (APACHE) at the patient's hospital admission:

    Time: During the 6 months study period

    Description: CPR, ESR, Ferritin, D-dimer, LDH,Troponins, Procalcitonin, Interleukin-6, Hemoglobin, Hematocrit, Erythrocytes, Leukocytes, MCV, HCM, MCHC, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, Glucose, Urea, Creatinine, BUN, Sodium, Potassium, Chlorine, Calcium, Serum albumin, Direct bilirubin, Indirect bilirubin, Alkaline phosphatase, AST, ALT, bleeding time, Prothrombin Time, Activated partial thromboplastin time, Arterial / Venous Blood Gasometry, pH, pCO2, HCO3, pO2, SaO2%, Lactate.

    Measure: Evaluate and determine the alteration profile in laboratory studies at the patient's hospital admission

    Time: During the 6 months study period

    Measure: Registration of chronic medications

    Time: During the 6 months study period

    Measure: Need for vasopressors

    Time: During the 6 months study period
    313 Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoC-2 Virus Infection (COVID-19). A Pilot, Randomized, Simple Blind, Placebo-controlled, Parallel-group Study

    Evaluation of the efficacy and safety of NTX in adult patients (≥18 years and <60 years), with SARS-CoV-2 infection with mild symptoms of COVID-19, compared to a placebo control arm. 135 patients will be randomized to either Nitazoxanide (n=90) or placebo (n=45) (2:1). Simple blind design. Primary endpoint: eradication of virus from patients' respiratory tract secretions by the 7th day of treatment.

    NCT04463264
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    MeSH:Infection Virus Diseases

    Primary Outcomes

    Description: Erradication will be considered a reduction of the viral load on day 7 greater than 35% with respect to placebo. Extraction of genomic material will be performed using a QIAgen mini kit (QIAmp viral RNA) validated by the CDC (United States Center for Disease Control and Prevention (https://www.fda.gov/media/134922/download) (CDC-006-00019) Viral load will be quantified with the following detection kits: Commercial Kit: PCR-EUA-CDC-nCoV-IFU. Commercial KIT SENTINEL - STAT-NAT Covid 19B (Berlín). Rational: In mild cases of COVID-19, 50% of the patients eradicated the virus within a period of 3 weeks, 25% eradicated the virus before the 13th day, 75% during the first month and the rest were " late eradicators." This latter subgroup of patients has been associated with severe cases of COVID-19 disease.

    Measure: Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th.

    Time: 7 day

    Secondary Outcomes

    Description: Consequently, in mild cases, viral eradication will likely occur more frequently during the first to second week of COVID-19 disease; less than 15% could eradicate the virus during the first week of symptom onset. From an epidemiological point of view, increasing the viral eradication rate from less than 15% to more than 35% during the first two weeks of treatment would be clinically relevant.(seven), 14 (fourteen) and 35 (thirty-five) after starting treatment compared to the baseline measurement.

    Measure: Comparative decrease of the viral load

    Time: 3 - 35 days

    Description: Clinical improvement according to the WHO COVID-19 ordinal scale. Minimun 0 (zero), (best), maximum 8 (eight) (worst)

    Measure: Clinical improvement

    Time: 1 - 35 days

    Description: Percentage of pneumonia patients meeting severity criteria.

    Measure: Pneumonia patients meeting severity criteria.

    Time: 1 - 35 days

    Description: Number of days with fever (axillary temperature higher than 37.5°C).

    Measure: Number of days with fever

    Time: 1 - 35 days

    Other Outcomes

    Description: Percentage of patients requiring mechanical ventilation through orotracheal intubation (OT) and/or ICU hospitalization.

    Measure: Patients requiring mechanical ventilation

    Time: 1 - 35 days

    Description: Mortality rate.

    Measure: Mortality rate.

    Time: 1- 35 days

    Description: Lymphocyte recovery (absolute lymphocyte count > 1000 / mm3).

    Measure: Lymphocyte recovery

    Time: 7 day

    Description: Days of ICU hospitalization.

    Measure: ICU hospitalization.

    Time: 1 - 35 days

    Description: Oxygen saturation (SpO2) > 92% (at ambient FiO2).

    Measure: Oxygen saturation

    Time: 1 - 35 days

    Description: Days of hospitalization

    Measure: Days of hospitalization

    Time: 1 - 35 days

    Description: Respiratory rate per minute (in afebrile state conditions).

    Measure: Respiratory rate

    Time: 1 - 35 days
    314 Safety and Efficacy of PHR 160 Spray on the Outcomes of Patients With COVID-19 a Multi-center Randomized Blinding Clinical Trial Study

    This study is a multi-center randomized, controlled, and blinded clinical trial study that will be performed in four medical-educational centers. In this study, the samples will be selected from among patients with SARS-CoV-2 as easy access and based on entry criteria and will be randomly divided into two groups, including a control group and an intervention group. The study will be conducted in four medical centers. From each center, 56 definitive Corona patients will be selected, who will be randomly divided into two groups of 28, for a total of 224 patients will enter the study. In the intervention group, in addition to receiving the test spray, Patients will also receive standard treatment

    NCT04463420
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PHR160 Spray
    2. Drug: Placebo
    3. Drug: Standard treatment

    Primary Outcomes

    Description: shortness of breath measured by Visual analog scale (VAS) dyspnea score. The minimum score is zero means shortness of breath and the highest score is 10 means the maximum intensity of shortness of breath.

    Measure: Dyspnea

    Time: up to 14 days

    Secondary Outcomes

    Description: The length of time the patient is hospitalized after the diagnosis of COVID-19

    Measure: long of hospitalization

    Time: up to 28 days

    Description: CT scans help determine how much the lungs are affected by COVID-19.

    Measure: Radiological Treatment Response

    Time: up to 14 days

    Description: In-hospital mortality

    Measure: Mortality

    Time: Up to 28 days

    Description: There will be known allergic reactions to the drugs.

    Measure: Allergic drug

    Time: up to 14 days

    Description: Normal blood cell count and CRP count (normal laboratory range)

    Measure: Laboratory Treatment Response

    Time: up to 14 days

    Description: Using an oximeter pulse, the amount of oxygen saturation is measured. If the patient is receiving oxygen, first cut off the oxygen for 5 minutes and then measure. If the oxygen drops below 90 degrees, oxygen therapy will be re-established immediately.

    Measure: O2 saturation without supplemental oxygen

    Time: up to 14 days

    Description: Complications in both groups should be evaluated and evaluated during treatment. protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions that measured by Physical examination.

    Measure: drug reactions Adverse

    Time: Up to 14 days
    315 A Trial of Favipiravir Therapy in Adults With Mild Coronavirus Disease COVID-19

    Favipiravir is a selective and potent inhibitor of influenza viral RNA polymerase. It acts as a purine analogue, which selectively inhibits viral RNA-dependent RNA polymerase (RdRps). It has the characteristic of acting on RNA viruses including Ebola and Coronaviruses especially novel coronavirus (2019-nCoV). The purpose of this study is to evaluate the clinical efficacy and safety of Favipiravir in comparison to placebo in the treatment of mild COVID-19 cases. It is a Multicenter, randomized double-blinded, parallel-group trial.

    NCT04464408
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Drug: Placebo

    Primary Outcomes

    Description: Time from randomization to negativity in RT-PCR nucleic acid test for COVID-19 within 15 days of randomization

    Measure: PCR negative

    Time: 15 days

    Secondary Outcomes

    Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory symptoms, and relief of cough (or other relevant symptoms at enrollment) that is maintained for at least 72 hours.

    Measure: Time from randomization to clinical recovery

    Time: 15 days

    Measure: Symptoms progression based on clinical evaluation using simple scoring system.

    Time: 28 days

    Measure: Rate of daily requirement of using antipyretics, analgesics, or antibiotics.

    Time: 15 days

    Measure: 28 days mortality.

    Time: 28 days

    Measure: Rate of requirement of hospitalization, ICU admission or Mechanical ventilation.

    Time: 28 days

    Description: incidence of GI symptoms secondary to the study drug.

    Measure: Incidence of Treatment-related Adverse Events [Safety and Tolerability]

    Time: 15 days
    316 A Randomized, Double-Blind, Placebo-Controlled, Multiple Continuous Intravenous Injection, Dose Escalation, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of M201-A in Healthy Japanese Subjects

    This Phase I is designed to evaluate the safety, tolerability and pharmacokinetics of multiple ascending doses of M201-A administered by multiple continuous intravenous injection in Healthy Japanese subjects.

    NCT04464681
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: M201-A Injection
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of participants with adverse events, serious adverse events, physical examinations, vital sign measurements, 12-lead ECGs, Holter ECG, clinical laboratory safety tests (including hematology, chemistry, and urinalysis), recording of concomitant medications and procedures.

    Measure: Number of participants with adverse events as a measure of safety and tolerability

    Time: Throughout the study duration up to day 11
    317 Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)

    This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.

    NCT04466098
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. ARDS (Moderate or Severe)
    3. COVID-19 Pneumonia
    Interventions
    1. Biological: Mesenchymal stromal cells
    2. Other: Placebo
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Measure: Incidence of grade 3-5 infusional toxicities and predefined hemodynamic or respiratory adverse events related to the infusion of MSC

    Time: Within 6 hours of the start of the infusion

    Secondary Outcomes

    Measure: Incidence of a reduction in one or more biomarkers of inflammation by day 7

    Time: Day 7 after first infusion

    Measure: Trend changes in PaO2:FiO2 ratio

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in Mean Airway Pressure

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in peak pressure

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in plateau pressure

    Time: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in Positive end-expiratory airway pressure (PEEP)

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Incidence of mortality

    Time: 28 days after first infusion

    Measure: Incidence of mortality

    Time: 100 days after first infusion

    Measure: Number of ICU-free days

    Time: 28 days after first infusion

    Measure: Number of days alive and ventilator free composite score 3

    Time: 28 days after first infusion

    Description: Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph

    Measure: Change in acute lung injury (ALI) score 2

    Time: Baseline and Day 28 after first infusion

    Measure: Incidence of serious adverse events

    Time: 28 days after first infusion

    Measure: Number of days alive off supplemental oxygen

    Time: 100 days after first infusion
    318 Pragmatic, Double-blind, Placebo-controlled Randomized Clinical Trial, Evaluating Hydroxychloroquine for Prevention of Hospitalization and Respiratory Complications in Non-hospitalized Patients With Confirmed or Probable COVID-19

    In December 2019, a group of patients with pneumonia of unknown cause was identified in Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some limited observational trials and also evidence from randomized trials have shown no benefit of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an outpatient setting in non-severe patients can provide important information related to prognosis and safety. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized, double-blind, placebo-controlled trial

    NCT04466540
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Description: To assess if the treatment is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day.

    Measure: Hospitalization

    Time: 30 days from randomization

    Secondary Outcomes

    Description: Affirmative answer in three or four items of the Global Initiative for Asthma (GINA) questionnaire

    Measure: Uncontrolled asthma after ≥ 5 days of starting study medication

    Time: within 30 days from randomization

    Description: Defined by clinical-radiological criteria - a history of cough and one or more of the following symptoms: sputum, dyspnea, chest pain, sweating or fever (T> 37.8o C) + Chest CT scan showing ground-glass opacity, focal consolidations or mixed opacities (including reverse halo sign), uni or bilateral

    Measure: Pneumonia

    Time: within 30 days from randomization

    Description: Defined by clinical criteria - Fever (T> 37.8o C) and otalgia + bulging of the tympanic membrane

    Measure: Otitis media

    Time: within 30 days from randomization

    Description: Day 0 of fever resolution will be defined as the first afebrile day (T <37.5o C) after inclusion in the study followed by at least two consecutive days. The temperature will be obtained through the participant report in the patient's diary

    Measure: Fever resolution time

    Time: within 30 days from randomization

    Description: Time to improve respiratory symptoms (cough, runny nose)

    Measure: Time to improve respiratory symptoms

    Time: within 30 days from randomization

    Description: Admission to ICU due to clinical reasons related to COVID-19

    Measure: Hospitalization in the Intensive Care Unit

    Time: within 30 days from randomization

    Description: Clinical need for Orotracheal Intubation as assessed by the physician responsible for the case

    Measure: Need for Orotracheal Intubation

    Time: within 30 days from randomization

    Description: Number of days on mechanical ventilation until extubation or death

    Measure: Mechanical Ventilation Time

    Time: within 30 days from randomization

    Description: Death due to any cause that occurred within 30 days after inclusion in the study

    Measure: Mortality

    Time: within 30 days from randomization

    Other Outcomes

    Description: Change in the frequency of hypoglycemic episodes in diabetic patients using hypoglycemic medication, perceived by clinical signs or symptoms or measured in a capillary or blood glucose device

    Measure: Hypoglycemia

    Time: within 30 days from randomization

    Description: Presence of cardiac arrhythmias in patients without known history of prolongation of the measure between Q wave and T wave in the heart's electrical cycle (QTc) or pre-existing heart disease;

    Measure: Palpitations

    Time: within 30 days from randomization

    Description: Change in visual acuity or new diagnosis of retinal disease not previously documented

    Measure: Reduced visual acuity

    Time: within 30 days from randomization

    Description: Change in bowel habit greater than three (3) diarrheal episodes per day during the use of hydroxychloroquine medication and 3 days after its end

    Measure: Diarrhea

    Time: within 30 days from randomization

    Description: Change in appetite during medication use hydroxychloroquine and 3 days after the end of treatment

    Measure: Anorexia

    Time: within 30 days from randomization

    Description: Perception of change in emotional lability (mood swings) during hydroxychloroquine use and 3 days after the end of treatment

    Measure: Emotional lability

    Time: within 30 days from randomization

    Description: Time from randomization to hospitalization

    Measure: Time to hospitalization after randomization

    Time: within 30 days from randomization

    Description: Clinical and vital signs assessed when admitted to hospital

    Measure: Assessment of the patient clinical status at the time of hospitalization

    Time: within 30 days from randomization
    319 A Randomized, Double-blind, Placebo-controlled Trial of Anti-SARS-CoV-2 Plasma in Hospitalized Non-ICU Patients With COVID-19

    The purpose of this study is to assess the efficacy and safety of the administration of anti-SARS-CoV-2 convalescent plasma in COVID-19 patients who are sick enough to warrant hospitalization, but not yet admitted to the ICU (prior to the onset of overwhelming disease including a systemic inflammatory response, sepsis, and/or ARDS).

    NCT04467151
    Conditions
    1. COVID-19
    Interventions
    1. Drug: anti-SARS-CoV-2 plasma
    2. Other: Placebo

    Primary Outcomes

    Description: Disease progression from the state at randomization (with a "3" or "4" on the WHO Ordinal Scale for Clinical Improvement) to requiring invasive mechanical ventilation (which is "6" or greater on the WHO scale) during the study period

    Measure: Disease progression measured by WHO scale

    Time: Day 0 through Day 28 (or hospital discharge)

    Secondary Outcomes

    Description: Comparison of the number of participants reaching a maximum daily WHO score of 5, 7, and 8 during the study period per group

    Measure: Comparison of maximum WHO score per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Comparison of the median and maximum daily WHO scores during the study period per group

    Measure: Comparison of decrease of median and maximum WHO score per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Comparison of time to clinical improvement, defined as time between randomization and time to improvement (WHO Ordinal Scale "2" first reached for at least 1 day)

    Measure: Comparison of time to clinical improvement per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Evaluate the time to reach score of at least 6 within 28 days

    Measure: Comparison of time to reach score of "6" or greater on the WHO scale

    Time: Day 0 through Day 28 (or hospital discharge)

    Other Outcomes

    Description: Evaluate number of days hospitalized

    Measure: Comparison of hospital length of stay per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Evaluate number of hours in the ICU

    Measure: Comparison of ICU length of stay per group

    Time: Day 0 through Day 28 (or hospital discharge)
    320 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2/3 Study, in Adult Subjects Hospitalized With Severe SARS-CoV-2 Positive Pneumonia

    A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the potential of opaganib to improve and/or stabilize the clinical status of the patient.

    NCT04467840
    Conditions
    1. COVID-19
    2. Lung Infection
    Interventions
    1. Drug: Opaganib
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To compare the proportion of patients requiring intubation and mechanical ventilation by Day 14 between subjects taking opaganib and those on placebo.

    Measure: Intubation and mechanical ventilation

    Time: 14 days

    Secondary Outcomes

    Description: Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.

    Measure: WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0

    Time: 14 days

    Description: To compare the time to intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

    Measure: Time to intubation and mechanical ventilation

    Time: 14 days

    Description: To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.

    Measure: Time to low oxygen flow via nasal cannula

    Time: 14 days

    Description: To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.

    Measure: Supplemental oxygen requirement

    Time: 14 days

    Description: To compare the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days (Day 1 to Day 14) between subjects taking opaganib and those on placebo.

    Measure: Total daily oxygen requirement

    Time: 14 days

    Description: To compare the time to two consecutive negative swabs for SARS-CoV-2 by PCR between subjects taking opaganib and those on placebo.

    Measure: Time to negative swabs for SARS-CoV-2

    Time: 14 days

    Description: To compare the proportion of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.

    Measure: Negative swabs for SARS-CoV-2 at day 14

    Time: 14 days

    Description: To compare the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C [100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14 between subjects taking opaganib and those on placebo.

    Measure: Fever

    Time: 14 days

    Description: To compare mortality 30 days post-baseline between subjects taking opaganib and those taking placebo

    Measure: Mortality

    Time: 30 days post baseline

    Other Outcomes

    Description: To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo

    Measure: Adverse events

    Time: Up to 14 days and at the end of the 4 weeks follow-up after the end of treatment

    Description: To compare the change in the systemic marker of inflammation, D-dimer, over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - D-dimer

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation, cardiac troponin, over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - cardiac troponin

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation, C-reactive protein [CRP], over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - C-reactive protein

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation lactate dehydrogenase [LDH] over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - lactate dehydrogenase

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation ferritin over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - ferritin

    Time: 14 days
    321 Phase 1 Double-Blinded, Randomized, Placebo Controlled Safety and Early Efficacy Trial of Cryopreserved Cord Blood Derived T-Regulatory Cell Infusions (CK0802) In The Treatment Of COVID-19 Induced Acute Respiratory Distress Syndrome (ARDS)

    To assess the safety and efficacy of CK0802 in treatment of patients with COVID-19 induced moderate-to-severe PNA-ARDS.

    NCT04468971
    Conditions
    1. COVID19
    2. ARDS
    Interventions
    1. Biological: CK0802
    2. Drug: Placebo

    Primary Outcomes

    Description: Regimen related ≥ grade 3 toxicity within 48 hours of first infusion (DLT)

    Measure: Regimen related ≥ grade 3 toxicity within 48 hours of first infusion

    Time: 48 hours

    Description: Alive and not intubated 28 days after the date of first infusion

    Measure: 28-day treatment success, defined as S28

    Time: 28 days

    Secondary Outcomes

    Description: Time to extubation

    Measure: Time to extubation

    Time: 28 days

    Description: Oxygenation requirement (PaO2/FiO2) change between day 0 and day +11

    Measure: Oxygenation improvement

    Time: 11 days

    Description: Ventilator free days measured at day 28

    Measure: Ventilator free days

    Time: 28 days

    Description: Organ failure free days measured at day 28

    Measure: Organ failure free days

    Time: 28 days

    Description: ICU free days measured at day 28

    Measure: ICU free days

    Time: 28 days

    Description: All-cause mortality at day 28

    Measure: All-cause mortality

    Time: 28 days
    322 A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia

    Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and acute respiratory distress syndrome (ARDS) in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.

    NCT04469114
    Conditions
    1. Covid19
    Interventions
    1. Drug: Tofacitinib 10 mg
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: 1, 2 or 3 on the 8-point National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity. The minimum value is 1 (worst outcome) and the maximum value is 8 (best outcome). Death. Hospitalized, on invasive mechanical ventilation or ECMO. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. Hospitalized, requiring supplemental oxygen. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise). Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care. Not hospitalized, limitation on activities and/or requiring home oxygen. Not hospitalized, with no limitations on activities.

    Measure: Death or respiratory failure ate Day 28

    Time: 28 days

    Secondary Outcomes

    Description: NIAID ordinal scale of disease severity

    Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14

    Time: 14 days

    Description: Categories 3 to 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 and Day 28

    Measure: Status of alive and not on mechanical ventilation or ECMO at Day 14 and 28 NIAID ordinal scale of disease severity at Day 14

    Time: 14 and 28 days

    Description: Categories 1 to 4 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity

    Measure: Status of requiring supplemental oxygen at Day 28

    Time: 28 days

    Description: Categories 7 and 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity

    Measure: Status of being alive and not hospitalized at Day 14 and 28

    Time: 14 and 28 days

    Description: NIAID ordinal scale of disease severity

    Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 NIAID ordinal scale of disease severity at Day 28

    Time: 28 days

    Description: Number of patients with resolution of fever, cough, and need for ventilatory or oxygen support.

    Measure: Number of patients with cure

    Time: 28 days

    Description: Number of patients at the ICU or on ventilatory support

    Measure: Number of patients at the ICU or on ventilatory support at Day 28

    Time: 28 days

    Description: Number of days free from mechanical ventilation

    Measure: Number of days free from mechanical ventilation at 28 days

    Time: 28 days

    Description: Number of days in hospital

    Measure: Number of days in hospital

    Time: 28 days

    Description: Number of days in ICU

    Measure: Number of days in ICU

    Time: 28 days
    323 A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Immunomodulatory Effect of the RIPK1 Inhibitor SAR443122 in Hospitalized Patients With Severe COVID-19

    Primary Objective: To evaluate the effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by C-reactive protein (CRP) levels in adult patients hospitalized with severe COVID-19 Secondary Objectives: - To evaluate the time to onset of effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by CRP levels - To evaluate the time to onset of effect of SAR443122 relative to the control arm on oxygenation status - To evaluate the effect of SAR443122 relative to the control arm on oxygenation status - To evaluate the effect of SAR443122 relative to the control arm on total duration of supplemental oxygen requirement - To evaluate the effect of SAR443122 relative to the control arm on length of ventilator support needed - To evaluate the effect of SAR443122 relative to the control arm on laboratory markers of severe COVID-19 - To evaluate the effect of SAR443122 relative to the control arm on mortality - To evaluate the effect of SAR443122 relative to the control arm on need for thrombolytic therapy - To evaluate the effect of SAR443122 relative to the control arm on need for vasopressor treatment - To evaluate the safety of SAR443122 as compared to the control arm up to End of Study

    NCT04469621
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Drug: SAR443122
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Relative change from baseline in CRP level on Day 7

    Measure: Relative change from baseline in CRP level

    Time: Day 7

    Secondary Outcomes

    Description: The time to 50% decrease from baseline in CRP level

    Measure: Time to 50% decrease from baseline in CRP level

    Time: Baseline to Day 28

    Description: The time to improvement of oxygenation as measured by oxygen saturation >/=92% breathing room air over 48 hrs or until discharge

    Measure: Time to improvement of oxygenation

    Time: Baseline to Day 28

    Description: Change from baseline in SPO2/FiO2 ratio at Day 7

    Measure: Change from baseline in SPO2/FiO2 ratio

    Time: Day 7

    Description: Number of Days without need for oxygen support and alive (oxygen saturation >=92% breathing room air) up to Day 28

    Measure: Number of Days without need for oxygen support and alive

    Time: Baseline to Day 28

    Description: Numbers of Ventilator-free days and alive up to Day 28

    Measure: Numbers of Ventilator-free days and alive

    Time: Baseline to Day 28

    Description: Change from baseline in white blood cell count and differential blood lymphocytes at Day 7 and End of treatment (EOT)

    Measure: Change from baseline in markers of inflammation: white blood cell count and differential blood lymphocytes

    Time: Day 7 and Day 15

    Description: Change from baseline in neutrophil to lymphocyte ratio at Day 7 and EOT

    Measure: Change from baseline in marker of inflammation: neutrophil to lymphocyte ratio

    Time: Day 7 and Day 15

    Description: Change from baseline in IL-6 at Day 7 and EOT

    Measure: Change from baseline in marker of inflammation: interleukin 6 (IL-6)

    Time: Day 7 and Day 15

    Description: Change from baseline in D-Dimer at Day 7 and EOT

    Measure: Change from baseline in D-Dimer

    Time: Day 7 and Day 15

    Description: Incidence of Deaths up to Day 28

    Measure: Incidence of Deaths

    Time: Baseline to Day 28

    Description: Percentage of participants receiving thrombolytic treatment up to Day 28

    Measure: Percentage of participants receiving thrombolytic treatment

    Time: Baseline to Day 28

    Description: Percentage of participants receiving vasopressor treatment up to Day 28

    Measure: Percentage of participants receiving vasopressor treatment

    Time: Baseline to Day 28

    Measure: Incidence of serious adverse events (SAEs), adverse events of special interest (AESI) and treatment-emergent adverse events (TEAEs) leading to treatment discontinuation

    Time: Baseline to Day 28

    Measure: Incidence of TEAEs leading to study discontinuation (primary reason)

    Time: Baseline to Day 28
    324 A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older

    The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273.

    NCT04470427
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: mRNA-1273
    2. Biological: Placebo

    Primary Outcomes

    Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose of mRNA-1273

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Measure: Number of Participants with Adverse Events (AEs) or Medically Attended AEs (MAAEs) Leading to Withdrawal

    Time: Up to Day 759 (2 years after second dose)

    Measure: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)

    Time: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose)

    Measure: Number of Participants with Unsolicited AEs

    Time: Up to Day 57 (28 days after each dose)

    Secondary Outcomes

    Description: Clinical signs indicative of severe COVID-19 as predefined for the study.

    Measure: Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of mRNA-1273

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 Infection as predefined for the study.

    Measure: Number of Participants with a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection regardless of symptomatology or Severity Starting 14 Days after Second Dose of mRNA-1273 or Placebo

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)]

    Description: Clinical signs indicative of secondary case definition of COVID-19 as predefined for the study.

    Measure: Number of Participants with a Secondary Case Definition of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 as predefined for the study.

    Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of mRNA-1273 or Placebo

    Time: Day 1 (first dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.

    Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo regardless of evidence of prior SARS-CoV-2 Infection

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.

    Measure: Number of Participants with a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Measure: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759

    Measure: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759

    Measure: Quantified Levels or GMT of S Protein-Specific Binding Antibody (bAb)

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759

    Measure: GMFR of S Protein Specific bAb

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759
    325 Phase 2, Randomized, Double-Blind Placebo Controlled Study of Intravenous Abatacept in the Treatment of Hospitalized COVID-19 Participants With Respiratory Compromise

    The purpose of this study is to evaluate the efficacy and safety of intravenous abatacept administered to hospitalized COVID-19 participants with respiratory compromise.

    NCT04472494
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Biological: Abatacept
    2. Other: Placebo

    Primary Outcomes

    Measure: Proportion of participants with composite end point of mechanical ventilation or death prior to or on Day 28

    Time: Up to 28 days

    Secondary Outcomes

    Measure: Change from baseline in the Ordinal 8-point Outcome Scale on Day 28

    Time: Day 28

    Measure: All-cause mortality on Day 28

    Time: Day 28

    Measure: Proportion of participants alive and free of respiratory failure on Day 28

    Time: Day 28

    Measure: Proportion of participants returned to room air by Day 28

    Time: Up to 28 days

    Measure: Proportion of participants alive and discharged home by Day 28

    Time: Up to 28 days

    Measure: Proportion of participants with Serious Adverse Events (SAEs)

    Time: Up to 60 days

    Measure: Proportion of participants with serious infections

    Time: Up to 60 days
    326 Sub-cutaneous Ivermectin in Combination With and Without Oral Zinc and Nigella Sativa: a Placebo Randomized Control Trial on Mild to Moderate COVID-19 Patients

    To measure the effect of Ivermectin (sub-cutaneous) with or without zinc and Nigella sativa in treating the COVID-19 patients to clear viral load of SARS-CoV-2 along with reduction in severity of symptoms and length of hospitalization of patients with COVID-19.

    NCT04472585
    Conditions
    1. Coronavirus Infection
    2. COVID
    3. Sars-CoV2
    Interventions
    1. Drug: Nigella Sativa / Black Cumin
    2. Drug: Ivermectin Injectable Solution
    3. Other: Placebo
    4. Drug: Zinc
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: time needed to turn positive COVID-19 PCR to negative

    Measure: qRT-PCR

    Time: 14 days

    Secondary Outcomes

    Description: time needed to make patients clinically better

    Measure: Severity of symptoms

    Time: 14 days
    327 A Safety, Tolerability, and Pharmacokinetic Study of Single-and Multiple-Ascending Doses of LY3473329 in Healthy Subjects

    The main purpose of this study in healthy participants is to learn more about the safety of LY3473329 and any side effects that might be associated with it. Blood tests will be performed to check how much LY3473329 gets into the bloodstream and how long the body takes to eliminate it. This is a two-part study. Participants may only enroll in one part. For each participant: - Part A will last up to about 19 weeks and may include 9 visits. - Part B will last up to about 28 weeks and may include 11 visits.

    NCT04472676
    Conditions
    1. Healthy
    Interventions
    1. Drug: LY3473329
    2. Drug: Placebo

    Primary Outcomes

    Description: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

    Measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

    Time: Baseline up to Day 137

    Secondary Outcomes

    Description: PK: AUC of LY3473329

    Measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3473329

    Time: Baseline up to Day 137

    Description: PK: Cmax of LY3473329

    Measure: PK: Maximum Observed Drug Concentration (Cmax) of LY3473329

    Time: Baseline up to Day 137
    328 Adaptive Design Phase 2 to 3, Randomized, Double-blind, to Evaluate Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BIO101 in the Prevention of the Respiratory Deterioration in Hospitalized COVID-19 Patients

    The COVA clinical study is a global multicentric, double-blind, placebo-controlled, group sequential and adaptive 2 parts phase 2-3 study targeting in patients with SARS-CoV-2 pneumonia. Part 1 is a Phase 2 exploratory Proof of Concept (PoC) study to provide preliminary data on the activity, safety and tolerability of BIO101 in the target population. Part 2 is a phase 3 pivotal randomized study to provide further evidence of safety and efficacy of BIO101 after 28 days of double-blind dosing. BIO101 is the investigational new drug that activates the Mas receptor (MasR) through the protective arm of the Renin Angiotensin System (RAS).

    NCT04472728
    Conditions
    1. Covid-19
    2. SARS-CoV2
    Interventions
    1. Drug: BIO101
    2. Drug: Placebo

    Primary Outcomes

    Description: For interim analysis intended to obtain indication of activity of BIO101. Primary endpoint: • Proportion of subjects with negative events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen

    Measure: End-of-Part 1 interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.

    Time: up to 28 days

    Description: For sample size re-assessment for part 2, time frame - up to 28 days: • Proportion of participants with negative events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring high-flow oxygen

    Measure: For part-2 sample size interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.

    Time: up to 28 days

    Description: • Proportion of participants with of subjects with negative events, of either of the following. All-cause mortality Respiratory failure, defined as any of the following: Mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen

    Measure: For the final analysis: Proportion of subjects with all cause mortality or respiratory failure.

    Time: up to 28 days

    Secondary Outcomes

    Description: • SpO2/FiO2

    Measure: Interim analysis; indication of activity of BIO101: Oxygen saturation by pulse oximetry (SpO2) SpO2 / Fraction of inspired oxygen (FiO2) ratio

    Time: 28 days

    Description: • Inflammatory markers including: IL 6 TNFα D-dimer

    Measure: Interim analysis; indication of activity of BIO101: Inflammatory markers

    Time: 28 days

    Description: • Renin Angiotensin System biomarkers: Angiotensin 2 Angiotensin-converting enzyme (ACE) levels

    Measure: Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers

    Time: 28 days

    Description: Proportion of participants with events of all-cause mortality Proportion of participants with 'positive' events: o official discharge from hospital care by the department due to improvement in patient condition (self-discharge by patient is not considered a positive event) Proportion of participants with events of respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen

    Measure: Key secondary endpoint for final analysis: Proportion of participants with positive or negative events

    Time: 28 days

    Description: Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2) SpO2/FiO2 Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen)

    Measure: Additional secondary endpoints for final analysis: Respiratory function

    Time: 28 days

    Description: For participants who experienced a positive event: proportion of participants with with sustained positive outcome (to asesss durability of effect after those participants discontinued study medication). Time to event: official discharge from hospital care due to improvement

    Measure: Additional secondary endpoints for final analysis:proportion of patients who experienced positive event

    Time: 28 days

    Description: Time to events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage); Requiring ECMO; Requiring high-flow oxygen • Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen)

    Measure: Additional secondary endpoints for final analysis:proportion of patients who experienced negative events

    Time: 28 days

    Description: National Early Warning Score 2 (NewS2): scores: 0-7

    Measure: Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2):

    Time: 28 days

    Description: Cmax: Peak Plasma concentration

    Measure: Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK)

    Time: 1day

    Description: tmax: Time to reach peak plasma concentration

    Measure: Additional secondary endpoint : Population Pharmacokinetics study (pop-PK)

    Time: 1 day

    Description: AUC: Area under the plasma concentration versus time curve

    Measure: Secondary endpoint: Population Pharmacokinetics study (pop-PK)

    Time: 1 day
    329 Efficacy of Iodine Complex in Mild to Moderate COVID-19 Patients

    The objective of this study is to measure the effect of Iodine complex in treating the COVID-19 patients to clear viral load of SARS-CoV-2 along with reduction in severity of symptoms and length of hospitalization of patients with COVID-19.

    NCT04473261
    Conditions
    1. Covid19
    2. SARS-CoV-2
    3. Corona Virus Infection
    Interventions
    1. Drug: Iodine Complex
    2. Drug: Iodine Complex
    3. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Time taken for viral load clearance

    Measure: qRT-PCR

    Time: 14 days

    Secondary Outcomes

    Description: Time taken for symptomatic response in patients

    Measure: Severity of Symptoms

    Time: 14 days
    330 A Phase I/II, First-in-human, Observer-blinded, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Safety and Immunogenicity of KBP-COVID-19 Vaccine in Healthy Seronegative Adults Aged 18-49 and 50-70

    This is an First In Human (FIH), observer-blinded, randomized, placebo-controlled, parallel group study to evaluate the safety and immunogenicity of KBP-COVID-19 vaccine in healthy CoV-2seronegative adult subjects in 2 age groups, Part A (18-49 years) and Part B (50-70 years).

    NCT04473690
    Conditions
    1. Covid19
    Interventions
    1. Biological: Low Dose of KBP-COVID-19
    2. Biological: High Dose of KBP-COVID-19
    3. Biological: Placebo

    Primary Outcomes

    Description: Occurrence of Adverse Events

    Measure: Solicited Administration site reactions

    Time: 7 days after vaccination

    Description: Occurrence of Adverse Events

    Measure: Solicited systemic events

    Time: 7 days after vaccination

    Secondary Outcomes

    Description: Safety Endpoints

    Measure: Unsolicited Adverse Events and medically attended adverse events

    Time: 43 days after vaccination

    Description: Safety Endpoints

    Measure: Serious Adverse Events, Medically Attended Adverse Events and New Onset Chronic Diseae

    Time: 365 days after vaccination

    Description: Immunogenicity

    Measure: Vaccine ELISA and neutralizing antibody titers for each treatment group

    Time: Baseline, Day 8, 15, 22, 29, 43, 90, 181, 273, 365

    Description: Immunogenicity

    Measure: Seroconversion rates

    Time: Days 8, 15, 22, 29, 43, 90, 181, 273, 365
    331 A Multi-center, Randomized, Double-blind, Parallel, Placebo-Controlled, Phase Ⅱ Clinical Trial to Evaluate Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients

    This study is a multi-center, randomized, double-blind, parallel, placebo-controlled, phase Ⅱ clinical trial to evaluate efficacy and safety of Pyramax in mild to moderate COVID-19 patients.

    NCT04475107
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Pyronaridine-Artesunate
    2. Drug: Placebo

    Primary Outcomes

    Description: * Patients who are rRT-PCR negative for COVID-19

    Measure: Proportion (%) of patients with virological clearance of SARS-CoV-2 at day 7 post-dose*

    Time: Day 7

    Secondary Outcomes

    Measure: Viral load reduction of SARS-CoV-2 at Day 3, 7, 10, and 14 post-dose compared to the baseline

    Time: Day 3, 7, 10, 14

    Description: * Patients who are rRT-PCR negative for COVID-19

    Measure: Proportion (%) of patients with virological clearance of SARS-CoV-2 at Day 3, 10, and 14 post-dose*

    Time: Day 3, 10, 14

    Measure: Change in WHO Ordinal Scale for Clinical Improvement at Day 3, 7, 10, 14, and 28 post-dose from the baseline

    Time: Day 3, 7, 10, 14, 28

    Measure: Change in NEWS score at Day 3, 7, 10, 14, and 28 post-dose from the baseline

    Time: Day 3, 7, 10, 14, 28

    Measure: Time to achieve normalization of body temperature, post-dose

    Time: Day 3, 7, 10, 14, 28

    Measure: Time to achieve normalization of respiratory rate, post-dose

    Time: Day 3, 7, 10, 14, 28

    Measure: Time to achieve normalization of oxygen saturation, post-dose

    Time: Day 3, 7, 10, 14, 28
    332 A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ST-2427 IV Infusion in Healthy Subjects

    This randomized, double-blind, placebo controlled, study will be conducted to evaluate the safety, tolerability, and pharmacokinetics of ST-2427. The study will be conducted in 2 parts. In Part A of this study, subjects will be randomized to receive a single dose of ST-2427 or placebo in a Single Ascending Dose (SAD) design. In Part B of this study, subjects will be randomized to receive up to 6 repeat doses of ST-2427 or placebo, administered twice-daily (BID) every 12 hours, in a Multiple Ascending Dose (MAD) design. In Part A and Part B, study drug (ST-2427 or placebo) will be administered intravenously (IV) over 1 hour. A total of 48 subjects will be enrolled. Subjects will be randomized in a 4:2 ratio of ST-2427 to placebo. Study drug will be blinded to all subjects and investigators.

    NCT04475198
    Conditions
    1. Acute, Post-operative Pain
    Interventions
    1. Drug: ST-2427
    2. Drug: Placebo
    MeSH:Pain, Postoperative

    Primary Outcomes

    Description: For purposes of monitoring safety, treatment-emergent adverse events (AEs) will be graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers (FDA 2007) which is appropriate for healthy subjects.

    Measure: Incidence and severity of treatment-emergent adverse events

    Time: Day 1 through Day 8

    Description: Blood pressure, including orthostatic blood pressure (BP; diastolic blood pressure [DBP], systolic blood pressure [SBP], will be used to analyze for change from baseline.

    Measure: Incidence and severity of adverse events assessed by blood pressure

    Time: Day 1 through Day 8

    Description: Cardiodynamic evaluation will be performed to evaluate the treatment effects on heart rate-corrected QT interval using the Fridericia (QTcF) corrections, using concentration-QTc analysis, and on other ECG parameters (heart rate, PR and QRS interval and treatment emergent T and U-wave abnormalities).

    Measure: Incidence and severity of adverse events assessed by ECG

    Time: Day 1 through Day 8

    Description: The Holter recordings will also be analyzed for the presence of arrhythmias and for derivation of heart rate variability (HRV).

    Measure: Incidence and severity of adverse events assessed by Continous Holter Monitoring

    Time: Day 1 through Day 8

    Description: Descriptive statistics will be used to evaluate the treatment effects on clinical laboratory assessments including clinical chemistry, hematology, and urinalysis.

    Measure: Incidence and severity of treatment-emergent events assessed by clinical laboratory assessments

    Time: Day 1 through Day 8

    Description: Body weight (kg) will be assessed for changes relative to baseline.

    Measure: Incidence and severity of adverse events assessed by body weight

    Time: Day 1 through Day 8

    Secondary Outcomes

    Description: PK modeling will be performed using compartmental methods. The maximum concentration of ST-2427 in whole blood after the ST-2427 infusion in the SAD, and after the first and fifth infusions of ST-2427 in the MAD will be measured.

    Measure: Pharmacokinetics of ST-2427 concentration in whole blood: Cmax

    Time: Day 1 through Day 5

    Description: PK modeling will be performed using compartmental methods. The elimination half-life of ST-2427 in whole blood after the ST-2427 infusion in the SAD, and after the first and fifth infusions of ST-2427 in the MAD will be measured.

    Measure: Pharmacokinetics of ST-2427 concentration in whole blood: Elimination half-life

    Time: Day 1 through Day 5

    Description: PK modeling will be performed using compartmental methods. The AUC (area under the curve) of ST-2427 in whole blood after the ST-2427 infusion in the SAD, and after the first and fifth infusions of ST-2427 in the MAD will be measured.

    Measure: Pharmacokinetics of ST-2427 concentration in whole blood: Area under the curve

    Time: Day 1 through Day 5

    Description: The ST-2427 concentrations in the urine will be measured in 4 hour increments by cohort for the SAD.

    Measure: Pharmacokinetics of ST-2427 concentration in urine

    Time: Day 1 through Day 5
    333 A Randomized, Investigator- /Subject-blind, Single- and Multiple-ascending Dose, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 Following Oral Administration in Healthy Male Participants

    This study will evaulate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single- and multiple-ascending doses (SAD and MAD) and food effect (FE) of RO6953958 following oral administration in healthy male participants.

    NCT04475848
    Conditions
    1. Autistic Disorder
    2. Autism Spectrum Disorder
    3. Child Development Disorders, Pervasive
    4. Mental Disorders
    5. Neurodevelopmental Disorders
    Interventions
    1. Drug: RO6953958
    2. Drug: Placebo
    MeSH:Disease Autism Spectrum Disorder Child Development Disorders, Pervasive Mental Disorders Autistic Disorder Neurodevelopmental Disorders Developmental Disabilities
    HPO:Autism Autistic behavior

    Primary Outcomes

    Measure: Percentage of Participants with Adverse Events in Part 1

    Time: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort)

    Measure: Percentage of Participants with Adverse Events in Part 2

    Time: From randomization up to 8 weeks

    Measure: Part 2: Change in suicide risk assessed using the Columbia Suicide Severity Rating Scale (C-SSRS)

    Time: From randomization up to 8 weeks

    Secondary Outcomes

    Measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1

    Measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1

    Measure: Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Terminal Elimination Phase Half-Life (T1/2) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Area Under the Concentration-Time Curve from Time 0 to 12 hours (AUC(0-12h)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Area Under the Concentration-Time Curve from Time Extrapolated to Infinity (AUC (0-inf)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Apparent Clearance (CL/F) of RO6953958 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Apparent Volume of Distribution (V/F) of RO6953958 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Cumulative Amount of Unchanged Drug Excreted into the Urine (Ae) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Fraction of the Administered Drug Excreted into the Urine (Fe) of RO6953958 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Part 1: Renal Clearance of the Drug from Urine (CLR) of RO6953958 in Fasted and Fed state

    Time: Day 1 to Day 5

    Measure: Parts 2: Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 and Day 10

    Measure: Parts 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 and Day 10

    Measure: Parts 2: Average Plasma Concentration (Cavg) of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14

    Measure: Part 2: Tmax of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 and Day 10

    Measure: Part 2: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14

    Measure: Part 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14

    Measure: Part 2: T1/2 of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14

    Measure: Part 2: CL/F of RO6953958

    Time: Day 1 to Day 14

    Measure: Part 2: V/F of RO6953958

    Time: Day 1 to Day 14

    Measure: Part 2: Ae of RO6953958

    Time: Day 1 to Day 14

    Measure: Part 2: Fe of RO6953958

    Time: Day 1 to Day 14

    Measure: Part 2: CLR of RO6953958

    Time: Day 1 to Day 14

    Measure: Part 2: Trough Plasma Concentration (Ctrough) of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14

    Measure: Part 2: Accumulation Ratio based on AUC (Rauc) of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14

    Measure: Part 2: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14

    Measure: Part 2: Accumulation Ratio based on Ctrough (RCtrough) of RO6953958 and its Metabolites RO7021594 and RO7045755

    Time: Day 1 to Day 14
    334 Reducing Asymptomatic Infection With Vitamin D in Coronavirus Disease

    This study is intended to address whether oral daily vitamin D supplementation reduces infection with SARS-CoV-2 in healthy young adults. The primary aim of the study is to demonstrate a reduction in 'silent' seroconversion rates, consistent with asymptomatic transmission of SARS-CoV-2, in a young healthy adult population following 24 weeks of taking oral vitamin D supplemented at a dose of 1000 I.U. daily, versus matching placebo. The secondary aims of this study are to explore: 1. Any effect on symptomatic illness. 2. The background 'point' prevalence and subsequent rate of increase in seropositivity for SARS-CoV-2 in healthy young adults. 3. The individual reductions in seropositivity to SARS-CoV-2 over time, and changes in seropositivity in a defined young adult population over time. 4. Where salivary Immunoglobulin A (IgA) may be used to provide an alternative/ complementary serological method 5. The effect (if any) of vitamin D supplementation on seroconversion rates stratified by: i) level of baseline vitamin D 'deficiency/ insufficiency/ sufficiency' status; ii) extent of BMI-defined normal/overweight/obesity cut-offs and iii) gender.

    NCT04476680
    Conditions
    1. SARS-CoV Infection
    2. Vitamin D Deficiency
    3. Covid19
    4. Acute Respiratory Tract Infection
    Interventions
    1. Dietary Supplement: Vitamin D 1000 IU
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Vitamin D Deficiency Asymptomatic Infections
    HPO:Low levels of vitamin D Respiratory tract infection

    Primary Outcomes

    Description: asymptomatic seroconversion for SARS-CoV-2

    Measure: Seroconversion

    Time: 24 weeks

    Description: asymptomatic seroconversion for SARS-CoV-2

    Measure: Interim analysis - seropositivity at 12 weeks

    Time: 12 weeks

    Secondary Outcomes

    Description: Sensitivity and specificity of dried blood spot assay compared with venous blood serology

    Measure: Dried Blood Spot performance

    Time: 24 weeks

    Description: Sensitivity and specificity of salivary IgA compared with venous blood serology

    Measure: Salivary IgA performance

    Time: 24 weeks

    Description: The background 'point' prevalence and subsequent rate of increase in seropositivity for SARS-CoV-2 in healthy young adults.

    Measure: Prevalence of SARS-CoV-2

    Time: 24 weeks

    Description: The individual reductions in seropositivity to SARS-CoV-2 over time, and changes in seropositivity in a defined young adult population over time

    Measure: Change in seropositivity

    Time: 24 weeks

    Description: The effect of vitamin D supplementation on seroconversion rates stratified by: i) level of baseline vitamin D 'deficiency/ insufficiency/ sufficiency' status; ii) extent of BMI-defined normal/overweight/obesity cut-offs, iii) gender iv) ethnicity

    Measure: Change in seroconversion rate

    Time: 24 weeks
    335 COVID-FISETIN: A Phase 2 Placebo-Controlled Pilot Study in Covid-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Hospitalized Adults

    The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.

    NCT04476953
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Placebo
    2. Drug: Fisetin

    Primary Outcomes

    Description: Number of participants to experience serious adverse events and hypersensitivity reactions.

    Measure: Serious Adverse Events

    Time: 6 months

    Description: change in oxygenation levels as measured by S/F ratio (SPO2/FiO2)

    Measure: Change in oxygenation status

    Time: baseline, Day 3, 7, 10, 14, 17 and 30; Months 3 and 6

    Secondary Outcomes

    Description: Number of participants to progress to severe or critical classification measure by the WHO/ NIH Baseline Severity Classification criteria descriptions of SARS-CoV-2 infection without symptoms, Mild COVID-19 (CoV), Moderate CoV, Severe CoV and Critical CoV

    Measure: COVID-19 Severity Category

    Time: 6 months
    336 Randomized, Double-Blind Clinical Trial of Ruxolitinib in Patients With Acute Respiratory Disorder Syndrome Due to SARS-CoV-2 Infection

    The COVID-19 pandemic has had a dramatic effect in public health worldwide. In Brazil, there have been more than 2 million confirmed cases and over 75,000 deaths since February 26, 2020. Based on reports of a hyperinflammatory state associated with COVID-19, the use of immunosuppressive drugs may be efficacious in the treatment of this disease. JAK inhibitors have been shown to harness inflammation in a number of different pathologic conditions. The aim of the present study is to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in patients with acute respiratory distress syndrome due to COVID-19.

    NCT04477993
    Conditions
    1. Severe Acute Respiratory Syndrome Coronavirus 2
    2. SARS-CoV2
    Interventions
    1. Drug: Janus Kinase Inhibitor (ruxolitinib)
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiration Disorders Respiratory Tract Diseases Syndrome

    Primary Outcomes

    Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 14.

    Time: 14 days

    Secondary Outcomes

    Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 28

    Time: 28 days

    Description: ICU admission, mechanical ventilation, death or consent withdrawal

    Measure: Time to treatment failure

    Time: 28 days

    Measure: Overall survival at days 14 and 28

    Time: 14 and 28 days

    Measure: Cumulative incidence of ICU admission rate at days 14 and 28

    Time: 14 and 28 days

    Measure: Cumulative incidence of mechanical ventilation at days 14 and 28

    Time: 14 and 28 days

    Measure: Duration of hospital stay

    Time: 28 days

    Measure: Duration of ICU stay

    Time: 28 days

    Measure: Duration of mechanical ventilation

    Time: 28 days

    Measure: Duration of non-invasive ventilation

    Time: 28 days

    Measure: Secondary hemophagocytic syndrome rate

    Time: 28 days

    Measure: Cumulative incidence nosocomial infection rate at days 14 and 28

    Time: 14 and 28 days

    Measure: Incidence of discontinuation of oxygen supplementation at days 14 and 28

    Time: 14 and 28 days

    Measure: Rate of grade 1-2 and 3-5 emerging adverse events at day 28

    Time: 28 days

    Measure: Cumulative dose of methylprednisolone at days 14 and 28

    Time: 14 and 28 days

    Measure: Change in PaO2/FiO2 ratio from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in d-dimer levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in ferritin levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in C reactive protein levels [mg/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in alanine aminotransferase [U/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in creatinine levels [mg/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in glucose levels [mg/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in hemoglobin levels [g/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in prothrombin time ratio from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in partial thromboplastin time ratio from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in bilirubin [mg/dl] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in CPK-MB [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in troponin [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in ADAMTS-13 [%] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in von Willebrand multimeters from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in E-selectin levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in P-selectin levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in endothelin [fmol/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in circulating microparticles from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in thromboelastography from baseline to days 14 and 28

    Time: 14 and 28 days
    337 Prevention of Severe Covid-19 in Infected Elderly by Early Administration of Convalescent Plasma With High-titers of Antibody Against SARS-CoV2.

    Trial design. Randomized, double-blind, placebo-controlled trial in a catchment population of 2,020,860 age-appropriate subjects in the state of Buenos Aires and 235,000 in the city of Buenos Aires. Institutions. Hospitals San Juan de Dios, Simplemente Evita, Dr. Carlos Bocalandro, Evita Pueblo, Sanatorio Antartida, Hospital Central de San Isidro, Clinica Olivos in the state of Buenos Aires with 38 regional and town hospitals acting as referral centers, and Hospital Militar Central, Sanatorio de Los Arcos, Hospital Universitario CEMIC, Sanatorio Sagrado Corazon, Sanatorio Finochietto, Sanatorio Anchorena, Centro Gallego, and in the city of Buenos Aires in Argentina. Study population. Subjects >= 75 years of age irrespective of presenting comorbidities or between 65-74 years of age with at least one comorbidity (hypertension, diabetes, obesity, chronic renal failure, and COPD) who experience the following signs and symptoms for less than 48 hours at the time of screening for SARS CoV2 by RT-PCR: (a) a temperature >=37.5°C and/or unexplained sweating and/or chills and (b) at least one of the following: dry cough, dyspnea, fatigue, myalgia, anorexia, sore throat, loss of taste and/or smell, rhinorrhea. Subjects consenting to screening will be tested by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for SARS-CoV-2 in a nasopharyngeal and an oropharyngeal swab and invited to participate when RNA for the virus is detected. Intervention. Eligible, consenting patients will be randomized using an electronic system to receive 250 ml of convalescent plasma with an IgG titer against SARS-CoV2 spike (S) protein >1:1,000 (COVIDAR IgG, Insituto Leloir, Argentina) or placebo (normal saline 0.9%) administered in a 1:1 ratio. Both treatment and placebo will be concealed using dark bags and tape to cover the infusion line. Treatment will be administered <72 hours from initiation of symptoms. Subjects will be monitored for 12 hours after treatment for adverse events. Clinical and laboratory monitoring. All participating subjects will be admitted to the hospital upon enrollment. Twenty-four hours after completing the infusion, a sample of venous blood (5 ml) will be obtained from all participants to measure anti-S IgG SARS-CoV2 in serum (COVIDAR IgG, Leloir) and preserved at -20°C until completion of the study. Patient evolution will be assessed daily by study physicians during hospitalization until day 25 and/or at home until day 15, in the event of earlier discharge from the hospital. Study physicians will use predesigned questionnaires to collect clinical information. An Independent Data Safety Monitoring Board (DSMB) will supervise participating subjects during the study. Endpoints. The primary endpoint of the trial is development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93% when breathing room air determined using a predefined protocol. Three other clinical endpoints include (a) life threatening respiratory disease, defined as need for 100% oxygen supplementation and/or non-invasive or invasive ventilation and/or admission to intensive care; (b) critical systemic illness, defined as respiratory failure (PaO2/FiO2 ≤ 200 mm Hg) and/or shock and/or multiorganic distress syndrome; and (c) death. Statistical analysis. The study is designed to have one interim analysis when the outcome results for 50% of the subjects is obtained. The minimally clinically important difference was set at a 40% relative reduction for an expected outcome rate of 50% in the control group reduced to 30% in the intervention group. A total sample size of 210 subjects (105 per trial arm) was estimated to have 80% power at a significance level (alpha) of 0.05 using a two-sided z-test with continuity correction. Ethical considerations. The trial has been approved by the institutional review boards of participating institutions and the Central Ethics Committee of the state of Buenos Aires. The study will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. Written informed consent will be obtained from all patients for screening and enrollment.

    NCT04479163
    Conditions
    1. COVID
    Interventions
    1. Biological: Convalescent Plasma
    2. Other: Placebo

    Primary Outcomes

    Measure: Development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93%

    Time: From 12 hours post infusion to day 15 post infusion

    Secondary Outcomes

    Measure: Life threatening respiratory disease

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Critical systemic illness, defined as respiratory failure

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Death

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Combination of secondary outcomes #2 (Life threatening respiratory disease) and/or #3 (Critical systemic illness, defined as respiratory failure) and//or #4 (death)

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Duration of oxygen support requirement in patients with covid-19 due to saturation in ambient air <93%.

    Time: From 12 hours post infusion to day 25 post infusion
    338 A Phase 1 Randomized, Single-blind, Placebo-controlled, Single Ascending Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Human Monoclonal Antibody, BRII-196 Administered Intravenously to Healthy Adult Volunteers

    This is a phase 1 study in which healthy adult volunteers will receive BRII-196 or placebo and will be assessed for safety, tolerability, and pharmacokinetics.

    NCT04479631
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BRII-196
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of adverse events (AEs) by CTCAE v5.0

    Time: up to 24 weeks

    Measure: Proportion of subjects with SAEs

    Time: up to 24 weeks

    Measure: Proportion of subjects with infusion-related reactions

    Time: up to 24 weeks

    Measure: Proportion of subjects with hypersensitivity reactions

    Time: up to 24 weeks

    Secondary Outcomes

    Measure: Serum Concentration of BRII-196

    Time: up to 24 weeks
    339 A Phase 1 Randomized, Single-blind, Placebo-controlled, Single Ascending Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Human Monoclonal Antibody, BRII-198 Administered Intravenously to Healthy Adult Volunteers

    This is a phase 1 study in which healthy adult volunteers will receive BRII-198 or placebo and will be assessed for safety, tolerability, and pharmacokinetics.

    NCT04479644
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BRII-198
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of adverse events (AEs) by CTCAE v5.0

    Time: up to 24 weeks

    Measure: Proportion of subjects with SAEs

    Time: up to 24 weeks

    Measure: Proportion of subjects with infusion-related reactions

    Time: up to 24 weeks

    Measure: Proportion of subjects with hypersensitivity reactions

    Time: up to 24 weeks

    Secondary Outcomes

    Measure: Serum Concentration of BRII-198

    Time: up to 24 weeks
    340 A Phase 1/2 Randomised, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Immunogenicity of ARCT-021 in Healthy Adult Subjects

    Determine safety and tolerability and immungenicity of investigational vaccine ARCT-021 in healthy adult volunteers.

    NCT04480957
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: ARCT-021 Dose 1
    2. Biological: ARCT-021 Dose 2
    3. Biological: ARCT-021 Dose 3
    4. Biological: ARCT-021 Dose 4
    5. Biological: ARCT-021 Dose Regimen 1
    6. Biological: ARCT-021 Dose Regimen 2
    7. Other: Placebo

    Primary Outcomes

    Description: Safety and tolerability of ARCT-021 assessed by determining the incidence, severity and dose-relationship of AEs by dose

    Measure: Incidence, severity and dose-relationship of AEs

    Time: 56 days

    Secondary Outcomes

    Description: SARS-CoV-2-specific serum neutralizing antibody levels, expressed as GMT

    Measure: Geometric mean titre for SARS-CoV-2-specific serum neutralizing antibody

    Time: Up to 56 days

    Description: SARS-CoV-2-specific serum neutralizing antibody levels, expressed as mean titer

    Measure: Mean titre for SARS-CoV-2-specific serum neutralizing antibody levels

    Time: Up to 56 days

    Description: GMFR in titre for SARS-CoV-2-spike protein specific neutralizing antibodies from before vaccination to each subsequent time point

    Measure: Geometric mean fold rise in titre for SARS-CoV-2-spike protein specific neutralizing antibody levels

    Time: Up to 56 days

    Other Outcomes

    Description: GMFR in SARS-CoV-2--spike protein-specific binding antibody levels from before vaccination to each subsequent time point

    Measure: Increase in SARS-CoV-2--spike protein-specific binding antibody levels

    Time: Up to 56 days

    Description: GMT for SARS-CoV-2--spike protein-specific binding antibody levels

    Measure: Geometric mean SARS-CoV-2--spike protein-specific binding antibody titre

    Time: Up to 56 days

    Description: Mean titer for SARS-CoV-2--spike protein-specific binding antibody levels

    Measure: Mean SARS-CoV-2--spike protein-specific binding antibody titre

    Time: Up to 56 days

    Description: Proportion of participants that are seronegative before vaccination achieving a titer of greater than or equal to 20 for SARS-CoV-2-specific serum neutralizing antibodies

    Measure: SARS-CoV-2-specific serum neutralizing antibody seroconversion rate

    Time: 56 days

    Description: Proportion of participants that are seropositive before vaccination achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific serum neutralizing antibody levels

    Measure: SARS-CoV-2-specific serum neutralizing antibody seroconversion rate (seropositive baseline)

    Time: 56 days
    341 A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19

    COVID-19 morbidity and mortality has been associated with Cytokine Release Syndrome (CRS) and Acute Respiratory Distress Syndrome (ARDS). ATI-450 is an oral small molecule MAPKAPK2 (MK2) inhibitor that potently inhibits multiple inflammatory cytokines. The investigator hypothesizes that MK2 pathway blockade during active COVID-19 infection in hospitalized participants will result in improvement in respiratory-failure free survival.

    NCT04481685
    Conditions
    1. Covid19
    Interventions
    1. Drug: ATI-450
    2. Drug: Placebo

    Primary Outcomes

    Description: Participants medical record

    Measure: Respiratory failure-free survival in participants with moderate-severe COVID-19 who are treated with ATI-450

    Time: Study day 14

    Secondary Outcomes

    Description: Using World Health Organization (WHO) COVID-19 Ordinal scale measuring: Proportion and time to participants with greater than 2 point improvement on the 7 point categorical scale. This scale measures illness severity over time and has a range of 0-7. 0- Uninfected: No clinical or virological evidence of infection. 1- Ambulatory: No limitation of activities. 2- Ambulatory: Limitation of activities. 3- Hospitalized, mild disease: Hospitalized, no oxygen. 4- Hospitalized, mild disease: Oxygen by mask or nasal prongs. 5- Hospitalized, severe disease: Non- invasive ventilation or high- flow oxygen. 6- Hospitalized, severe disease: Intubation and mechanical ventilation. 7- Hospitalized, severe disease: Ventilation + organ support; pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO).

    Measure: Change in 7 point-ordinal scale

    Time: Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months

    Description: Peripheral capillary pulse oximeter to measure: Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) ratio over time, sustainment of normalization in 24 hours, and relative shifts in SpO2/FiO2 categories (<235, between 235 and 315, greater than 315) over time

    Measure: Change in oxygen saturation-normalization

    Time: Baseline and continuous throughout hospitalization up to 14 days

    Description: Derived from medical record

    Measure: Need for advanced respiratory care

    Time: Baseline and continuous throughout hospitalization up to 14 days

    Description: Noted in participant medical record

    Measure: All-cause mortality

    Time: Baseline and through day 60

    Description: CTCAE v5.0

    Measure: Percentage of adverse events (AEs)

    Time: Baseline through day 14 or at discharge

    Description: CTCAE v5.0

    Measure: Percentage of serious adverse events (SAEs)

    Time: Baseline through day 14 or at discharge

    Description: Standard daily temperature measurement and obtained from participant medical record

    Measure: Proportion of participants with normalization of fever for 24 hours

    Time: Baseline through day 14 or at discharge

    Description: Noted in participant medical record

    Measure: Number of participants who develop new bacterial infection

    Time: Continuous throughout hospitalization up to 14 days

    Description: Noted in participant medical record

    Measure: Number of participants who develop new fungal infection

    Time: Continuous throughout hospitalization up to 14 days

    Description: Noted in participant medical record

    Measure: Incidence of Adult Respiratory distress Syndrome (ARDS2)

    Time: From day 1 though day 14 or at discharge

    Description: Serum collected from blood and assayed on Luminex panel performed by University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core

    Measure: Change in serum cytokine Interleukin (IL)-6

    Time: Baseline, day 3, day 7 (or discharge day 7 and

    Description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core

    Measure: Change in serum cytokine IL-8

    Time: Baseline, day 3, day 7 (or discharge day 7 and

    Description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core

    Measure: Change in serum cytokines IL-1β

    Time: Baseline, day 3, day 7 (or discharge day 7 and

    Description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core

    Measure: Change in serum cytokine Tumor Necrosis Factor (TNF-α)

    Time: Baseline, day 3, day 7 (or discharge day 7 and
    342 A Phase 2 Study of BIO 300 Oral Suspension in Discharged COVID-19 Patients

    Randomized, double-blinded, placebo-controlled, two-arm study to evaluate the effectiveness and safety of BIO 300 Oral Suspension (BIO 300) for the mitigation of impaired pulmonary function in 2019 Coronavirus Disease (COVID-19) patients recently discharged from the hospital. Patients will be randomized 1:1 to receive BIO 300 or placebo. All patients will receive the same background current standard of care.

    NCT04482595
    Conditions
    1. Pulmonary Fibrosis
    Interventions
    1. Drug: BIO 300 Oral Suspension
    2. Drug: Placebo
    MeSH:Pulmonary Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)

    Measure: Change in DLCO

    Time: 12 Weeks

    Description: 6 minute walk test (6MWT)

    Measure: Change in 6 Minute Walk Test

    Time: 12 Weeks

    Secondary Outcomes

    Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)

    Measure: Change in DLCO

    Time: 6 Months and 12 Months

    Description: 6 minute walk test (6MWT)

    Measure: Change in 6 Minute Walk Test

    Time: 6 Months and 12 Months

    Description: Forced vital capacity (FVC)

    Measure: Change in FVC

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Forced expiratory volume in one second (FEV1)

    Measure: Change in FEV1

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)

    Measure: Change in FEV1/FVC Ratio

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Oxygen saturation (pulse oximetry) at rest and during the 6 minute walk test (6MWT)

    Measure: Change in Pulse Oximetry at Rest and During the 6MWT

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Evidence of pulmonary fibrosis on computerized tomography (CT) scans of the lungs based on a 4-point Likert scale, where 0 is no evidence of fibrosis and 3 is severe fibrosis

    Measure: Change in Pulmonary Fibrosis on CT Scan

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Patient reported outcome to measure impact on overall health, daily life, and perceived well-being in patients with impaired pulmonary function. Scores range from 0-100 with higher scores indicating more limitations.

    Measure: Change in St. George's Respiratory Questionnaire (SGRQ) Scores

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of blood serum levels for alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) (all reported as Units/L)

    Measure: Change in Clinical Laboratory Values for Serum Enzymes

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of blood serum levels for bilirubin, C-reactive protein (CRP), creatinine, blood urea nitrogen (BUN), cholesterol and triglycerides (all reported as mg/dL)

    Measure: Change in Clinical Laboratory Values

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of blood serum levels for troponin T, d-dimer and ferritin (all reported as ng/mL)

    Measure: Change in Clinical Laboratory Values

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of blood serum levels for albumin (g/dL)

    Measure: Change in Clinical Laboratory Values for Albumin

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of white blood cell, red blood cell and platelet counts

    Measure: Change in Complete Blood Counts with Differential

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Mortality at 12 months after initiating treatment

    Measure: All-Cause Mortality

    Time: 12 Months

    Description: Incidence of hospitalization after initial discharge and initiating treatment

    Measure: Incidence of Re-Hospitalization

    Time: 12 Months

    Description: Evaluate the safety of BIO 300 Oral Suspension treatment

    Measure: Adverse Events Related to BIO 300 Oral Suspension

    Time: 12 Months

    Other Outcomes

    Description: Duration of supplemental oxygen use

    Measure: Change in Duration of Supplemental Oxygen Use

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Prescribed supplemental oxygen flow rate at night, rest and exertion

    Measure: Change in Supplemental Oxygen Use

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Expression levels of serum-derived cytokines (IL-1b, IL-6, IL-8, TNFa, and TGFb1)

    Measure: Change in Serum Cytokine Expression

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
    343 Phase I/Phase II Trial of Off-the-Shelf Allogeneic Hybrid TREG/Th2 Cell (RAPA-501-ALLO) Therapy for Severe, Post-Intubation Stage 3 COVID-19 Disease

    The first-in-human Phase 1 study component will evaluate two dose levels of RAPA-501-ALLO off the shelf cells in patients with post-intubation, stage 3 COVID-19 disease, with key endpoints of safety, biologic and potential disease-modifying effects. The randomized, double-blind, placebo-controlled Phase 2b study component will evaluate infusion of RAPA-501 ALLO off the shelf cells or a control infusion, with the primary endpoint assessing whether RAPA-501 cells reduce 30-day mortality. The COVID-19 pandemic is a disaster playing out with progressive morbidity and mortality. As of October 19, 2020, an estimated 40.3 million people have contracted the virus and 1,116,000 deaths have resulted globally. The United States has the highest totals with an estimated 8.2 million people diagnosed and 220,000 deaths. In stages 1 and 2 of COVID-19, viral propagation within the patient is predominant. As such, therapeutic interventions focus on immune molecules (convalescent serum, monoclonal antibodies) and anti-viral medications (remdesivir). In marked contrast, the most severe and deadly form of COVID-19, stage 3, is driven not by viral propagation, but by an out-of-control immune response (hyperinflammation) caused by increases in immune molecules known as cytokines and chemokines. As such, therapeutic interventions for stage 3 disease focus on anti-inflammatory medications such as anti-cytokine therapy (anti-IL-6 drugs) or corticosteroid therapy. Unfortunately, such interventions do not address the full pathogenesis of stage 3 COVID-19, which includes hyperinflammation due to "cytokine storm" and "chemokine storm," tissue damage, hypercoagulation, and multi-organ failure (including lung, heart, kidney and brain). The pulmonary component of stage 3 disease includes acute respiratory distress syndrome (ARDS), which is a final-common-pathway of patient death due to a myriad of conditions, including pneumonia, sepsis, and trauma. There is a dire need for novel cellular treatments that can deliver both a broad-based immune modulation effect and a tissue regenerative effect, such as RAPA-501-ALLO off-the-shelf allogeneic hybrid TREG/Th2 Cells. Stage 3 COVID-19 carries an estimated 30-day mortality of over 50% in spite of ICU utilization, mechanical ventilation, and supportive care therapies to manage ARDS and multiorgan failure. Narrowly acting targeted anti-inflammatory approaches such as anti-IL-6 therapeutics have not been particularly effective in stage 3 COVID-19 and the broad anti-inflammatory pharmaceutical approach of corticosteroid therapy, has only modestly tempered stage 3 disease in some studies. Cell therapy is also being evaluated in stage 3 COVID-19, in particular, mesenchymal stromal cells (MSC) and now, with the current RAPA-501-ALLO protocol, regulatory T (TREG) cells. TREG therapy has a mechanism of action that includes a multi-faceted anti-inflammatory effect, which puts TREG therapy at the forefront of future curative therapy of a wide range of autoimmune and neurodegenerative diseases, plus transplant complications, such as graft-versus-host disease (GVHD) and graft rejection. In addition, TREG therapy can provide a tissue regenerative effect, which places TREG cell therapy at the lead of novel regenerative medicine efforts to repair a myriad of tissue-based diseases, such as diseases of the skin, muscle, lung, liver, intestine, heart (myocardial infarction) and brain (stroke). RAPA-501-ALLO off-the-shelf cell therapy offers this potential dual threat mechanism of action that incorporates both anti-inflammatory and tissue repair effects for effective treatment of COVID-19 and multiple lethal conditions. RAPA-501-ALLO cells are generated from healthy volunteers, cryopreserved, banked, and are then available for off-the-shelf therapy anytime. During manufacturing, T cells are "reprogrammed" ex vivo using a novel, patented 7-day two-step process that involves T cell de-differentiation and subsequent re-differentiation towards the two key anti-inflammatory programs, the TREG and Th2 pathways, thus creating a "hybrid" product. The hybrid phenotype inhibits inflammatory pathways operational in COVID-19, including modulation of multiple cytokines and chemokines, which attract inflammatory cells into tissue for initiation of multi-organ damage. The hybrid TREG and Th2 phenotype of RAPA-501-ALLO cells cross-regulates Th1 and Th17 populations that initiate hyperinflammation of COVID-19. RAPA-501 immune modulation occurs in a T cell receptor independent manner, thus permitting off-the-shelf cell therapy. Finally, in experimental models of viral pneumonia and ARDS, TREG cells mediate a protective effect on the lung alveolar tissue. Because of this unique mechanism of action that involves both anti-inflammatory and tissue protective effects, the allogeneic RAPA-501 T cell product is particularly suited for evaluation in the setting of post-intubation, Stage 3 COVID-19.

    NCT04482699
    Conditions
    1. Severe COVID-19 Disease
    Interventions
    1. Biological: RAPA-501-Allo off-the-shelf Therapy of COVID-19
    2. Other: Placebo

    Primary Outcomes

    Description: On the phase 1 study component, determine the safety of allogeneic RAPA-501 cells when administered at dose level 1 (Cohort 1, 40 x 106 cells) and dose level 2 (Cohort 2, 160 x 106 cells).

    Measure: Dose-Limiting Toxicity (DLT)

    Time: 30 days after the first infusion of allogeneic RAPA-501 cells.

    Description: On the phase II study component, determine whether allogeneic RAPA-501 cells result in a mortality rate that is reduced relative to the randomized placebo-control cohort.

    Measure: Mortality Rate

    Time: 30 days after the first infusion of allogeneic RAPA-501 cells.

    Secondary Outcomes

    Description: Number of days requiring ventilation support.

    Measure: Ventilation Support

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: Number of days of hospitalization among survivors.

    Measure: Days of Hospitalization

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: Number of deaths due to any cause.

    Measure: Number of Deaths

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection.

    Measure: Incidence of Infection

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: GVHD incidence and severity.

    Measure: GVHD Incidence

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Other Outcomes

    Description: COVID-19 viral load, as determined by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent test on nasopharyngeal and/or endotracheal tube swab samples.

    Measure: Viral Load

    Time: Six months after treatment initiation.

    Description: Development of potentially protective host immunity to COVID-19, as determined by serologic studies.

    Measure: Host Immunity

    Time: Six months after treatment initiation.

    Description: Peripheral blood immune counts, including CD4+ and CD8+ T cells, NK cells, and B cells.

    Measure: Peripheral Blood Immune Counts

    Time: Six months after treatment initiation.

    Description: T cell expression of co-stimulation molecules (including CD28) and checkpoint receptor molecules (including PD-1).

    Measure: T Cell Expression

    Time: Six months after treatment initiation.

    Description: Peripheral blood micro-chimerism, as determined by PCR amplification of donor and host STR loci.

    Measure: Peripheral Blood Micro-chimerism

    Time: Six months after treatment initiation.
    344 Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)

    This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.

    NCT04482712
    Conditions
    1. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
    2. Respiratory Failure
    3. Sars-CoV2
    Interventions
    1. Drug: Rapamycin
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury Syndrome

    Primary Outcomes

    Description: The proportion of participants who survive without respiratory failure

    Measure: Survival rate

    Time: 4 weeks

    Secondary Outcomes

    Description: The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8

    Measure: Change in Clinical Status assessed by the World Health Organization (WHO) scale

    Time: Baseline to 4 weeks

    Description: An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8)

    Measure: Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale

    Time: Baseline to 4 weeks

    Other Outcomes

    Description: Total number of deaths during the study period

    Measure: All cause mortality

    Time: 4 weeks

    Description: Number of days on ECMO

    Measure: Duration of ECMO

    Time: Up to 4 weeks

    Description: Number of days participants are on supplemental oxygen

    Measure: Duration of supplemental oxygen

    Time: Up to 4 weeks

    Description: Days of hospitalization

    Measure: Length of hospital stay

    Time: Up to 4 weeks

    Description: Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)

    Measure: Length of time to SARS-CoV2 negativity

    Time: Up to 4 weeks
    345 A Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose, Phase I Study to Evaluate the Tolerability, Safety, Pharmacokinetics of SCTA01 in Healthy Subjects

    The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics of SCTA01(anti-SARS-CoV-2 monoclonal antibody) in Healthy Chinese Subjects.

    NCT04483375
    Conditions
    1. Coronavirus Disease 2019(COVID-19)
    Interventions
    1. Biological: SCTA01
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: DLT will be assessed by DAIDS v2.1. The measurements include clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs

    Measure: Dose-limiting toxicity(DLT)

    Time: 7 days

    Description: MTD will be assessed by DAIDS v2.1. The measurements include clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs.

    Measure: Maximal Tolerable Dose(MTD)

    Time: 12 weeks

    Secondary Outcomes

    Description: Area under the curve from the time of dosing to the last measurable concentration time t (AUC0-t)

    Measure: AUC0-t

    Time: 12 weeks

    Description: Area Under the Concentration Time Curve (AUC) From Time Zero to Infinity (AUC 0-∞)

    Measure: AUC0-∞

    Time: 12 weeks

    Description: Elimination Phase Half-life(t1/2)

    Measure: t1/2

    Time: 12 weeks

    Description: Time to the Maximum Concentration(Tmax)

    Measure: Tmax

    Time: 12 weeks

    Description: Positive rate of anti-SCT A01 antibody

    Measure: Anti-drug antibody(ADA)

    Time: 12 weeks

    Description: Adverse events as assessed by DAIDS v2.1, including clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs

    Measure: Adverse events

    Time: 12 weeks
    346 PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams (PROTECT)

    In this 16-week randomized control study, health care workers will receive a bolus dose followed by a weekly dose of vitamin D or a placebo bolus and weekly dose. This study will test whether high-dose of vitamin D supplementation decreases the incidence of laboratory-confirmed COVID19 infection (primary outcome), reduces illness severity, duration, as well as work absenteeism among health care workers (HCW) in setting at high-risk of contact with COVID-19 cases in high COVID-19 incidence areas.

    NCT04483635
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: Placebo
    2. Dietary Supplement: Vitamin D

    Primary Outcomes

    Description: self-obtained mid-turbinate nasopharyngeal (NP) swabs analysed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test (NAAT), following standard operating procedures certified by the Quebec Public Health Laboratory of the National Public Health Institute (complemented by NP swabs obtained clinically for screening or diagnostic purposes analyzed using the same technique.

    Measure: Change in incidence of laboratory-confirmed COVID-19 infection

    Time: up to 16 weeks

    Secondary Outcomes

    Description: 5-category ordinal variable [asymptomatic, mild (managed at home); moderate (hospitalisation without supplemental oxygen; severe (oxygen supplementation); critical (mechanical ventilation/death)

    Measure: Distribution of disease severity

    Time: up to 16 weeks

    Description: Duration of COVID+ test: that is, between first COVID+ test to first COVID- test

    Measure: Duration of COVID-19 positivity

    Time: up to 16 weeks

    Description: SARS-CoV-2 IgG Diasorin on Liaison XL platform

    Measure: Number of participants with COVID-19 positive IgG serology

    Time: up to 16 weeks

    Description: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases

    Measure: Number of workday absences due to COVID-19 suspected/confirmed infection

    Time: up to 16 weeks

    Description: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases

    Measure: Number of workday absences for any reason

    Time: up to 16 weeks

    Description: Number and distribution of adverse health events

    Measure: Changes in adverse health events

    Time: up to 16 weeks
    347 Sulodexide in the Treatment of Early Stages of COVID-19

    Problem: The COVID- 19 pandemic has not only affected our healthcare system, but the impact on the worldwide financial systems and our "normal" way of life is still to be determined. Although the percentage of patients infected with COVID-19 that need hospital care is low, Its high rate of contagiousness makes the total number of patients in need of hospital care cripple any healthcare system, limiting the space available for other patients in need of critical care, who cannot be admitted or even prefer not to attend the hospital in fear of infection. Early investigations report an Increase risk of thromboembolic complications, and a systemic inflammatory response not clearly understood. There is a possible vascular endothelial dysfunction due to chronic comorbidities (Hypertension, diabetes, obesity, chronic kidney disease, lung disease) as a risk factor for a more severe presentation. Justification: Sulodexide is a two-compound drug, each of them with different endothelial action that can be beneficial in COVID-19 patients. Glycosaminoglycans: Can help restore venous and arterial endothelial glycocalyx which can downregulate or limit the response to inflammatory molecules, by maintaining the integrity lost in certain chronic diseases (high blood pressure, diabetes). Heparin compound: It has an antithrombotic effect that could help reduce the incidence of thromboembolic complications, and also add to the anti-inflammatory response due to it anti-thrombin action (similar or a bit less to that of low molecular weight heparin) with less risk of major bleeding. It's a medication that can be used orally with minimal adverse effects and is less expensive than low molecular weight heparin. Hypothesis: We hypothesize that sulodexide instituted early in populations at significant risk and symptomatic patients affected with COVID-19 (shortness of breath, fever, weakness, diarrhoea) and risk factors of diabetes, hypertension, COPD, atherosclerosis, chronic kidney disease, will provide improvement in endothelial integrity, decrease inflammatory responses, and improved clinical outcomes with decreased hospital admission, decrease VTE and arterial complications, morbidity, and mortality. Objective: To use sulodexide in patients that have early onset of COVID-19 symptoms to mitigate the progression of the disease process that can allow them to recover at home, and limit the need of hospital care and a more severe clinical manifestation

    NCT04483830
    Conditions
    1. Covid19
    Interventions
    1. Drug: Sulodexide
    2. Drug: Placebo

    Primary Outcomes

    Description: need for hospital care admission

    Measure: hospital care

    Time: 21 days since start of trial participation

    Description: number of total days in hospital care

    Measure: days of hospital care

    Time: 21 days since start of trial participation

    Description: total days in need of supplemental oxigen via facial mask or nasal

    Measure: days of need suplemental oxigen

    Time: 21 days since the start of trial participation

    Description: total value in ng/dl of d-dimmer

    Measure: serum level of d-dimmer

    Time: change betwen basal level and at 14 day follow-up

    Description: total value in mg/dl

    Measure: serum level of creatinine

    Time: change between basal level ans at 14 day followup

    Secondary Outcomes

    Description: presence of a tromboembolic event

    Measure: thromboembolic event

    Time: 21 days from start of trial

    Description: the need for the use of endotraqueal tube mechanical ventilation

    Measure: need for mechanical ventilation

    Time: 21 days from the start of the trial
    348 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Severe COVID-19 Patients

    The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel SARS-CoV-2 (nCoV2) and severe symptoms of COVID-19 disease.

    NCT04483973
    Conditions
    1. Covid19
    2. Coronavirus
    3. Coronavirus Infection
    4. Corona Virus Infection
    Interventions
    1. Drug: Ebselen
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: 30 days

    Secondary Outcomes

    Description: Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement

    Measure: WHO Ordinal Scale

    Time: 30 days

    Description: Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)

    Measure: Degree of supplemental oxygen

    Time: 30 days

    Description: Peripheral oxygen saturation measured by pulse oximetry

    Measure: Peripheral Oxygen Saturation (SpO2)

    Time: 30 days
    349 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Moderate COVID-19 Patients

    The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel SARS-CoV-2 (nCoV2) and moderate symptoms of COVID-19 disease.

    NCT04484025
    Conditions
    1. Covid19
    2. Corona Virus Infection
    3. Coronavirus
    4. Coronavirus Infection
    Interventions
    1. Drug: Ebselen
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: 30 days

    Secondary Outcomes

    Description: Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement

    Measure: WHO Ordinal Scale

    Time: 30 days

    Description: Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)

    Measure: Degree of supplemental oxygen

    Time: 30 days

    Description: Peripheral oxygen saturation measured by pulse oximetry

    Measure: Peripheral Oxygen Saturation (SpO2)

    Time: 30 days
    350 Virologic and Immunologic Response to Disulfiram in Early Symptomatic COVID+ Outpatients

    Disulfiram a safe, easily dosed, FDA-approved drug for the treatment of alcohol dependence has been identified to be a potential therapeutic target for SARS-CoV-2 infection. Disulfiram may have both antiviral (inhibiting viral replication via blocking the Mpro protease and zinc ejection) and anti-inflammatory effects (via inhibition of NF-kB-induced and NLRP inflammasome-induced cytokine release) on SARS-CoV-2. We will test disulfiram 2000 mg/day for 3 consecutive days (doses shown to be well tolerated and safe in a recent phase 2b trial) in 60 symptomatic COVID PCR+ individuals in a randomized (1:1) clinical trial evaluating the effect on COVID symptoms severity, SARS-CoV-2 viral load, and biomarkers of inflammation over 31 days.

    NCT04485130
    Conditions
    1. Covid19
    Interventions
    1. Drug: Disulfiram
    2. Drug: Placebo

    Primary Outcomes

    Description: The safety and tolerability of a 3 day course of disulfiram. The number of adverse events and their grade will be determined for each participant.

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time: 31 days

    Description: The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant.

    Measure: Change in COVID-19 symptom severity score as assessed by a 5-point adapted somatic symptom severity score (SSS-8)

    Time: 31 days

    Secondary Outcomes

    Description: Quantitative SARS-CoV-2 viral load measures will be determined at each visit for each participant.

    Measure: Virologic impact of 3 days of disulfiram, as measured by the fold-change in copies of SARS-CoV-2 virus per million cells between Baseline and Day 31.

    Time: 31 days

    Description: High sensitivity plasma cytokine measures for interleukin 6, interleukin 1-beta, and other pro-inflammatory cytokines will be determined at each visit for each participant.

    Measure: Immunologic impact of 3 days of disulfiram, as measured by the fold-change in plasma levels of pro-inflammatory cytokines (e.g, interleukin 6, interleukin 1-beta, etc.).

    Time: 31 days
    351 A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Assess the Safety and Efficacy of IGV-001, an Autologous Cell Immunotherapy With Antisense Oligonucleotide (IMV-001) Targeting IGF-1R, in Newly Diagnosed Patients With Glioblastoma Multiforme - the ImmuneSense Study

    The purpose of this study is to assess progression-free survival (PFS) in newly diagnosed Glioblastoma Multiforme (GBM) participants treated with IGV-001 as compared with placebo.

    NCT04485949
    Conditions
    1. Glioblastoma Multiforme
    2. Glioblastoma
    Interventions
    1. Biological: IGV-001 Cell Immunotherapy
    2. Biological: Placebo
    3. Procedure: Standard of Care (SOC): Radiation Therapy
    4. Drug: SOC: Temozolomide
    MeSH:Glioblastoma
    HPO:Glioblastoma multiforme

    Primary Outcomes

    Description: PFS is defined as the time from randomization to event or censoring.

    Measure: Progression-free Survival (PFS)

    Time: Up to 36 months

    Secondary Outcomes

    Description: OS is defined as the time from randomization to death due to any cause.

    Measure: Overall Survival (OS)

    Time: Up to 48 months

    Description: PFS is defined as the time from randomization to event or censoring. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.

    Measure: PFS in Participants With O6-methylguanine-DNA Methyltransferase (MGMT) With Methylation [MGMT+] and MGMT Without Methylation [MGMT-]

    Time: Up to 36 months

    Description: OS is defined as the time from randomization to death due to any cause. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.

    Measure: OS in Participants With MGMT+ and MGMT-

    Time: Up to 48 months

    Description: EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.

    Measure: Change From Baseline in Participant-reported Quality of Life (QoL) Questionnaires Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Lif questionnaire (QLQ) -C30 Scores

    Time: Baseline, Month 36

    Description: The QLQ-BN20 is a questionnaire specifically designed as the QLQ-C30 supplement for the evaluation of quality of life in brain tumor participants. It includes 4 multi-item sub-scales: future uncertainty, visual disorder, motor dysfunction, communication deficits, and 7 single-item scales: headaches, seizures, drowsiness, itchy skin, hair loss, weakness of legs, and bladder control. All items are rated on a 4-point Likert-type scale ('1=not at all', '2=a little', '3=quite a bit' and '4=very much'), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

    Measure: Change From Baseline in Participant-reported QoL Questionnaires Based on EORTC QLQ Brain Module (EORTC QLQ-BN20) Scores

    Time: Baseline, Month 36

    Description: The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance.

    Measure: Change From Baseline in Mini-Mental Status Examination (MMSE) Scores

    Time: Baseline, Month 36

    Description: Time to KPS deterioration was defined as the time from screening to the first date of deterioration of the KPS score. Deterioration of KPS is defined as a stable or increasing steroid dose-dependent stabilization of a KPS score of <70 over 2 consecutive visits no more than 2 months apart. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.

    Measure: Time to Definitive Deterioration Karnofsky Performance Status (KPS) Score

    Time: Baseline until KPS deterioration (up to 36 months)

    Description: An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 from mild (Grade 1) to death (Grade 5). SAE is an AE or adverse reaction which is considered serious if it results in any of the following outcomes: death, life-threatening AE, require hospitalizations or prolongation of hospitalizations, results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect and is a medically important event.

    Measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time: Up to 12 months or until the last progression visit, whichever comes first

    Measure: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities

    Time: Up to 12 months or until the last progression visit, whichever comes first

    Measure: Number of Participants With Clinically Significant Vital Signs Measurements

    Time: Up to 12 months or until the last progression visit, whichever comes first

    Measure: Number of Participants With Clinically Significant Physical Examination Findings

    Time: Up to 12 months or until the last progression visit, whichever comes first
    352 Phase 3, Randomized, Double-Blind, Placebo-Controlled, Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

    Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

    NCT04486313
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    3. Dietary Supplement: Vitamin Super B-Complex

    Primary Outcomes

    Description: To evaluate the effect of nitazoxanide in reducing the time to sustained response compared to placebo in subjects with mild or moderate COVID-19

    Measure: Reducing the Time to Sustained Response

    Time: Up to 21 days

    Secondary Outcomes

    Description: To evaluate the effect of nitazoxanide in reducing the rate of progression to severe COVID-19 illness compared to placebo

    Measure: Reducing the Rate of Progression

    Time: Up to 21 days
    353 A Multicenter, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of XC221, Tablets, 100 mg in Patients With COVID-19

    The innovative drug XC221 100 mg tablet is designed for the treatment of COVID-19 (SARS-CoV-2 infection). A multicenter, adaptive, randomized, double-blind, placebo-controlled Phase III clinical study is aimed to assess the efficacy and safety of XC221 100 mg tablet, in COVID-19 patients during a 14-day treatment. The primary objective of the study is to demonstrate the efficacy of XC221 100 mg tablet (200 mg daily dose) in achieving clinical improvement of COVID-19 symptoms. The secondary objective of the study is to evaluate the safety of XC221 100 mg tablet (200 mg daily dose) in COVID-19 patients.

    NCT04487574
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: XC221
    2. Drug: Placebo

    Primary Outcomes

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Patient rate with a transition to category 3 or lower according to the WHO scale by Day 14 after the beginning of drug administration.

    Time: Day 1 - Day 14

    Secondary Outcomes

    Description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; RR ≤ 22 / min without oxygen therapy; SpO2 ≥ 95% without oxygen therapy.

    Measure: Time till clinical improvement, which is described by presence of all of the following factors during 48 hours in a row.

    Time: Day 1 - Day 28

    Description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; RR ≤ 22 / min without oxygen therapy; SpO2 ≥ 95% without oxygen therapy.

    Measure: Patient rate with clinical improvement by day 2-28. Presence of all of the following factors during 48 hours in a row.

    Time: Day 1 - Day 28

    Measure: Patient rate with a negative test result for SARS-CoV-2 by Day 7±1, 15±1, 21 ±1 and 28 ± 1.

    Time: Day 1 - Day 28

    Measure: Duration of hospitalization.

    Time: Day 1 - Day 28

    Measure: Patient rate transferred to the intensive care unit (ICU) during hospitalization.

    Time: Day 1 - Day 28

    Measure: Duration of ICU stay.

    Time: Day 1 - Day 28

    Measure: Patient rate with ARDS during hospitalization.

    Time: Day 1 - Day 28

    Measure: Presence of a fatal outcome.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring oxygen therapy by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring high-flow oxygen therapy by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring non-invasive ventilation by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring invasive ventilation by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring extracorporeal membrane oxygenation (EMO) by Day 2-28.

    Time: Day 1 - Day 28

    Measure: The total duration of oxygen therapy by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of high-flow oxygen therapy by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of non-invasive ventilation by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of invasive ventilation of lungs by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of EMO by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: Patient rate with Sp02 > 95% by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration of Sp02 by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Measure: Average time to reach SpO2 ≥ 95%.

    Time: Day 1 - Day 28

    Measure: Patient rate with RR < 22 / min by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration in RR by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Measure: Average time to reach RR ≤ 22 / min.

    Time: Day 1 - Day 28

    Measure: Patient rate with body temperature < 37.5°C by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration in body temperature by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Measure: Average time until the patient reaches a body temperature of ≤37.5°C.

    Time: Day 1 - Day 28

    Measure: Patient rate with CT-1 according to CT data by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration in CT data by 1 point in terms of severity (CT-1, CT-2, CT-3, CT-4) by Day 7, 10, 15, 18, 21 and 28 compared to the baseline value.

    Time: Day 1 - Day 28

    Measure: Average time to reach CT-1 according to CT data.

    Time: Day 1 - Day 28

    Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).

    Measure: Patient rate with a score < 2 according to the Daytime and Nighttime Cough Scale by Day 2-28.

    Time: Day 1 - Day 28

    Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).

    Measure: Mean change in Daytime and Nighttime Cough scores by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).

    Measure: Average time to reach < 2 points when assessed according to the Daytime and Nighttime Cough Scale.

    Time: Day 1 - Day 28

    Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.

    Measure: Patient rate with a score < 1 for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28.

    Time: Day 1 - Day 28

    Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.

    Measure: Average change in score for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.

    Measure: Average time to reach a score of < 1 for each symptom (general fatigue, feeling of congestion in the chest, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale.

    Time: Day 1 - Day 28

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Patient rate with a transition decrease to category 3 or lower according to the WHO scale by Day 2-13 and Day 15-28.

    Time: Day 1 - Day 28

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Mean WHO grade change by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Average time to reach the 3rd category or below according to the WHO scale.

    Time: Day 1 - Day 28

    Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.

    Measure: Patient rate with a NEWS score < 2 by Day 2-28.

    Time: Day 1 - Day 28

    Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.

    Measure: Average change in NEWS score by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.

    Measure: Average time to reach a NEWS score ≤ 2.

    Time: Day 1 - Day 28

    Other Outcomes

    Description: (Search Outcome)

    Measure: Concentration of IL-6 on Days 3 ± 1, 7 ± 1, 15 ± 1.

    Time: Day 1 - Day 15
    354 Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection

    In this study, a total of 80 patients with severe coronavirus disease 2019 (COVID-19) infection will be randomized to receive Duvelisib or a placebo. Participants will be enrolled at Emory University Hospital and at the University of Pennsylvania and will be identified and recruited by their treating physician and research team.

    NCT04487886
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Duvelisib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.

    Measure: Number of Participants Requiring Mechanical Ventilation or Dying

    Time: Up to Day 29

    Secondary Outcomes

    Description: Time to recovery (in days) is defined as a score of greater than 5 from the following eight categories from the NIAID ordinal scale. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities.

    Measure: Days to Recovery

    Time: Up to Day 29

    Description: The number of days spent hospitalized will be compared between study arms.

    Measure: Duration of Hospitalization

    Time: Up to Day 29

    Description: The incidence of death within 29 days of randomization will be compared between study arms.

    Measure: Incidence of Death

    Time: Up to Day 29

    Description: Comparing the proportion of subjects in each group requiring ICU transfer within 29 days of randomization

    Measure: Proportion of Participants Transferred to ICU

    Time: Up to Day 29

    Description: The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active and 5 = dead. Median ECOG performance will be compared between study arms.

    Measure: Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score

    Time: Day 15, Day 29

    Description: The incidence of grade III-V adverse events or Serious Adverse Events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, will be compared between study arms.

    Measure: Incidence of Grade III-V Adverse Events

    Time: Up to Day 29

    Description: The incidence of documented secondary bacterial or viral infections among participants will be compared between study arms.

    Measure: Incidence of Secondary Bacterial or Viral Infections

    Time: Up to Day 29

    Description: The mean frequency of Th1 T cells in blood mononuclear cells will be compared between study arms.

    Measure: Change in Th1 T Cell Frequency

    Time: Weeks 1, 2, and 4

    Description: The mean frequency of Th17 T cells in blood mononuclear cells will be compared between study arms.

    Measure: Change in Th17 T Cell Frequency

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-2 will be compared between study arms.

    Measure: Change in Interleukin-2 (IL-2)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-2R will be compared between study arms.

    Measure: Change in Interleukin-2 receptor (IL-2R)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-6 will be compared between study arms.

    Measure: Change in Interleukin-6 (IL-6)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-7 will be compared between study arms.

    Measure: Change in Interleukin-7 (IL-7)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-8 will be compared between study arms.

    Measure: Change in Interleukin-8 (IL-8)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-10 will be compared between study arms.

    Measure: Change in Interleukin-10 (IL-10)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IP-10 will be compared between study arms.

    Measure: Change in Interferon gamma-induced Protein 10 (IP-10)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker MIP-1a will be compared between study arms.

    Measure: Change in Macrophage Inflammatory Protein 1alpha (MIP-1a)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker MCP-1 will be compared between study arms.

    Measure: Change in Monocyte Chemoattractant Protein-1 (MCP-1)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker G-CSF will be compared between study arms.

    Measure: Change in Granulocyte Colony-stimulating Factor (G-CSF)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker TNF-alpha will be compared between study arms.

    Measure: Change in Tumor Necrosis Factor (TNF)-alpha

    Time: Weeks 1, 2, and 4

    Description: VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.

    Measure: Change in Vasoactive Intestinal Peptide (VIP)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the Tregs will be compared between study arms.

    Measure: Change in Gene Expression Profile of Regulatory T Cells (Tregs)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.

    Measure: Change in Gene Expression Profile of cluster of differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage colony-stimulating factor (GM-CSF)+

    Time: Weeks 1, 2, and 4

    Description: Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.

    Measure: Change in Gene Expression Profile of CD8+ T cell immunoglobulin and mucin domain-containing protein 3 (Tim3)+ Programmed cell death protein 1 (PD-1)+

    Time: Weeks 1, 2, and 4

    Description: Mean levels of CD14+CD16+ monocytes will be compared between study arms.

    Measure: Change in Gene Expression Profile of cluster of differentiation 14 (CD14)+ cluster of differentiation (CD16)+ monocytes

    Time: Weeks 1, 2, and 4

    Description: Mean levels of SARS-CoV-2 viremia in respiratory specimens will be compared between study arms.

    Measure: Change in SARS-CoV-2 Viremia

    Time: Weeks 1, 2, and 4

    Description: Median titers of IgG antibodies to SARS-CoV-2 will be compared between study arms.

    Measure: Change in Immunoglobulin G (IgG) Antibodies

    Time: Weeks 1, 2, and 4

    Description: Median titers of IgM antibodies to SARS-CoV-2 will be compared between study arms.

    Measure: Change in Immunoglobulin M (IgM) Antibodies

    Time: Weeks 1, 2, and 4

    Description: Overall survival is defined as days from randomization to death and censored at last follow up.

    Measure: Overall Survival

    Time: Up to Day 29
    355 A Phase 2 Double-blind Placebo-controlled Study Investigating the Safety and Efficacy of EDP1815 in the Treatment of Patients Hospitalized With SARS-CoV-2 Infection

    Evelo will investigate the safety and efficacy of EDP1815 in the treatment of patients hospitalized with SARS-CoV-2 Infection

    NCT04488575
    Conditions
    1. Covid19
    Interventions
    1. Drug: EDP1815
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Pulmonary function as measured by the change in Oxygen Saturation (SpO2) / Fraction of Inspired Oxygen (FiO2) [S/F ratio]

    Measure: Change from baseline to the lowest S/F oxygen ratio

    Time: 14 days

    Secondary Outcomes

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using change in S/F ratio at days 4, 7, 10 and 14/discharge day.

    Measure: Change in S/F Ratio

    Time: 14 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage change in S/F ratio at days 4, 7, 10 and 14/discharge day.

    Measure: Percentage change in S/F Ratio

    Time: 14 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants at each level on the WHO OSCI score at days 4, 7, 14, 21 and 42

    Measure: Percentage of participants at each level on the WHO OSCI score

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants with shifts from each level of the WHO OSCI score at baseline at days 4, 7, 14, 21 and 42

    Measure: Percentage of participants with shifts from each level of the WHO OSCI score at baseline

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants remaining at their baseline score on the WHO OSCI (or lower) at days 4, 7, 14, 21 and 42

    Measure: Percentage of participants remaining at their baseline score on the WHO OSCI (or lower)

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants reporting each level of the WHO OSCI score at their worst post-baseline day

    Measure: Percentage of participants reporting each level of the WHO OSCI score at their worst post-baseline day

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the time in days spent at each participant's worst reported WHO OSCI score (excluding death).

    Measure: The time in days spent at each participant's worst reported WHO OSCI score (excluding death).

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the intubation and mechanical-ventilation free survival, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 6 or more.

    Measure: Intubation and mechanical-ventilation free survival

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using overall survival, defined as the time in days from start of treatment to death by any cause

    Measure: Overall survival

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days requiring oxygen therapy

    Measure: Number of days requiring oxygen therapy

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days with pyrexia ≥ 38C

    Measure: Number of days with pyrexia

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using maximum daily temperature

    Measure: Maximum daily temperature

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using minimum and maximum SpO2 levels

    Measure: SpO2 level

    Time: 42 days

    Description: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to discharge, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 2 or less.

    Measure: Time to discharge

    Time: 42 days

    Description: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to oxygen saturation (SpO2) ≥94% on room air without further requirement for oxygen therapy.

    Measure: Time to oxygen saturation (SpO2) ≥94%

    Time: 42 days

    Description: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to recovery, defined as the time in days from symptom onset to alleviation of all COVID-19 symptoms.

    Measure: Time to recovery

    Time: 42 days

    Description: The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing AEs by seriousness and relationship to treatment

    Measure: Number of participants experiencing AEs by seriousness and relationship to treatment

    Time: 42 days

    Description: The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing clinically significant abnormal changes in safety lab parameters

    Measure: Incidence of clinically significant abnormal lab parameters

    Time: 42 days
    356 A Double-Blind Randomized, Placebo-Controlled, Single and Repeated Oral Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including Food Effect) of GSK3882347 in Healthy Participants

    This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, first time in human (FTIH) study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetics (PK) of GSK3882347 in healthy adult men and Woman of Non Childbearing Potential (WONCBP). Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each participant in the SAD cohort will receive a single dose of GSK3882347 or placebo (PBO) in 3:1 ratio and in Part 2 (MAD), participants will be randomized in a 4:1 ratio to receive active treatment and placebo. Part 1 will consist of two cohorts with a maximum of four-period for each cohort, the food effect evaluation will be conducted in last period (Period 4) in only one of the cohorts based on the observed human pharmacokinetics (PK). Part 2 will consist of maximum of four cohorts for each of the MAD dose or placebo.

    NCT04488770
    Conditions
    1. Urinary Tract Infections
    Interventions
    1. Drug: GSK3882347
    2. Drug: Placebo
    MeSH:Urinary Tract Infections

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

    Measure: Part 1: Number of participants with Adverse events (AEs)

    Time: Up to Week 15

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

    Measure: Part 2: Number of participants with AEs

    Time: Up to Week 4

    Description: Treatment related AE is any untoward medical occurrence in a clinical study participant, having causal relation with the use of a study intervention.

    Measure: Part 1: Number of participants with treatment related AEs

    Time: Up to Week 15

    Description: Treatment related AE is any untoward medical occurrence in a clinical study participant, having causal relation with the use of a study intervention.

    Measure: Part 2: Number of participants with treatment related AEs

    Time: Up to Week 4

    Description: Number of participants with clinically significant abnormal findings in hematology parameters will be assessed.

    Measure: Part 1: Number of participants with clinically significant abnormal findings in hematology parameters

    Time: Up to Week 15

    Description: Number of participants with clinically significant abnormal findings in hematology parameters will be assessed.

    Measure: Part 2: Number of participants with clinically significant abnormal findings in hematology parameters

    Time: Up to Week 4

    Description: Number of participants with clinically significant abnormal findings in clinical chemistry parameters will be assessed.

    Measure: Part 1: Number of participants with clinically significant abnormal findings in clinical chemistry parameters

    Time: Up to Week 15

    Description: Number of participants with clinically significant abnormal findings in clinical chemistry parameters will be assessed.

    Measure: Part 2: Number of participants with clinically significant abnormal findings in clinical chemistry parameters

    Time: Up to Week 4

    Description: Number of participants with abnormal urinalysis parameters will be assessed.

    Measure: Part 1: Number of participants with abnormal urinalysis results

    Time: Up to Week 15

    Description: Number of participants with abnormal urinalysis parameters will be assessed.

    Measure: Part 2: Number of participants with abnormal urinalysis results

    Time: Up to Week 4

    Description: Number of participants with clinically significant abnormal vital signs will be assessed.

    Measure: Part 1: Number of participants with clinically significant abnormal vital signs

    Time: Up to Week 15

    Description: Number of participants with clinically significant abnormal vital signs will be assessed.

    Measure: Part 2: Number of participants with clinically significant abnormal vital signs

    Time: Up to Week 4

    Description: Number of participants with abnormal ECG parameters will be assessed.

    Measure: Part 1: Number of participants with clinically significant abnormal Electrocardiogram (ECG) findings

    Time: Up to Week 15

    Description: Number of participants with abnormal ECG parameters will be assessed.

    Measure: Part 2: Number of participants with clinically significant abnormal ECG findings

    Time: Up to Week 4

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Area under the concentration-time curve from time zero to 24 hours after dosing (AUC [0-24]) of GSK3882347 single dose

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hour post dose in each treatment period]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of GSK3882347 single dose

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: AUC extrapolated from time zero to infinity (AUC[0-inf]) of GSK3882347 single dose

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Maximum plasma concentration (Cmax) of GSK3882347 single dose (nanograms per milliliter)

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Plasma concentrations at 24 hours after dosing (C24h) of GSK3882347 single dose

    Time: Day 1: 24 hour post dose in each treatment period

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Time to Cmax (Tmax) of GSK3882347 single dose

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Lag time for absorption (tlag) of GSK3882347 single dose

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Terminal elimination half-life (T1/2) of GSK3882347 single dose

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 2: AUC over the dosing interval tau (AUC[0-tau]) of GSK3882347 repeat dose

    Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 2: Cmax of GSK3882347 repeat dose

    Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 2: Tmax of GSK3882347 repeat dose

    Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]

    Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 2: Plasma concentrations over the dosing interval (Ctau) of GSK3882347 repeat dose

    Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]

    Description: Urine samples will be collected at indicated time points for the assessment of urinary concentration.

    Measure: Part 1: Urine concentration at 22-24 hours collection time point

    Time: Day 1 [22-24 hours post dose in each treatment period]

    Description: Urine samples will be collected at indicated time points for the assessment of urinary concentration.

    Measure: Part 2: Urine concentration at 22-24 hours collection time point

    Time: Days 1 and 7 [22-24 hours post dose]

    Description: Urine samples will be collected at indicated time intervals for the assessment of amount excreted in urine of unchanged GSK3882347.

    Measure: Part 1: Amount excreted in urine (Ae) of unchanged GSK3882347

    Time: Day 1 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48- 60, 60-72, 72-84, and 84-96 hour post dose in each treatment period]

    Description: Urine samples will be collected at indicated time intervals for the assessment of amount excreted in urine of unchanged GSK3882347.

    Measure: Part 2: Amount excreted in urine (Ae) of unchanged GSK3882347

    Time: Days 1 and 7 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hour post dose]

    Description: Urine samples will be collected at indicated time points for the assessment of fraction of the dose excreted in urine GSK3882347.

    Measure: Part 1 Fraction of the dose excreted in urine (fe) following single dose GSK3882347

    Time: Day 1 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48- 60, 60-72, 72-84, and 84-96 hours post dose in each treatment period]

    Description: Urine samples will be collected at indicated time points for the assessment of fraction of the dose excreted in urine GSK3882347.

    Measure: Part 2: Fraction of the dose excreted in urine (fe) following single dose GSK3882347

    Time: Days 1 and 7 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 post dose in each of the 4 cohorts]

    Description: Urine samples will be collected at indicated time points for the assessment renal clearance of GSK3882347.

    Measure: Part 1: Renal clearance (CLr) following single dose GSK3882347

    Time: Day 1 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48- 60, 60-72, 72-84, and 84-96 hours post dose]

    Description: Urine samples will be collected at indicated time points for the assessment renal clearance of GSK3882347.

    Measure: Part 2: Renal clearance (CLr) following single dose GSK3882347

    Time: Days 1 and 7 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 post dose]

    Secondary Outcomes

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: AUC from time zero to 12 hours after dosing (AUC[0-12]) following single dose of GSK3882347

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hour post dose in each treatment period]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Plasma concentrations at 12 hours (C12) following single dose of GSK3882347

    Time: Day 1 [12 hour post dose in each treatment period]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Apparent oral clearance (CL/F) following single dose of GSK3882347

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Apparent volume of distribution after non-intravenous administration (Vd/F) following single dose of GSK3882347

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 1: Mean residence time (MRT) following single dose of GSK3882347

    Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 2: AUC[0-12] following repeat dose of GSK3882347

    Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, and 12, hour post dose]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 2: C12 following repeat dose of GSK3882347

    Time: Days 1 and Day 7 [12 hour post dose]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.

    Measure: Part 2: Observed accumulation ratio (Ro) using AUC(0-tau) following repeat dose of GSK3882347

    Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24, hour post dose]

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347. The time invariance will be estimated by calculating the ratio of AUC(0-tau) on Day 7 to AUC(0-inf) on Day 1.

    Measure: Part 2: Time invariance of GSK3882347 using AUC(0-tau) (repeat dose) and AUC(0-inf) (single dose)

    Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24, hour post dose]

    Description: Blood samples will be collected at indicated time points to confirm achievement of steady-state of GSK3882347 after repeated dosings.

    Measure: Part 2: Plasma concentrations over the dosing interval (Ctau) of GSK3882347 after repeat doses

    Time: Pre-dose on Days 3 through 7
    357 Sildenafil for Treating Patients With COVID-19 and Perfusion Mismatch: A Pilot Randomised Trial

    This randomised trial aims to assess the role of sildenafil in improving oxygenation amongst hospitalised patients with COVID19.

    NCT04489446
    Conditions
    1. Covid19
    2. SARS-COV2 Infection
    Interventions
    1. Drug: Sildenafil
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.

    Measure: Arterial Oxygenation

    Time: One hour after sildenafil administration

    Description: Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.

    Measure: Arterial Oxygenation

    Time: Daily until the end of follow-up (up to 15 days after randomisation)

    Description: Mean difference in the alveolo-arterial gradient between study groups.

    Measure: Alveolo-arterial gradient

    Time: One hour after sildenafil administration

    Description: Mean difference in the alveolo-arterial gradient between study groups.

    Measure: Alveolo-arterial gradient

    Time: Daily until the end of follow-up (up to 15 days after randomisation)

    Secondary Outcomes

    Description: Proportion of patients requiring admission to an intensive care unit in each study group

    Measure: Intensive care unit admission

    Time: Up to two weeks after randomisation

    Description: Proportion of patients requiring noninvasive mechanical ventilation o high-flow nasal cannula unit in each study group

    Measure: Noninvasive Mechanical Ventilation or Requirement of High-Flow Nasal Cannula

    Time: Up to two weeks after randomisation

    Description: Proportion of patients requiring invasive mechanical ventilation in each study group

    Measure: Invasive mechanical ventilation

    Time: Up to two weeks after randomisation

    Description: Proportion of patients that survived COVID19 in each study group

    Measure: Survival

    Time: Up to two weeks after randomisation

    Other Outcomes

    Description: Adverse events attributable to sildenafil use.

    Measure: Adverse events

    Time: Up to two weeks after randomisation
    358 Phase I, Randomized, Double Blinded, Placebo Control Study to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Placebo to Treat Acute Pulmonary Inflammation Due to COVID-19 With Moderate to Severe Symptoms

    The purpose of this study is to demonstrate the safety of Umbilical Cord Tissue Derived Mesenchymal Stem Cells (UCMSCs) administered intravenously in patients with acute pulmonary inflammation due to COVID-19 with moderately severe symptoms

    NCT04490486
    Conditions
    1. COVID-19
    2. Acute Respiratory Distress Syndrome
    3. Corona Virus Infection
    Interventions
    1. Biological: UCMSCs
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Safety of UCMSCs will be reported as the percentage of participants in each treatment group that experienced a treatment related SAEs.

    Measure: Percent of participants with treatment related Serious Adverse Events (SAE)

    Time: 12 months

    Secondary Outcomes

    Description: Change in serum inflammatory marker levels including Interleukin (IL) IL-6, IL-2, Tumor Necrosis Factor Alpha (TNF-a) and procalcitonin will be evaluated in ng/L.

    Measure: Change in inflammatory marker levels

    Time: Baseline, Day 30

    Description: Change in serum systemic inflammatory marker levels including D-dimer, high sensitivity C-reactive protein (hsCRP) and ferritin will be evaluated in mg/L.

    Measure: Change in systemic inflammatory marker levels

    Time: Baseline, Day 30

    Description: Assessed using blood samples or nose/throat swabs.

    Measure: COVID-19 Viral Load

    Time: Up to 30 Days

    Description: Sequential Organ Failure Assessment (SOFA) will be used to assess organ failure including the cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs. SOFA score ranges from 0-24 with the higher score indicating worse outcomes.

    Measure: Change in SOFA score

    Time: Baseline, Up to 30 Days

    Description: Sodium, Potassium, Chloride and Carbon Dioxide (CO2) will be evaluated in mmol/L. Changes from baseline to Day 30 will be compared between groups.

    Measure: Change in electrolytes levels

    Time: Baseline, Up to 30 Days

    Description: Serum Lactate Dehydrogenase (LDH) levels assessed in U/L. Changes in LDH from baseline to Day 30 will be compared between groups.

    Measure: Change in LDH levels

    Time: Baseline, Up to 30 Days

    Description: ICU monitoring status will be reported as the number of subjects discharged from the ICU within 7 days.

    Measure: Number of subjects discharged from the ICU

    Time: Up to 7 Days

    Description: Percentage of participants requiring less use of vasoactive agents will be reported.

    Measure: Percentage of participants with less requirement for vasoactive agents

    Time: Up to 30 Days

    Description: Percentage of participant deaths throughout the study period.

    Measure: Rate of Mortality

    Time: Up to 30 Days

    Description: The percentage of participants with changes in serum immune marker levels including Cluster of Differentiation (CD) CD 4+ and CD 8+, as evaluated by treating physician will be reported.

    Measure: Percentage of participants with changes in immune marker expression

    Time: Up to 30 Days

    Description: Percentage of participants with changes in their chest imaging such as ground-glass opacity, local patch shadowing, bilateral patch shadowing and interstitial abnormalities will be reported. Imaging will be assessed by treating physician using chest radiography or chest Computed Tomography (CT).

    Measure: Percentage of participants with changes in radiologic findings

    Time: Up to 30 Days

    Description: Percentage of participants showing less pneumonia symptoms will be reported as evaluated by treating physician using chest radiography or chest CT.

    Measure: Percentage of participants with less pneumonia symptoms

    Time: Up to 30 Days
    359 Safety, Immunogenicity, Infectivity, and Dose-Finding Study of an Investigational Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Infants and Toddlers

    The primary objectives of the study are: - To assess the safety profile of each dose of the study product after each and any administration in all infants and toddlers regardless of baseline neutralizing antibody serostatus. - To characterize the RSV-A serum neutralizing antibody responses to the study product in each vaccine group after vaccination in Respiratory Syncytial Virus (RSV) seronegative participants. The secondary objectives of the study are: - To quantify the amount of vaccine virus shed by each participant by baseline neutralizing antibody serostatus. - To determine the proportion of vaccinated infants and toddlers in each vaccine group infected with the vaccine virus after vaccination by baseline neutralizing antibody serostatus. - To characterize the RSV-A serum neutralizing antibody responses to the study product in each vaccine group after vaccination in RSV seropositive participants. - To characterize serum RSV-A anti-F immunoglobulin G antibody responses to the study product in each vaccine group after vaccination by baseline neutralizing antibody serostatus. - To characterize serum RSV-A antibody responses (neutralizing and anti-F immunoglobulin G) to the study product in each vaccine group after the RSV season by baseline neutralizing antibody serostatus.

    NCT04491877
    Conditions
    1. Respiratory Syncytial Virus Infection
    Interventions
    1. Biological: RSV vaccine formulation 1
    2. Biological: RSV vaccine formulation 2
    3. Biological: Placebo
    MeSH:Respiratory Syncytial Virus Infections

    Primary Outcomes

    Description: Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination.

    Measure: Number of participants reporting immediate adverse events

    Time: Within 30 minutes after vaccination

    Description: Solicited administrative site reaction: rhinorrhea. Solicited systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability.

    Measure: Number of participants reporting solicited reactions

    Time: Within 28 days after vaccination

    Description: Unsolicited adverse events are spontaneously reported adverse events.

    Measure: Number of participants reporting unsolicited adverse events

    Time: Within 28 days after vaccination

    Description: Adverse events of special interest pre-defined adverse event collected using the same process as for other adverse events.

    Measure: Number of participants reporting adverse events of special interest

    Time: Within 28 days after vaccination

    Description: Medically attended adverse events are adverse events with a new onset or a worsening of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department.

    Measure: Number of participants reporting medically attended adverse events

    Time: Within 28 days after vaccination

    Description: Serious adverse events are collected throughout the study, from Day 0 up to 1 month after the end of the RSV season.

    Measure: Number of participants reporting serious adverse events

    Time: Day 0 to maximum Month 12

    Description: Vaccine induced RSV-A serum neutralizing antibody levels assessed in RSV seronegative participants in Cohorts 1, 2, 3, and 4.

    Measure: Vaccine-induced RSV-A serum neutralizing antibody levels after first vaccine administration

    Time: Day 56

    Description: Vaccine induced RSV-A serum neutralizing antibody levels are assessed in RSV seronegative participants in Cohorts 2 and 4.

    Measure: Vaccine-induced RSV-A serum neutralizing antibody levels after second vaccine administration

    Time: Day 84

    Secondary Outcomes

    Description: Titers are assessed by plaque assay.

    Measure: Titer of vaccine virus shedding (plaque assay)

    Time: 7 and 10 days after vaccination

    Description: Titers are assessed by PCR.

    Measure: Titer of vaccine virus shedding (polymerase chain reaction [RT-PCR])

    Time: 7 and 10 days after vaccination

    Description: Infection is defined as detection of vaccine in nasal wash by culture or PCR and / or a ≥ 4-fold rise in serum neutralizing antibodies or in serum antibodies to RSV F. Infectivity is assessed on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4.

    Measure: Number of participants infected with the vaccine virus

    Time: Day 56 and Day 84

    Description: RSV-A serum neutralizing antibody levels assessed in seropositive participants on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4.

    Measure: Vaccine-induced RSV-A serum neutralizing antibody levels

    Time: Day 56 and Day 84

    Description: RSV-A F binding antibody levels assessed on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4.

    Measure: Vaccine-induced RSV-A F binding antibody levels

    Time: Day 56 and Day 84

    Description: Serum RSV-A antibody titers (neutralizing and anti-F) are assessed after the end of the RSV season (on average end of March in the Northern Hemisphere and end of September in the Southern Hemisphere).

    Measure: RSV-A antibody titers after the RSV surveillance season

    Time: Within 1 month after the end of the RSV season
    360 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-3)

    ACTT-3 will evaluate the combination of interferon beta-1a and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.

    NCT04492475
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Interferon beta-1a
    2. Other: Placebo
    3. Drug: Remdesivir

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.

    Measure: Time to recovery

    Time: Day 1 through Day 29

    Secondary Outcomes

    Measure: Change from baseline in alanine aminotransferase (ALT)

    Time: Day 1 through Day 29

    Measure: Change from baseline in aspartate aminotransferase (AST)

    Time: Day 1 through Day 29

    Measure: Change from baseline in C-reactive protein (CRP)

    Time: Day 1 through Day 29

    Measure: Change from baseline in creatinine

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in hemoglobin

    Time: Day 1 through Day 29

    Measure: Change from baseline in international normalized ratio (INR)

    Time: Day 1 through Day 29

    Measure: Change from baseline in platelets

    Time: Day 1 through Day 29

    Measure: Change from baseline in total bilirubin

    Time: Day 1 through Day 29

    Measure: Change from baseline in white blood cell count (WBC) with differential

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 29

    Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of invasive mechanical ventilation

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of non invasive ventilation/high flow oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days

    Measure: Duration of oxygen use

    Time: Day 1 through Day 29

    Description: For any reason.

    Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics

    Time: Day 1 through Day 10

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Mean change in the ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Participant's clinical status at Day 15 by ordinal scale

    Time: Day 15

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale

    Time: Days 3, 5, 8, 11, 22, and 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 28-day mortality

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.

    Measure: Time to recovery for participants not on mechanical ventilation (baseline ordinal score of 4, 5, or 6)

    Time: Day 1 through Day 29
    361 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation

    The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.

    NCT04492514
    Conditions
    1. COVID 19
    2. SARS-CoV 2
    3. Pneumonia
    Interventions
    1. Drug: Mavrilimumab
    2. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of subjects alive and off oxygen at day14

    Measure: Primary Outcome Measure:

    Time: Day 14

    Secondary Outcomes

    Description: Proportion of subjects alive and without respiratory failure at 28 days

    Measure: Secondary Outcome Measures:

    Time: 28 days
    362 A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Multi-Centre, Dose-Ranging Study of AZD5718 in Participants With Proteinuric Chronic Kidney Disease

    The purpose of the study is to evaluate the dose-response efficacy, safety, and pharmacokinetics (PK) of AZD5718 in participants with proteinuric chronic kidney disease.

    NCT04492722
    Conditions
    1. Chronic Kidney Disease
    Interventions
    1. Drug: AZD5718
    2. Drug: Dapagliflozin 10 mg
    3. Drug: Placebo
    MeSH:Kidney Diseases Renal Insufficiency, Chronic
    HPO:Abnormality of the kidney Chronic kidney disease Nephropathy

    Primary Outcomes

    Description: To evaluate the dose response effect of AZD5718 on urine ACR at 20 weeks

    Measure: Change from baseline in urine ACR to Week 20

    Time: Week 1 to Week 20

    Secondary Outcomes

    Description: To evaluate the dose response effect of AZD5718 on urine ACR at 12 weeks

    Measure: Change from baseline in urine ACR to Week 12

    Time: Week 1 to Week 12

    Description: To assess the safety and tolerability profile of AZD5718 treatment

    Measure: Number of participants with adverse events and serious adverse events

    Time: Screening to Week 24

    Description: To evaluate the effect of AZD5718 on ambulatory blood pressure

    Measure: Change from baseline in 24-hours mean systolic blood pressure to Week 12

    Time: Week 1 to Week 12

    Description: To assess the PK of AZD5718 after repeated oral dosing for 20 weeks

    Measure: Plasma concentrations of AZD5718

    Time: Week 2 to Week 20

    Description: To assess the effect of AZD5718 on renal function

    Measure: Change from baseline in estimated glomerular filtration rate (eGFR) to Week 12

    Time: Week 1 to Week 12
    363 A Phase IIb, Randomized, Partially Blind, Active Controlled, Dose-range Finding Study of GSK3640254 Compared to a Reference Arm of Dolutegravir, Each in Combination With Nucleoside Reverse Transcriptase Inhibitors, in HIV-1 Infected Antiretroviral Treatment-naive Adults

    Infection with HIV-1 continues to be a serious health threat throughout the world, with more than 40 million individuals infected worldwide. The current standard of care treatment for HIV-1 is combination anti-retroviral therapy (cART) with recommendations to start regardless of cluster of differentiation 4 (CD4) plus (+) T-cell count, committing people living with HIV to lifelong, lifesaving therapy. However, the chronic exposure to cART has identified anti-retroviral (ARV)-associated long-term toxicities (central nervous system [CNS] or cardiovascular [CV]/metabolic effects, renal disease), creating a need to address and prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 maturation inhibitor (MI) and has completed a short-term, monotherapy, proof of concept (POC) Phase 2a study. This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses [100, 150 and 200 milligrams {mg}]), active controlled clinical trial. It will aim to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine [ABC/3TC] or emtricitabine/tenofovir alafenamide [FTC/TAF]), in approximately 240 treatment-naïve HIV-1 infected adults. In the experimental arms, GSK3640254 will be administered in 3 blinded doses until the last participant completes their Week 48 study visit (Week 48 Secondary Endpoint study milestone). Thereafter, participants whose most recent HIV-1 ribonucleic acid (RNA) less than (<)50 copies/milliliters (c/mL) in the GSK3640254 arms will move into the Non-Randomised Phase and will be switched from their blinded dose to the open label optimal dose. Simultaneously, these participants will also be switched from their dual NRTI therapy to DTG. The total study duration will be approximately 7 years.

    NCT04493216
    Conditions
    1. HIV Infections
    Interventions
    1. Drug: GSK3640254
    2. Drug: ABC/3TC
    3. Drug: FTC/TAF
    4. Drug: Dolutegravir
    5. Drug: Placebo
    MeSH:HIV Infections

    Primary Outcomes

    Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Week 24.

    Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 24

    Time: At Week 24

    Secondary Outcomes

    Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Weeks 48 and 96.

    Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Weeks 48 and 96

    Time: At Weeks 48 and 96

    Description: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.

    Measure: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: Change from Baseline in level of plasma HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.

    Measure: Change from Baseline in plasma HIV-1 RNA at Weeks 24, 48 and 96 (c/mL)

    Time: Baseline and Weeks 24, 48 and 96

    Description: Absolute values of CD4+ cells at Weeks 24, 48, and 96 will be assessed.

    Measure: Absolute values of CD4+ cell counts at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: Change from Baseline in CD4+ cells at Weeks 24, 48 and 96 will be assessed.

    Measure: Change from Baseline in CD4+ cell counts at Weeks 24, 48 and 96 (Cells per cubic millimeters [cells/mm^3])

    Time: Baseline and Weeks 24, 48 and 96

    Description: All SAEs, deaths and AEs leading to treatment discontinuation will be assessed.

    Measure: Number of participants with serious adverse events (SAEs), Deaths and adverse events (AEs) leading to treatment discontinuation at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: All AEs will be assessed.

    Measure: Number of participants with AEs at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: Severity of AEs will be assessed.

    Measure: Severity of AEs at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: Number of participants with AEs in GI, Psych/CNS will be assessed at Weeks 24, 48 and 96.

    Measure: Number of participants with AEs in Gastrointestinal (GI), Psychological (Psych)/Central nervous system (CNS) at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: Plasma samples will be collected for analyzing phenotypic resistance at Weeks 24, 48 and 96 using PhenoSense genotype testing (GT) for reverse transcriptase (RT) (NRTI and non-nucleoside reverse transcriptase inhibitors [NNRTI]) and Protease inhibitor (PI), PhenoSense Integrase, PhenoSense Gag assays for GSK3640254.

    Measure: Number of participants who develop phenotypic resistance at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: Plasma samples will be collected for analyzing genotypic resistance at Weeks 24, 48 and 96 using PhenoSense GT for RT and Protease genotype, GeneSeq Integrase, and Gag genotype (using a Next Generation Sequencing platform).

    Measure: Number of participants who develop genotypic resistance at Weeks 24, 48 and 96

    Time: At Weeks 24, 48 and 96

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.

    Measure: Maximum observed concentration (Cmax) of GSK3640254 at steady state at Week 24

    Time: At Week 24

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.

    Measure: Cmax of GSK3640254 at steady state at Week 48

    Time: At Week 48

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.

    Measure: AUC over the dosing interval (AUC [0-tau]) of GSK3640254 at Week 24

    Time: At Week 24

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.

    Measure: AUC (0-tau) of GSK3640254 at steady state at Week 48

    Time: At Week 48

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.

    Measure: Plasma concentration at the end of the dosing (Ctau) of GSK3640254 at steady state at Week 24

    Time: At Week 24

    Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.

    Measure: Ctau of GSK3640254 at steady state at Week 48

    Time: At Week 48
    364 A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3739937 in Healthy Participants

    Human immunodeficiency virus 1 (HIV-1) infections continues to be a serious health threat throughout the world and development of medicines with new mechanism of action have an important role to play. The purpose of this study is to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937. The information collected in this study will help in further clinical development of GSK3739937, including a Phase IIA Proof of Concept (PoC) study in HIV-infected participants as well as a FTIH study of long acting formulation of GSK3739937 administered parenterally (subcutaneously or intramuscularly). This randomized, placebo controlled, single and repeat-dose escalation study of GSK3739937 in healthy participants and will be executed in two-part. In Part 1 single ascending dose (SAD), approximately 18 participants will be randomized with approximately 9 participants within each of Cohort 1 and Cohort 2. In Part 2 multiple ascending dose (MAD), approximately 30 participants will be randomized with approximately 10 participants within each of Cohorts 3 to 5. Approximately 48 participants will be enrolled in the study and all doses will be administered after a moderate fat meal. Maximum duration of study participation will be approximately 22 weeks in Part 1 and approximately 18 weeks in Part 2.

    NCT04493684
    Conditions
    1. HIV Infections
    Interventions
    1. Drug: GSK3739937
    2. Drug: Placebo
    MeSH:HIV Infections

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

    Measure: Part 1: Cohort 1-2: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

    Time: Up to Day 44

    Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets (Giga cells per liter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the hematology parameters: RBC count.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) count (Trillion cells per liter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be e collected to analyze the hematology parameters: MCV.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Mean Corpuscular Volume (MCV) (Femtoliter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the hematology parameter: MCH.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) (Picogram)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the hematology parameter: percent of reticulocytes.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage of reticulocyte)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the hematology parameter: Hb.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Hemoglobin (Hb) (Grams per deciliter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the chemistry parameter: ALT, AST, and ALP.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphate (ALP) (International units per Liter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.

    Measure: Part 1:Cohort 1-2:Change from Baseline in bicarbonate,calcium,glucose,chloride,magnesium,phosphate,potassium,sodium,blood urea nitrogen (BUN),cholesterol,high density lipoprotein (HDL),low density lipoprotein (LDL),triglycerides (Millimole per Liter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase

    Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (units per liter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, direct bilirubin and creatinine.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Blood samples will be collected to analyze the chemistry parameter: total protein.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: total protein (Gram per Liter)

    Time: Baseline (Day -1) and up to Day 44

    Description: Urine samples will be collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.

    Measure: Part 1: Cohort 1-2: Number of Participants With Abnormal Urinalysis

    Time: Baseline (Day -1) and up to Day 44

    Description: SBP and DBP will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeters of mercury)

    Time: Baseline (Day -1) and up to Day 44

    Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute)

    Time: Baseline (Day -1) and up to Day 44

    Description: Temperature was will be in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Temperature (Degrees Celsius)

    Time: Baseline (Day -1) and up to Day 44

    Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute)

    Time: Baseline (Day -1) and up to Day 44

    Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.

    Measure: Part 1: Cohort 1-2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

    Time: Baseline (Day 1, Pre-dose) and up to Day 44

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

    Measure: Part 2: Cohort 3-4: Number of Participants With AEs and SAEs

    Time: Up to Day 28

    Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.

    Measure: Part 2: Cohort 3-4:Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets (Giga cells per liter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the hematology parameters: RBC count.

    Measure: Part 2: Cohort 3-4:Change From Baseline in Hematology Parameters: RBC count (Trillion cells per liter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the hematology parameters: MCV.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameters: MCV (Femtoliter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the hematology parameter: MCH.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: MCH (Picogram)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the hematology parameter: Percent of reticulocytes

    Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage reticulocyte)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the hematology parameter: Hb.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Hb (Grams per deciliter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be e collected to analyze the chemistry parameter: ALT, AST and ALP.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: ALT, AST and ALP (International units per Liter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase

    Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (units per liter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL and triglycerides.

    Measure: Part 2: Cohort 3-4: Change From Baseline in bicarbonate, glucose, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL and triglycerides (Millimoles per liter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, creatinine and direct bilirubin

    Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinin and Direct Bilirubin (Micromoles per liter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Blood samples will be collected to analyze the chemistry parameter: total protein.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: Total protein (Grams per liter)

    Time: Baseline (Day -1) and up to Day 28

    Description: Urine samples collected at given time points to analyze the abnormal findings for pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.

    Measure: Part 2: Cohort 3-4: Number of Participants With Abnormal Urinalysis

    Time: Baseline (Day -1) and up to Day 28

    Description: SBP and DBP measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: DBP and SBP (Millimeters of mercury)

    Time: Baseline (Day -1) and up to Day 28

    Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute)

    Time: Baseline (Day -1) and up to Day 28

    Description: Temperature will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: Temperature (Degrees Celsius)

    Time: Baseline (Day -1) and up to Day 28

    Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute)

    Time: Baseline (Day -1) and up to Day 28

    Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.

    Measure: Part 2: Cohort 3-4: Number of Participants With Abnormal ECG Findings

    Time: Baseline (Day -1) and up to Day 28

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

    Measure: Part 2: Cohort 5: Number of Participants With AEs and SAEs

    Time: Up to Day 42

    Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.

    Measure: Part 2: Cohort 5:Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets (Giga cells per liter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the hematology parameters: RBC count

    Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameters: RBC count (Trillion cells per liter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the hematology parameters: MCV.

    Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameters: MCV (Femtoliter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the hematology parameter: MCH.

    Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: MCH (Picogram)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.

    Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the hematology parameter: Percent of reticulocytes

    Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage reticulocyte)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the hematology parameter: Hb.

    Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Hb (Grams per deciliter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be e collected to analyze the chemistry parameter: ALT, AST, and ALP.

    Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: ALT, AST, ALP (International units per Liter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase

    Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (Units per liter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL, and triglycerides.

    Measure: Part 2: Cohort 5:Change From Baseline in Bicarbonate, glucose (non-fasting), Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL Cholesterol, LDL Cholesterol and Triglycerides (Millimoles per liter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, creatinine and direct bilirubin

    Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine and Direct Bilirubin (Micromoles per liter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Blood samples will be collected to analyze the chemistry parameter: total protein.

    Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: Total protein (Grams per liter)

    Time: Baseline (Day -1) and up to Day 42

    Description: Urine samples collected at given time points to analyze the abnormal findings for pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.

    Measure: Part 2: Cohort 5: Number of Participants With Abnormal Urinalysis

    Time: Baseline (Day -1) and up to Day 42

    Description: SBP and DBP measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: DBP and SBP (Millimeters of mercury)

    Time: Baseline (Day -1) and up to Day 42

    Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute)

    Time: Baseline (Day -1) and up to Day 42

    Description: Temperature will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: Temperature (Degrees Celsius)

    Time: Baseline (Day -1) and up to Day 42

    Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.

    Measure: Part 2: Cohort 5: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute)

    Time: Baseline (Day -1) and up to Day 42

    Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.

    Measure: Part 2: Cohort 5: Number of Participants With Abnormal ECG Findings

    Time: Baseline (Day -1) and up to Day 42

    Secondary Outcomes

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-24) of GSK3739937.

    Measure: Part 1: Cohort 1-2:Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 hours (AUC[0-24]) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose

    Description: Blood samples will be collected at indicated time points for the PK analysis of AUC(0-t) of GSK3739937.

    Measure: Part 1: Cohort 1-2: AUC From zero (pre-dose) to t (AUC [0-t]) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-inf) of GSK3739937.

    Measure: Part 1: Cohort 1-2: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.

    Measure: Part 1: Cohort 1-2: Apparent Terminal Phase Half-life (T1/2) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.

    Measure: Part 1: Cohort 1-2: Apparent Oral Clearance (CL/F) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.

    Measure: Part 1: Cohort 1-2: Maximum Observed Concentration (Cmax) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of C24 of GSK3739937.

    Measure: Part 1: Cohort 1-2: Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937

    Time: At 24 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of Clast of GSK3739937.

    Measure: Part 1: Cohort 1-2: Last Quantifiable Concentration (Clast) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.

    Measure: Part 1: Cohort 1-2: Time of Occurrence of Cmax (Tmax) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of Tlag of GSK3739937.

    Measure: Part 1: Cohort 1-2: Lag Time (Tlag) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of Tlast of GSK3739937.

    Measure: Part 1: Cohort 1-2: Time to Reach Clast (Tlast) of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-24) of GSK3739937.

    Measure: Part 2: Cohort 3-4: AUC (0-24) of GSK3739937 on Day 1

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)

    Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.

    Measure: Part 2: Cohort 3-4: Cmax of GSK3739937 on Day 1

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)

    Description: Blood samples will be collected at indicated time points for the analysis of C24 of GSK3739937.

    Measure: Part 2: Cohort 3-4: C24 of GSK3739937 on Day 1

    Time: At 24 hours post-dose on Day 1 (pre-dose on Day 2)

    Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.

    Measure: Part 2: Cohort 3-4: Tmax of GSK3739937 on Day 1

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)

    Description: Blood samples will be collected at indicated time points for the analysis of Tlag of GSK3739937.

    Measure: Part 2: Cohort 3-4: Tlag of GSK3739937 on Day 1

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)

    Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.

    Measure: Part 2: Cohort 3-4: Tmax of GSK3739937 on Day 14

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.

    Measure: Part 2: Cohort 3-4: Cmax of GSK3739937 on Day 14

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) of GSK3739937.

    Measure: Part 2: Cohort 3-4: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of Ctau of GSK3739937.

    Measure: Part 2: Cohort 3-4: Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14

    Time: At 24 hours post-dose on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.

    Measure: Part 2: Cohort 3-4: T1/2 of GSK3739937 on Day 14

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.

    Measure: Part 2: Cohort 3-4: CL/F of GSK3739937 on Day 14

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.

    Measure: Part 2: Cohort 5: Tmax of GSK3739937 on Day 28

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.

    Measure: Part 2: Cohort 5: Cmax of GSK3739937 on Day 28

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) of GSK3739937.

    Measure: Part 2: Cohort 5: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 28

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of Ctau of GSK3739937.

    Measure: Part 2: Cohort 5: Plasma Trough Concentration (Ctau) of GSK3739937: Day 28

    Time: At 24 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.

    Measure: Part 2: Cohort 5:T1/2 of GSK3739937: Day 28

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.

    Measure: Part 2: Cohort 5: CL/F of GSK3739937: Day 28

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-inf) Following Single Dose of GSK3739937.

    Measure: Part 1: Cohort 1-2: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of Cmax Following Single Dose of GSK3739937.

    Measure: Part 1: Cohort 1-2: Dose Proportionality for Cmax Following Single Dose of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) Following Repeated Dose of GSK3739937.

    Measure: Part 2: Cohort 3-4: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) Following Repeated Dose of GSK3739937.

    Measure: Part 2: Cohort 5: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of Ctrough Following Repeated Dose of GSK3739937.

    Measure: Part 2: Cohort 3-4: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3739937

    Time: At 24 hours post-dose on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of Ctrough Following Repeated Dose of GSK3739937.

    Measure: Part 2: Cohort 5: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3739937

    Time: At 24 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of Cmax Following Repeated Dose of GSK3739937.

    Measure: Part 2: Cohort 3-4: Dose Proportionality (Cmax) Following Repeated Dose of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of Cmax Following Repeated Dose of GSK3739937.

    Measure: Part 2: Cohort 5: Dose Proportionality (Cmax) Following Repeated Dose of GSK3739937

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of Predicted accumulation ratio Rp based on AUC.

    Measure: Part 1: Cohort 1-2: Predicted accumulation ratio Rp based on AUC

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

    Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]).

    Measure: Part 2: Cohort 3-4: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]).

    Measure: Part 2: Cohort 5: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of Cmax (R [CMAX]).

    Measure: Part 2: Cohort 3-4: Accumulation Ratio of Cmax (R [CMAX])

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of Cmax (R [CMAX]).

    Measure: Part 2: Cohort 5: Accumulation Ratio of Cmax (R [CMAX])

    Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of C(Tau) (R[CTAU]).

    Measure: Part 2: Cohort 3-4: Accumulation Ratio of C(Tau) (R[CTAU])

    Time: At 24 hours post-dose on Day 1 and Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of C(Tau) (R[CTAU]).

    Measure: Part 2: Cohort 5: Accumulation Ratio of C(Tau) (R[CTAU])

    Time: At 24 hours post-dose on Day 1 and Day 28

    Description: Blood samples will be collected at indicated time points for the analysis of pre-dose Concentration of GSK3739937.

    Measure: Part 2: Cohort 3-4: Pre-dose Concentration of GSK3739937 from Day 2 to Day 14

    Time: Pre-dose from Day 2 to Day 14

    Description: Blood samples will be collected at indicated time points for the analysis of Pre-dose Concentration of GSK3739937.

    Measure: Part 2: Cohort 5: Pre-dose Concentration of GSK3739937 from Day 2 to Day 28

    Time: Pre-dose from Day 2 to Day 28
    365 BARCONA: A Phase II/III, Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19)

    This multi-center, double-blind, placebo-controlled, randomized Phase 2/3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in approximately 400-440 patients hospitalized with confirmed COVID-19. The Phase 2 portion of the trial will include approximately 40 patients and is designed to provide an early interim analysis of safety. The Phase 3 portion of the trial will include approximately 360-400 additional patients, and is designed to determine whether bardoxolone methyl increases the probability of recovery at Day 29 when compared with matching placebo. Patients will be randomized using permuted block randomization in a 1:1 fashion to either once-daily administration of bardoxolone methyl (20 mg) or matching placebo and treatment will be administered for the duration of hospitalization (until recovery), with a maximum treatment duration of 29 days.

    NCT04494646
    Conditions
    1. Covid19
    Interventions
    1. Drug: Bardoxolone methyl
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Incidence of Serious Adverse Events in Phase 2

    Time: Day 29

    Description: Recovery is defined as alive, free of respiratory failure (e.g., need for noninvasive, or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of renal replacement therapy (RRT).

    Measure: Proportion of participants who have recovered in Phase 3

    Time: Day 29

    Secondary Outcomes

    Measure: Average number of renal replacement therapy (RRT)-free days

    Time: Day 29

    Measure: Average number of mechanical ventilation-free days

    Time: Day 29

    Measure: Incidence of All-Cause Mortality

    Time: Day 29

    Description: Deterioration is defined by a 1-point worsening scale: 0- Uninfected; no viral RNA detected, 1- Asymptomatic; viral RNA detected, 2- Symptomatic; Independent, 3- Symptomatic; assistance needed, 4- Hospitalized; no oxygen therapy, 5- Hospitalized; oxygen by mask or nasal prongs, 6- Hospitalized; oxygen by NIV or High flow, 7- Intubation & Mechanical ventilation; pO2/FIO2 >/= 150 or SpO2/FIO2 >/=200, 8- Mechanical ventilation pO2/FIO2 < 150 (SpO2/FIO2 <200) or vasopressors, 9- Mechanical ventilation pO2/FIO2 < 150 and vasopressors, dialysis or ECMO, 10- Death

    Measure: Proportion of participants who experienced deterioration from baseline

    Time: Day 29
    366 A Phase 2 Trial to Evaluate the Safety and Tolerability of Clazakizumab® [Anti-Interleukin (IL)-6 Monoclonal] Compared to Placebo for the Treatment of COVID-19 Infection

    The purpose of this study is to investigate the effectiveness and safety of treatment with clazakizumab compared to a placebo (inactive substance). We are proposing to try this drug to treat coronavirus disease 2019 (COVID-19) infection. Patients with COVID-19 infection have been shown to have increases in certain inflammatory processes. Clazakizumab is an antibody (immune system protein) that blocks certain inflammatory processes. The treatment plan is to attempt to inhibit or block these inflammatory processes in order to try to limit the damage COVID-19 causes to the lungs.

    NCT04494724
    Conditions
    1. COVID-19 Infection
    Interventions
    1. Drug: Clazakizumab
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Description: Proportion of participants who experience treatment-related adverse events (TEAE) ≥ Grade 3 (CTCAE v5.0) during the first 24 hours after infusion of clazakizumab or placebo

    Measure: Primary Endpoint

    Time: 24 hours

    Secondary Outcomes

    Description: Proportion of participants who need mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) after the first dose of clazakizumab or placebo

    Measure: Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO)

    Time: 14 days

    Description: Proportion of participants who experience infusion-related reactions during the first 24 hours after infusion of clazakizumab or placebo

    Measure: Infusion-related reactions during 24 hours from the time of infusion

    Time: 24 hours

    Description: Proportion of participants alive at day 28 after the first dose of clazakizumab or placebo

    Measure: Patient survival at 28 days

    Time: 28 days

    Description: Proportion of participants alive at day 60 after the first dose of clazakizumab or placebo

    Measure: Patient survival at 60 days

    Time: 60 days

    Description: Proportion of participants who require an open-label dose of clazakizumab

    Measure: Requirement for open-label clazakizumab

    Time: 14 days

    Description: Number of days in the ICU following the first dose of clazakizumab or placebo

    Measure: Time in the intensive care unit (ICU)

    Time: 60 days

    Description: Number of days in the hospital following the first dose of clazakizumab or placebo

    Measure: Time in the hospital

    Time: 60 days

    Description: Number of days from first dose of clazakizumab or placebo to requiring mechanical ventilation

    Measure: Time to mechanical ventilation

    Time: 60 days

    Description: Difference in WHO Clinical Progression Scale between clazakizumab and placebo

    Measure: Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14

    Time: 14 days

    Description: Difference in WHO Clinical Progression Scale between clazakizumab and placebo

    Measure: Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28

    Time: 28 days

    Description: Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 14 from baseline between clazakizumab or placebo

    Measure: Change in Radiologic Assessment of Lung Edema (RALE) at day 14

    Time: 14 days

    Description: Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 28 from baseline between clazakizumab or placebo

    Measure: Change in Radiologic Assessment of Lung Edema (RALE) at day 28

    Time: 28 days
    367 A Stage 2/3, Adaptive, Randomized, Controlled, Double-blind Study to Investigate the Pharmacokinetics, Efficacy and Safety of the Hyperimmune Equine Serum (INM005) in Adult Patients With Moderate to Severe Confirmed SARS-CoV2 Disease.

    This study aims to analyze the efficacy and safety of passive immunotherapy by administering an equine hyperimmune serum (INM005) against the SARS-CoV2 RBD to Covid19 patients. Improvement of the clinical course 28 days after the start of treatment will be evaluated.

    NCT04494984
    Conditions
    1. Covid19
    Interventions
    1. Drug: INM005
    2. Drug: Placebo

    Primary Outcomes

    Description: The primary endpoint will be the proportion of patients who show a change in symptoms 28 days after the administration of the first dose. A responding subject is defined as a subject with improvement in at least 2 categories on the 8-point World Health Organization (WHO) ordinal scale of clinical status or a subject who is discharged.

    Measure: Clinical changes in COVID-19 symptoms

    Time: 4 weeks

    Secondary Outcomes

    Description: INM005 product concentration in serum at different time points after dosing

    Measure: Pharmacokinetics evaluation of INM005

    Time: 1 week

    Description: Time to achieve a change in at least 2 categories on the 8-point WHO ordinal scale of clinical status. Time to discharge (days). Time to intensive care unit (ICU) discharge (days).

    Measure: Time to progression of disease

    Time: 4 weeks

    Description: Proportion of patients who present change in at least 2 categories on the 8-point WHO ordinal scale of clinical status at 7 and 14 days after the start of the treatment.

    Measure: Disease progression

    Time: up to 2 weeks

    Description: Proportion of patients discharged at 28 days

    Measure: Discharge

    Time: up to 4 weeks

    Description: Proportion of patients who require ICU hospitalization

    Measure: Intensive care unit (ICU) hospitalization

    Time: up to 4 weeks

    Description: Proportion of patients who require MVA

    Measure: Mechanical ventilation assistance (MVA)

    Time: up to 4 weeks

    Description: Proportion of patients who die due to complications from COVID19

    Measure: Mortality

    Time: up to 4 weeks

    Description: Change in viral load from baseline to 7 and 21 days after the start of the treatment.

    Measure: Changes in viral load

    Time: up to 3 weeks

    Other Outcomes

    Description: Measurement of anti SARS-CoV2 antibodies titer levels. IgG (0, 21 days)

    Measure: Anti SARS-CoV2 antibodies levels

    Time: 3 weeks

    Description: Changes in Troponin T levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in Troponin T levels

    Time: 3 weeks

    Description: Changes in D-dimer levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in D-dimer levels

    Time: 3 weeks

    Description: Changes in Ferritin levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in Ferritin levels

    Time: 3 weeks

    Description: Changes in LDH levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in LDH levels

    Time: 3 weeks

    Description: Changes in C-reactive protein levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in C-reactive protein levels

    Time: 3 weeks

    Description: Measurement of anti-INM005 antibodies: baseline and 21 days

    Measure: Immunogenicity

    Time: 3 weeks
    368 A Phase 1, Randomised, Double-Blind, Placebo-Controlled, Dosage-Escalation, Single Centre Study to Evaluate the Safety and Immunogenicity of an Adjuvanted SARS-CoV-2 Sclamp Protein Subunit Vaccine in Healthy Adults Aged 18 to 55 Years Old and Healthy Older Adults, Aged 56 Years and Over

    This study is being conducted to look at the safety and immune response (how the immune system of the human body reacts) to a vaccine for SARS-CoV-2 (the virus responsible for COVID-19 infection) when administered as an intramuscular injection (an injection directly into the muscle) to the upper arm of healthy participants, on two occasions at least 28 days apart.

    NCT04495933
    Conditions
    1. SARS-CoV2
    2. Covid19
    Interventions
    1. Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg
    2. Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg
    3. Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg
    4. Other: Placebo

    Primary Outcomes

    Description: - the frequency of solicited local reactogenicity adverse events (AEs)

    Measure: Frequency of Solicited local reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the frequency of solicited systemic reactogenicity AEs

    Measure: Frequency of Solicited systemic reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the grading of solicited local reactogenicity adverse events (AEs)

    Measure: Grading of Solicited local reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the grading of solicited systemic reactogenicity AEs

    Measure: Grading of Solicited systemic reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the frequency, duration, intensity and relationship to vaccination of unsolicited local adverse events (AEs)

    Measure: Unsolicited adverse events (AEs)

    Time: 28 days following each vaccination (at Days 1 and 29)

    Description: - the frequency, duration, intensity and relationship to vaccination of Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study (including decision by the Principal Investigator [PI] not to proceed with the second dose) at any time during the study

    Measure: Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study

    Time: through study completion (394 days)

    Description: - Geometric mean titre (GMT) of the serum antibody response compared to placebo

    Measure: Geometric Mean Titer (GMT) of the serum antibody response

    Time: 28 days following each vaccination (Days 29 and 57)

    Description: GMT of the serum NAb titres to SARS-CoV-2 virus compared to placebo

    Measure: Geometric Mean Titer (GMT) of the serum neutralizing antibody (NAb) response to SARS-CoV-2 virus

    Time: 28 days following each vaccination (Days 29 and 57)

    Secondary Outcomes

    Description: GMT of the serum antibody response compared to placebo

    Measure: Total serum antibody immune responses

    Time: through study completion (394 days)

    Description: proportion of participants with greater than or equal to 4 fold increase in titre above baseline compared to placebo.

    Measure: proportion of participants with ≥ 4 fold increase in titer above baseline

    Time: through study completion (394 days)

    Description: GMT of the serum neutralizing antibody (NAb) immune responses compared to placebo

    Measure: GMT of the serum neutralizing antibody (NAb) titres

    Time: through study completion (394 days)
    369 A Prospective, Double-Blind, Placebo-controlled Study of Suramin in Subjects With Furosemide-Resistant Acute Kidney Injury (AKI): Efficacy in Preventing Dialysis Dependent AKI

    This is a prospective, double-blind, randomized, placebo-controlled study to assess the effects of suramin as a potential treatment option to prevent subjects with AKI from progressing to Kidney Disease Improving Global Outcomes (KDIGO) Stage III or dialysis dependent AKI.

    NCT04496596
    Conditions
    1. Acute Kidney Injury
    Interventions
    1. Drug: Suramin
    2. Drug: Placebo
    MeSH:Acute Kidney Injury
    HPO:Acute kidney injury

    Primary Outcomes

    Description: The difference between the effect of a 3.0 mg/kg infusion of suramin versus placebo will be based on meeting 2 or more of the composite event endpoints of: peak serum creatinine (Cr) of 6 mg/dL or above from investigational product (IP) infusion through Day or progression to KDIGO Stage III within 72 hours (hr) from IP infusion or death or dialysis from IP infusion through Day 7.

    Measure: To evaluate and compare the efficacy of a single 3.0 mg/kg infusion of suramin versus placebo in subjects with diuretic unresponsive AKI

    Time: 7 days
    370 A Randomized, Placebo-controlled Trial, to Evaluate the Safety and Immunogenicity of the COVID-19 Vaccine, a Measles Vector-based Vaccine Candidate Against COVID-19 in Healthy Volunteers Consisting of an Unblinded Dose Escalation and a Blinded Treatment Phase

    This is a randomized, placebo-controlled, two center, Phase I trial in healthy adult volunteer participants consisting of two phases, an unblinded dose escalation and a double blind treatment phase to investigate the safety, tolerability and immunogenicity of a novel measles-vector based vaccine candidate against SARS-CoV-2 infection (TMV-083).

    NCT04497298
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Two COVID-19 vaccine candidate (TMV-083) administrations - Low dose
    2. Biological: Two COVID-19 vaccine candidate (TMV-083) administrations - High dose
    3. Biological: One COVID-19 vaccine candidate (TMV-083) administration - High dose
    4. Other: Placebo

    Primary Outcomes

    Description: Rate of solicited Adverse Event up to 14 days after each injection. Rate of unsolicited AE up to 28 days after the last injection. Rate of serious adverse events (SAEs), serious adverse reactions (SARs), suspected unexpected serious adverse reactions (SUSARs) and adverse events of special interest (AESI) all along the study period.

    Measure: To assess the safety and tolerability of the COVID-19 vaccine following one or two consecutive intramuscular injections in healthy volunteers

    Time: Day 390

    Secondary Outcomes

    Description: SARS-CoV-2 specific antibodies up to study day 390 as measured by spike protein-specific ELISA

    Measure: To assess induction of SARS-CoV-2 spike protein-binding antibodies upon one or two administrations of the COVID-19 vaccine by means of ELISA up to study day 390

    Time: Day 390

    Description: SARS-CoV-2 specific antibodies up to study day 390 for each cohort as measured by serum neutralization assay

    Measure: To assess induction of SARS-CoV-2 neutralizing antibodies upon one or two administrations of the COVID-19 vaccine by means of serum neutralization assay up to study day 390

    Time: Day 390

    Description: SARS-CoV-2 spike protein-specific cell-mediated immune response up to study day 390 induced by one or two doses as measured by intracellular staining and flow cytometry

    Measure: To assess SARS-CoV-2 spike protein-specific, cell-mediated immune responses up to study day 390, induced by one or two doses of vaccine, by means of intracellular staining and flow cytometry.

    Time: up to Day 390

    Description: Occurrence of measles virus shedding as evidenced by a positive RT-PCR for saliva, nasal swab, urine, or blood sample in sentinel groups.

    Measure: To assess potential measles virus shedding by means of RT-qPCR of saliva, nasal swab, urine, or blood samples in sentinel groups on day 0 and up to day 42

    Time: up to Day 42

    Other Outcomes

    Description: Measles virus antibody levels as assessed by standard ELISA assays on day 0 and day 28.

    Measure: To assess the anti-measles antibody levels at baseline and on day 28 by ELISA

    Time: up to Day 28

    Description: SARS-CoV-2 N protein specific antibody up to study day 390 as measured by ELISA to differentiate the response to the COVID-19 vaccine from infection

    Measure: To assess the natural exposure of the subjects to SARS-CoV-2 during the duration of the trial by means of N protein-specific ELISA

    Time: Day 390

    Description: Occurrence of confirmed COVID-19 (i.e. asymptomatic, paucisymptomatic or symptomatic) cases in the study participant all along the study period

    Measure: To assess the occurrence of COVID-19 cases in study participants all along the duration of the study

    Time: Day 390
    371 A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of LY3819253 in Preventing SARS-CoV-2 Infection and COVID-19 in Skilled Nursing and Assisted Living Facility Residents and Staff; a NIAID and Lilly Collaborative Study

    The purpose of this study is to evaluate whether LY3819253 prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease - 2019 (COVID-19) in facility staff and residents in contracted skilled nursing and assisted living facility networks with a high risk of SARS-CoV-2 exposure. Participants with a high risk of SARS-CoV-2 exposure will receive LY3819253 or placebo via an injection into a vein. Samples will be taken from the nose. Blood samples will be drawn. Participation could last up to 25 weeks and may include up to 19 visits.

    NCT04497987
    Conditions
    1. COVID-19
    2. SARS-CoV2
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Percentage of Participants with SARS-CoV-2 Infection

    Measure: Percentage of Participants with SARS-CoV-2 Infection

    Time: Week 4

    Secondary Outcomes

    Description: Percentage of Participants with Moderate or Worse Severity COVID-19

    Measure: Percentage of Participants with Moderate or Worse Severity COVID-19

    Time: Week 8

    Description: Percentage of Participants with Mild or Worse Severity COVID-19

    Measure: Percentage of Participants with Mild or Worse Severity COVID-19

    Time: Week 8

    Description: Percentage of Participants Who are Hospitalized due to COVID-19

    Measure: Percentage of Participants Who are Hospitalized due to COVID-19

    Time: Week 8

    Description: Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death

    Measure: Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death

    Time: Week 8

    Description: Percentage of Participants Who Die Due to COVID-19

    Measure: Percentage of Participants Who Die Due to COVID-19

    Time: Week 8
    372 A Phase 1/Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Safety, Tolerability and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Younger and Older Participants

    The primary objective of this early Phase 1 study is to identify the V591 dose that achieves the target immune response in humans based on preclinical or early clinical data.

    NCT04498247
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Biological: V591
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants with at Least 1 Solicited Injection Site Adverse Event

    Time: Up to ~5 days after vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants with at Least 1 Solicited Systemic Adverse Event

    Time: Up to ~14 days after vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants with at Least 1 Unsolicited Adverse Event

    Time: Up to ~28 days after vaccination

    Description: A serious adverse event is "life threatening," requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect.

    Measure: Percentage of Participants with at Least 1 Serious Adverse Event

    Time: Up to ~365 days (±14 days) after vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants who Discontinued Study Treatment due to an Adverse Event

    Time: Up to ~365 days (±7 days) after vaccination

    Description: A medically attended adverse event (MAAE) is an AE in which medical attention is received during an unscheduled, non-routine outpatient visit, such as an emergency room visit, office visit, or an urgent care visit with any medical personnel for any reason.

    Measure: Percentage of Participants with at Least 1 Medically Attended Adverse Event

    Time: Up to ~365 days (±14 days) after vaccination

    Secondary Outcomes

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies (nAb) as Measured by Plaque Reduction Neutralization Test (PRNT): All Panels

    Time: Day 29

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA): All Panels

    Time: Day 29

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by PRNT: Panels A,B, I and J

    Time: Day 85

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike IgG Antibodies as Measured by ELISA: Panels A,B, I and J

    Time: Day 85

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by PRNT: Panels K and L

    Time: Day 197

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike IgG Antibodies as Measured by ELISA: Panels K and L

    Time: Day 197

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum nAb as Measured by PRNT

    Time: Panels C-E and G-H: Days 1, 15, 29, 57, 85, 115, 211, and 365; Panels A,B, I and J: Days 1, 15, 29, 57, 71, 85, 115, 211, and 422; Panels F, K and L: Days 1, 15, 29, 85, 169, 197, 365 and 534

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike IgG Antibodies as Measured by ELISA

    Time: Panels C-E and G-H: Days 1, 15, 29, 57, 85, 115, 211, and 365; Panels A,B, I and J: Days 1, 15, 29, 57, 71, 85, 115, 211, and 422; Panels F, K and L: Days 1, 15, 29, 85, 169, 197, 365 and 534
    373 COVID-19 Outpatient Thrombosis Prevention Trial: A Multi-center Adaptive Randomized Placebo-controlled Platform Trial Evaluating the Efficacy and Safety of Anti-thrombotic Strategies in COVID-19 Adults Not Requiring Hospitalization at Time of Diagnosis

    A multi-center adaptive randomized placebo-controlled platform trial evaluating the efficacy and safety of anti-thrombotic strategies in COVID-19 adults not requiring hospitalization at time of diagnosis

    NCT04498273
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Apixaban 2.5 MG
    2. Drug: Apixaban 5MG
    3. Drug: Aspirin
    4. Drug: Placebo
    MeSH:Thrombosis

    Primary Outcomes

    Description: The primary outcome will be a composite endpoint of need for hospitalization for cardiovascular/pulmonary events, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality for up to 45 days after initiation of assigned treatment.

    Measure: Hospitalization for cardiovascular/pulmonary events

    Time: 45 days
    374 A Phase I and Pilot Study Evaluating the Effect of NT-I7, a Long Acting Interleukin-7, to Increase Lymphocyte Counts and Enhance Immune Clearance of SARS-CoV-2

    Lymphopenia is common in patients with COVID-19 and is associated with worse clinical outcomes. NT-I7 is a long-acting human interleukin-7 (IL-7) that has been shown to increase absolute lymphocyte count (ALC) and CD4+ and CD8+ T cell counts with a well-tolerated safety profile in humans. In this study, patients who have tested positive for SARS-CoV-2 by PCR testing without severe disease and with ALC <1500 cells/mm3 will be enrolled.

    NCT04498325
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Drug: NT-I7
    2. Drug: Placebo
    3. Procedure: Blood for research purposes
    4. Procedure: Blood for pharmacokinetic samples
    5. Procedure: Nasopharyngeal, oropharyngeal, or saliva swab
    6. Procedure: Blood for anti-drug antibody (ADA)

    Primary Outcomes

    Description: The safe tolerated dose is defined as the dose level immediately below the dose level at which 1 patient of a cohort of 3 patients experiences dose-limiting toxicity within 14 days after administration of NT-I7 Dose limiting toxicities (DLT) are defined as: A serious adverse event that is at least possibly related to NT-I7 A grade 3 or higher adverse event that is at least possibly related to NT-I7 (excluding injection site swelling, irritation or discomfort) A clinically significant lab abnormality that is at least possibly related to NT-I7

    Measure: Safe and tolerable dose of NT-I7 (Phase I only)

    Time: Completion of DLT assessment window of Phase I portion of study (estimated to be 8 months)

    Measure: Percent change in absolute lymphocyte count (ALC)

    Time: From baseline to Day 14

    Secondary Outcomes

    Measure: Percent change in absolute lymphocyte count (ALC)

    Time: From baseline through Day 21

    Description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva

    Measure: Change in SARS-CoV-2 viral load

    Time: From baseline to Day 7

    Description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva

    Measure: Change in SARS-CoV-2 viral load

    Time: From baseline to Day 14

    Measure: COVID-19 Symptom severity as measured by WHO Ordinal Scale for clinical improvement

    Time: From baseline, day 7, day 14, and day 21

    Measure: Time to resolution of COVID-19 symptoms

    Time: From baseline through Day 21

    Description: -A treatment emergent adverse event (TEAE) is defined as any event that begins or worsens on or after date of first dose of study treatment.

    Measure: Incidence of treatment-emergent adverse events

    Time: From baseline through Day 21

    Description: -If quantitative PCR is not available

    Measure: Number of participants by PCR result status (positive or negative)

    Time: -From baseline to Day 7

    Description: -If quantitative PCR is not available

    Measure: Number of participants by PCR result status (positive or negative)

    Time: From baseline to Day 14
    375 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Multicenter Study to Evaluate the Efficacy and Safety of F-652 (IL-22:IgG2 Fusion Protein) in Patients With Moderate to Severe COVID-19

    This is an interventional, multicenter, 2-arm, parallel-group, randomized, double-blind, placebo controlled, dose-escalation, safety and efficacy study of F-652 treatment versus placebo in patients aged 18 years or older with a COVID-19 diagnosis confirmed by PCR. Eligible patients will have moderate to severe COVID-19 symptoms within 5 days post hospitalization and a positive COVID-19 testing.

    NCT04498377
    Conditions
    1. Covid19
    Interventions
    1. Biological: F-652
    2. Biological: Placebo

    Primary Outcomes

    Description: The proportion of patients with a greater or equal 2-point change in the NIAID 8-point ordinal scale from baseline to Day 29

    Measure: NIAID 8-point ordinal scale

    Time: Study day 1 before dose to day 29
    376 Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients

    The aim of this study is to test Cenicriviroc (CVC) as a means to reduce the severity of the lung disease COVID-19 caused by an infection with SARS-CoV-2. The safety of CVC, when administered to COVID-19 patients, will also be assessed. Furthermore, the clinical trial aims to answer the question of whether patients with pre-existing conditions, who have an increased risk of severe COVID-19 progression, benefit more and particularly from CVC. CVC is an orally available dual inhibitor of the chemokine receptors CCR2 and CCR5, which is expected to reduce (hyper-) inflammation in COVID-19. The main goal of the study is to determine whether CVC helps increase the number of patients who are symptom-free and not hospitalized after 14 days compared to a placebo. Approximately 66.7% of the patients enrolled in the study will receive CVC and 33.3% will get an optically identical pill (placebo). Subjects will be assessed daily while hospitalized. Discharged patients will be asked to attend study visits at Days 8, 15, 22, and 29 and 85. All subjects will undergo a series of clinical, safety, and laboratory assessments. Blood samples and oropharyngeal (OP) swabs will be obtained on Day 1; 3, 5 (while hospitalized); and Day 8, 15 and 29 (if able to return to clinic or still hospitalized). The presence of anti-SARS-CoV-2 antibodies will be determined on Days 29 and 85.

    NCT04500418
    Conditions
    1. Covid19
    Interventions
    1. Drug: Cenicriviroc (CVC)
    2. Drug: Placebo

    Primary Outcomes

    Description: The Primary Endpoint will be the subject's responder status defined by achieving a score of "1" or "2" (discharged from hospital e.g.) on Day 15 on the following 7-point scale: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high-flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO (Extracorporeal membrane oxygenation); Death.

    Measure: Subject´s Responder status (score on the 7-point ordinal scale on Day 15)

    Time: 14 days after enrollment (Day 15)

    Secondary Outcomes

    Description: 7-point ordinal scale to be assessed on Day 15 (and Day 1 for baseline comparison), analyses of ordinal change of 2 or more, compared with baseline ordinal change of 1 or more, compared with baseline

    Measure: Evaluation of change in clinical condition based on the 7-point ordinal scale

    Time: day of enrollment and 15 days after enrollment

    Description: 7-point ordinal scale assessed on: Days 8, 22, 29 (and Day 1 for baseline comparison), analyses of: Responder status (achieving a score of a "1" or a "2") ordinal change of 2 or more, compared with baseline ordinal change of 1 or more, compared with baseline

    Measure: Evaluation of change in clinical condition based on the 7-point ordinal scale and Responder Status

    Time: day of enrollment, 8 days, 22 days and 29 days after enrollment

    Description: Analysis of: Length of time spent in the ICU (days) Length of time spent in the hospital (days) Days alive and out of hospital through Day 29 Days free of endotracheal tube-based ventilation through Day 29

    Measure: Hospital resource utilization comparison

    Time: 29 days after enrollment, 85 days after enrollment
    377 A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19

    This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.

    NCT04501978
    Conditions
    1. Covid19
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo
    3. Drug: Remdesivir

    Primary Outcomes

    Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary ordinal outcome (Stage 1)

    Time: Day 5

    Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary+ ordinal outcome (Stage 1)

    Time: Day 5

    Description: Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.

    Measure: Time from randomization to sustained recovery (Stage 2)

    Time: Up to Day 90

    Secondary Outcomes

    Measure: All-cause mortality

    Time: Thru Day 90

    Measure: Composite of time to sustained recovery and mortality

    Time: Thru Day 90

    Measure: Days alive outside short-term acute care hospital

    Time: Up to Day 90

    Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary ordinal outcome

    Time: Days 1-7, 14 and 28

    Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary+ ordinal outcome

    Time: Days 1-7

    Description: Total of: Respiratory rate (breaths per minute) scored from 0 to +3; Oxygen saturation (%) scored from 0 to +3; Any supplemental oxygen scored from 0 to +2; Temperature scored from 0 to +3; Systolic BP scored from 0 to +3; Heart rate (beats per minute) scored from 0 to +3.; and AVPU (alert, voice, pain, unresponsive) scored from 0 to +3. A higher score denotes a worse outcome.

    Measure: Change in New Early Warning (NEW) Score

    Time: Baseline to Day 5

    Measure: Incidence of clinical organ failure

    Time: Thru Day 28

    Measure: Composite of death or serious clinical COVID-19 related events

    Time: Thru Day 90

    Measure: Composite of cardiovascular events and thromboembolic events

    Time: Thru Day 90

    Measure: Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death

    Time: Thru Days 5 and 28

    Measure: Incidence of infusion reactions

    Time: Thru Day 0

    Measure: Composite of SAEs or death

    Time: Thru Day 90

    Measure: Change in SARS-CoV-2 neutralizing antibody levels

    Time: Baseline to Days 1, 3, 5, 28 and 90

    Measure: Change in overall titers of antibodies

    Time: Baseline to Days 1, 3, 5, 28 and 90

    Measure: Change in neutralizing antibody levels

    Time: Baseline to Days 1, 3, 5, 28 and 90
    378 A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19

    The purpose of this study is to assess safety and clinical efficacy of rivaroxaban in people with mild Coronavirus Disease 2019 who are at increased risk of disease progression.

    NCT04504032
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Rivaroxaban
    2. Drug: Placebo

    Primary Outcomes

    Measure: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs)

    Time: Up to approximately 35 days

    Measure: Number of Participants With AEs Leading to Study Discontinuation

    Time: Up to approximately 35 days

    Measure: Number of Participants With Serious Adverse Events (SAEs)

    Time: Up to approximately 35 days

    Description: Disease progression is defined as the proportion of participants who progress to moderate or severe disease category or higher (Gates Medical Research Institute ordinal scale ≥3). The assessments will be performed using Gates Medical Research Institute ordinal scale.

    Measure: Proportion of Participants With Disease Progression

    Time: Up to Day 28

    Secondary Outcomes

    Description: Time to disease resolution is defined as symptoms resolution (new onset Coronavirus Disease 2019 [COVID-19] symptoms resolved, and pre-existing symptoms returned to baseline) with viral clearance (two consecutive negative diagnostic tests) through Day 28. Baseline refers to health status prior to contracting new onset COVID-19 symptoms.

    Measure: Median Time to Disease Resolution

    Time: Up to Day 28

    Description: Time to disease resolution is defined as symptoms resolution only (new onset COVID-19 symptoms resolved, and preexisting symptoms returned to baseline) through Day 28. Baseline refers to health status prior to contracting new onset COVID-19 symptoms.

    Measure: Median Time to Disease Resolution

    Time: Up to Day 28

    Measure: Proportion of Participants With Disease Progression

    Time: Days 8, 14, and 21

    Measure: Proportion of Participants Who Achieve Disease Resolution

    Time: Days 8, 14, 21, and 28

    Measure: Mean Gates Medical Research Institute Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Change From Baseline in Gates Medical Research Institute Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Mean World Health Organization Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Change From Baseline in World Health Organization Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Incidence of Hospitalization

    Time: Days 8, 14, 21, and 28

    Measure: Number of Days of Hospitalization

    Time: Days 8, 14, 21, and 28
    379 A Randomized, Double-blind, Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) Doses of GSK3494245 in Healthy Participants

    This is a Phase 1, double-blind, randomized, placebo-controlled, first time in human (FTIH) study to assess the safety, tolerability and PK of a single dose of GSK3494245. The study will consist of 3 cohorts, conducted in a sequential manner. Cohorts 1 and 2 will consist of a single ascending dose (SAD), crossover design where each participant will receive a maximum of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. At each dose level, GSK3494245 and placebo will be administered in a 3:1 ratio, within each period, according to the randomization schedule in a blinded manner. Cohort 3 will comprise of a 2-way crossover which includes 1 dosing regimen under fasted then fed conditions and 1 regimen under fed then fasted conditions in a 1:1 ratio. The fed conditions will investigate the effect of safety, tolerability and PK of a single dose of GSK3494245 following food administration.

    NCT04504435
    Conditions
    1. Leishmaniasis
    Interventions
    1. Drug: GSK3494245
    2. Drug: Placebo
    MeSH:Leishmaniasis

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

    Measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

    Time: Up to 14 days post last dose in each treatment period

    Description: Treatment emergent AE and SAE are any untoward medical occurrences in a clinical study participant, having causal relation with the use of a study intervention.

    Measure: Number of participants with treatment emergent AEs and SAEs

    Time: Up to 14 days post last dose in each treatment period

    Description: Blood samples will be collected for the assessment of hematology parameters.

    Measure: Number of participants with clinically significant abnormal findings in hematology parameters

    Time: Up to 14 days post last dose in each treatment period

    Description: Blood samples will be collected for the assessment of chemistry parameters

    Measure: Number of participants with clinically significant abnormal findings in clinical chemistry parameters

    Time: Up to 14 days post last dose in each treatment period

    Description: Urine samples will be collected for the assessment of urinalysis parameters.

    Measure: Number of participants with urinalysis findings

    Time: Up to 14 days post last dose in each treatment period

    Description: Number of participants with abnormal vital signs will be assessed.

    Measure: Number of participants with clinically significant abnormal findings in vital signs

    Time: Up to 14 days post last dose in each treatment period

    Description: Triplicate 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS interval, QT interval, Corrected QT (QTc) interval.

    Measure: Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters

    Time: Up to 14 days post last dose in each treatment period

    Description: Telemetry is the continuous monitoring of a participants heart rate and rhythm from a remote location. Continuous cardiac telemetry will start in a supine position after at least 5 minutes rest.

    Measure: Number of participants with abnormal cardiac telemetry findings

    Time: Up to 24 hours post dose on Day 1

    Secondary Outcomes

    Description: Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fasting condition.

    Measure: Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration under fasting condition

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 minutes [min], 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fed condition.

    Measure: AUC (0-t) of GSK3494245 following single dose administration under fed condition

    Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate AUC (0-inf) of GSK3494245 under fasting condition.

    Measure: AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245 under fed condition.

    Measure: AUC (0-inf) of GSK3494245 following single dose administration under fed condition

    Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fasting condition.

    Measure: Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting condition

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fed condition.

    Measure: Cmax of GSK3494245 following single dose administration under fed condition

    Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fasting condition.

    Measure: Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting condition

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fed condition.

    Measure: Tmax of GSK3494245 following single dose administration under fed condition

    Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.

    Measure: Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting condition

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.

    Measure: t1/2 of GSK3494245 following single dose administration under fed condition

    Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Urine samples will be collected at the indicated time points to evaluate Ae0-24h of GSK3494245.

    Measure: Amount of GSK3494245 excreted in urine over 24 hours (Ae0-24h) following single dose administration

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Urine samples will be collected at the indicated time points to evaluate fe% of GSK3494245

    Measure: Fraction of dose excreted in urine over 24 hours (fe%) of GSK3494245 following single dose administration

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Urine samples will be collected at the indicated time points to evaluate CLr of GSK3494245.

    Measure: Renal Clearance (CLr) of GSK3494245 following single dose administration

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245.

    Measure: Dose-proportionality assessment using AUC(0-inf) following single dose of GSK3494245

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)

    Description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245.

    Measure: Dose-proportionality assessment using Cmax following single dose of GSK3494245

    Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
    380 Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients With Mild-Moderate COVID-19

    This is a Phase 3, multi-center, randomized, double blind, placebo controlled, clinical study of bucillamine (2 dosage levels) in patients with mild-moderate COVID-19. Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine 200 mg TID or placebo TID for up to 14 days. After the first interim analysis when a single dose is selected, patients will then be randomized 2:1 to the selected bucillamine dose or placebo The study will be overseen by an independent Data and Safety Monitoring Board (DSMB). Up to 10 centers in the United States will conduct this study. Up to 1000 patients will be enrolled in this study. Patients will participate in the study approximately 45 days.

    NCT04504734
    Conditions
    1. Covid19
    Interventions
    1. Drug: Bucillamine
    2. Drug: Placebo
    3. Drug: Bucillamine

    Primary Outcomes

    Description: Proportion of patients meeting a composite endpoint of hospitalization or death

    Measure: Efficacy: Frequency of hospitalization or death

    Time: From time of first dose through Day 28 following randomization

    Secondary Outcomes

    Description: Number of adverse events

    Measure: Safety: Changes in adverse events from baseline to end of study

    Time: From time of first dose through Day 28 following randomization
    381 Tenecteplase With Concomitant Anticoagulation for Severe Acute Respiratory Failure in Patients With COVID-19

    This is a placebo-controlled, double blind, randomized, Phase II dose escalation study intended to evaluate the potential safety and efficacy of tenecteplase for the treatment of COVID-19 associated respiratory failure. The hypothesis is that administration of the drug, in conjunction with heparin anticoagulation, will improve patients' clinical outcomes.

    NCT04505592
    Conditions
    1. COVID-19
    2. Respiratory Failure
    3. ARDS
    Interventions
    1. Drug: Tenecteplase
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days

    Measure: Number of participants free of respiratory failure

    Time: 28 Days

    Description: Safety as assessed by number of occurrences of intracranial bleeding or major bleeding

    Measure: Number of occurrences of bleeding

    Time: 28 days

    Secondary Outcomes

    Measure: Number of participants with in-hospital deaths at 14 days

    Time: 14 days

    Measure: Number of participants with death at 28 days

    Time: 28 days

    Measure: Number of ventilator-free days

    Time: 28 days

    Description: Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation

    Measure: Number of respiratory failure-free days

    Time: 28 days

    Measure: Number of vasopressor-free days

    Time: 28 days

    Measure: Vasopressor doses at 24 hours

    Time: 24 hours

    Measure: Vasopressor doses at 72 hours

    Time: 72 hours

    Description: The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).

    Measure: P/F ratio at 24 hours

    Time: 24 hours

    Description: The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).

    Measure: P/F ratio at 72 hours

    Time: 72 hours

    Measure: Number of ICU-free days

    Time: 28 days

    Measure: Hospital length of stay

    Time: 28 days

    Measure: Number of participants with new-onset renal failure

    Time: 28 days

    Measure: Number of participants with need for renal replacement therapy

    Time: 28 days
    382 A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older

    The study will enroll up to 60,000 participants in order to evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical COVID-19, as compared to placebo, in adult participants.

    NCT04505722
    Conditions
    1. Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 at Different Stages of the Protocol
    Interventions
    1. Biological: Ad26.COV2.S
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Secondary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus

    Time: 1 Day post-vaccination (Day 2) to end of study (2.1 Years)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease COVID-19 Regardless of Their Serostatus

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19)

    Time: 1 Day post-vaccination (Day 2) to end of study (2.1 Years)

    Description: Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), linked to objective measures such as decreased oxygenation, X-ray or CT findings) or linked to any molecularly confirmed, COVID-19 at least 14 days post vaccination will be reported.

    Measure: Number of Participants with First Occurrence of COVID-19 Requiring Medical Intervention

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: The viral load of SARS-CoV-2 will be assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs will be used to detect and/or quantify SARS-CoV-2.

    Measure: SARS-CoV-2 Viral Load as Assessed by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) in Participants with Molecularly Confirmed, Moderate to Severe/Critical COVID-19

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Molecularly confirmed mild COVID-19 is defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Mild COVID-19 includes: Fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, or chills, without shortness of breath or dyspnea.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Mild COVID-19

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Molecularly confirmed moderate and severe/critical COVID-19 defined as a positive SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case Definition at the time of finalization of this protocol: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed COVID-19 Defined by the US Food and Drug Administration (FDA) Harmonized case Definition

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.

    Measure: Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Serologic conversion between baseline and (Day 1; pre-vaccination), Day 71, 6 Months, 1 year post-vaccination using an ELISA and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein will be reported.

    Measure: Serologic Conversion Between Baseline and (Day 1; Pre-vaccination), Day 71, 6 Months and 1- Year Post-vaccination using an Enzyme-linked Immunosorbent Assay (ELISA)

    Time: Between baseline (Day 1; pre-vaccination) and Day 71, 6 Months, 1-Year post-vaccination (up to 52 Weeks)

    Description: Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 14 days after vaccination (Day 15) to end of Study (2.1 Years) will be reported.

    Measure: Number of Participants with First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed)

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

    Measure: Number of Participants with Serious Adverse Events (SAEs)

    Time: Up to 104 Weeks

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.

    Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs)

    Time: Up to 6 Months

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs.

    Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs) Leading to Study Discontinuation

    Time: Up to 104 Weeks

    Description: Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post-vaccination (day of vaccination and the subsequent 7 days).

    Measure: Number of Participants with Solicited Local Adverse Events (AEs) During 7 Days Following Vaccination

    Time: Up to Day 8 (7 Days after first vaccination on Day 1)

    Description: Participants will be instructed on how to record daily temperature using a thermometer provided for home use. Participants should record the temperature in the e-Diary in the evening of the day of vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement is made on any given day, the highest temperature of that day will be recorded in the e-Diary. Fever is defined as endogenous elevation of body temperature >= 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily basis for 7 days post-vaccination (day of vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.

    Measure: Number of Participants with Solicited Systemic AEs During 7 Days Following Vaccination

    Time: Up to Day 8 (7 Days after first vaccination on Day 1)

    Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Number of Participants with Unsolicited Local Adverse Events (AEs) During 28 Days Post-vaccination

    Time: Up to Day 29 (28 Days after first vaccination on Day 1)

    Description: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported

    Measure: SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA)

    Time: Up to 104 Weeks

    Description: SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.

    Measure: SARS-CoV-2 Binding Antibodies Assessed by ELISA

    Time: Up to 104 Weeks
    383 A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD7442 in Healthy Adults

    In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs). The study is intended to enable future studies of AZD7442's efficacy in preventing and treating COVID-19.

    NCT04507256
    Conditions
    1. COVID-19
    Interventions
    1. Combination Product: AZD7442
    2. Other: Placebo

    Primary Outcomes

    Description: Safety and tolerability will be evaluated in terms of number of participants with AEs/SAEs, abnormal values of vital signs, safety laboratory parameters, 12 lead safety electrocardiogram, injection site reactions, and physical examination.

    Measure: Number of participants with adverse events (AEs) and serious AEs

    Time: From Day 1 to up to last follow-up day (Day 361)

    Secondary Outcomes

    Description: Cmax will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Observed maximum concentration (Cmax) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: Tmax will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Time to reach maximum concentration (Tmax) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: t½λz will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Terminal elimination half life, estimated as (ln2)/λz (t½λz) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: AUClast will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Area under the concentration curve from time zero to the time of last quantifiable concentration (AUClast) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: AUCinf will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Area under the concentration time curve from time zero extrapolated to infinity (AUCinf) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: Vss will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Volume of distribution at steady state (Vss) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: Vz will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Volume of distribution at terminal phase (Vz) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: CL will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Systemic clearance (CL) (IV infusion)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: Cmax will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Cmax (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: Tmax will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Tmax (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: t½λz will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: t½λz (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: AUClast will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: AUClast (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: AUCinf will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: AUCinf (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: CL/F will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Extravascular systemic clearance (CL/F) (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: F will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Bioavailability (F) (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: Vz/F will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Extravascular terminal-phase volume of distribution (Vz/F) (IM injection)

    Time: From Day 1 to up to last follow-up day (Day 361)

    Description: The incidence of ADAs to AZD7442 in serum will be summarised by number and percentage of participants who are ADA positive. The ADA titer will be listed by participant at different time points.

    Measure: Number and percentage of participants who are ADA positive

    Time: From Day 1 to up to last follow-up day (Day 361)
    384 A Multicenter, Randomized, Placebo-Controlled, Pragmatic Phase 3 Study Investigating the Efficacy and Safety of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19 Infection

    The purpose of this study is to evaluate whether rivaroxaban reduces the risk of a composite endpoint of major venous and arterial thrombotic events, all-cause hospitalization, and all-cause mortality compared with placebo in outpatients with acute, symptomatic Coronavirus Disease 2019 (COVID-19) Infection.

    NCT04508023
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Drug: Rivaroxaban
    2. Other: Placebo
    3. Other: Standard of Care (SOC)
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Time to first occurrence of a composite endpoint of symptomatic venous thromboembolism (VTE), myocardial infarction (MI), ischemic stroke, acute limb ischemia, noncentral nervous system (non-CNS) systemic embolization, all-cause hospitalization, and all-cause mortality will be assessed.

    Measure: Time to First Occurrence of a Composite Endpoint of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, All-cause Hospitalization and All-cause Mortality

    Time: Up to Day 35

    Secondary Outcomes

    Description: Time to first occurrence of a composite endpoint of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-CNS systemic embolization, and all-cause mortality will be assessed.

    Measure: Time to First Occurrence of a Composite Endpoint of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, and All-cause Mortality

    Time: Up to Day 35

    Description: Time to first occurrence of all-cause hospitalization will be assessed.

    Measure: Time to First Occurrence of All-cause Hospitalization

    Time: Up to Day 35

    Description: Time to first occurrence of symptomatic VTE which includes DVT or pulmonary embolism (PE) will be assessed.

    Measure: Time to First Occurrence of Symptomatic VTE

    Time: Up to Day 35

    Description: Time to first occurrence of an ER visit will be assessed.

    Measure: Time to First Occurrence of an Emergency Room (ER) Visit

    Time: Up to Day 35

    Description: Time to first occurrence of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-CNS systemic embolization, and all-cause hospitalization will be assessed.

    Measure: Time to First Occurrence of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, and All-cause Hospitalization

    Time: Up to Day 35

    Description: Percentage of participants who are hospitalized or dead from any cause at Day 35 will be assessed.

    Measure: Percentage of Participants who are Hospitalized or Dead From Any Cause

    Time: Day 35

    Description: Time to all-cause mortality up to Day 35 will be assessed.

    Measure: Time to All-cause Mortality up to Day 35

    Time: Up to Day 35

    Description: Time to first occurrence of ISTH critical site and fatal bleeding will be assessed.

    Measure: Time to First Occurrence of International Society on Thrombosis and Hemostasis (ISTH) Critical Site and Fatal Bleeding

    Time: Up to 37 Days (last dose on Day 35 plus 2 Days)

    Description: Time to first occurrence of ISTH major bleeding will be assessed. Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome.

    Measure: Time to First Occurrence of ISTH Major Bleeding Events

    Time: Up to 37 Days (last dose on Day 35 plus 2 Days)

    Description: Time to first occurrence of clinically relevant non-major bleeding will be assessed. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, or unscheduled contact with a physician, or temporary cessation of study treatment, or discomfort such as pain, or impairment of activities of daily life.

    Measure: Time to First Occurrence of Clinically Relevant Non-major Bleeding

    Time: Up to 37 Days (last dose on Day 35 plus 2 Days)
    385 A Phase III, Observer-blind, Randomized, Placebo-controlled Study of the Efficacy, Safety and Immunogenicity of SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 Years in Indonesia

    This phase III trial aims to assess the efficacy, safety and immunogenicity of SARS-CoV-2 Vaccine (inactivated) and lot-to-lot consistency evaluation

    NCT04508075
    Conditions
    1. SARS-CoV2 Infection
    Interventions
    1. Biological: SARS-CoV-2 vaccine (inactivated)
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Percentage of laboratory-confirmed COVID-19 cases

    Measure: Incidence of laboratory-confirmed COVID-19 after the second dose

    Time: 14 days to 6 months after the second dose

    Secondary Outcomes

    Description: Percentage of suspected COVID-19 cases

    Measure: Incidence of suspected COVID-19 cases

    Time: within 14 days to 6 months after the second dose.

    Description: Percentage of laboratory-confirmed cases (severe, critical, death)

    Measure: Incidence of laboratory-confirmed cases (severe, critical and death)

    Time: within 14 days to 6 months after the second dose

    Description: Percentage of subjects with four-fold increasing anti-S antibody IgG titer (ELISA) compare to baseline and between batches

    Measure: Seroconversion rate anti-S antibody IgG titer (ELISA)

    Time: 14 days after two doses of vaccination

    Description: Percentage of subjects with four-fold increasing anti-S antibody IgG titer (ELISA) compare to baseline and between batches

    Measure: Seroconversion rate anti-S antibody IgG titer (ELISA)

    Time: 6 months after two doses of vaccination

    Description: Percentage of subjects with four-fold increasing serum neutralizing antibody compared to baseline and between batches

    Measure: Seropositive rate of neutralizing antibodies

    Time: 14 days after two doses of vaccination

    Description: Percentage of subjects with four-fold increasing serum neutralizing antibody compared to baseline and between batches

    Measure: Seropositive rate of neutralizing antibodies

    Time: 6 months after two doses of vaccination

    Other Outcomes

    Description: Number of Local reactions and systemic events

    Measure: Local reaction and systemic events

    Time: 30 minutes to 14 days after each vaccination

    Description: Number of Local reactions and systemic events

    Measure: Local reaction and systemic events occurring after the last vaccination

    Time: 14 days to 28 days following last vaccination

    Description: Number of any SAE occur

    Measure: Serious adverse events during study

    Time: 6 months after the last dose
    386 A Randomized, Double-blind, Placebo-controlled Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.COV2.S in Adults

    The purpose of this study is to assess the safety and reactogenicity of Ad26.COV2.S administered intramuscularly (IM) at 2-dose levels, as 2-dose schedule in healthy participants aged greater than or equal to 20 to less than or equal to 55 years and greater than or equal to 65 years in good health with or without stable underlying conditions.

    NCT04509947
    Conditions
    1. Healthy
    Interventions
    1. Biological: Ad26.COV2.S
    2. Biological: Placebo

    Primary Outcomes

    Description: Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically questioned and which are noted by participants in their diary for 7 days post first vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling and induration at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Number of Participants with Solicited Local Adverse Events (AEs) for 7 days after First Vaccination

    Time: Day 8 (7 days after first vaccination on Day 1)

    Description: Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically questioned and which are noted by participants in their diary for 7 days post second vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling and induration at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Number of Participants with Solicited Local AEs for 7 days after Second Vaccination

    Time: Day 64 (7 days after second vaccination on Day 57)

    Description: Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia.

    Measure: Number of Participants with Solicited Systemic AEs for 7 days after First Vaccination

    Time: Day 8 (7 days after first vaccination on Day 1)

    Description: Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia.

    Measure: Number of Participants with Solicited Systemic AEs for 7 days after Second Vaccination

    Time: Day 64 (7 days after second vaccination on Day 57)

    Description: Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Number of Participants with Unsolicited AEs for 28 days after First Vaccination

    Time: Day 29 (28 days after first vaccination on Day 1)

    Description: Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Number of Participants with Unsolicited AEs for 28 days after Second Vaccination

    Time: Day 85 (28 days after second vaccination on Day 57)

    Description: SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

    Measure: Number of Participants with Serious Adverse Events (SAEs)

    Time: Up to 12 months

    Secondary Outcomes

    Description: SARS-CoV-2 neutralization will be measured by VNA to analyse the neutralizing antibodies to the wild-type virus and/or pseudovirion expressing S protein.

    Measure: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Neutralization as measured by Virus Neutralization Assay (VNA)

    Time: Up to 12 months

    Description: SARS-CoV-2 binding antibodies will be measured by ELISA to analyse the antibodies binding to the SARS-CoV-2 S protein.

    Measure: SARS-CoV-2-Binding Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)

    Time: Up to 12 months
    387 Randomized Trial of Bicalutamide to Block TMPRSS2 in Males With COVID-19 Infection

    COVID-19 outcomes are worse in male patients. Androgen signaling, therefore, is a target for clinical exploration. TMPRSS2 is a membrane protease required for COVID pathogenesis that is regulated by androgens. Blocking TMPRSS2 with bicalutamide may reduce viral replication and improve the clinical outcome. Therefore, the study proposes to test bicalutamide at 150 mg oral daily dosing in a double-blind placebo-controlled randomized trial in male patients with early symptomatic COVID-19 disease.

    NCT04509999
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Bicalutamide 150 Mg Oral Tablet
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: COVID-19 symptom relief at day 28, and % of COVID-19 symptom relief and its 95% confidence interval (CI) will be calculated using the exact binomial distribution and compared using Fisher's exact test.

    Measure: Proportion x 100 = percent of patients with improved COVID-19 symptoms

    Time: Day 28
    388 MET-Covid Trial - METformin for Prevention and Outpatient Treatment of COVID-19

    The purpose of this trial is to: 1. Determine whether metformin can reduce the severity of COVID-19 disease; 2. Determine whether metformin can prevent symptomatic COVID-19 disease; 3. Determine whether metformin can prevent SARS-CoV-2 infection (seroconversion of SARS-CoV2 antibody tests or PCR positivity)

    NCT04510194
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Drug: Metformin
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum concentrations of c-reactive protein (mg/L) from baseline to 5 days and baseline to 10 days.

    Measure: Change in C-Reactive Protein

    Time: 10 days

    Description: This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum concentrations of albumin (g/dL) from baseline to 5 days and baseline to 10 days.

    Measure: Change in Albumin

    Time: 10 days

    Description: This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum viral load (copies per ml of blood) from baseline to 5 days and baseline to 10 days.

    Measure: Change in Viral load

    Time: 10 days

    Description: Outcome reported as the percent of participants in each arm who expire due to COVID-19 within 28 days of the initiation of treatment.

    Measure: Rate of Death due to COVID-19

    Time: 28 days

    Description: Outcome reported as the percent of participants in each arm who are admitted to hospital due to COVID-19 within 14 days of the initiation of treatment.

    Measure: Rate of Hospitalization due to COVID-19

    Time: 14 days

    Description: Outcome reported as the percent of participants in each arm who utilize emergency department services due to COVID-19 within 14 days of the initiation of treatment.

    Measure: Rate of Emergency Department Utilization

    Time: 14 days

    Description: This is the primary outcome for the Prevention Cohort. Outcome reported as the percent of participants in each arm who discontinue use of the study drug due to any reason.

    Measure: Incidence of all-cause study medicine discontinuation

    Time: 28 days

    Secondary Outcomes

    Description: Outcome measured using a visual analog Scale of COVID-19 symptom maximum severity at days 14 and 28 among those who develop PCR or antibody positivity. Scale ranges from 1-10 with higher scores indicating great symptom severity.

    Measure: Incidence of Possible COVID-19 Symptoms

    Time: 14 days, 28 days

    Description: Outcome reported as the percent of participants who fall into each of 8 ordinal categories on days 7, 14, and 28 of study treatment. Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating

    Time: 7, 14, and 28 days

    Description: The PROMIS Gobal-10 is a 10-item short-form survey measuring symptoms, functioning, and healthcare-related quality of life for a wide variety of chronic diseases and conditions. Nine items are rated on a 5-point scale. Item 7 is rated on an 11-point scale and then transformed to a 5-point scale. Items 3, 6, 7, and 8 are scored in reverse. Item scores are summed to calculate a total raw score. Raw scores are then matched with a t-score using a scoring table. Outcome will be reported as t-score. T-scores range from 16.2 to 67.7 with higher scores indicating greater global health.

    Measure: Global Health Survey (PROMIS survey)

    Time: 60 days

    Description: Outcome reported as the percent of participants in the treatment and placebo groups who contract SARS-CoV-2 during participation in the prevention arm of the study.

    Measure: Seroconversion of SARS-Cov2 Antibodies OR SARS-Cov2 PCR Positivity (Prevention Cohort Only)

    Time: up to 3 months
    389 Multicenter, Randomized, Double Blind, Parallel Placebo Controlled, Phase III Clinical Trial to Evaluate the Protective Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above

    This is a multicenter, randomized, double blind, parallel placebo controlled, phase 3 clinical trial to evaluate the protective efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy population 18 years old and above.

    NCT04510207
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell)
    2. Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell)
    3. Biological: Placebo

    Primary Outcomes

    Measure: The incidence of COVID-19 cases after two-doses of vaccination

    Time: From14 days after the second dose to 6 month after the second dose

    Secondary Outcomes

    Measure: The incidence of severe cases of SARS-CoV-2 pneumonia and deaths accompanied by COVID-19 after two-doses of vaccination

    Time: From14 day after the second dose to 6 month after the second dose

    Measure: The incidence of any adverse reactions/events

    Time: 28 days after each immunization

    Measure: The incidence of serious adverse events (SAE)

    Time: From the beginning of the first dose to 12 months after the second immunization

    Measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody

    Time: 14 days after full course of immunization

    Measure: The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody

    Time: 14 days after full course of immunization

    Measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody

    Time: 14 days after full course of immunization

    Measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody

    Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization

    Measure: The 4-fold increase rate of anti-SARS-CoV-2 neutralizing antibody

    Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization

    Measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody

    Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization

    Other Outcomes

    Measure: the anti-SARS-CoV-2 neutralizing antibody protective level against COVID-19

    Time: 14 days after 2 doses of vaccination

    Measure: The occurrence of ADE

    Time: From the beginning of the first dose to 12 months after the second immunization
    390 Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial

    The purpose of this study is to evaluate whether Canakinumab has beneficial effects on patients with Type 2 diabetes mellitus and coronavirus disease 19 (COVID19).

    NCT04510493
    Conditions
    1. Coronavirus Infection
    2. Diabetes Mellitus, Type 2
    Interventions
    1. Drug: Canakinumab
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Diabetes Mellitus Diabetes Mellitus, Type 2
    HPO:Diabetes mellitus Type II diabetes mellitus

    Primary Outcomes

    Description: Treatment and placebo will be compared on the basis of the unmatched win-ratio approach of Pocock. When comparing two patients, the winner will be determined by the first component in which the two patients differ (4 weeks after randomization): longer survival time longer ventilation-free time longer ICU-free time shorter hospitalization time If there is no difference between treatment and Placebo: the win ratio is 1. If there is a difference between treatment and Placebo: the win ratio is not 1.

    Measure: unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)

    Time: within 4 weeks after treatment with canakinumab or placebo

    Secondary Outcomes

    Description: Time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever comes first. "The seven-category ordinal scale consists of the following categories: not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalized, not requiring supplemental oxygen; hospitalized, requiring supplemental oxygen; hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and death"

    Measure: Time to clinical improvement

    Time: From randomization up to 4 weeks

    Description: Death rate during the 4-week period after study treatment

    Measure: Death rate

    Time: 4 weeks

    Description: Admission to the intensive care unit from the medical ward during the 4-week period after study treatment

    Measure: Admission to intensive care unit (ICU)

    Time: 4 weeks

    Description: Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)

    Measure: Secondary worsening of disease

    Time: 4 weeks

    Description: Prolonged hospital stay > 3 weeks

    Measure: Prolonged hospital stay

    Time: >3 weeks

    Description: Ratio to baseline in the glycated hemoglobin

    Measure: Change in ratio to baseline in the glycated hemoglobin

    Time: Baseline, Day 29 and Day 90

    Description: Ratio to baseline in the fasting glucose

    Measure: Change in ratio to baseline in the fasting glucose

    Time: Baseline, Day 29

    Description: Ratio to baseline in the fasting insulin

    Measure: Change in ratio to baseline in the fasting insulin

    Time: Baseline, Day 29

    Description: Ratio to baseline in the fasting c-peptide

    Measure: Change in ratio to baseline in the fasting c-peptide

    Time: Baseline, Day 29

    Description: Ratio to baseline in the C-reactive protein (CRP)

    Measure: Ratio to baseline in the C-reactive protein (CRP)

    Time: Baseline, Day 29 and Day 90

    Description: Ratio to baseline in the D-dimer

    Measure: Change in ratio to baseline in the D-dimer

    Time: Baseline, Day 29

    Description: Ratio to baseline in the Natriuretic peptide (NTproBNP)

    Measure: Change in ratio to baseline in the Natriuretic peptide (NTproBNP)

    Time: Baseline, Day 29 and Day 90

    Description: Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)

    Measure: Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)

    Time: Baseline, Day 29 and Day 90

    Description: Type of antidiabetic treatment at Day 29

    Measure: Type of antidiabetic treatment at Day 29

    Time: Day 29

    Description: Number of antidiabetic treatment at Day 29

    Measure: Number of antidiabetic treatment at Day 29

    Time: Day 29

    Description: Type of antidiabetic treatment at three months

    Measure: Type of antidiabetic treatment at three months

    Time: Month 3

    Description: Number of antidiabetic treatment at three months

    Measure: Number of antidiabetic treatment at three months

    Time: Month 3
    391 A Phase II, Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder

    This study will investigate the efficacy and safety of RO6889450 as monotherapy in participants experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder.

    NCT04512066
    Conditions
    1. Schizophrenia, Schizoaffective Disorder
    Interventions
    1. Drug: RO6889450
    2. Drug: Placebo
    3. Drug: Risperidone
    MeSH:Schizophrenia Psychotic Disorders
    HPO:Psychosis Schizophrenia

    Primary Outcomes

    Measure: Change from Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score

    Time: Baseline to Week 4

    Secondary Outcomes

    Measure: Proportion of Participants with at least 20% or 50% Improvement from Baseline in the PANSS Total Score

    Time: Baseline to Week 12

    Measure: Change from Baseline in the PANSS Factor Scores

    Time: Baseline to Week 12

    Measure: Proportion of Participants with at Least 20% or 50% Improvement in the PANSS Factor Scores

    Time: Baseline to Week 12

    Measure: Change from Baseline in Clinical Global Impression Severity (CGI-S) Scores

    Time: Baseline to Week 12

    Measure: Clinical Global Impression - Improvement (CGI-I) Scores

    Time: Baseline to Week 12

    Measure: Clinical Global Impression - Improvement Most Troubling Symptoms (CGI-I MTS)

    Time: Baseline to Week 12

    Measure: Change from Baseline in Clinical Global Impression - Severity Most Troubling Symptoms (CGI-S MTS)

    Time: Baseline to Week 12

    Measure: Time from First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ)

    Time: Baseline to Week 4

    Measure: Percentage of Participants with Adverse Events (AEs)

    Time: Baseline to Week 12

    Measure: Change from Baseline in Electrocardiogram (ECG) Intervals

    Time: Baseline to Week 12

    Measure: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)

    Time: Baseline to Week 12

    Measure: Change from Baseline in Extrapyramidal Symptom Rating Scale (ESRS-A)

    Time: Baseline to Week 12

    Measure: Maximum Concentration (Cmax) of RO6889450

    Time: Baseline to Week 12

    Measure: Area Under the Concentration-Time Curve at Steady State (AUCss) of RO6889450

    Time: Baseline to Week 4
    392 Pilot Study to Evaluate Safety and Efficacy of Anti-SARS-CoV-2 Equine Immunoglobulin F(ab')2 Fragments (INOSARS) in Hospitalized Patients With COVID-19

    This is a two-center, randomized, placebo-controlled pilot study of anti-SARS-CoV-2 equine immunoglobulin fragments F(ab')2 (INOSARS) to evaluate safety and preliminary efficacy in the treatment of hospitalized COVID-19 patients. Clinical improvement at 28 days from the start of treatment will be evaluated.

    NCT04514302
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Placebo
    2. Drug: Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS)

    Primary Outcomes

    Description: The primary endpoint is the proportion of patients with clinical improvement at 28 days after treatment. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale. Scale categories as follows: 1 = not hospitalized; 2 = not hospitalized with limitation of activities and/or oxygen requirement; 3 = hospitalized not requiring supplemental oxygen and not requiring active medical care, 4 = hospitalized requiring active medical care without requiring oxygen supplementation; 5 = hospitalized requiring oxygen supplementation; 6 = hospitalized requiring high-flow oxygen or non-invasive mechanical ventilation; 7 = hospitalized requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8 = death.

    Measure: Proportion of patients with improvement in clinical status

    Time: 28 days

    Secondary Outcomes

    Description: Time from the day of treatment until the first day with clinical improvement, defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale.

    Measure: Time to clinical improvement

    Time: 28 days

    Description: Proportion of participant death or non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation requirement.

    Measure: Proportion of patients that reach a score of 6, 7 or 8 in the NIAID 8-point ordinal scale

    Time: 28 days

    Description: Measured in days

    Measure: Duration of hospitalization

    Time: 28 days

    Description: Proportion of patients that have a negative polymerase chain reaction assay for SARS-CoV-2 at 72 hrs from start of treatment.

    Measure: SARS-CoV-2 PCR negativization rate

    Time: 3 days

    Description: Proportion of patients with clinical improvement at day 7. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale

    Measure: Proportion of patients with clinical improvement at day 7

    Time: 7 days

    Description: Proportion of patients that present within 24 hours of treatment with immediate adverse events defined as: skin rash and/or respiratory findings (dyspnea, wheezing, bronchospasm, hypoxia) and/or circulatory compromise (reduction of blood pressure or associated symptoms, i.e. syncope).

    Measure: Proportion of patients with immediate adverse events (< 24 hours)

    Time: 24 hours

    Description: Proportion of patients that present events associated with serum sickness (type 3 hypersensitivity), vasculitis, glomerulonephritis, arthritis.

    Measure: Proportion of patients with late adverse events (1 - 28 days)

    Time: 28 days
    393 A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, First-In-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AK119 in Healthy Subjects

    This is a first-in-human (FIH), Phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, PK and immunogenicity of AK119, a humanized monoclonal antibody targeting the CD73. The study will consist of 4 cohorts of healthy subjects. Eight subjects will be enrolled per cohort, randomized in a 3:1 ratio to receive a single dose of either the active drug AK119 (N=6) or matching placebo (N=2). Approximately 32 subjects (24 receiving active drug and 8 receiving placebo) will participate in this study.

    NCT04516564
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Drug: AK119
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Incidence of treatment-emergent AEs

    Time: From signing of informed consent till end of study (approximately 64 days postdose)

    Secondary Outcomes

    Measure: Maximum serum concentration (Cmax) of AK119

    Time: From baseline till end of study (approximately 64 days postdose)

    Measure: Area under the concentration-time curve (AUC) of serum concentration of AK119

    Time: From baseline till end of study (approximately 64 days postdose)

    Measure: Percentage of subjects who develop detectable anti-drug antibodies (ADAs)

    Time: From baseline till end of study (approximately 64 days postdose)
    394 A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19

    The aim of the study is to assess the safety, efficacy, and immunogenicity of AZD1222 for the prevention of COVID-19.

    NCT04516746
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Biological: AZD1222
    2. Biological: Placebo

    Primary Outcomes

    Description: A binary response, whereby a participant is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19 in adults ≥ 18 years of age

    Time: 1 year

    Description: Incidence of adverse events. Incidence of serious adverse events, medically attended adverse events, and adverse events of special interest.

    Measure: The safety and tolerability of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age

    Time: a: 28 days post each dose of study Intervention. / b: from Day 1 post-treatment through Day 730.

    Description: Incidence of local and systemic solicited adverse events.

    Measure: The reactogenicity of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age (Substudy only)

    Time: 7 days post each dose of study intervention.

    Secondary Outcomes

    Description: The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection

    Time: 1 year

    Description: The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness for a participant occurring at or after 15 days post second dose of study intervention using criteria from the CDC.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of symptomatic COVID-19 using CDC criteria

    Time: 1 year

    Description: The incidence of the first case of SARS-CoV-2 RT-PCR positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using University of Oxford defined symptom criteria.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of University of Oxford defined symptomatic COVID-19

    Time: 1 year

    Description: The incidence of SARS-CoV-RT-PCR-positive severe or critical symptomatic illness occurring 15 days or more post second dose of study intervention.

    Measure: The efficacy of 2 IM doses of AZD12222 compared to placebo for the prevention of severe or critical symptomatic COVID-19.

    Time: 1 year

    Description: The incidence of COVID-19-related Emergency Department visits occurring ≥ 15 days post second dose of study intervention

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19-related Emergency Department visits

    Time: 1 year

    Description: Post-treatment GMTs and GMFRs in SARS-CoV-2 S, RBD antibodies (MSD serology assay); The proportion of participants who have a post-treatment seroresponse (≥ 4-fold rise in titers) to the S, RBD antigens of AZD1222 (MSD serology assay)

    Measure: Antibody responses to AZD1222 S antigen following 2 IM doses of AZD1222 or placebo (Substudy and Illness Visits only)

    Time: 28 days post each dose

    Description: Post-treatment GMTs and GMFRs in SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay); Proportion of participants who have a post-treatment seroresponse (≥ 4-fold rise in titers) to AZD1222 as measured by SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay)

    Measure: Anti-SARS-CoV-2 neutralizing antibody levels in serum following 2 IM doses of AZD1222 or placebo (Sub-study and Illness Visits only)

    Time: 28 days post each dose
    395 A Phase II, Randomised, Double-blind, Placebo-controlled Clinical Trial to Assess the Safety and Efficacy of AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19

    The ARCADIA Trial is a randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with either Type 1 or Type 2 diabetes, hospitalised with COVID-19.

    NCT04516759
    Conditions
    1. Covid19
    Interventions
    1. Drug: AZD1656
    2. Other: Placebo

    Primary Outcomes

    Description: Clinical Improvement measured as the percentage of subjects at Day 14 who are in categories 1-3 according to the WHO 8-point Ordinal Scale for Clinical Improvement, comparing AZD1656 treatment to placebo

    Measure: Clinical Improvement by Day 14

    Time: Day 1 to Day 14

    Secondary Outcomes

    Description: Clinical Improvement measured as the percentage of patients categorised at each severity rating on the WHO 8-point Ordinal Scale at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo.

    Measure: *Title: Clinical Improvement at Day 7, 14 and 21

    Time: Day 1 to Day 21

    Description: Degree of glycaemic control as measured by the need to increase baseline medication requirements or the need to add additional diabetic medications to maintain appropriate blood glucose levels in patients receiving AZD1656 compared with placebo

    Measure: Glycaemic Control

    Time: Day 1 to Day 21

    Description: Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo

    Measure: Occurrence of Adverse Events

    Time: Day 1 to Day 28

    Description: Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo

    Measure: Occurrence of Serious Adverse Events

    Time: Day 1 to Day 28

    Description: Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo

    Measure: Duration of Hospitalisation

    Time: Day 1 to Day 21

    Description: Time from hospital admission to receiving intubation/mechanical ventilation in patients receiving AZD1656 compared with placebo

    Measure: Time to Intubation/ Mechanical Intervention

    Time: Day 1 to Day 21

    Description: Mortality rate in patients receiving AZD1656 compared with placebo.

    Measure: Mortality Rate

    Time: Day 1 to Day 28

    Other Outcomes

    Description: Plasma AZD1656 levels during first 7 days of treatment in patients receiving AZD1656 compared with placebo.

    Measure: Pharmacokinetic Analysis

    Time: Day 1 to Day 7

    Description: Immunophenotyping panel to be conducted by Flow Cytometry: between group comparison (AZD1656 versus placebo)

    Measure: Immunophenotyping Analysis

    Time: Day 1 to Day 21

    Description: Immunochemistry panel to be conducted using the Meso Scale Discovery (MSD) U-Plex multiplex assay.

    Measure: Immunochemistry Analysis

    Time: Day 1 to Day 21

    Description: Measurement of hsTroponin and NTproBNP to determine extent of cardiac injury in patients receiving AZD1656 compared with placebo

    Measure: Cardiac Injury

    Time: Day 1 to Day 21

    Description: Measurement of 25-hydroxyvitamin D levels before treatment to determine whether there is any correlation between baseline vitamin D level and clinical improvement in patients treated with AZD1656 versus placebo.

    Measure: Correlation of clinical outcomes with pre-treatment vitamin D levels (by measurement of 25-hydroxyvitamin D levels).

    Time: Day 1 to Day 21

    Description: Sub group analysis of patient ethnicity, to determine whether there is any correlation between patient ethnicity and clinical improvement in patients treated with AZD1656 versus placebo.

    Measure: Correlation of patient ethnicity with clinical improvement

    Time: Day 1 to Day 21
    396 FEnofibRate as a Metabolic INtervention for Coronavirus Disease 2019

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoC-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with a high incidence of acute respiratory distress syndrome (ARDS) and death. Aging, obesity, diabetes, hypertension and other risk factors associated with abnormal lipid and carbohydrate metabolism are risk factors for death in COVID-19. Recent studies suggest that COVID-19 progression is dependent on metabolic mechanisms. Moreover, gene expression analyses in cultured human bronchial cells infected with SARS-CoV-2 and lung tissue from patients with COVID-19, indicated a marked shift in cellular metabolism, with excessive intracellular lipid generation. In this cell culture system, fenofibrate (a widely available low-cost generic drug approved by the FDA and multiple other regulatory agencies around the world to treat dyslipemias) at concentrations that can be achieved clinically, markedly inhibited SARS-CoV-2 viral replication. Fenofibrate also has immunomodulatory effects that may be beneficial in the setting of COVID-19. The aim of this trial is to assess the clinical impact of fenofibrate (145 mg/d of Tricor or dose-equivalent preparations for 10 days, with dose adjustment in chronic kidney disease ([CKD]) to improve clinical outcomes in patients with COVID-19.

    NCT04517396
    Conditions
    1. Covid19
    Interventions
    1. Other: Fenofibrate
    2. Other: Placebo
    3. Other: Usual care

    Primary Outcomes

    Description: The primary endpoint of the trial will be a global rank score that ranks patient outcomes according to 5 factors: (1) time to death; (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); (3) The inspired concentration of oxygen/percent oxygen saturation (FiO2/SpO2) ratio area under the curve; (4) For participants enrolled as outpatients who are subsequently hospitalized, the number of days out of the hospital during the 30 day-period following randomization; (5) For participants enrolled as outpatients who don't get hospitalized during the 30-day observation period, the modified Borg dyspnea scale

    Measure: Hierarchical composite endpoint

    Time: Up to 30 days

    Secondary Outcomes

    Measure: Number of days alive, out of the intensive care unit, free of mechanical ventilation/extracorporeal membrane oxygenation, or maximal available respiratory support in the 30 days following randomization

    Time: Up to 30 days

    Description: A seven-category ordinal scale consisting of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and 7, death.

    Measure: Seven-category ordinal scale

    Time: At 15 days

    Description: A global rank score similar to the primary endpoint, but using a more comprehensive COVID-19 symptom scale instead of the dyspnea Borg scale

    Measure: Hierarchical composite endpoint

    Time: Up to 30 days

    Other Outcomes

    Measure: All-Cause Death

    Time: Up to 30 days

    Measure: Number of days alive and out of the hospital during the 30 days following randomization

    Time: Up to 30 days

    Description: A global rank score similar to the primary endpoint, but built only with factors 1-4 of the primary endpoint

    Measure: Hierarchical composite endpoint

    Time: Up to 30 days
    397 Efficacy and Safety of Lactobacillus Plantarum and Pediococcus Acidilactici as Co-adjuvant Therapy for Reducing the Risk of Severe Disease in Adults With SARS-CoV-2 and Its Modulation of the Fecal Microbiota: A Randomized Clinical Trial

    Clinical research focused to evaluate the effect as coadyuvant of a combination of L. plantarum and P. acidilactici in adults positive for SARS-CoV-2 with mild clinical COVID-19 symptoms. Main objective is to evaluate how this combination of probiotics reduce the risk to progress to moderate or severe COVID and associated advantages such as reduce the risk of death. Adittionnally this RCT is launching to explore the benefits of this combination of strains to modulate fecal microbiome and explore how this correlate with clinical improvement.

    NCT04517422
    Conditions
    1. SARS-CoV Infection
    Interventions
    1. Dietary Supplement: Probiotics
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Frequency of randomized subjects who progress from mild to moderate or severe COVID-19, as evaluated by WHO Clinical Progression Scale

    Measure: Severity progression of COVID-19

    Time: 30 days

    Description: Length of stay at Intensive care unit

    Measure: Stay at ICU

    Time: 30 days

    Description: Mortality ratio for all the causes related to COVID-19

    Measure: Mortality ratio

    Time: 30 days

    Secondary Outcomes

    Description: Frequency of lung abnormalities clasified by severity and measured by x-ray and artificial intelligence

    Measure: Lung abnormalities

    Time: 30 days

    Description: Description of SARS-Cov-2 viral load evaluated by RT-PCR at screening and on days 15 and 30

    Measure: Viral load

    Time: 30 days

    Description: Levels of Immunoglobulin G and Immunoglobulin M evaluated on day 15 and 30

    Measure: Levels of immunoglobulins

    Time: 30 days

    Description: Frequency and severity of gastrointestinal manifestation evaluated by Gastrointestinal Symptom Rating Scale (GSRS)

    Measure: Gastrointestinal manifestations, where 0 means good health status and 5 worse status

    Time: 30 days

    Description: Changes on fecal microbiome evaluated by 16S analysis on day 1st and 30th

    Measure: Fecal microbiome

    Time: 30 days

    Description: Frequency of adverse events reported on dairy report form after randomization and until day 30

    Measure: Adverse events

    Time: 30 days

    Description: Change on C-reactive high sensitivity protein (hsCRP) and D-Dimer

    Measure: Change on Serum Biomarkers

    Time: Days 1st, 15th and 30th after randomization
    398 Efficacy and Safety of GMRx2 (a Single Pill Combination Containing Telmisartan/Amlodipine/Indapamide) Compared to Placebo for the Treatment of Hypertension

    Recent hypertension guidelines recommend combination therapy as initial treatment for many or most patients. Several trials suggest triple low-dose combination therapy may be highly effective in terms of achieving blood pressure control without increasing adverse effects. This trial is designed to investigate the efficacy and safety of GMRx2 in participants with high blood pressure compared to placebo.

    NCT04518306
    Conditions
    1. Hypertension
    Interventions
    1. Drug: Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg
    2. Drug: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
    3. Drug: Placebo
    MeSH:Hypertension
    HPO:Hypertension

    Primary Outcomes

    Measure: Difference in change in home SBP from baseline to Week 4

    Time: 4 weeks

    Secondary Outcomes

    Measure: Difference in change in clinic seated mean SBP from baseline to Week 4

    Time: 4 weeks

    Measure: Difference in change in clinic seated mean DBP from baseline to Week 4

    Time: 4 weeks

    Measure: Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 4

    Time: 4 weeks

    Measure: Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 4

    Time: 4 weeks

    Measure: Difference in change in home seated mean DBP from baseline to Week 4

    Time: 4 weeks

    Measure: Difference in change in trough home seated mean SBP from baseline to week 4

    Time: 4 weeks

    Measure: Difference in change in trough home seated mean DBP from baseline to week 4

    Time: 4 weeks

    Measure: Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 4

    Time: 4 weeks

    Measure: Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 4

    Time: 4 weeks

    Other Outcomes

    Description: Percentage of participants discontinued trial medication due to AE/SAE from baseline to Week 4

    Measure: Safety Outcomes

    Time: 4 weeks

    Description: Percentage of participants with an SAE from baseline to Week 4

    Measure: Safety Outcomes

    Time: 4 weeks

    Description: Percentage of participants with symptomatic hypotension from baseline to Week 4

    Measure: Safety Outcomes

    Time: 4 weeks

    Description: Percentage of participants with serum sodium concentration below 135 mmol/l at Week 4

    Measure: Safety Outcomes

    Time: 4 weeks

    Description: Percentage of participants with serum sodium concentration above 145 mmol/l at Week 4

    Measure: Safety Outcomes

    Time: 4 weeks

    Description: Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 4

    Measure: Safety Outcomes

    Time: 4 weeks

    Description: Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 4

    Measure: Safety Outcomes

    Time: 4 weeks

    Description: • Percentage of participants with eGFR drop of over 30% from baseline to Week 4

    Measure: Safety Outcomes

    Time: 4 weeks
    399 Adaptive Platform Treatment Trial for Outpatients With COVID-19 (Adapt Out COVID)

    Drug studies often look at the effect one or two drugs have on a medical condition, and involve one company. There is currently an urgent need for one study to efficiently test multiple drugs from more than one company, in people who have tested positive for COVID-19 but who do not currently need hospitalization. This could help prevent disease progression to more serious symptoms and complications, and spread of COVID-19 in the community. This study looks at the safety and effectiveness of different drugs in treating COVID-19 in outpatients. Participants in the study will be treated with either a study drug or with placebo.

    NCT04518410
    Conditions
    1. Coronavirus
    2. Covid19
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)

    Measure: Duration of COVID-19 symptoms (Phase 2)

    Time: Up to Day 28

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 3 (Phase 2)

    Time: Day 3

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 7 (Phase 2)

    Time: Day 7

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 14 (Phase 2)

    Time: Day 14

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 21 (Phase 2)

    Time: Day 21

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 28 (Phase 2)

    Time: Day 28

    Measure: Incidence of new adverse event (AE) ≥ Grade 3 (Phase 2)

    Time: Thru Day 28

    Description: ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted ton address medical needs of those with severe COVID-19

    Measure: Cumulative incidence of death from any cause or hospitalization (Phase 3)

    Time: Thru Day 28

    Measure: Proportion of participants with new adverse event (AE) ≥ Grade 3 (Phase 3)

    Time: Thru Day 28

    Secondary Outcomes

    Description: ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted ton address medical needs of those with severe COVID-19

    Measure: Cumulative incidence of death from any cause or hospitalization (Phase 2)

    Time: Thru Day 28

    Description: Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)

    Measure: Duration of COVID-19 symptoms (Phase 3)

    Time: Up to Day 28

    Description: Measured as detectable or undetectable, from participant-collected nasal swabs

    Measure: Presence of SARS-CoV-2 RNA (Phases 2 and 3)

    Time: Thru Day 28

    Description: Measured from participant-collected nasal swabs

    Measure: Level of SARS-Cov-2 RNA (Phases 2 and 3)

    Time: Thru Day 28

    Description: Based on symptom severity scores. Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3). For participants who are alive at 28 days and not previously hospitalized, the severity ranking will be based on the area under the curve (AUC) of the symptom score associated with COVID-19 disease over time. Participants hospitalized or who die during follow-up through 28 days will be ranked as worse than those alive and never hospitalized as follows (in worsening rank order): alive and not hospitalized at 28 days; hospitalized but alive at 28 days; and died at or before 28 days.

    Measure: COVID-19 severity ranking (Phases 2 and 3)

    Time: From Day 0 thru Day 28

    Description: Progression of one or more COVID-19-associated symptoms to a worse status than recorded at study entry, prior to start of investigational product or placebo

    Measure: Incidence of ≥1 worsening symptom of COVID-19 (Phases 2 and 3)

    Time: Thru Day 28

    Description: Defined as the last day in the participant's study diary on which a temperature ≥ 38°C (100.4°F) was recorded or a potentially antipyretic drug was taken.

    Measure: Duration of fever (Phases 2 and 3)

    Time: Thru Day 28

    Description: As recorded in participant's study diary

    Measure: Time to self-report return to usual (pre-COVID-19) health (Phases 2 and 3)

    Time: Thru Day 28

    Measure: Cumulative incidence of death from any cause or hospitalization (Phases 2 and 3)

    Time: Day 0 thru Week 24

    Description: Measured by pulse oximeter and categorized as <96% versus ≥96%

    Measure: Oxygen saturation level (Phase 2)

    Time: Thru Day 28

    Description: Measured by AUC and above assay lower limit of quantification

    Measure: Level of SARS-CoV-2 RNA from site-collected NP swabs (Phase 2)

    Time: Days 0, 3, 7, 14, 21 and 28

    Description: Measured by AUC and above assay lower limit of quantification

    Measure: Level of SARS-CoV-2 RNA from saliva (Phase 2)

    Time: Days 0, 3, 7, 14, 21 and 28

    Description: Measured by AUC and above assay lower limit of quantification

    Measure: Level of SARS-CoV-2 RNA from self-collected nasal swabs (Phase 2)

    Time: Daily at Days 0-14, plus Days 21 and 28

    Description: From site-collected NP swabs

    Measure: Level of SARS-CoV-2 RNA (Phase 2)

    Time: Days 3, 7, 14, 21 and 28

    Description: Measured as detectable or undetectable

    Measure: Post-treatment presence of SARS-CoV-2 RNA in saliva (Phase 2)

    Time: Days 3, 7, 14, 21 and 28

    Description: Measured from saliva samples

    Measure: Post-treatment level of SARS-CoV-2 RNA (Phase 2)

    Time: Days 3, 7, 14, 21 and 28

    Measure: Incidence of new adverse event (AE) ≥ Grade 3 (Phase 3)

    Time: Thru Week 24

    Description: Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Concentration of investigational agent (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Level of anti-drug antibodies (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Area under the concentration-time curve. Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: AUC (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Total body clearance (CL) (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: T1/2. Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Elimination half-life (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Maximum plasma concentration of LY3819253. Analyses of samples collected from placebo-treated participants are not planned

    Measure: Cmax (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Minimum plasma concentration of LY3819253. Analyses of samples collected from placebo-treated participants are not planned

    Measure: Cmin (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24
    400 A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate CSL324 in Coronavirus Disease 2019 (COVID-19)

    This is a phase 2, prospective, multicenter, randomized, double blind, placebo controlled, parallel group study to evaluate the safety and efficacy of intravenous (IV) administration of CSL324, administered in combination with SOC treatment, in subjects with COVID 19. For the purposes of this study, standard of care (SOC) may include any written or established treatment protocol followed at the study site for the treatment of severe COVID-19 or its complications, including off-label use of marketed pharmaceutical products and / or products with emergency use authorization granted for the treatment of COVID-19 (ie, not yet marketed) (eg, remdesivir).

    NCT04519424
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Biological: CSL324
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Proportion of subjects progressing to endotracheal intubation or death prior to endotracheal intubation

    Time: Randomization to Day 28

    Secondary Outcomes

    Measure: Proportion of deaths from all causes

    Time: Randomization to Day 28

    Measure: Proportion of subjects intubated

    Time: Randomization to Day 28

    Measure: Median length of stay in hospital

    Time: Randomization to Day 28

    Measure: Number and proportion of subjects with at least a 2-point improvement in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale

    Time: Randomization to Day 28

    Measure: Number and proportion of subjects within each of the categories of the NIAID ordinal scale

    Time: Daily up to Day 28

    Measure: Proportion of subjects using continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP)

    Time: Randomization to Day 28

    Measure: Proportion of subjects using high-flow nasal cannula (HFNC)

    Time: Randomization to Day 28

    Measure: Proportion of subjects using extracorporeal membrane oxygenation (ECMO)

    Time: Randomization to Day 28

    Measure: Maximum Change in Sequential Organ Failure Assessment (SOFA) score

    Time: Randomization to Day 28

    Measure: Change in SOFA score and in individual components of the SOFA score

    Time: Baseline to Day 28

    Measure: Number and proportion of subjects experiencing adverse events (AEs)

    Time: Up to 60 days

    Measure: Number and proportion of subjects experiencing serious adverse events (SAEs)

    Time: Up to 60 days

    Measure: Number and proportion of subjects experiencing adverse events of special interest (AESIs)

    Time: Up to 60 days

    Measure: Presence of anti-CSL324 antibodies

    Time: Up to 28 days

    Measure: Maximum concentration (Cmax) of CSL324

    Time: Up to 28 days

    Measure: Time to reach maximum concentration (Tmax) of CSL324

    Time: Up to 28 days

    Measure: Area under the concentration-time curve (AUC0-last) of CSL324

    Time: Up to 28 days

    Measure: Trough concentration (Ctrough) of CSL324

    Time: Before dose on Day 4 and Day 8
    401 A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Repeated Subcutaneous Doses of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (REGN10933+REGN10987) in Adult Volunteers

    The primary objectives are: - To assess the occurrence of adverse events of special interest (AESIs) in participants treated with repeated subcutaneous (SC) doses of REGN10933+REGN10987 compared to placebo - To assess the concentrations of REGN10933 and REGN10987 in serum over time after single and repeated SC administration The secondary objectives are: - To assess the safety and tolerability of repeated SC doses of REGN10933+REGN10987 compared to placebo - To assess attainment of target concentrations of REGN10933 and REGN10987 in serum after single and repeated SC administration - To assess the immunogenicity of REGN10933 and REGN10987

    NCT04519437
    Conditions
    1. Healthy
    2. Chronic Stable Illness
    Interventions
    1. Drug: REGN10933+REGN10987
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Baseline

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 29

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 57

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 85

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 113

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 141

    Measure: Concentrations of REGN10933 in serum over time

    Time: Up to 52 weeks

    Measure: Concentrations of REGN10987 in serum over time

    Time: Up to 52 weeks

    Secondary Outcomes

    Measure: Proportion of participants with treatment-emergent adverse events (TEAEs)

    Time: Up to 52 weeks

    Measure: Severity of TEAEs

    Time: Up to 52 weeks

    Measure: Proportion of participants who achieve or exceed target concentration in serum of REGN10933

    Time: Up to 52 weeks

    Measure: Proportion of participants who achieve or exceed target concentration in serum of REGN10987

    Time: Up to 52 weeks

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933

    Time: Up to 52 weeks

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987

    Time: Up to 52 weeks
    402 Phase Ib Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine, LID/ΔM2-2/1030s, Lot RSV#010A, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age

    The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of a recombinant, live-attenuated respiratory syncytial virus (RSV) vaccine, LID/ΔM2-2/1030s, in RSV-seronegative infants and children 6 to 24 months of age.

    NCT04520659
    Conditions
    1. RSV Infection
    Interventions
    1. Biological: RSV LID/ΔM2-2/1030s
    2. Biological: Placebo
    MeSH:Respiratory Syncytial Virus Infections

    Primary Outcomes

    Description: May include fever, acute otitis media, rhinorrhea, pharyngitis, cough without lower respiratory infection (LRI), or hoarseness

    Measure: Frequency of Grade 1 or higher solicited adverse events (AEs)

    Time: Measured through Day 28

    Description: May include wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi, rales

    Measure: Frequency of Grade 2 or higher lower respiratory infections (LRI)

    Time: Measured through Day 28

    Measure: Frequency of serious adverse events (SAEs)

    Time: Measured through Day 56

    Measure: Percentage of vaccinees with a ≥4-fold rise in serum RSV-neutralizing antibody titer

    Time: Measured at Day 56

    Description: Detected by immunoplaque assay and/or RT-qPCR. Group 1 participants only.

    Measure: Peak titer of vaccine virus shed

    Time: Measured through Day 28

    Description: Defined as shedding vaccine virus, detected by immunoplaque assay and/or RT-qPCR, and/or ≥4-fold rise in RSV-specific serum antibodies, detected by enzyme-linked immunosorbent assay (ELISA) against the RSV F protein and/or an RSV-PRNT

    Measure: Proportion of vaccinees infected with vaccine virus in Group 1

    Time: Measured through Day 56

    Secondary Outcomes

    Measure: Frequency of RSV-medically attended acute respiratory illness (MAARI)

    Time: Measured during RSV season (from October 16 through March 31)

    Measure: Maximum grade of RSV MAARI

    Time: Measured during RSV season (from October 16 through March 31

    Measure: Frequency of RSV-medically attended acute lower respiratory illness (MAALRI)

    Time: Measured during RSV season (from October 16 through March 31)

    Measure: Maximum grade of RSV MAALRI

    Time: Measured during RSV season (from October 16 through March 31)

    Measure: Percentage of vaccinees with a ≥4-fold rise in serum RSV F IgG

    Time: Measured at Day 56
    403 A Double-blind, Randomized, Placebo-controlled, Multi-center, Phase II Study to Evaluate the Efficacy and Safety of DWJ1248 in Patients With Mild to Moderate COVID-19

    To evaluate the efficacy and safety after administration of DWJ1248 in patients with mild to moderate COVID-19 compared to the placebo.

    NCT04521296
    Conditions
    1. Mild to Moderate COVID-19
    Interventions
    1. Drug: DWJ1248
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to reach undetectable SARS-CoV-2 RNA level

    Measure: Time to SARS-CoV-2 eradication

    Time: Up to 28 days

    Secondary Outcomes

    Description: Percent of patients with undetectable SARS-CoV-2 RNA level

    Measure: Rate of SARS-CoV-2 eradication

    Time: Days 4, 7, 10, and 14

    Measure: Time to clinical improvement of subjective symptoms

    Time: Up to 28 days
    404 A Double-blind, Placebo-controlled, Phase 2 Trial of Sublingual Low-Dose Thimerosal in Adults With Symptomatic SARS-CoV-2 Infection

    Clinical trial to compare sublingual low does thimerosal in adults that have symptoms of SARS-CoV-2 Infection against placebo to show a difference in physical characteristics and viral levels.

    NCT04522830
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: BTL-TML-COVID
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Change from baseline in the physical component summary of the short form-36 Quality of Life Instrument

    Measure: Mean duration and severity of disease

    Time: Two days

    Secondary Outcomes

    Description: AEs will be assessed by the investigator as to severity, duration and relationship to treatment

    Measure: Incidence/Safety of Adverse Events

    Time: Baseline through 10 days
    405 The C3 Nitazoxanide for Mild to Moderate COVID-19 in HIV-infected and HIV-uninfected Adults With Enhanced Risk: a Double-blind, Randomised, Placebo-controlled Trial in a Resource-poor Setting

    COVID-19 due to SARS-CoV-2 infection is a rapidly escalating global pandemic for which there is no proven effective treatment. COVID-19 is multi-dimensional disease caused by viral cytopathic effects and host-mediated immunopathology. Therapeutic approaches should logically be based on interventions that have direct anti-viral effects and favourably modulate the host immune response. Thus, an optimal drug regimen in ambulatory patients should collectively (i) target and reduce viral replication, (ii) upregulate host innate immune anti-viral responses, (iii) have favourable immunomodulatory properties, and (iv) minimise disease progression to hospitalisation thus circumventing the 'cytokine storm' that likely underpins ARDS and multi-organ failure. Nitazoxanide (NTZ) is an antiprotozoal drug that is FDA-approved for treating Cryptosporidium and Giardia and has an excellent safety record for a variety of indications, but primarily as an anti-parasitic agent. It has proven broad anti-viral activity as it amplifies cytoplasmic RNA sensing, potently augments type I interferon and autophagy-mediated anti-viral responses, has immunomodulatory properties e.g inhibits macrophage IL-6 production, and interferes with SARS-CoV-2 glycosylation. It has been shown to have anti-viral activity against several viruses including Ebola, influenza, hepatitis B and C, rotavirus and norovirus. With regard to respiratory viral infections, NTZ was evaluated in uncomplicated influenza and demonstrated a reduction in the median time to symptom recovery. By contrast, NTZ failed to show benefit in hospitalised patients with severe influenza suggesting that, as with oseltamivir (Tamiflu), it likely needs to be administered early in the course of the disease. NTZ has proven in vitro activity against SARS-CoV-2. NTZ inhibited the SARs-CoV-2 at a low-micromolar concentrations and in vivo evaluation in patients with COVID-19 has been strongly recommended. NTZ has an excellent drug-drug interaction profile. No clinically significant interactions are expected with commonly used antihypertensive agents, antidiabetics drugs, antiretroviral agents, steroids or commonly prescribed analgesics / anti-inflammatory agents. The investigators propose NTZ for the treatment of mild COVID-19 in non-hospitalised patients with HIV co-infection and/or enhanced risk for progression to severe disease (age > 50 years and/ or with comorbidity). The investigators will perform a randomised controlled trial enrolling 960 patients with mild disease. The primary outcome measure will be the proportion progressing to severe disease (hospitalisation) based on the WHO clinical progression scale (progression to stage 4 and beyond). Secondary outcome measures will include disease rates in contacts and effect on viral load, productive infectiousness using viral cultures, and ability to abrogate the generation of infectious aerosols using novel cough aerosol sampling technology. Recruitment is stratified and thus the study is powered to detect progression to severe disease in HIV-infected persons.

    NCT04523090
    Conditions
    1. Covid19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo

    Primary Outcomes

    Description: Time-specific (30- and 60-day) disease severity based on the WHO clinical progression scale

    Measure: Time specific disease severity

    Time: 60 days

    Secondary Outcomes

    Description: Need for hospitalisation and length of hospital stay (in those admitted to hospital because of disease progression).

    Measure: Progression to severe disease

    Time: 60 days

    Description: Length of time on high flow nasal oxygen or in the ventilator.

    Measure: Need for respiratory support (high flow nasal oxygen, non-invasive ventilation, or intubation) in those admitted to hospital because of disease progression.

    Time: 60 days

    Description: Time-specific all cause of mortality

    Measure: In-hospital and 30- and 60-day all-cause mortality. available).

    Time: 60 days

    Description: SARS-CoV-2 viral parameters [duration and burden of viral load and duration of viral culture positivity (viral shedding)

    Measure: Time-specific viral load as measured by RT-PCR using NP swabs and sputum (where available).

    Time: 60 days

    Description: Assessment of SARS-CoV-2 presence in droplets and aerosols generated COVID-19 positive participants ( and infectiousness)

    Measure: Cough aerosol sampling positivity

    Time: 60 days
    406 A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Safety and Efficacy of Antroquinonol in Hospitalized Patients With Mild to Moderate Pneumonia Due to COVID-19

    To evaluate the safety andefficacy of antroquinonol treatment of mild to moderate pneumonia due to COVID-19, as measured by the proportion of patients alive and free of respiratory failure.

    NCT04523181
    Conditions
    1. Covid-19
    Interventions
    1. Drug: Antroquinonol
    2. Drug: Placebo

    Primary Outcomes

    Description: The proportion of patients who are alive and free of respiratory failure (e.g., no need for invasive mechanical ventilation, non invasive ventilation, high flow oxygen, or ECMO) on Day 14

    Measure: recover ratio

    Time: 14 day

    Secondary Outcomes

    Description: Clinical change score as measured by the WHO COVID-19 Clinical Improvement Ordinal Scale

    Measure: Time to 2-point improvement

    Time: 28 day

    Description: time for patient discharge

    Measure: Duration of hospitalization

    Time: 28 day

    Description: measured as study days from start of treatment to first negative SARS CoV 2 PCR test

    Measure: Time to virological clearance

    Time: 28 day
    407 Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (BNT162b1) in Chinese Healthy Subjects: A Phase I, Randomized, Placebo-controlled, Observer-blind Study

    This is a phase I, randomized, placebo-controlled, observer-blind study, for evaluation of safety and immunogenicity of SARS-CoV-2 mRNA vaccine (BNT162b1) in Chinese healthy population. After randomization, the trial for each subject will last for approximately 12 months. Screening period is 2 weeks prior to randomization (Day -14 to Day 0), and each dose of either SARS-CoV-2 vaccine (BNT162b1) or placebo will be given intramuscularly (IM).

    NCT04523571
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: BNT162b1
    2. Other: Placebo

    Primary Outcomes

    Measure: Occurrence of solicited local reactions in the subjects (e.g., vaccination sites: pain/tenderness, erythema/redness, induration/swelling) during the 14-days after each dose of BNT162b1 or placebo.

    Time: 14 days following each dose administration

    Measure: Occurrence of solicited systematic reactions (e.g., nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) during 14-day after each dose of BNT162b1 or placebo.

    Time: 14 days following each dose administration

    Measure: Occurrence of adverse event (AE) associated with vaccination in subjects during the 21-day period after prime vaccination of BNT162b1 or placebo.

    Time: 21-day period after prime vaccination

    Measure: Occurrence of AE associated with vaccination in subjects during the 28-day period after boost dose of BNT162b1 or placebo.

    Time: 28-day period after boost dose

    Secondary Outcomes

    Measure: The proportion of subjects experiencing serious adverse events (SAEs), occurring up to Day 21 after prime vaccination and Day 28 after boost vaccination, up to Month 3, 6 and 12.

    Time: Day 21 after prime vaccination, Day 28 after boost vaccination, and Month 3, 6 and 12

    Measure: The proportion of subjects experiencing AE associated with BNT162b1, occurring up to Month 3, 6 and 12.

    Time: up to Month 3, 6 and 12

    Measure: The proportion of subjects experiencing abnormal markers of hematology, blood chemistry and urine analysis, occurring at Hour 24 and Day 7 after prime vaccination and Day 7 period after boost dose of BNT162b1 or placebo.

    Time: Hour 24 and Day 7 after prime vaccination and Day 7 after boost dose

    Measure: Geometric mean titer (GMT) of anti-S1 IgG antibody at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: GMT of anti-receptor binding domain (RBD) immunoglobulin G (IgG) antibody at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: GMT of SARS-CoV-2 neutralizing antibody (including true virus-based SARS-CoV-2 neutralizing test) at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Fold increase in antibody anti-S1 IgG antibody titers, as compared to baseline, at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Fold increase in antibody anti-RBD IgG antibody titers, as compared to baseline, at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Fold increase in SARS-CoV-2 neutralizing antibody titers (virus neutralizing test), as compared to baseline, at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Seroconversion rates (SCR) defined as a minimum of 4-fold increase of antibody titers, as compared to baseline, at Day 7, Day 21 after prime vaccination, and at Day 7, Day 21 after boost vaccination.

    Time: Day 7, Day 21 after prime vaccination, and Day 7, Day 21 after boost vaccination
    408 Paracetamol Discontinuation in the Elderly After Long-term Consumption

    To investigate if long-term treatment of paracetamol can be discontinued without no worsening on pain, health-related quality-of-life and level of function compared to continuing paracetamol treatment in patients aged 65 years or more.

    NCT04523740
    Conditions
    1. Pain, Chronic
    2. Pain, Medication
    3. Pain, Discontinuation
    Interventions
    1. Drug: Placebo
    2. Drug: Paracetamol
    MeSH:Chronic Pain
    HPO:Chronic pain

    Primary Outcomes

    Description: Comparison of changes in visual analog scale (VAS) pain intensity during the last 24 hours, from baseline value at week 2 between the control and intervention group. VAS is a 0-100 mm scale where 0 is "no pain" and 100 is "worst pain"

    Measure: Visual analog scale (VAS) pain during til last 24 hours

    Time: Change from baseline value at week 2

    Secondary Outcomes

    Description: Comparison of changes in EQ5D-5L index from baseline values at week 2 between the control and intervention group. EQ-5D is an abbreviation for "European Quality of life - 5 Dimensions" and measures Quality of Life. The scale has five subcomponents with scores from 1 (best) to 5 (worst). The five subcomponents constitute a health state that is translated into an index value using the Danish Crosswalk Index Value Calculator from Euroqol's website. The index value is anchored at 0 = death and 1 = full health and the range in the Danish population is from -0.624 (worse than death) to 1.0 (full health). Higher values / increases in index value is better than lower values / decreases in index value.

    Measure: EQ5D-5L index

    Time: Change from baseline value at week 2

    Description: Number of participants that initiate other regular analgesics or withdraw from the trial

    Measure: Treatment failure.

    Time: Week 2

    Description: Functional level is measured by grib strength with a Hand Dynamometer

    Measure: Grip strength

    Time: Change from baseline value at week 2

    Description: Functional level is measured by a sitting-rising test

    Measure: Sitting-rising test

    Time: Change from baseline value at week 2

    Description: Collected from a trial diary. Visual analog scale (VAS) is a 0-100 mm scale where 0 is "no pain" and 100 is "worst pain"

    Measure: Sum of daily visual analog scale (VAS) pain

    Time: Sum from baseline to week 2

    Description: Did the intervention change the participants' paracetamol consumption after ending the treatment period.

    Measure: Followup: Number of regular users (3 grams of paracetamol or more per day) since ending treatment period.

    Time: week 26

    Description: Comparison of changes from baseline and week 2 values at week 26 (post treatment period). Visual analog scale (VAS) is a 0-100 mm scale where 0 is "no pain" and 100 is "worst pain"

    Measure: Followup: Visual analog scale (VAS) pain during til last 24 hours

    Time: Week 26

    Description: Comparison of changes in EQ5D-5L index from baseline and week 2 values at week 26 (post treatment period) between the control and intervention group. EQ-5D is an abbreviation for "European Quality of life - 5 Dimensions" and measures Quality of Life. The scale has five subcomponents with scores from 1 (best) to 5 (worst). The five subcomponents constitute a health state that is translated into an index value using the Danish Crosswalk Index Value Calculator from Euroqol's website. The index value is anchored at 0 = death and 1 = full health and the range in the Danish population is from -0.624 (worse than death) to 1.0 (full health). Higher values / increases in index value is better than lower values / decreases in index value.

    Measure: Followup: EQ5D-5L index

    Time: Week 26

    Description: Number of participants who initiated regular use of other analgesics and comparison of changes between the control and intervention group (post treatment period)

    Measure: Trial failure

    Time: Week 26
    409 Phase I Study to Evaluate the Safety, Tolerability, Pharmacodynamics (PD) and Pharmacokinetics (PK) of DWRX2003 (Niclosamide IM Depot) Injection Following Intramuscular Administration in Healthy Volunteers

    This study is to assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of Niclosamide (DWRX2003) following escalating doses of DWRX2003 administered as an intramuscular injection in healthy volunteers.

    NCT04524052
    Conditions
    1. Healthy
    Interventions
    1. Drug: DWRX2003
    2. Drug: Placebo

    Primary Outcomes

    Description: AE rate, incidence, severity and causality of adverse events (AEs) and serious adverse events (SAEs)

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: follow-up 48 days after dosing

    Secondary Outcomes

    Description: Maximum measured plasma concentration over the time span specified

    Measure: pharmacokinetic changes of niclosamide from baseline in each dose group: Cmax

    Time: follow-up 48 days after dosing

    Description: Time of the maximum measured plasma concentration

    Measure: pharmacokinetic changes of niclosamide from baseline in each dose group: Tmax

    Time: follow-up 48 days after dosing

    Description: Change in C reactive protein levels

    Measure: pharmcodynamic analysis of niclosamide from baseline in each dose group and time point: CRP

    Time: on Day 3, 7, 10 and 14
    410 A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Camostat Mesilate Compared to Standard of Care in Subjects With Mild-Moderate COVID-19

    This study will evaluate the efficacy of oral Foipan® (camostat mesilate) compared with the current standard of care in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with mild-moderate COVID-19 disease. Patients will attend 4 study visits over a period of up to 28 days.

    NCT04524663
    Conditions
    1. Covid19
    Interventions
    1. Drug: Camostat Mesilate
    2. Drug: Placebo
    3. Other: Standard of Care Treatment

    Primary Outcomes

    Description: This outcome is defined as the time in days from randomization to the first of two consecutive negative RT-PCR results of self-collected nasal swabs.

    Measure: Time until cessation of shedding of SARS-CoV-2 virus

    Time: Up to 28 days

    Secondary Outcomes

    Description: Number of symptomatic patients with clinical worsening, defined as the development of respiratory distress or symptoms that require hospitalization.

    Measure: Clinical worsening of COVID-19 disease in symptomatic patients

    Time: Up to 28 days

    Description: Number of patients that develop antibodies to SARS-CoV-2.

    Measure: Development of antibodies to SARS-CoV-2

    Time: Up to 28 days

    Description: This outcome is defined as absence of moderate or severe symptoms for at least 24 hours for those reporting moderate or severe symptoms at baseline

    Measure: Time until resolution of symptoms

    Time: Up to 28 days

    Description: Progression of respiratory symptoms defined as a two-level increase of a symptom on the Daily Symptom Status Questionnaire within a 24 hour period, or a one-level increase of a symptom on the Daily Symptom Status Questionnaire observed/sustained for a consecutive 48 hour period.

    Measure: Time until progression of symptoms

    Time: Up to 28 days

    Measure: Drug level on day five, one hour after a dose taken on an empty stomach

    Time: Day 5, 1 hour post dose
    411 A Phase 1, Randomized, Double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of CT-P59 in Healthy Subjects

    This is a Phase I study that randomized, double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose Study to evaluate Safety, Tolerability and Pharmacokinetics of CT-P59 in Healthy Subjects.

    NCT04525079
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: CT-P59
    2. Drug: Placebo

    Primary Outcomes

    Description: Proportion of patients with Treatment Emergent Adverse Events (TEAEs) Proportion of patients with Treatment Emergent Serious Adverse Events (TESAEs) Proportion of patients with TEAEs of special interest (IRR hypersensitivity/anaphylactic reaction

    Measure: Primary safety outcome

    Time: Day 14

    Secondary Outcomes

    Description: Proportion of patients with Treatment Emergent Adverse Events (TEAEs) Proportion of patients with Treatment Emergent Serious Adverse Events (TESAEs) Proportion of patients with TEAEs of special interest (IRR including hypersensitivity/anaphylactic reaction) Incidence of ADA and NAbs to CT-P59 (positive or negative)

    Measure: To evaluate the safety of CT-P59

    Time: Up to 90 Days

    Description: 1. Pharmacokinetic (PK) parameter: Area under the serum concentration-time curve from time zero to infinity, calculated using the linear up and low down trapezoidal rule(AUC0-inf) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 2. PK parameter: Dose normalized AUC0-inf (normalized to total body dose)(AUC0-inf/Dose) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 3. PK parameter: AUC from time zero to the last quantifiable concentration, calculated using the linear up and log down trapezoidal rule(AUC0-last) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 4. PK parameter: Dose normalized AUC0-last (normalized to total body dose)(AUC0-last/Dose) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 5. PK parameter: Maximum observed serum concentration(Cmax) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 6. PK parameter: Dose normalized Cmax(normalized to total body dose)(Cmax/Dose) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 7. PK parameter: Time to Cmax(Tmax) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 8. PK parameter: Terminal elimination half-life(t1/2) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 9. PK parameter: Percentage of the area extrapolated for calculation of AUC0-inf(%AUCext) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 10. PK parameter: Terminal elimination rate constant estimated from the linear regression of the natural log-transformed concentration over time at the terminal phase(λz) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 11. PK parameter: Total body clearance(CL) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 12. PK parameter: Volume of distribution during the terminal phase(Vz) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days
    412 High Dose Vitamin-D Substitution in Patients With COVID-19: a Randomized Controlled, Multi Center Study

    The world is currently facing a pandemic with the coronavirus (SARS-CoV-2) which leads to the disease of COVID-19. Risk factors for a poor outcome of COVID-19 have so far been identified as older age and co-morbidity including chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD) and current smoking status. Previous studies found, that vitamin D deficiency is more prevalent among patients with these risk factors. There are observational studies reporting independent associations between low serum concentrations of 25-hydroxyvitamin D (the major circulating vitamin D metabolite) and susceptibility to acute respiratory tract infection. Vitamin D substitution in patients with COVID-19 who show a vitamin D deficiency should therefore be investigated for efficacy and safety. The study is designed as a randomized, placebo-controlled, double blind study. The objective of the study is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with a single high dose of vitamin D compared to standard treatment only.

    NCT04525820
    Conditions
    1. Covid19
    2. Vitamin D Deficiency
    3. Corona Virus Infection
    4. ARDS
    5. Coronavirus
    6. SARS-CoV Infection
    Interventions
    1. Drug: Single high dose vitamin D
    2. Drug: Placebo
    3. Drug: Treatment as usual vitamin D
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Vitamin D Deficiency
    HPO:Low levels of vitamin D

    Primary Outcomes

    Description: Overall duration of the hospitalization from day of admission until the day of discharge or fatality

    Measure: Length of hospitalization

    Time: Administration to Discharge from hospital care (mean duration is between 14 and 22 days for Patients with COVID 19)

    Secondary Outcomes

    Description: Did the patient need a intensive care treatment during the hospitalization (yes/no)

    Measure: Need of intensive care

    Time: Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: Day of admission to ICU until discharge or fatality

    Measure: Lenght of the Intensive Care Treatment

    Time: Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: Percentage of patient died during hospitalization

    Measure: Overall mortality

    Time: During the length of hospitalisation (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: percentage of patients with 25-hydroxyvitamin D > 50nmol/L (>20ng/mL) at day 7 - The values of calcium, phosphorus, 24-hydroxyvitamin D, 1.25-dihydroxyvitamin D, parathyroid hormone.

    Measure: Development of vitamin D levels

    Time: Day 1 (Baseline) and Day 7 after the first administration of the high dose vitamin D or the placebo and at discharge (mean hospital stay is between 14 and 22 days for Patients with COVID-19)

    Description: percentage of patients developing a sepsis

    Measure: Development of sepsis

    Time: During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)

    Other Outcomes

    Description: We assess every other complications which occurs due to COVID-19

    Measure: Complications due to COVID-19

    Time: During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: The BP will be assessed daily in mmHg

    Measure: Blood pressure (BP)

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: The heart rate will be assessed daily in bpm

    Measure: Heart rate

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: The SpO2 will be assessed daily in %

    Measure: Peripheral oxygen saturation (SpO2)

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Requirement for oxygen will be assessed daily (yes/no) if yes how many liters per minute

    Measure: Percentage of patients who require oxygen

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Breathing frequence will be assessed daily in breaths per minute

    Measure: Breathing frequency

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: GCS will be assessed daily 3 to 15 points. It describes the extent of impaired consciousness. 15 points means no impairment, 3 points means severe impairment of consciousness.

    Measure: Glasgow Coma Scale (GCS)

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Assessing the history of smoking in pack years (PY). the assessment will be made with the following options for answering Current smoker: Smoking for how many years? Cigarettes per day? Former smoker, how many years smoked? How many cigarettes per day Life-long non-smoker

    Measure: Percentage of patients are smokers, former smokers or lifelong non-smokers

    Time: Assessing of the smoking Status at Basleine

    Description: Assessed in No/ Mild/ Moderate /Severe

    Measure: Current Symptoms

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Temperature will be assessed daily in degrees celsius

    Measure: Temperature

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
    413 A Proof of Concept Study of the Safety and Efficacy of VIB7734 for the Treatment and Prevention of Acute Lung Injury (ALI) in Patients With SARS-CoV-2 Infection

    The study aims to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Subjects will be administered a single dose of VIB7734 injected under the skin, assessed for efficacy for 28 days and followed for an additional 42 days.

    NCT04526912
    Conditions
    1. Acute Lung Injury
    Interventions
    1. Drug: VIB7734
    2. Drug: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

    Primary Outcomes

    Description: Critical illness is defined by respiratory failure (requiring any of the following: endotracheal intubation, oxygen delivered by high flow nasal cannula, non-invasive positive pressure ventilation, extracorporeal membrane oxygenation or clinical diagnosis of respiratory failure) or shock (systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg, or requiring vasopressors)

    Measure: The proportion of patients who achieve treatment success through Day 28, defined as avoidance of death and critical illness

    Time: Day 1 (Baseline) through Day 28

    Secondary Outcomes

    Description: Defined as measure of safety

    Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent fatal and life-threatening SAEs, Treatment-emergent Serious Adverse Events

    Time: Day 1 (Baseline) through Day 70

    Description: Safety evaluation via review of labs (white blood cell (WBC) with differential counts, hemoglobin, platelet count, liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin levels), serum chemistry, cardiac troponin coagulation markers (prothrombin time [PT], partial thromboplastin time [PTT], D dimer, fibrinogen), and urinalysis)

    Measure: Change in safety laboratory parameters

    Time: Day 1 (Baseline) through Day 70
    414 A Global Multicenter, Randomized, Double-blind, Placebo -Controlled, Adaptive Designed Phase Ⅲ Clinical Trial to Evaluate the Efficacy, Safety and Immunogenicity of Ad5-nCoV in Adults 18 Years of Age and Older

    This study is a global multicenter, randomized, double-blind, placebo -controlled, adaptive designed phase Ⅲ clinical trial, in order to evaluate the efficacy, safety and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in adults 18 years old and above.

    NCT04526990
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
    2. Biological: Placebo

    Primary Outcomes

    Description: The efficacy of Ad5-nCoV in preventing virologically confirmed (PCR positive) COVID-19 disease

    Measure: Incidence of COVID-19 cases

    Time: day 28 to 12 months post vaccination

    Description: Evaluate the incidence of severe adverse events (SAE)

    Measure: Incidence of SAE

    Time: Within 12 months

    Secondary Outcomes

    Description: Evaluate the efficacy of Ad5-nCoV in preventing severe COVID-19 disease caused by SARS-CoV-2 infection

    Measure: Incidence of severe COVID-19 cases

    Time: Day 14 to 12 months post vaccination

    Description: Incidence of solicited adverse reactions within 7 days after vaccination, in a subset

    Measure: Incidence of solicited adverse reactions

    Time: Day 0-7 post vaccination

    Description: Incidence of unsolicited adverse events within 28 days after vaccination in a subset

    Measure: Incidence of unsolicited adverse events

    Time: Day 0-28 post vaccination

    Description: The seroconversion rate of S-RBD IgG antibody post vaccination

    Measure: Immunogencity of S-RBD IgG antibody (ELISA method)

    Time: Day 28 post vaccination

    Description: The seroconversion rate of neutralizing antibody

    Measure: Immunogencity of neutralizing antibody

    Time: Day 28 post vaccination

    Description: Number of cell-mediated immune response against SARS-CoV-2

    Measure: Cell-mediated immune profile

    Time: Day 28 post vaccination
    415 Multicenter, Randomized, Double-blind, Placebo-controlled Pilot Study of Treamid Efficacy and Safety in the Rehabilitation of Patients After COVID-19 Pneumonia

    The innovative drug Treamid is planned for use in the rehabilitation of patients after COVID-19 pneumonia in a pilot, multicenter, randomized, double-blind, placebo-controlled Phase II clinical study to assess the efficacy and safety of Treamid, tablets, 50 mg in patients with fibrotic changes in the lungs after COVID-19 pneumonia during a 28-day treatment. The primary objective of the study is to demonstrate the efficacy of Treamid tablet, 50 mg in change in forced vital capacity (FVC) and/or diffusing capacity of lung for carbon monoxide (DLCO) at Week 4. The secondary objective of the study is to evaluate the safety of Treamid tablet, 50 mg and pharmacokinetics (PK).

    NCT04527354
    Conditions
    1. SARS-CoV-2 Infection
    2. Fibrosis Lung
    Interventions
    1. Drug: Treamid
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinically significant changes include a relative ≥ 10% increase in FVC or a relative increase in FVC within the range from ≥ 5% to <10% and a relative ≥ 15% in DLCO

    Measure: Rate of clinically significant change in FVC and/or DLCO at Week 4 relative to the baseline value

    Time: Day 1- Day 28

    Secondary Outcomes

    Measure: Change in distance covered for 6 minutes (6MWD) at Weeks 2 and 4 from the baseline value (based on 6-minute walk test)

    Time: Day 1- Day 28

    Measure: Change in the score of the Borg scale at Weeks 2 and 4 from the baseline value (based on the 6-minute walk test)

    Time: Day 1- Day 28

    Measure: Change in forced expiratory volume for the first second (FEV1) according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

    Time: Day 1- Day 28

    Measure: Change in FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

    Time: Day 1- Day 28

    Measure: Change in FEV1/FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

    Time: Day 1- Day 28

    Measure: Change in DLCO according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

    Time: Day 1- Day 28

    Measure: Change in Total Lung Capacity (TLC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

    Time: Day 1- Day 28

    Measure: Change in Functional Residual Capacity (FRC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

    Time: Day 1- Day 28

    Description: Classification of lung damage includes the following stages: CT-0 (norm), CT-1 (< 25% of lung damage), CT-2 (25-50% of lung damage), CT-3 (50-75% of lung damage), CT-4 (> 75% of lung damage)

    Measure: The rate of reduction in the lung damage degree based on the computed tomography (CT) at Week 4 relative to the baseline value

    Time: Day 1- Day 28

    Measure: Change in mMRC Dyspnea Score in Week 1, Week 2, Week 3, and Week 4 from the baseline value

    Time: Day 1- Day 28

    Measure: Change in the overall score of the KBILD Questionnaire at Week 2 and Week 4 relative to the baseline value

    Time: Day 1- Day 28

    Other Outcomes

    Measure: The rate of adverse events (AEs)

    Time: Day 1- Day 28

    Measure: The rate of serious adverse events (SAEs)

    Time: Day 1- Day 28

    Description: Blood sampling for the PK study of the parameter Сtrough will be performed for all patients prior to administration of the Treamid / Placebo at Week 0, Week 2, and Week 4 visits.

    Measure: Residual concentration Ctrough of the active substance of Treamid

    Time: Day 1- Day 28
    416 Colchicine in Moderate Symptomatic COVID-19 Patients: Double Blind, Randomized, Placebo Controlled Trial to Observe the Efficacy

    This is a prospective, double blind, randomized, placebo controlled clinical trial. The participants will be randomized into two groups (group A and group B). Patients of group-A are the treatment group. They will be treated with optimal treatment based on the algorithm proposed in National Guidelines on Clinical Management of Coronavirus Disease 2019 (Covid-19) Version 7.0, 28 May 2020, along with Colchicine for 14 days. The patients in group-B will be controlled group. They will be treated with optimal treatment based on the algorithm proposed in National Guideline along with a placebo.

    NCT04527562
    Conditions
    1. Covid19
    Interventions
    1. Drug: Colchicine
    2. Drug: Placebo

    Primary Outcomes

    Description: Seven-category ordinal scale. The scale is recommended by the WHO R&D Blueprint expert group. The seven-category ordinal scale consisted of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death

    Measure: Time to develop clinical deterioration, defined as the time from randomization to a deterioration of two points (from the status at randomization) on a Seven-category ordinal scale.

    Time: 14 days following randomization

    Secondary Outcomes

    Measure: Length of hospital stay

    Time: 14 days following randomization

    Measure: Number of participant requiring increased amount of supplemental oxygen

    Time: 14 days following randomization

    Measure: Number of participants requiring mechanical ventilation

    Time: 14 days following randomization

    Measure: Number of participants who die

    Time: 14 days following randomization
    417 A Phase 2, Randomized, Double-Blind, Placebo-controlled Study of the Safety and Efficacy of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized Due to COVID-19

    A phase 2, placebo-controlled study of the safety and efficacy of STI-5656 (Abivertinib Maleate) in subjects hospitalized due to COVID-19

    NCT04528667
    Conditions
    1. Covid19
    Interventions
    1. Drug: STI-5656
    2. Drug: Placebo

    Primary Outcomes

    Description: Proportion of subjects whoa re alive and discharged from the hospital by Day 29

    Measure: Proportion of subjects discharged from hospital

    Time: Randomization through Day 29

    Secondary Outcomes

    Description: Types, frequencies, and severities of adverse events and their relationships to STI-5656, including serious adverse events

    Measure: Incidence of adverse events (safety)

    Time: Randomization through study completion through Day 36

    Description: Time from onset of COVID-19 symptoms to hospital admission, time from hospitalization to start of treatment (D1), and time from D1 to hospital discharge

    Measure: Time to hospital admission, treatment, and discharge

    Time: Randomization through study completion through Day 36

    Description: Number of days hospitalized from randomization through Day 36

    Measure: Number of days hospitalized

    Time: Randomization to Day 36

    Description: Change in clinical status as assessed using a 0-8 ordinal scale, where a lower score equals better outcome, at Days 3, 10, and 36

    Measure: Change in clinical status as assessed using a 0-8 ordinal scale

    Time: Randomization to Day 3, Day 10, and Day 36

    Description: Change in RT-PCR test results (or equivalent) at Days 3, 10, and 36

    Measure: Change in RT-PCR test results

    Time: Randomization to Day 3, Day 10, and Day 36

    Description: Change in C-reactive protein (CRP) levels at Day 3 and Day 10

    Measure: Change in C-reactive protein levels

    Time: Randomization to Day 3 and Day 10

    Description: Area under the serum concentration-time curve (AUC) of STI-5656

    Measure: AUC of STI-5656 (PK)

    Time: Randomization through Day 8

    Description: Maximum observed serum concentration (Cmax) of STI-5656

    Measure: Cmax of STI-5656 (PK)

    Time: Randomization through Day 8

    Description: Apparent serum terminal elimination half life (t½) of STI-5656

    Measure: t½ of STI-5656 (PK)

    Time: Randomization through Day 8

    Description: Change in cytokine levels (including IL-6, TNF-a, IFNγ, IL1β) at Day 3 and Day 10

    Measure: Change in cytokine levels

    Time: Randomization to Day 3 and Day 10

    Description: Time to Cmax (Tmax) of STI-5656

    Measure: Tmax of STI-5656 (PK)

    Time: Randomization through Day 8
    418 Ivermectin to Prevent Hospitalizations in COVID-19: Randomized, Double-blind, Placebo-controlled

    It is a single-center, prospective, randomized, double-blind, placebo-controlled study carried out by the Ministry of Public Health of the Province of Corrientes, Argentina, in coordination with the Corrientes Institute of Cardiology "Juana F. Cabral". Patients who meet all the inclusion criteria and none of the exclusion criteria are randomized via the web system to receive placebo or ivermectin. The need for hospitalization in patients with COVID-19 is assessed as the primary end point. As secondary end points are evaluated: time to hospitalization (in days); use of invasive mechanical ventilation; time to invasive mechanical ventilation (in days); dialysis; all-cause mortality; negative of the swab at 3 ± 1 days and 12 ± 2 days after entering the study and ivermectin safety. Intermediate internal analyzes of study objectives and serious adverse events will be performed, including 125; 250 and 375 patients in order to assess the possible need for early termination of the study. For these intermediate internal analyzes, the Haybittle-Peto rule will be followed, therefore a value of p <0.001 will be considered significant

    NCT04529525
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo

    Primary Outcomes

    Description: Hospitalization will be considered when at least 24 hours have elapsed in a health institution, in any of its services.

    Measure: Percentage of Hospitalization of medical cause in patients with COVID-19 in each arm

    Time: through study completion, an average of 30 days

    Secondary Outcomes

    Description: Number of days elapsed

    Measure: Time to hospitalization

    Time: through study completion, an average of 30 days

    Description: All patients who are connected to invasive mechanical ventilation support

    Measure: Percentage of Use of invasive mechanical ventilation support in each arm

    Time: through study completion, an average of 30 days

    Description: Number of days elapsed

    Measure: Time to invasive mechanical ventilation support

    Time: through study completion, an average of 30 days

    Description: All patients who require temporary or permanent renal replacement therapy

    Measure: Percentage of dialysis in each arm

    Time: through study completion, an average of 30 days

    Description: Death of the patient, from any cause.

    Measure: All-cause mortality

    Time: through study completion, an average of 30 days

    Description: Negative Nasal Swab Using Polymerase Chain Reaction Technique

    Measure: Negative of the swab at 3±1 days and 12±2 days after entering the study

    Time: At days 3±1 and 12±2

    Description: According to the adverse events that patients may present.

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])

    Time: through study completion, an average of 30 days
    419 A Randomised, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Novel Rifaximin Formulations in Healthy Volunteers

    Phase 1, Randomised, Placebo-Controlled, Single-Ascending Dose and Multiple-Dose with 3 novel RIFAXIMIN Formulations. 2 phases: Single-Ascending Dose (SAD) Phase and a Multiple-Dose (MD) Phase, Plus optional open-label, crossover Food Effect (FE) Evaluation Primary objective: evaluate the safety and tolerability of three novel formulations of rifaximin in healthy volunteers. Secondary objective: evaluate the pharmacokinetics (PK) of the novel formulations and to assess for the presence of exploratory biomarkers.

    NCT04529811
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: Rifaximin Novel Formulation
    2. Drug: Placebo

    Primary Outcomes

    Measure: Percentage of participants with adverse events

    Time: Up to 18 days
    420 Randomized, Blind, Placebo-controlled Phase- i Study and Randomized, Open Phase Phase-ii Study of QAZCOVID-IN®- COVID-19 Inactivated Vaccine in Healthy Adult Volunteers From 18 Years Old and Elder

    Randomized, blind, placebo-controlled phase- i study and randomized, open phase phase-ii study of QAZCOVID-IN®- COVID-19 inactivated vaccine in healthy adult volunteers from 18 years old and elder

    NCT04530357
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    3. Vaccine Adverse Reaction
    Interventions
    1. Biological: QazCovid-in® - COVID-19 inactivated vaccine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Frequency of adverse reaction in the seven days following each immunization per age group

    Measure: Frequency of adverse events up to seven days after immunization

    Time: Seven days after each immunization

    Description: Frequency of adverse reaction in the 21 days following each immunization per age group

    Measure: Frequency of adverse events up to 21 days after immunization

    Time: 21 days after each immunization

    Description: The proportion of volunteers with increased levels of the immune response of specific neutralizing antibody titers in ELISA greater than ≥ 4 times 21 days following the second vaccination compared with a placebo.

    Measure: The proportion of volunteers with increased levels of the immune response of specific neutralizing antibody titers in ELISA following the vaccination, compared with a placebo

    Time: at days 0, 21, 27, 42

    Secondary Outcomes

    Description: Incidence of serious adverse events during the study.

    Measure: Incidence of serious adverse events during the study

    Time: throughout the study, an average of 42 days

    Description: Cell-mediated immune profile

    Measure: Cell-mediated immune profile

    Time: at days 0, 7, 21, 27, 42
    421 Outpatient Use of Ivermectin in COVID-19

    Covid 19, a novel coronavirus, causes infection that, while mild to moderate in many people, can lead to severe disease in a significant portion. Currently, it is expected that the majority, 81%, of patients with COVID-19 will have mild to moderate disease, with 14% having more severe disease (2). There exists a number of candidate drugs that may inhibit SARS-CoV-2 infection or progression of disease. Simple, safe and low-cost strategies that may be the best solution to inhibit infection and limit transmission and spread of infection. Ivermectin is a drug initially synthesized and used as an anthelmintic. It has been found to have activity against several RNA viruses such as the SARS-CoV-2 by mechanisms that inhibit importin α/β-mediated nuclear transport that may prevent viral proteins from entering the nucleus to alter host cell function. A recent in vitro study showed that a single dose of ivermectin could kill COVID-19 in vitro within 48 hours. A recent multi-continent retrospective study of 1,400 patients demonstrated an association of ivermectin use with lower in-hospital mortality 1.4% versus 8.5%. Given these findings and its safety profile, cost and ease of administration, Ivermectin warrants study as a potential treatment to prevent progression of COVID 19 infection.

    NCT04530474
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin Pill
    2. Drug: Placebo

    Primary Outcomes

    Description: Clinical Improvement as measured by a standardized scale

    Measure: Clinical Improvement

    Time: 28 days
    422 The Effect of Melatonin and Vitamin C on COVID-19

    This is a double-blind placebo controlled trial that seeks to evaluate the impact of melatonin and vitamin C on symptoms and outcomes of patients with COVID-19.

    NCT04530539
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Dietary Supplement: Vitamin C
    2. Dietary Supplement: melatonin
    3. Dietary Supplement: Placebo
    4. Other: Symptom Survey
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Symptom severity will be tracked electronically

    Measure: Symptom Severity

    Time: 14 days

    Secondary Outcomes

    Description: Determine symptom course of those with moderate or severe symptoms

    Measure: Symptom progression

    Time: 14 days
    423 Selective Estrogen Modulation and Melatonin in Early COVID-19

    This study is a randomized, double-blind, controlled clinical trial to evaluate the effects of toremifene and/or melatonin in adults with mild COVID-19.

    NCT04531748
    Conditions
    1. Covid19
    Interventions
    1. Drug: Toremifene
    2. Drug: Melatonin
    3. Other: Placebo

    Primary Outcomes

    Description: Score total of 0-12 assessed daily. Each category based on severity of symptoms of Cough, Shortness of breath, Fatigue/tiredness and daily temperature on a rating scale of 0-3.

    Measure: Peak increase in COVID-19 Sign and Symptom score

    Time: Screening to 28 days

    Secondary Outcomes

    Description: Daily mean values

    Measure: Nadir Oxygen Saturation

    Time: Day 1 through day 14

    Description: Daily mean values

    Measure: Peak Heart Rate

    Time: Day 1 through day 14

    Description: Score total of 0-12 assessed daily. Each category based on severity of symptoms of Cough, Shortness of breath, Fatigue/tiredness and daily temperature on a rating scale of 0-3.

    Measure: Time to COVID-19 Sign and Symptom score resolution

    Time: Screening to 28 days

    Description: not hospitalized, no limitation of activities (or resumption of normal activity) not hospitalized but limitation on activities hospitalized, not requiring supplemental oxygen hospitalized, requiring supplemental oxygen (low-flow, e.g., nasal prong) hospitalized, requiring non-invasive ventilation and/or high-flow oxygen hospitalized, on invasive ventilation or ECMO death

    Measure: Time to WHO 7-point ordinal scale score of 3 or higher

    Time: Day 1 to Day 30
    424 First-In-Human, Randomized, Double-Blinded, Placebo-Controlled Trial in Healthy Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Ascending Intravenous and Subcutaneous Doses of ARGX-117 Co-mixed With rHuPH20

    This is a phase 1, first-in-human, double-blinded, randomized, placebo-controlled, escalating single and multiple dose levels trial to evaluate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of ARGX-117 administered IV and/or SC. Up to 104 healthy, adult male and female subjects of non-childbearing potential will be enrolled in this trial.

    NCT04532125
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Biological: ARGX-117
    2. Biological: Placebo
    3. Biological: ARGX-117 + rHuPH20
    4. Biological: placebo+rHuPH20

    Primary Outcomes

    Measure: Number of (S)AE

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)

    Secondary Outcomes

    Measure: Area Under The Curve (AUC)

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)

    Description: Maximum observed serum concentration

    Measure: Maximum serum concentrations (Cmax)

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)

    Description: Time calculated to reach Cmax

    Measure: Time to reach maximum serum concentrations (Tmax)

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)

    Description: Functional complement activity

    Measure: Free C2 concentration

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)

    Description: Functional complement activity

    Measure: Total C2 concentration

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)

    Description: Functional complement activity

    Measure: CH50 titers

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)

    Description: Immunogenicity against ARGX-117

    Measure: Level of anti-drug antibodies

    Time: Up to 17 weeks (arm 1) and up to 22 weeks (arm 2)
    425 A First-in-Human, Randomized, Double-Blind, Placebo Controlled, Single Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Healthy Subjects

    The primary purpose of this study is to investigate the safety and tolerability of BGB-DXP593 administered intravenously as a single dose in healthy participants

    NCT04532294
    Conditions
    1. Covid19
    Interventions
    1. Drug: BGB DXP593
    2. Drug: Placebo

    Primary Outcomes

    Measure: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)

    Time: Up to 113 days

    Measure: Number of participants experiencing Serious Adverse Events (SAEs)

    Time: Up to 113 days

    Secondary Outcomes

    Measure: Maximum observed plasma concentration (Cmax) of BGB-DXP593

    Time: Up to 113 days

    Measure: Area under the plasma concentration-time curve (AUC) from time zero to the time of the last quantifiable concentration (AUCt) of BGB-DXP593

    Time: Up to 113 days

    Measure: AUC from time zero to infinity (AUCinf) of BGB-DXP593

    Time: Up to 113 days

    Measure: AUC from time zero to Day 29 (AUC0-29) of BGB-DXP593

    Time: Up to Day 29

    Measure: Time to maximum observed plasma concentration (tmax) of BGB-DXP593

    Time: Up to 113 days

    Measure: Terminal half life (t1/2) of BGB-DXP593

    Time: Up to 113 days

    Measure: Clearance (CL) of BGB-DXP593

    Time: Up to 113 days

    Measure: Volume of distribution (Vz) of BGB-DXP593

    Time: Up to 113 days

    Measure: Immunogenic response to BGB-DXP593 as assessed by the Detection of antidrug antibodies (ADA)

    Time: Up to 113 days
    426 The Impact of Growth Hormone in Obese Cases With Covid-19

    The use of growth hormone in obese cases with COVID-19 may help them to recover earlier.

    NCT04532554
    Conditions
    1. Covid19
    Interventions
    1. Drug: Growth Hormone
    2. Drug: Placebo

    Primary Outcomes

    Description: need to be hospitalized due to deterioration

    Measure: Need for hospitalization

    Time: one to two weeks

    Secondary Outcomes

    Description: Time to recovery from symptoms and signs

    Measure: Time to recovery

    Time: one to four weeks

    Description: Percentage of reduction in CRP

    Measure: Percentage of reduction in CRP

    Time: one to two weeks

    Description: Percentage of reduction in LDH

    Measure: Percentage of reduction in LDH

    Time: one to two weeks

    Description: Percentage of reduction in Ferritin

    Measure: Percentage of reduction in Ferritin

    Time: one to two weeks

    Description: Time to recovery from leucopenia

    Measure: Time to recovery from leucopenia

    Time: one to two weeks
    427 A Double-blind Placebo-controlled Study to Assess the Efficacy and Safety of Oral Tafenoquine Versus Placebo in Patients With Mild to Moderate COVID-19 Disease

    A clinical study to assess the efficacy and safety of oral tafenoquine compared to placebo in patients with mild to moderate COVID 19 disease.

    NCT04533347
    Conditions
    1. COVID 19 Disease
    Interventions
    1. Drug: Tafenoquine Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of patients with clinical recovery of COVID-19 symptoms on Day 12 [± 1 day]

    Time: Day 12 [± 1 day]

    Secondary Outcomes

    Measure: Proportion of patients with negative SARS-CoV-2 RT-PCR on Day 12 [± 1 day]

    Time: Day 12 [± 1 day]

    Measure: Hospitalization rates due to COVID-19 symptoms (excluding admittance only for administrative or observations purposes)

    Time: Up to 28 Days

    Measure: Number of COVID-19-related medical follow up visits [Doctor's office or emergency room (ER) visit]

    Time: Up to 28 Days

    Measure: Proportion of patients with COVID-19 symptoms at Day 12 by individual symptoms

    Time: Day 12 [± 1 day]
    428 A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV

    This is a study to evaluate the effectiveness and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in a minimum of approximately 2,960 to a maximum of approximately 4,164 healthy HIV-negative (HIV-) adult participants and in approximately 240 medically stable HIV-positive (HIV+) adult participants in up to 15 sites across South Africa. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in these study populations. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study.

    NCT04533399
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant
    2. Other: Placebo

    Primary Outcomes

    Description: Number of human immunodeficiency virus negative (HIV-) participants with first occurrence of positive (+) polymerase chain reaction (PCR), (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 assessed from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Cohort 1: HIV- Participants with Symptomatic Mild, Moderate, or Severe COVID-19

    Time: Day 28 to Day 386

    Description: Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 assessed from Day 28 (7 days after second vaccination) through the length of the study.

    Measure: Cohort 1: HIV- Participants with Symptomatic Moderate or Severe COVID-19

    Time: Day 28 to Day 386

    Description: Numbers and percentages (with 95% confidence intervals [CIs]) of HIV- participants with solicited AEs, local and systemic, for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity.

    Measure: Cohort 1: HIV- Participants with Solicited Adverse Events (AEs)

    Time: 28 days

    Description: Numbers and percentages (with 95% CI) of HIV- participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 35 by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness.

    Measure: Cohort 1: HIV- Participants with Unsolicited AEs

    Time: 35 days

    Description: Numbers and percentages (with 95% CIs) of HIV+ participants with solicited AEs, local and systemic, for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity.

    Measure: Cohort 2: HIV+ Participants with Solicited AEs

    Time: 28 days

    Description: Numbers and percentages (with 95% CI) of HIV+ participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 35 by MedDRA classification, severity score, and relatedness.

    Measure: Cohort 2: HIV+ Participants with Unsolicited AEs

    Time: 35 days

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs at Day 35.

    Measure: Cohort 2: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs)

    Time: Day 35

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Day 35.

    Measure: Cohort 2: Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs)

    Time: Day 35

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCR at Day 35. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre existing titer.

    Measure: Cohort 2: Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs)

    Time: Day 35

    Secondary Outcomes

    Description: Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe COVID-19.

    Measure: Cohort 1: HIV- Participants with Individual Strata of Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19

    Time: Day 28 to Day 386

    Description: Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with COVID-19 requiring hospitalization.

    Measure: Cohort 1: HIV- Participants with COVID-19 Requiring Hospitalization

    Time: Day 28 to Day 386

    Description: Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV- participants.

    Measure: Cohort 1: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification

    Time: Day 28 to Day 386

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.

    Measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.

    Measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as Seroresponse Rates (SRRs)

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as SRRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV- participants.

    Measure: Cohort 1: HIV- Participants with Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs)

    Time: 386 days

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.

    Measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SRRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as SRRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV+ participants.

    Measure: Cohort 2: HIV+ Participants with MAAEs, AESIs, and SAEs

    Time: 386 days

    Description: Counts and proportions of symptomatic virologically confirmed, mild, moderate, and severe COVID-19 outcomes in HIV+ participants as previously described in the second primary efficacy endpoint for Cohort 1 (HIV- participants).

    Measure: Cohort 2: HIV+ Participants with Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19

    Time: Day 28 to Day 385

    Description: Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV+ participants.

    Measure: Cohort 2: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification

    Time: Day 28 to Day 385
    429 A 12-week Randomized, Double-Blind Controlled Trial to Evaluate the Tolerability and Gastrointestinal Response of a Novel, Multi-Strain Synbiotic (PDS-08™) in Children Ages 3-17

    Recent data support the use of specific probiotic strains in a pediatric population. However, given the wide number of commercial products available, and contradictory data in the literature, healthcare providers and consumers are uncertain about whether or not to use probiotics in children and which one(s) to choose. While much progress has been made in understanding the gastrointestinal microbiota and its role in the balanced development of the infant immune system, the tolerability and efficacy of introducing beneficial microbes into the pediatric gastrointestinal tract remain underexplored. The purpose of this study is to investigate the effect of a 9 strain synbiotic consortium comprised of strains with previous pediatric clinical data for use in modulating airway sensitivity, gastrointestinal discomfort, dermatological inflammation, and reduction in the duration and severity of upper respiratory tract infections in a pediatric population.

    NCT04534036
    Conditions
    1. Constipation
    2. Signs and Symptoms
    3. Digestive Signs and Symptoms
    4. Infrequent or Difficult Evacuation
    Interventions
    1. Dietary Supplement: PDS-08
    2. Other: Placebo
    MeSH:Constipation Signs and Symptoms, Digestive
    HPO:Colonic inertia Constipation

    Primary Outcomes

    Description: Assessed as the change from baseline and compared to placebo for the continuous variable estimated using a linear mixed model.

    Measure: Percentage of participants who are spontaneous bowel movement responders, defined as having an average of ≥ 4 complete spontaneous bowel movements (CSBMs) per week and an average increase of ≥ 1 CSBM from baseline, by age group: 3-6, 7-12, 13-17 years.

    Time: Baseline-Day 84

    Secondary Outcomes

    Description: Assessed by daily stool characteristics reported using the seven-point ordinal BSFS score. The BSFS classifies human stool into seven types and scores them accordingly. Type 1: Separate hard lumps (hard to pass) Type 2: Sausage-shaped and lumpy Type 3: Like a sausage but with cracks on its surface Type 4: Like a sausage, smooth and soft Type 5: Soft blobs with clear cut edges (passed easily) Type 6: Fluffy pieces with ragged edges, a mushy stool Type 7: Watery, no solid pieces, entirely liquid. Types 1 and 2 indicate constipation, with 3 through 5 represent the ideal stool form, and 6 and 7 tend towards diarrhea. For a given assessment week, the weekly stool consistency is defined as the sum of non-missing stool consistency score for spontaneous bowel movements during that week divided by the number of non-missing stool consistency scores for spontaneous bowel movements during that week. The parameter will be analyzed using a linear mixed model.

    Measure: Average increase from baseline of Bristol Stool Form Scale (BSFS) score by ≥ 1 point (stool characterized as an increase to either type 2 or 3 or 4) in the intervention group, compared to the placebo group.

    Time: Baseline-Day 84

    Measure: Decrease of ≥ 10% in time spent emptying bowel from beginning to end of bowel movement, compared to baseline.

    Time: Baseline-Day 84

    Description: Assessed by online daily symptom-tracking of stool-quality, regularity, ease of expulsion, bloating, and flatulence.

    Measure: Changes in subjective assessment of gut tolerability as reported by parents or direct relative guardians, indicated by sustained (longer than 7 days of) abdominal pain, severe bloating, heartburn, acid reflux, or indigestion.

    Time: Baseline-Day 84

    Description: Microbiota composition will be identified through fecal samples for total genomic DNA extraction in participants supplemented with PDS-08 or placebo. Metagenomic sequencing will yield a total observable species count and maintenance will be defined as within 20% of the total observed species count when compared to baseline.

    Measure: Maintenance or increase of diversity within the PDS-08 treatment group.

    Time: Baseline-Day 84

    Measure: Significant increase in QoL measured by the KINDL questionnaire with respect to mean change from baseline score (p<0.05).

    Time: Baseline-Day 84

    Measure: Exploratory: number of respiratory tract infections in the PDS-08 group compared to placebo.

    Time: Baseline-Day 84

    Measure: Exploratory: number and percent of participants with reduction in number of acne lesions from baseline as measured by global count of blemishes.

    Time: Baseline-Day 84

    Measure: Exploratory outcomes: changes in fecal calprotectin, histamine, bacterial enzymes (β-glucosidase and β-glucuronidase), β-defensin (hBD2) and short chain fatty acids in treatment group compared to the placebo group.

    Time: Baseline-Day 84
    430 Bacillus Calmette-Guerin Against Covid-19 for Prevention and Amelioration of Severity Trial

    The purpose of this study is to assess the efficacy of Bacille Calmette-Guérin (BCG) vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities. The investigators hypothesize that BCG vaccination can reduce severity of Covid-19 disease. Patients who are residents of participating long-term care facilities (LTCFs), with the ability to understand and cooperate with study procedures, who agree to participate in the study will be randomly assigned to receive BCG vaccination or a placebo. Participants will be followed for up to twelve months to assess severity of Covid-19 outcomes.

    NCT04534803
    Conditions
    1. Covid19
    Interventions
    1. Drug: BCG Vaccine
    2. Other: Placebo

    Primary Outcomes

    Description: Number of people diagnosed with severe Covid-19 disease as documented in the electronic heath record; severe Covid-19 disease is defined as any instance of death, hospitalization, or non-hospitalization but requiring new administration of supplemental oxygen or having a decline in oxygen saturation of 10%, change from ambulant to non-ambulant for 3 or more days, or any new change in mental health status.

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities.

    Time: 12 months

    Secondary Outcomes

    Description: Number of cases of any COVID-19 disease, defined as a positive SARS-Cov-2 test (per PCR or serology), plus fever (as documented in EHR) or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR.) Number of cases of asymptomatic SARS-CoV-2 infection, defined as evidence of SARS-CoV-2 infection (by PCR or seroconversion), absence of associated respiratory illness (as documented in EHR), and no evidence of exposure prior to randomization (baseline serology will be negative). Number of cases of critical care admissions with SARS-CoV-2, defined as the number of admissions to critical care associated with a positive SARS-CoV-2 test. Number of cases of critical care admission duration with SARS-CoV-2, defined as the number of days admitted to critical care (using medical/hospital records) associated with a positive SARS-CoV-2 test.

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of cases)

    Time: 12 months

    Description: 5. Number of cases of critical care admissions, defined as the number of admissions to critical care. 6. Number of cases of mechanical ventilation with SARS-CoV-2, defined as the number of participants needing mechanical ventilation (as documented by EHR) and associated with a positive SARS-CoV-2 test. 7. Number of cases of mechanical ventilation, defined as the number of participants needing mechanical ventilation. 8. Number of cases of All-Cause Mortality, defined as death reported by the long-term care facility. 9. Number of cases of any fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR).

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of cases), continued

    Time: 12 months

    Description: Number of episodes of fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR). Number of episodes of any COVID-19 disease, defined as a positive SARS-Cov-2 test (per PCR or serology), plus fever (as documented in EHR) or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR.) Number of episodes of local and systemic adverse events to BCG vaccination measured over the 3 months following randomization (type and severity of local and systemic adverse events will be collected and graded using toxicity grading scale).

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of episodes)

    Time: 12 months

    Description: Number of days of symptom duration of fever or respiratory illness, defined as number of days with symptoms in any episode of illness that meets the case definition for fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR). Number of days of COVID-19 symptom duration, defined as the number of days with symptoms in any episode of illness that meets the case definition for any COVID-19 disease.

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of days)

    Time: 12 months
    431 A PHASE 1B, 2-PART, DOUBLE-BLIND, PLACEBO-CONTROLLED, SPONSOR-OPEN STUDY, TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF SINGLE ASCENDING (24-HOUR, PART 1) AND EXTENDED (120-HOUR, PART 2) INTRAVENOUS INFUSIONS OF PF-07304814 IN HOSPITALIZED PARTICIPANTS WITH COVID-19

    It is Phase 1b, 2-part, double-blind, placebo-controlled study to evaluate safety, tolerability, and pharmacokinetics of PF-07304814, in patients with SARS-CoV-2 virus infection and with mild-to-moderate symptoms.

    NCT04535167
    Conditions
    1. Viral Disease
    Interventions
    1. Drug: PF-07304814
    2. Drug: Placebo
    MeSH:Virus Diseases

    Primary Outcomes

    Description: Adverse Events (AEs)

    Measure: Frequency of treatment-emergent adverse events (TEAEs)

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Number of participants who withdraw due to treatment-emergent adverse events (TEAEs)

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of treatment-emergent adverse events (TEAEs), causally related to study intervention

    Time: 0 hours up to 41 days

    Description: Serious Adverse Events

    Measure: Frequency of treatment-emergent serious adverse events

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of treatment-emergent infusion site reactions

    Time: 0 hours up to 41 days

    Description: Percent change in laboratory parameters

    Measure: Magnitude of abnormal hematologic laboratory findings

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of abnormal chemistry values

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of abnormal hematologic laboratory findings

    Time: 0 hours up to 41 days

    Description: Percent change in urinalysis parameters

    Measure: Magnitude of abnormal urinalysis findings

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in PR values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in RR values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in QTc values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in QTcF values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in QRS values

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in pulse rate measurements

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in temperature values

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in respiratory rate values

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in systolic blood pressure

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in diastolic blood pressure

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in pulse oximetry/SpO2 measurement

    Time: 0 hours up to 41 days

    Secondary Outcomes

    Description: plasma PK parameters

    Measure: Change in concentration at 24 hours (C24[end of infusion]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration, dose normalised, at 24 hours (C24 (dn) [end of infusion]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration at 120 hours (C120[end of infusion]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in maximum observed concentration (Cmax) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in maximum observed concentration, dose normalised (Cmax [dn]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration at steady state (Css) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration at steady state, dose normalised (Css [dn]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in terminal half life (t1/2) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in clearance (CL) of PF-07304814

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in area-under-the-curve plasma concentration from 0 to time extrapolated to infinity (AUCinf) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in area-under-the-curve plasma concentration from 0 to last quantifiable concentration (AUClast) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in area-under-the-curve plasma concentration from 0 to time extrapolated to infinity, dose normalised (AUCinf [dn]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in steady state volume of distribution (Vss) of PF-00835231

    Time: 0 to 32 hours

    Description: urinary PK parameters (Cohort 2 only)

    Measure: Cumulative amount of unchanged drug excreted into urine (Ae)

    Time: 0 to 36 hours

    Description: urinary PK parameters (Cohort 2 only)

    Measure: Percent of dose excreted as unchanged drug (Ae%) over dosing period

    Time: 0 to 36 hours
    432 A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of Dose Levels and Vaccination Intervals of Ad26.COV2.S in Healthy Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older

    The primary purpose of this study is to assess humoral immune responses of 3 dose levels of Ad26.COV2.S administered intramuscularly (IM) as a 2-dose schedule (56 days apart); Ad26.COV2.S administered IM as a single vaccination; and to test both compressed and expanded 2-dose schedules of Ad26.COV2.S (28 and 84 days apart).

    NCT04535453
    Conditions
    1. Healthy
    Interventions
    1. Biological: Ad26.COV2.S
    2. Other: Placebo

    Primary Outcomes

    Description: Serological response to vaccination as measured by VNA titers 28 days after Vaccination 2 will be reported.

    Measure: Groups 1-6: Serological Response to Vaccination as Measured by Virus Neutralization Assay (VNA) Titers 28 days after Vaccination 2

    Time: 28 days after Vaccination 2 (Day 85)

    Description: Serological response to vaccination as measured by enzyme-linked immunosorbent assay (S-ELISA, ELISA Units/mL [EU/mL]) 28 days after Vaccination 2 will be reported.

    Measure: Groups 1-6: Serological Response to Vaccination as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) 28 days after Vaccination 2

    Time: 28 days after Vaccination 2 (Day 85)

    Description: The GMTs for vaccine were reported. The antibody levels elicited by the vaccine were measured by VNA.

    Measure: Groups 1-6: Virus Neutralization Assay Geometric Mean Titer (GMT) 28 Days After Vaccination 2

    Time: 28 Days after Vaccination 2 (Day 85)

    Description: The GMCs for vaccine were reported. The antibody levels elicited by the vaccine were measured by ELISA.

    Measure: Groups 1-6: Enzyme-linked Immunosorbent Assay Geometric Mean Concentrations (GMCs) 28 Days After Vaccination 2

    Time: 28 Days after Vaccination 2 (Day 85)

    Description: Serological response to vaccination as measured by VNA titers 28 days after Vaccination 1 will be reported.

    Measure: Groups 1-6: Serological Response to Vaccination as Measured by VNA Titers 28 days after Vaccination 1

    Time: 28 Days after Vaccination 1 (Day 29)

    Description: Serological response to vaccination as measured by enzyme-linked immunosorbent assay (S-ELISA, EU/mL) 28 days after Vaccination 1 will be reported.

    Measure: Groups 1-6: Serological Response to Vaccination as Measured by Enzyme-Linked Immunosorbent Assay 28 days after Vaccination 1

    Time: 28 Days after Vaccination 1 (Day 29)

    Description: The GMTs for vaccine were reported. The antibody levels elicited by the vaccine were measured by VNA.

    Measure: Groups 1-6: Virus Neutralization Assay Geometric Mean Titer 28 Days After Vaccination 1

    Time: 28 Days after Vaccination 1 (Day 29)

    Description: The GMTs for vaccine were reported. The antibody levels elicited by the vaccine were measured by ELISA.

    Measure: Groups 1-6: Enzyme-Linked Immunosorbent Assay Geometric Mean Concentrations 28 Days After Vaccination 1

    Time: 28 Days after Vaccination 1 (Day 29)

    Description: Serological response to vaccination as measured by VNA titers 28 days after Vaccination 2 will be reported.

    Measure: Groups 7-8: Serological Response to Vaccination as Measured by Virus Neutralization Assay (VNA) Titers 28 days after Vaccination 2

    Time: 28 days after Vaccination 2 (Day 85)

    Description: Serological response to vaccination as measured by enzyme-linked immunosorbent assay (S-ELISA, EU/mL) 28 days after Vaccination 2 will be reported.

    Measure: Groups 7-8: Serological Response to Vaccination as Measured by Enzyme-Linked Immunosorbent Assay 28 days after Vaccination 2

    Time: 28 days after Vaccination 2 (Day 57)

    Description: The GMTs for vaccine were reported. The antibody levels elicited by the vaccine were measured by VNA.

    Measure: Groups 7-8: Virus Neutralization Assay GMTs 28 Days After Vaccination 2

    Time: 28 Days after Vaccination 2 (Day 57)

    Description: The GMCs for vaccine were reported. The antibody levels elicited by the vaccine were measured by ELISA.

    Measure: Groups 7-8: Enzyme-linked Immunosorbent Assay Geometric Mean Concentrations 28 Days After Vaccination 2

    Time: 28 Days after Vaccination 2 (Day 57)

    Description: Serological response to vaccination as measured by VNA titers 28 days after Vaccination 2 will be reported.

    Measure: Groups 9-10: Serological Response to Vaccination as Measured by Virus Neutralization Assay (VNA) Titers 28 days after Vaccination 2

    Time: 28 days after Vaccination 2 (Day 113)

    Description: Serological response to vaccination as measured by enzyme-linked immunosorbent assay (S-ELISA, EU/mL) 28 days after Vaccination 2 will be reported.

    Measure: Groups 9-10: Serological Response to Vaccination as Measured by ELISA 28 days after Vaccination 2

    Time: 28 days after Vaccination 2 (Day 113)

    Description: The GMTs for vaccine were reported. The antibody levels elicited by the vaccine were measured by VNA.

    Measure: Groups 9-10: Virus Neutralization Assay GMT 28 Days After Vaccination 2

    Time: 28 Days after Vaccination 2 (Day 113)

    Description: The GMCs for vaccine were reported. The antibody levels elicited by the vaccine were measured by ELISA.

    Measure: Groups 9-10: Enzyme-linked Immunosorbent Assay GMCs 28 Days After Vaccination 2

    Time: 28 Days after Vaccination 2 (Day 113)

    Description: Solicited local AEs include (injection site pain/tenderness, erythema and swelling at the study vaccine injection site and the extent (largest diameter) of any erythema and swelling [using the ruler supplied]) will be noted in the participant diary after 7 days after each vaccination.

    Measure: Groups 1-6: Number of Participants with Solicited Local AEs for 7 Days after Each Vaccination

    Time: 7 days after each vaccination (Up to 64 Days)

    Description: Solicited local AEs include (injection site pain/tenderness, erythema and swelling at the study vaccine injection site and the extent (largest diameter) of any erythema and swelling [using the ruler supplied]) will be noted in the participant diary after 7 days after each vaccination.

    Measure: Groups 7-8: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after Each Vaccination

    Time: 7 days after each vaccination (Up to 64 Days)

    Description: Solicited local AEs include (injection site pain/tenderness, erythema and swelling at the study vaccine injection site and the extent (largest diameter) of any erythema and swelling [using the ruler supplied]) will be noted in the participant diary after 7 days after each vaccination.

    Measure: Groups 9-10: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after Each Vaccination

    Time: 7 days after each vaccination (Up to 64 Days)

    Description: Solicited systemic AEs (include body temperature, fatigue, headache, nausea, myalgia) will be noted in the participant diary after 7 days of each vaccination.

    Measure: Groups 1-6: Number of Participants with Solicited Systemic AEs for 7 Days after Each Vaccination

    Time: 7 days after each vaccination (Up to 64 Days)

    Description: Solicited systemic AEs (include body temperature, fatigue, headache, nausea, myalgia) will be noted in the participant diary after 7 days of each vaccination.

    Measure: Groups 7-8: Number of Participants with Solicited Systemic AEs for 7 Days after Each Vaccination

    Time: 7 days after each vaccination (Up to 64 Days)

    Description: Solicited systemic AEs (include body temperature, fatigue, headache, nausea, myalgia) will be noted in the participant diary after 7 days of each vaccination.

    Measure: Groups 9-10: Number of Participants with Solicited Systemic AEs for 7 Days after Each Vaccination

    Time: 7 days after each vaccination (Up to 64 Days)

    Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Groups 1-6: Number of Participants with Unsolicited AEs for 28 Days After Each Vaccination

    Time: 28 days after each vaccination (Up to 85 Days)

    Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Groups 7-8: Number of Participants with Unsolicited AEs for 28 Days After Each Vaccination

    Time: 28 days after each vaccination (Up to 85 Days)

    Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Groups 1-10: Number of Participants with Unsolicited AEs for 28 Days After Each Vaccination

    Time: 28 days after each vaccination (Up to 85 Days)

    Description: SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

    Measure: Groups 1-10: Number of Participants with Serious Adverse Events (SAEs)

    Time: Up to Day 450

    Secondary Outcomes

    Description: Serological response to vaccination as measured by VNA titers 7 days after antigen presentation will be reported.

    Measure: Groups 1-10: Serological Response to Vaccination as Measured by VNA Titers 7 Days After Antigen Presentation

    Time: 7 days after antigen presentation (Day 176 [Groups 1-6]; Day 148 [Groups 7-8]; Day 204 [Groups 9-10])

    Description: Serological response to vaccination as measured by enzyme-linked immunosorbent assay (S-ELISA, EU/mL) 7 days after antigen presentation will be reported.

    Measure: Groups 1-10: Serological Response to Vaccination as Measured by ELISA 7 Days After Antigen Presentation

    Time: 7 days after antigen presentation (Day 176 [Groups 1-6]; Day 148 [Groups 7-8]; Day 204 [Groups 9-10])

    Description: The GMTs for vaccine were reported. The antibody levels elicited by the vaccine were measured by VNA.

    Measure: Groups 1-10: VNA GMT 7 Days After Antigen Presentation

    Time: 7 days after antigen presentation (Day 176 [Groups 1-6]; Day 148 [Groups 7-8]; Day 204 [Groups 9-10])

    Description: The GMCs for vaccine were reported. The antibody levels elicited by the vaccine were measured by ELISA.

    Measure: Groups 1-10: Enzyme-Linked Immunosorbent Assay Geometric Mean Concentrations 7 Days After Antigen Presentation

    Time: 7 days after antigen presentation (Day 176 [Groups 1-6]; Day 148 [Groups 7-8]; Day 204 [Groups 9-10])

    Description: Solicited local AEs (include injection site pain/tenderness, erythema and swelling at the study vaccine injection site and the extent [largest diameter] of any erythema and swelling [using the ruler supplied]) will be noted in the participant diary 7 days after antigen presentation.

    Measure: Groups 1-10: Number of Participants with Solicited Local Adverse Events for 7 Days After Antigen Presentation

    Time: 7 days after antigen presentation (Day 176 [Groups 1-6]; Day 148 [Groups 7-8]; Day 204 [Groups 9-10])

    Description: Solicited systemic AEs include (body temperature, fatigue, headache, nausea, myalgia) will be noted in the participant diary 7 days after antigen presentation.

    Measure: Groups 1-10: Number of Participants with Solicited Systemic Adverse Events for 7 Days After Antigen Presentation

    Time: 7 days after vaccination (Up to Day 175 [Groups 1-6]; Day 148 [Groups 7-8]; Day 204 [Groups 9-10])

    Description: Number of participants with unsolicited AEs for 28 days after antigen presentation will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Groups 1-10: Number of Participants with Unsolicited AEs for 28 Days After Antigen Presentation

    Time: 28 days after antigen presentation (Day 197 [Groups 1-6]; Day 169 [Groups 7-8]; Day 225 [Groups 9-10])

    Description: Number of participants with SAEs throughout the study (from antigen presentation until end of the study) will be reported. SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

    Measure: Groups 1-10: Number of Participants with Serious Adverse Events Throughout the Study

    Time: Up to Day 450

    Description: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported.

    Measure: Groups 1-10: SARS-CoV-2 Neutralizing Antibody Titers as Assessed by VNA

    Time: Up to Day 450

    Description: SARS-CoV-2 binding antibodies as assessed by ELISA to measure humoral immune response will be reported.

    Measure: Groups 1-10: SARS-CoV-2 Binding Antibodies Measured as Assessed by ELISA

    Time: Up to Day 450
    433 Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients: Randomized, Double-blind, and Placebo-controlled

    This is a phase 1 clinical trial to verify the safety and efficacy of DW-MSC in COVID-19 patients. A total of 9 subjects are randomly allocated. Subjects who meet the final inclusion and exclusion criteria are randomized to the test groups (low-dose group and high-dose group) or control group (placebo group) in a ratio of 1:1:1. Subjects assigned to the test groups were administered intravenously once with 5 x 10^7cells of DW-MSC for the low-dose group or 1 x 10^8cells for the high-dose group after registration. Subjects assigned to the control group were administered with placebo in the same manner as the test drug (DW-MSC). At this time, all of the existing standard co-treatment are allowed. DW-MSC is adjunct therapy to standard therapy. This clinical trial is a double-blind trial, in which a randomized method will be used. To maintain the double-blindness of the study, statistician who do not participate in this study independently generate randomization code. Subjects will be randomized to the test groups (low-dose group and high-dose group) or the control group (placebo group) in a 1:1:1 ratio. After the completion of the trial, the randomization code will be disclosed after unlocking the database and unblinding procedures. Follow Up period: observed for 28 days after a single administration

    NCT04535856
    Conditions
    1. Covid19
    2. Corona Virus Infection
    3. SAR
    Interventions
    1. Drug: allogeneic mesenchymal stem cell
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Incidence of TEAE* in Treatment group * TEAE: Treatment-Emergent Adverse Event All adverse reactions will be organized according to System Organ Class (SOC) and Preferred Term (PT) using MedDRA (Medical Dictionary for Regulatory Activities), and the incidence of treatment-emergent adverse events will be summarized for the coded adverse reactions.

    Measure: Incidence of TEAE* in Treatment group

    Time: 28 days

    Secondary Outcomes

    Description: Survival rate is defined as the rate of subjects surviving until Day 14 and Day 28, and the number and rate of surviving subjects for each administration group is given.

    Measure: Survival rate

    Time: until Day 14 and Day 28

    Description: Duration of hospitalization is defined as the number of days in the hospital until Day 28, and descriptive statistics (number of subjects, mean, standard deviation, median, minimum, maximum) are given for each administration group.

    Measure: Duration of hospitalization

    Time: 28 days

    Description: Clinical improvement measured by Ordinal scale change for clinical improvement from baseline to Day 14 and 28

    Measure: Clinical improvement Ordinal scale

    Time: from baseline to Day 14 and Day 28

    Description: Clinical improvement measured by National EWS (National Early Warning Score) change from baseline to Day 7, 14, 28. EWS Points, Risk and Interpretation as follows: 0~4: Low clinical risk; interpretation= Ward-based response 3~4 : Low~medium clinical risk; interpretation= Urgent ward-based response 5~6: Medium clinical risk; interpretation= Key threshold for urgent response

    Measure: Clinical improvement National EWS

    Time: from baseline to Day 7, 14 and Day 28

    Description: Clinical improvement measured by Oxygenation index (PaO2/FiO2) change from baseline (Day 1, 3, 7, 10, 14, 28)

    Measure: Clinical improvement Oxygenation index

    Time: Day 1, 3, 7, 10, 14, 28

    Description: Clinical improvement measured by Lung involvement change by Imaging from baseline (Day 7, 14, 28)

    Measure: Clinical improvement Lung involvement change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for WBC

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for Lymphocytes

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for ESR

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for CRP

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for Fibrinogen

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for IL-6, TNF-α, IL-1β, IF-γ (Day 7, 14, 28)

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28
    434 A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ensifentrine Over 24 Weeks (With a 48-week Safety Subset) in Subjects With Moderate to Severe COPD

    The purpose of this study is to determine if ensifentrine is safe and effective for the treatment of patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

    NCT04535986
    Conditions
    1. Chronic Obstructive Pulmonary Disease
    Interventions
    1. Drug: Ensifentrine
    2. Drug: Placebo
    MeSH:Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive
    HPO:Chronic pulmonary obstruction Pulmonary obstruction

    Primary Outcomes

    Description: Change from baseline of Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h

    Measure: Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h

    Time: 12 weeks

    Secondary Outcomes

    Description: Change from baseline of Average FEV1 AUC0-4h post-dose at Week 12

    Measure: Average FEV1 AUC0-4h post-dose at Week 12

    Time: 12 weeks

    Description: Change from baseline in Peak FEV1 over 4 hours post dose at Week 12

    Measure: Peak FEV1 over 4 hours post dose at Week 12

    Time: 12 weeks

    Description: Change from baseline as a weekly average of Evaluating-Respiratory Symptoms (E-RS) Total Score at Week 24

    Measure: Weekly average of Evaluating-Respiratory Symptoms (E-RS) Total Score at Week 24

    Time: 24 weeks

    Description: Change from baseline of SGRQ total score at Week 24

    Measure: St. George's Respiratory Questionnaire (SGRQ) total score at Week 24

    Time: 24 weeks

    Description: Change from baseline of Morning trough FEV1 at Week 12

    Measure: Morning trough FEV1 at Week 12

    Time: 12 weeks

    Description: The proportion of St. George's Respiratory Questionnaire (SGRQ) responders at Week 24.

    Measure: St. George's Respiratory Questionnaire (SGRQ)

    Time: 24 weeks

    Description: Change from baseline of Rescue medication use at Week 24

    Measure: Rescue medication use at Week 24

    Time: 24 weeks

    Description: Transitional Dyspnea Index (TDI) at Week 24

    Measure: Transitional Dyspnea Index (TDI) at Week 24

    Time: 24 weeks

    Description: Change from baseline Evening trough FEV1 at Week 12

    Measure: Evening trough FEV1 at Week 12

    Time: 12 weeks

    Description: Change from baseline Peak FEV1

    Measure: Peak FEV1 at Week 6 and Week 24

    Time: 6 and 24 weeks

    Description: Change from baseline morning trough FEV1

    Measure: Morning trough FEV1 at Week 6 and Week 24

    Time: 6 and 24 weeks

    Description: Change from baseline evening trough FEV1

    Measure: Evening trough FEV1 at Week 6 and Week 24

    Time: 6 and 24 weeks

    Description: Change from baseline FEV1 AUC0-4h

    Measure: FEV1 AUC0-4h at Week 6 and Week 24

    Time: 6 and 24 weeks

    Description: Change from baseline E-RS Total Score

    Measure: Evaluating-Respiratory Symptoms (E-RS) Total Score at Week 6 and Week 12

    Time: 6 and 12 weeks

    Description: Change from baseline SGRQ responder analysis

    Measure: St. George's Respiratory Questionnaire (SGRQ) responder analysis at Week 6 and Week 12

    Time: 6 and 12 weeks

    Description: Change from baseline TDI

    Measure: TDI at Week 6 and Week 12

    Time: 6 and 12 Weeks

    Description: Change from baseline of SGRQ total score at Weeks 6 and 12

    Measure: St. George's Respiratory Questionnaire (SGRQ) total score at Weeks 6 and 12

    Time: 6 Weeks and 12 weeks

    Description: Change from baseline of Rescue medication use at Weeks 6 and 12

    Measure: Rescue medication use at Weeks 6 and 12

    Time: 12 weeks
    435 A Cluster-Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Vitamin D3 Supplementation to Reduce Disease Severity in Persons With Newly Diagnosed COVID-19 Infection and to Prevent Infection in Household Members

    The Vitamin D and COVID-19 Trial (VIVID) is a nationwide randomized clinical trial in 2700 U.S. men and women to investigate whether taking a daily dietary supplement of vitamin D for 4 weeks reduces the risk of hospitalization and/or death in participants newly diagnosed with COVID-19, and reduces the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their closest household contacts (as documented by seroconversion).

    NCT04536298
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: vitamin D
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Measure: Hospitalization or death in index cases

    Time: 4 weeks

    Secondary Outcomes

    Description: Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization or death

    Measure: Self-reported disease severity in index cases

    Time: 4 weeks

    Measure: Time to hospitalization or death in index cases

    Time: 4 weeks

    Measure: ICU admission/ventilation support in index cases

    Time: 4 weeks

    Measure: SARS-CoV-2 infection in close household contacts

    Time: 4 weeks

    Description: Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization or death

    Measure: Self-reported disease severity in close household contacts

    Time: 4 weeks
    436 COVID-FIS: A Phase 2 Placebo-Controlled Pilot Study in COVID-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Older Adults in Nursing Homes

    The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.

    NCT04537299
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Drug: Fisetin
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Ordinal Scale for Clinical Improvement (minimum=0 and maximum=8; higher score = worse outcome)

    Measure: Change in COVID-19 Severity

    Time: baseline, Day 2, 7, 10, 14, 17, 30, 90 and 180
    437 Bacillus Calmette-Guérin Vaccination To Prevent Serious Respiratory Tract Infection And Covid-19 In Vulnerable Elderly - An Adaptive Randomized Controlled Trial

    On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. Worldwide, the number of confirmed cases continues to rise, leading to significant morbidity and mortality. In the Netherlands, although the incidence is currently low due to social distancing measures, recurrence of infections is expected once measures are going to be lifted. Although individuals of any age can acquire SARS-CoV-2, adults of middle and older age are at highest risk for developing severe COVID-19 disease. Moreover, recent reports demonstrate that mortality rates rise significantly among patients 60 years and older. Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences in vulnerable populations are urgently needed. Bacille Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but also induces protection against various respiratory infections, including those with a viral etiology. We hypothesize that BCG vaccination reduces clinically relevant respiratory tract infections requiring medical intervention, including COVID-19, in vulnerable elderly. The objective of this trial is to determine the impact of BCG vaccination on the incidence of clinically relevant respiratory infections or COVID-19 in vulnerable elderly. The trial is designed as an adaptive multi-center double-blind randomized placebo-controlled trial. The attempt is to include 5,200 to 7,000 vulnerable elderly, defined as ≥60 years of age being discharged from hospital in the last 6 weeks, or visiting a medical outpatient clinic, thrombosis care services, or chronic renal replacement departments. Patients with contraindications to BCG vaccination as stipulated in the Summary of Product Characteristics (SPC) and patients with a history of COVID-19 will be excluded. Participants will be randomized between intracutaneous administration of BCG vaccine (Danish strain 1331) or placebo (0.1ml 0.9% NaCl) in a 1:1 ratio.The trial has an adaptive primary endpoint. Based on accrual of the two endpoints, the primary endpoint will be either (a) COVID-19 or (b) clinically relevant respiratory tract infection requiring medical intervention, potentially including COVID-19 episodes. The other will be declared secondary endpoint. Other secondary endpoints include: all SARS-CoV-2 infections (including asymptomatic infections), influenza infection, acute respiratory infection (ARI; all infections regardless of medical intervention), ARI-related hospital admission, COVID-19 related hospital admission, pneumonia, mental, physical and social functioning, serious adverse events and adverse events, and death.

    NCT04537663
    Conditions
    1. Respiratory Tract Infections
    2. Covid19
    Interventions
    1. Drug: Bacille Calmette-Guérin (BCG)
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: Clinically relevant relevant respiratory tract infection is composed of clinical symptoms in combination with the need for medical intervention. Exact criteria for clinically relevant respiratory tract infection and COVID-19 are described in the protocol. A blinded adjudication committee will determine the status of the primary endpoints of all participants with a potential primary endpoint, based on information provided in a standardized narrative using data reported by the participant and from GP and hospital medical records when relevant. For detection of ARI, symptoms are checked on a weekly (from week 1-4) or bi-weekly basis (from week 4 onward).

    Measure: The trial has an adaptive primary endpoint. Based on predefined objective and quantitative criteria the primary endpoint will be either a clinically relevant respiratory tract infection, or COVID-19.

    Time: 180 days

    Secondary Outcomes

    Description: Cumulative incidence of SARS-CoV-2 infection regardless of symptomatology defined as having had COVID-19 as described under primary endpoints above and/or SARS-CoV-2 positive test in real time as part of the test-and-trace program of the Dutch government and/of documented SARS-CoV-2 seroconversion at 6 months. Seroconversion will be defined as antibody-positive at 6 months but negative at baseline.

    Measure: Cumulative incidence of SARS-CoV-2 infection (irrespective the presence of symptoms)

    Time: 180 days

    Measure: Cumulative incidence of asymptomatic, mild/moderate, and severe (requiring hospitalization) SARS-CoV-2 infection.

    Time: 180 days

    Description: Defined as either of 1) ARI + microbiological evidence of influenza infection, 2) seroconversion of influenza between enrolment and month 6.

    Measure: Influenza infection

    Time: 180 days

    Description: Meeting the definition stated in the primary outcome. Irrespective of requiring an intervention.

    Measure: An acute respiratory tract infection

    Time: 180 days

    Description: Meeting the definition stated in the primary outcome including the requirement of an intervention.

    Measure: Medically attended acute respiratory tract infection

    Time: 180 days

    Description: Meeting the definition stated in the primary outcome including the need of hospitalization.

    Measure: Acute respiratory tract infection related hospital admission

    Time: 180 days

    Measure: Pneumonia diagnosed by a GP or medical specialist

    Time: 180 days

    Description: Using the Katz Activities of Daily Living (ADL) scale, from A (fully independent) to G (dependent in feeding, continence, transferring, going to toilet, dressing, and bathing)

    Measure: Functioning in daily activities

    Time: 180 days

    Measure: Serious adverse events and adverse events.

    Time: 180 days

    Measure: Major cardiovascular events

    Time: 180 days

    Measure: All cause 6-month mortality

    Time: 180 days

    Measure: History of falls

    Time: 180 days

    Description: Using the EQ5D quality of life instrument, with questions on 4 domains (mobility, self-care, usual activities, pain discomfort) and the percepted health of the participant with 100 meaning the best health you can imagine, and 0 meaning the worst health you can imagine

    Measure: Quality of life using the EQ5D quality of life instrument

    Time: 180 days

    Description: Using the 6-item Lawton Activities of Daily Living questionnaire, with scores ranging from 0 (low function, dependent) to 8 (high function, independent) for women (0 through 5 for men)

    Measure: Activities in daily living

    Time: 180 days
    438 A Study of Brexanolone for Acute Respiratory Distress Syndrome Due to COVID-19

    The purpose of this study is to evaluate the efficacy and safety of brexanolone in participants on ventilator support for acute respiratory distress syndrome (ARDS) due to COVID-19.

    NCT04537806
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. COVID-19
    Interventions
    1. Drug: Brexanolone
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Respiratory failure is defined based on resource utilization, requiring at least one of the following: endotracheal intubation and mechanical ventilation; oxygen delivered by high-flow nasal cannula; noninvasive positive pressure ventilation or extracorporeal membrane oxygenation (ECMO).

    Measure: Percentage of Participants Who are Alive and Free of Respiratory Failure at Day 28

    Time: Day 28

    Secondary Outcomes

    Measure: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

    Time: Up to Day 28

    Measure: All-cause Mortality Through Day 28

    Time: Up to Day 28
    439 Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 474121 in Young and Elderly Healthy Male and Female Subjects (Double-blind, Randomised, Placebo-controlled, Parallel Group Design) and Evaluation of Midazolam Interaction in Young Healthy Male and Female Subjects (Nested, Open, Fixed-sequence, Intra-individual Comparison)

    The main objectives of this trial are to investigate safety and tolerability of BI 474121 in healthy male and female young and elderly subjects following oral administration of multiple rising doses per day over 14 days.

    NCT04537897
    Conditions
    1. Healthy
    Interventions
    1. Drug: BI 474121
    2. Drug: Midazolam
    3. Drug: Placebo

    Primary Outcomes

    Measure: Percentage of subjects with drug-related adverse events

    Time: Up to 23 days

    Secondary Outcomes

    Description: After the first dose of BI 474121

    Measure: Area under the concentration-time curve of the analyte in plasma from 0 to 24h (AUC0-24)

    Time: Up to Day 1

    Description: After the first dose of BI 474121

    Measure: Maximum measured concentration of the analyte in plasma (Cmax)

    Time: Up to Day 1

    Description: After the last dose of BI 474121

    Measure: Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUCτ,ss)

    Time: Up to Day 14

    Description: After the last dose of BI 474121

    Measure: Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmax,ss)

    Time: Up to Day 14

    Description: After each of three doses Midazolam

    Measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)

    Time: Up to Day 14

    Description: After each of three doses Midazolam

    Measure: Maximum measured concentration of the analyte in plasma (Cmax)

    Time: Up to Day 14
    440 A Randomized, Placebo-Controlled, Participant- and Investigator-Blind, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of LY3819253 Administered Subcutaneously to Healthy Participants

    The purpose of this study is to test the safety and tolerability of LY3819253 when it is given by injection just under the skin to healthy participants. Blood tests will be done to check how much LY3819253 is in the bloodstream and how long the body takes to eliminate it. Participation could last up to 16 weeks and may include up to six visits to the study center, with a one-week overnight stay.

    NCT04537910
    Conditions
    1. Healthy
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo

    Primary Outcomes

    Description: PK: AUC(0-inf)

    Measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time 0 to Infinity (AUC[0-inf])

    Time: Day 1 through Day 85
    441 A Phase 1b/2a Study in Participants With Early Stage COVID-19 to Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation

    The primary objective of this study is to characterize the impact of inhaled remdesivir (RDV) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in participants with early stage coronavirus disease 2019 (COVID-19).

    NCT04539262
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Remdesivir (RDV)
    2. Drug: Placebo
    MeSH:Respiratory Aspiration

    Primary Outcomes

    Description: Time-weighted Average Change in SARS-CoV-2 viral load is defined as area under the concentration versus time curve (AUC) of viral load change divided by time between baseline through Day 7

    Measure: Time-weighted Average Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7

    Time: Baseline, Day 7

    Secondary Outcomes

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events

    Time: First dose date up to 5 days plus 30 days

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities

    Time: First dose date up to 5 days plus 30 days

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation

    Time: First dose date up to 5 days plus 30 days

    Measure: Proportion of Participants Progressing From Early Stage Coronavirus Disease 2019 (COVID-19) to Hospitalization or Death by Day 14

    Time: Day 14

    Description: AUC0-24h is defined as the concentration of drug over time between time 0 to time 24 hours. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: AUClast is defined as the concentration of drug from time zero to the last observable concentration. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: AUClast of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: CLss/F is defined as apparent oral clearance at steady state after administration of the drug. CLss/F = Dose/AUCtau, where "Dose" is the dose of the drug Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: CLss/F of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: t1/2 of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Vz/F is defined as the apparent volume of distribution of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Vz/F of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Cmax is defined as the maximum observed concentration of drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Cmax of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Tmax is defined as the time (observed time point) of Cmax. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Tmax of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Clast is defined as the last observable concentration of drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Clast of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Tlast is defined as the time (observed time point) of Clast. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Tlast of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: AUCtau of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: λz of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Ctau is defined as the observed drug concentration at the end of the dosing interval. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Ctau of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Measure: Change in SARS-CoV-2 Viral Load From Baseline to Day 4

    Time: Baseline, Day 4

    Measure: Change in SARS-CoV-2 Viral Load From Baseline to Day 7

    Time: Baseline, Day 7

    Measure: Change in SARS-CoV-2 Viral Load From Baseline to Day 14

    Time: Baseline, Day 14

    Measure: Time to Negative SARS-CoV-2 Polymerase Chain Reaction (PCR)

    Time: First dose date up to 14 days
    442 A Phase Ib/II, Single Center, Placebo-Controlled, Randomized, Blinded Study in Adult Patients (> 18 Years) With COVID-19 Respiratory Disease, to Evaluate, Safety, Tolerability and Mechanistic Effect of Alvelestat on Top of Standard of Care (COSTA)

    The purpose of this study is to determine the safety, tolerability and pharmacokinetics (PK), and explore the mechanistic and clinical effect of alvelestat (an oral neutrophil elastase inhibitor) orally twice per day for 10 days added to standard of care in adult patients (≥18 years) with COVID-19 respiratory disease.

    NCT04539795
    Conditions
    1. Covid19
    Interventions
    1. Drug: Alvelestat
    2. Drug: Placebo

    Primary Outcomes

    Description: Safety Outcome Assessment

    Measure: Numbers and % of subjects who experience at least 1 treatment-emergent adverse event

    Time: to day 60

    Measure: Mortality rate

    Time: to Day 90

    Description: clinically significant safety monitoring labs tests

    Measure: Adverse events of special interest

    Time: to Day 14 (acute treatment period) or EoT

    Secondary Outcomes

    Description: neutrophil elastase

    Measure: Effect of alvelestat on blood pharmacodynamic biomarkers of inflammation

    Time: to day 10
    443 Multicenter, Randomized, Double Blind, Placebo Controlled Parallel Group Study Evaluating Efficacy, Reactogenicity and Safety of Recombinant Vaccine Ad5-nCoV Against Novel Coronavirus Infection in Adult Volunteers

    This study is a phase III clinical trial to evaluate efficacy, reactogenicity and safety of the vaccine Ad5-nCoV compared with placebo in volunteers at the age from 18 to 85 years，with the randomized, double-blind design

    NCT04540419
    Conditions
    1. Covid19
    Interventions
    1. Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Proportion of subjects with four-fold and higher increment of anti-receptor-binding domain antibodies [receptor-binding domain, RBD] of S-protein SARS-CoV-2).

    Measure: Superiority of the vaccine Ad5-nCoV to placebo by the level of seroconversion

    Time: Day 28 after vaccination

    Secondary Outcomes

    Description: Geometric mean titer of RBD и S-protein SARS-CoV-2 antibodies.

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (titer of SARS-CoV-2 antibodies)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Level of seroconversion (proportion of persons with four-fold and higher increment of RBD и S-protein SARS-CoV-2 antibodies).

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (level of seroconversion)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Geometric mean fold rise of RBD и S-protein SARS-CoV-2 antibodies.

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (rise of SARS-CoV-2 antibodies)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Quantity of T-cells.

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (T-cell response)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Frequency of confirmed COVID-19 (confirmed case of COVID-19: presence of clinical signs and positive result of laboratory test for RNA of virus SARS-CoV-2) (exploratory analysis).

    Measure: Frequency of confirmed COVID-19

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency of confirmed cases of COVID-19, requiring hospitalization. (confirmed case of COVID-19: presence of clinical signs and positive result of laboratory test for RNA of virus SARS-CoV-2) (exploratory analysis).

    Measure: Frequency of confirmed cases of COVID-19, requiring hospitalization

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency of cases with severe course of COVID-19 (confirmed case of COVID-19: presence of clinical signs and positive result of laboratory test for RNA of virus SARS-CoV-2) (exploratory analysis).

    Measure: Frequency of cases with severe course of COVID-19

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency of death due to COVID-19 (exploratory analysis).

    Measure: Frequency of death due to COVID-19.

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency and character of general and local postvaccinal reactions.

    Measure: Reactogenicity of the vaccine Ad5-nCoV compared with placebo

    Time: Day 0 (day of vaccination), Day 2, Day 7

    Description: Frequency and character of adverse events and serious adverse events.

    Measure: Frequency and character of adverse events and serious adverse events.

    Time: Day 0 - Month 6

    Description: Results of evaluation of vital parameters: Systolic blood pressure Diastolic blood pressure The researcher evaluates each of the vital parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on vital parameters (blood pressure)

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of evaluation of vital parameters: • Heart rate. The researcher evaluates each of the vital parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on vital parameters (heart rate)

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of evaluation of vital parameters: • Respiratory rate. The researcher evaluates each of the vital parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on vital parameters (respiratory rate)

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of physical examination includes examination of organs and systems: General state Ears, nose, throat Skin and examination of the injection site The lymph nodes The cardiovascular system Respiratory system Nervous system Abdominal organs Kidneys and urinary system Musculoskeletal system. During the physical examination, the researcher evaluates each of the systems in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of physical examination

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of electrocardiography: • Heart rate (HR) The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of electrocardiography (Heart rate)

    Time: Day -7-1 (Screening), Day 2

    Description: Results of electrocardiography: Intervals RR, PQ, QT QRS complex Corrected QT interval (QTcF). The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of electrocardiography

    Time: Day -7-1 (Screening), Day 2

    Description: Results of serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH). The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of serum chemistry (enzymes)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of serum chemistry: total bilirubin, creatinine, urea, fasting glucose. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of serum chemistry

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of serum chemistry: total protein, C-reactive protein. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of serum chemistry

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: hemoglobin The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (hemoglobin)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: hematocrit. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (hematocrit)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: erythrocytes. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (erythrocytes)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: platelets, leukocytes and leukocyte formula (neutrophils, lymphocytes, monocytes, eosinophils, basophils (absolute number). The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: erythrocyte sedimentation rate The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (erythrocyte sedimentation rate)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of coagulogram: activated partial thromboplastin time, prothrombin time. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of coagulogram

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of coagulogram: fibrinogen. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of coagulogram (fibrinogen)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: relative density. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (relative density)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: pH. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (pH)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: leukocytes, erythrocytes, cylinders . The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: protein . The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (protein)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis:glucose . The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (glucose)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of determination of immunoglobulin E serum concentrations.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of determination of immunoglobulin E serum concentrations.

    Time: Day -7-1 (Screening), Day 28
    444 Phase I Study to Evaluate the Safety, Tolerability, and Pharmacodynamics (PD) of DWRX2003 (Niclosamide IM Depot) Injection Following Intramuscular Administration in COVID-19 Patients

    This study is designed to assess the safety and tolerability of single doses of DWRX2003 in COVID-19 patients.

    NCT04541485
    Conditions
    1. COVID-19 Patients
    Interventions
    1. Drug: DWRX2003
    2. Drug: Placebo

    Primary Outcomes

    Description: Incidence, severity and causality of adverse events (AEs) and serious adverse events (SAEs)

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: follow-up 42 days after dosing

    Secondary Outcomes

    Measure: Time to SARS-CoV-2 eradication (days) by Nasopharyngeal specimen

    Time: follow-up 42 days after dosing

    Measure: Rate of SARS-CoV-2 eradication by Nasopharyngeal specimen

    Time: at Day 3, 7, 10 and 14
    445 "Nintedanib for the Treatment of SARS-Cov-2 Induced Pulmonary Fibrosis"

    Currently, there is no approved treatment for COVID-19 in France, either for the acute phase, nor for the late chronic phase. the investigator suggest that nintedanib has the potential to block the development of lung fibrosis when initiated early enough to inhibit the activation of mesenchymal cells and the progression of virus-induced pulmonary fibrosis. Computerized Tomography (CT) manifestations of fibrosis or fibrous stripes are described in COVID-19 (Ye, Eur Radiol 2020). Pan et al observed fibrous stripes in 17% patients in the early phase of the disease (Pan, Eur Radiol 2020). Ye et al observed bronchiectasis in 2 patients (15.4%) and evidence of pulmonary fibrosis in 3 patients (23.7%) at HRCT performed at 4 weeks (Ye, Eur Radiol 2020). Long term data are still lacking in patients with COVID-19 and the investigators do not know how many patients will have fibrotic sequelae from the acute illness.

    NCT04541680
    Conditions
    1. SARS-Cov-2 Induced Pulmonary Fibrosis
    Interventions
    1. Drug: Nintedanib 150 MG [Ofev]
    2. Other: Placebo
    MeSH:Pulmonary Fibrosis Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Change in Forced Vital Capacity over 12 months assessed by Annual Rate of Decline in FVC in Overall Population

    Measure: The primary objective is to assess whether nintedanib slows the progression of lung fibrosis in COVID-19 survivors as assessed by the decline in the forced vital capacity (FVC) over 12 months compared to placebo.

    Time: at inclusion and 12 months.

    Secondary Outcomes

    Description: Rate of decline in DLCO estimated by linear regression of DLCO from baseline to 12 months from DLCO measurement at inclusion, 6 and 12 months

    Measure: compare the rate of decline of DLCO over 12 months

    Time: at inclusion, 6 and 12 months

    Description: Absolute change from baseline in the Six-minute walk test (6MWT) at 12 months

    Measure: compare exercise capacity at 12 months

    Time: at 12 months

    Description: HRCT fibrosis score and HRCT fibrosis extension (visual and computer-based assessment) at inclusion and 12 months

    Measure: compare high resolution CT (HRCT) lung opacities extension at 12 months

    Time: at inclusion and 12 months

    Description: Absolute change from baseline in the total score on the St. George's Respiratory Questionnaire questionnaire at 12 months

    Measure: compare change in health-related quality of life

    Time: at 12 months

    Description: Absolute change from baseline in the Dyspnea score (Multidimensional Dyspnea Profile and mMRC score) at 3, 6, 9 and 12 months

    Measure: compare the evolution of dyspnea over time

    Time: at 3, 6, 9 and 12 months

    Description: The absolute change from baseline Hospital Anxiety and Depression score at 3, 6, 9 and 12 months

    Measure: compare change in Depression and anxiety over time

    Time: at 3, 6, 9 and 12 months

    Description: Biomarker assay (KL-6, NT-proBNP, CRP, D-dimers) at inclusion and 12 months

    Measure: compare change in lung injury, pulmonary hypertension and inflammation biomarkers

    Time: at inclusion and 12 months

    Description: Percentage of patients with a tricuspid regurgitation velocity > 2.5, 2.8 and 3.4 m/sec evaluated at baseline and at 12 months.

    Measure: pulmonary hypertension prevalence at inclusion and 12 months

    Time: at inclusion and 12 months

    Description: MUC5B at risk allele detection at inclusion

    Measure: association between genetic susceptibility (MUC5B polymorphism) and lung fibrosis in COVID-19 survivors

    Time: at inclusion

    Description: Incidence of clinical or biological adverse events with nintedanib versus placebo over 12 months

    Measure: safety of nintedanib

    Time: over 12 months
    446 A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ensifentrine Over 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

    The purpose of this study is to determine if ensifentrine is safe and effective for the treatment of patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

    NCT04542057
    Conditions
    1. Chronic Obstructive Pulmonary Disease
    Interventions
    1. Drug: Ensifentrine
    2. Drug: Placebo
    MeSH:Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive
    HPO:Abnormal lung morphology Chronic pulmonary obstruction Pulmonary obstruction

    Primary Outcomes

    Description: Change from baseline of Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h

    Measure: Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h

    Time: 12 weeks

    Secondary Outcomes

    Description: Change from baseline of Average FEV1 AUC0-4h post-dose at Week 12

    Measure: Average FEV1 AUC0-4h post-dose at Week 12

    Time: 12 weeks

    Description: Change from baseline of Peak FEV1 over 4 hours post-dose at Week 12

    Measure: Peak FEV1 over 4 hours post-dose at Week 12

    Time: 12 weeks

    Description: Change from baseline as a weekly average of Evaluating-Respiratory Symptoms (E-RS) Total Score at Week 24

    Measure: Evaluating-Respiratory Symptoms (E-RS) Total Score at Week 24

    Time: 24 weeks

    Description: Change from baseline of SGRQ total score at Week 24

    Measure: St. George's Respiratory Questionnaire (SGRQ) total score at Week 24

    Time: 24 weeks

    Description: Change from baseline of Morning trough FEV1 at Week 12

    Measure: Morning trough FEV1 at Week 12

    Time: 12 weeks

    Description: The proportion of St. George's Respiratory Questionnaire (SGRQ) responders at Week 24.

    Measure: St. George's Respiratory Questionnaire (SGRQ) responders at Week 24

    Time: 24 weeks

    Description: Change from baseline of Rescue medication use at Week 24

    Measure: Rescue medication use at Week 24

    Time: 24 weeks

    Description: Transitional Dyspnea Index (TDI) at Week 24

    Measure: Transitional Dyspnea Index (TDI) at Week 24

    Time: 24 weeks

    Description: Change from baseline Evening trough FEV1 at Week 12

    Measure: Evening trough FEV1 at Week 12

    Time: 12 weeks

    Description: Change from baseline Peak FEV1

    Measure: Peak FEV1 at Week 6 and Week 24

    Time: 6 or 24 weeks

    Description: Change from baseline morning trough FEV1

    Measure: Morning trough FEV1 at Week 6 and Week 24

    Time: 6 or 24 weeks

    Description: Change from baseline evening trough FEV1

    Measure: Evening trough FEV1 at Week 6 and Week 24

    Time: 6 or 24 weeks

    Description: Change from baseline FEV1 AUC0-4h

    Measure: FEV1 AUC0-4h at Week 6 and Week 24

    Time: 6 or 24 weeks

    Description: Change from baseline E-RS Total Score

    Measure: Evaluating-Respiratory Symptoms (E-RS) Total Score at Week 6 and Week 12

    Time: 6 or 12 weeks

    Description: Change from baseline SGRQ responder analysis

    Measure: SGRQ responder analysis at Week 6 and Week 12

    Time: 6 or 12 weeks

    Description: Change from baseline TDI

    Measure: TDI at Week 6 and Week 12

    Time: 6 or 12 weeks

    Description: Change from baseline of SGRQ total score

    Measure: St. George's Respiratory Questionnaire (SGRQ) total score at Weeks 6 and 12

    Time: 6 or 12 weeks

    Description: Change from baseline of Rescue medication use

    Measure: Rescue medication use at Weeks 6 and 12

    Time: 6 or 12 weeks
    447 Identification and Validation of Biomarkers for Breast Cancer Resistance Protein

    This is a randomized, two-arm crossover study. Subjects will undergo a placebo and rosuvastatin phase and eltrombopag and rosuvastatin phase to identify biomarkers for Breast Cancer Resistance Protein (BCRP).

    NCT04542382
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: Placebo
    2. Drug: Rosuvastatin (Placebo arm)
    3. Drug: Rosuvastatin (Inhibitor arm)
    4. Drug: Eltrombopag

    Primary Outcomes

    Description: Mean difference in area under the curve (AUC) between rosuvastatin 10mg + placebo versus rosuvastatin 10mg + eltrombopag 75mg

    Measure: Composite of pharmacokinetics of co-administration of rosuvastatin and eltrombopag in healthy volunteers.

    Time: 24 and 72 hours

    Description: Mean difference in Cmax between rosuvastatin 10mg + placebo versus rosuvastatin 10mg + eltrombopag 75mg

    Measure: Composite of pharmacokinetics of co-administration of rosuvastatin and eltrombopag in healthy volunteers.

    Time: 24 hour

    Secondary Outcomes

    Description: Mean difference in BCRP biomarker Cmax between rosuvastatin 10mg + placebo vs rosuvastatin 10mg + eltrombopag 75mg

    Measure: Composite of BCRP biomarkers of co-administration of rosuvastatin and eltrombopag in healthy volunteers.

    Time: 24 and 72 hours
    448 A Phase 2 Randomized Double Blind, Placebo-controlled Study on the Safety and Efficacy of Niclosamide in Patients With COVID-19

    This is a two-part, Phase 2, multicentre, randomized, double blind, 2-arm placebo-controlled study in adults with moderate COVID-19 with gastrointestinal signs and symptoms

    NCT04542434
    Conditions
    1. Covid19
    Interventions
    1. Drug: Niclosamide Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Description: All-cause mortality

    Measure: Mortality

    Time: From Day 1 to 6 weeks

    Description: Proportion of patients with Treatment Emergent Adverse Events (TEAE) leading to study drug discontinuation

    Measure: TEAE

    Time: From Day 1 to 6 weeks

    Description: Serious adverse event (SAE) coded by System Organ Class (SOC) and Preferred Term (PT), using the Medical Dictionary for Regulatory Activities (MedDRA)

    Measure: SAEs

    Time: From Day 1 to end of study

    Description: Change in safety laboratory tests from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided

    Measure: Safety laboratory

    Time: From Day 1 to 6 weeks

    Description: Change in sitting systolic and diastolic blood pressure from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: Blood pressure

    Time: From Day 1 to 6 weeks

    Description: time to fecal RNA virus clearance (rectal swab or stool sample) assessed by RT-qPCR in the niclosamide group, compared to the placebo group (Part 2 only)

    Measure: fecal RNA virus clearance

    Time: From Day 1 to 6 weeks

    Description: Change in body temperature from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: Body temperature

    Time: From Day 1 to 6 weeks

    Description: Change in heart rate from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: Heart rate

    Time: From Day 1 to 6 weeks

    Description: Change in SaO2 from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: SaO2

    Time: From Day 1 to 6 weeks

    Description: Change in ECG parameters including: 1. PR interval 2. RR interval 3. QRS interval 4 QT interval 5. HR interval 6. QtcF interval. All intervals summarized descriptively by visit from baseline to 6 weeks

    Measure: ECG

    Time: From Day 1 to 6 weeks
    449 A Randomized, Multi-center, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Monoclonal Antibody VIR-7831 for the Early Treatment of Coronavirus Disease 2019 (COVID-19) in Non-hospitalized Patients

    This is a phase 2/3 study in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 or placebo and will be assessed for safety, tolerability, efficacy, and pharmacokinetics.

    NCT04545060
    Conditions
    1. Covid19
    Interventions
    1. Biological: VIR-7831
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of participants who have progression of COVID-19 through Day 29

    Time: Up to Day 29

    Secondary Outcomes

    Measure: Occurence of of adverse events (AEs)

    Time: Up to 24 weeks

    Measure: Occurrence of serious adverse events (SAEs)

    Time: Up to 24 weeks

    Measure: Occurrence of adverse events of special interest (AESI)

    Time: Up to 24 weeks

    Measure: Incidence and titers (if applicable) of serum ADA to VIR-7831

    Time: Up to 24 weeks

    Measure: Cmax

    Time: Up to 24 weeks

    Measure: Clast

    Time: Up to 24 weeks

    Measure: Tmax

    Time: Up to 24 weeks

    Measure: Tlast

    Time: Up to 24 weeks

    Measure: AUCinf

    Time: Up to 24 weeks

    Measure: AUClast

    Time: Up to 24 weeks

    Measure: %AUCextrap

    Time: Up to 24 weeks

    Measure: t1/2

    Time: Up to 24 weeks

    Measure: Vz

    Time: Up to 24 weeks

    Measure: Vss

    Time: Up to 24 weeks

    Measure: CL

    Time: Up to 24 weeks

    Measure: Proportion of participants who have progression of COVID-19 as defined by hospitalization >24 hrs or death at Day 8, Day 15, or Day 22

    Time: Up to Day 22

    Measure: Proportion of participants who progress to develop severe and/or critical respiratory COVID-19 as manifest by requirement for and method of supplemental oxygen at Day 8, Day 15, Day 22, or Day 29

    Time: Up to Day 29

    Description: Severity and duration of participant-reported symptoms of COVID-19 related illness using the 34-item COVID-19 adapted FLU-PRO (Influenza Patient-reported outcome) instrument. Higher scores mean worse outcome.

    Measure: Severity and duration of participant-reported symptoms of COVID-19 related illness using the FLU-PRO patient-reported outcome instrument

    Time: Up to 12 weeks

    Measure: Detection of SARS-CoV-2 in nasal secretions by PCR at baseline and during follow-up period through Day 29

    Time: Up to Day 29

    Measure: 29-day, 60-day, and 90-day all-cause mortality

    Time: Up to 90 days
    450 An International Multicenter, Adaptive, Randomized Double-Blind, Placebo-Controlled Trial of the Safety, Tolerability and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Hospitalized Patients at Onset of Clinical Progression of COVID-19

    This protocol will serve as a platform for assessing treatments for adult patients hospitalized for medical management of COVID-19 without related serious end-organ failure. Trials will involve sites around the world strategically chosen to ensure rapid enrollment. This trial will compare hyperimmune intravenous immunoglobulin (hIVIG) with matched placebo, when added to standard of care (SOC), for preventing further disease progression and mortality related to COVID-19. SOC will include remdesivir unless it is contraindicated for an individual patient.

    NCT04546581
    Conditions
    1. COVID
    2. COVID-19
    3. SARS-CoV-2
    4. SARS (Severe Acute Respiratory Syndrome)
    Interventions
    1. Drug: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
    2. Other: Placebo
    3. Drug: Remdesivir
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction 4. Serious end-organ dysfunction 3. Moderate end-organ dysfunction 2. Limiting symptoms due to COVID-19 1. No limiting symptoms due to COVID-19 Outcome is reported as the percent of participants in each of 7 categories.

    Measure: Ordinal Outcome Scale - Day 7

    Time: 7 days

    Secondary Outcomes

    Description: Outcome reported as the percent of participants who expire for any reason by day 28 post treatment.

    Measure: All-cause mortality through Day 28

    Time: 28 days

    Description: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 14, and 28 of follow-up using the primary ordinal outcome. Outcome is reported as the percent of participants in each of 7 categories.

    Measure: Ordinal Outcome Scale

    Time: 3 days, 5 days, 14 days, and 28 days

    Description: The National Early Warning Score (NEWS) is used to determine the degree of illness of a patient and prompt critical care intervention. The score takes into account respiratory rate, oxygen saturation, use of respiratory support, body temperature, blood pressure, and heart rate. These data are entered into a program to calculate a NEW score. Scores range from -3 to +3 with scores closer to zero representing a lower degree of illness. Scores will be collected at baseline and day 7 and the change in score at these 2 time points will be reported.

    Measure: Change in National Early Warning Score (NEWS)

    Time: 7 days

    Description: Time to worsening is defined as the 3 least favorable categories on the primary ordinal scale. Outcome is reported as the percent of participants in each arm who are characterized as categories 5, 6, and 7 on the primary ordinal scale at 7, 14, and 28 days post treatment.

    Measure: Time to Worsening

    Time: 7 days, 14 days, and 28 days

    Description: Outcome is reported as the percent of participants in each arm who are alive and discharged from the hospital to home or rehabilitation at days 7, 14, and 28 post treatment.

    Measure: Discharge Status

    Time: 7 days, 14 days, and 28 days

    Description: Outcome is reported as the mean number of days alive and outside the hospital from study entry to Day 28 for participants in each arm.

    Measure: Days Alive Outside the Hospital

    Time: 28 days

    Description: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 7, 14, and 28 post treatment limited to using the pulmonary elements of the primary ordinal outcome (e.g., requirement for invasive ventilation). Outcome is reported as the percent of participants in each arm who fall into each of the 7 categories of the primary ordinal outcome with regard to their pulmonary dysfunction only.

    Measure: Pulmonary-only Components of the Primary Ordinal Outcome

    Time: 3 days, 5 days, 7 days, 14 days, and 28 days

    Description: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 7, 14, and 28 post treatment limited to using the thrombotic conditions (e.g., arterial thrombosis) in the primary ordinal outcome. Outcome is reported as the percent of participants in each arm who fall in each of the 7 categories of the primary ordinal outcome with regard to thrombotic conditions only.

    Measure: Thrombotic Components of the Primary Ordinal Outcome

    Time: 3 days, 5 days, 7 days, 14 days, and 28 days

    Description: Time to recovery is defined as the 2 most favorable categories on the primary ordinal scale. Outcome is reported as the percent of participants in each arm who are characterized as categories 1 or 2 at 7, 14, and 28 days post treatment.

    Measure: Time to recovery

    Time: 7 days, 14 days, and 28 days

    Description: Clinical organ dysfunction is defined by new onset of any one or more of the following. Outcome is reported as the percent of participants in each arm who meet any 1 of the following criteria by day 28 post treatment. A) Respiratory dysfunction B) Cardiac and vascular dysfunction C) Renal dysfunction D) Hepatic dysfunction E) Neurological dysfunction F) Haematological dysfunction G) Serious infection

    Measure: Clinical Organ Dysfunction

    Time: 28 days

    Description: Outcome is reported as the percent of participants in each arm who experience a new grade 3 or 4 event, a serious adverse event (SAE), or death through day 7 (primary safety endpoint) post treatment.

    Measure: Safety and Tolerability - Adverse Events

    Time: 7 days

    Description: Outcome is reported as the percent of participants in each arm for who had any grade of reaction during the infusion or within 2 hours afterwards, for whom the infusion is interrupted prior to completion, or for whom the infusion is stopped prior to completion.

    Measure: Safety and Tolerability - Infusion Reactions, Interruptions, or Cessation

    Time: approximately 2 hours

    Description: Outcome is reported as the percent of participants in each arm who experience a serious adverse event (SAE) or death through day 28 post treatment.

    Measure: Safety and Tolerability - Serious Adverse Events

    Time: 28 days

    Description: Outcome is reported as the percent of participants in each arm who experience an adverse event (AE) of any grade present (new or continuing) on days 1, 3, 7, and 28 post treatment.

    Measure: Safety and Tolerability - Prevalence of Adverse Events

    Time: 1 day, 3 days, 7 days, and 28 days

    Description: Outcome reported as the change in anti-SARS-CoV-2 IgG antibody level in blood from baseline to 1, 3, 7, and 28 days post treatment. Outcome is reported in units of antibody titer.

    Measure: Change in Neutralizing Antibody Level

    Time: 1 day, 3 days, 7 days, and 28 days
    451 A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) Plus Standard Medical Treatment (SMT) Versus Placebo Plus SMT in Hospitalized Subjects With COVID-19

    The purpose of the study is to determine if liquid alpha1-proteinase inhibitor (human) (liquid alpha1-PI) plus SMT can reduce the proportion of participants dying or requiring intensive care unit (ICU) admission on or before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical ventilation on Day 29 versus placebo plus SMT in hospitalized participants with COVID-19.

    NCT04547140
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
    2. Drug: Placebo
    3. Drug: Standard Medical Treatment
    MeSH:Alpha 1-Antitrypsin Deficiency

    Primary Outcomes

    Measure: Percentage of Participants Dying or Requiring ICU Admission

    Time: Up to Day 29

    Measure: Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation

    Time: Day 29

    Secondary Outcomes

    Measure: Change from Baseline in National Early Warning Score (NEWS)

    Time: Day 1 through Day 29

    Measure: Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours

    Time: Day 1 through Day 29

    Measure: Time to Hospital Discharge

    Time: Day 1 through Day 29

    Measure: Duration of ICU Stay

    Time: Up to Day 29

    Measure: Duration of Any Oxygen Use

    Time: Day 1 through Day 29

    Measure: Duration of Mechanical Ventilation

    Time: Up to Day 29

    Measure: Mean Change from Baseline in Ordinal Scale

    Time: Day 1 through Day 29

    Measure: Absolute Value Change from Baseline in Ordinal Scale

    Time: Day 1 through Day 29

    Measure: Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale

    Time: Day 15 and Day 29

    Measure: Time to Sustained Normalization of Temperature

    Time: Up to Day 29

    Measure: Percentage of Participants with Normalization of Fever

    Time: Up to Day 29

    Measure: Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS)

    Time: Up to Day 29

    Measure: Length of Time to Clinical Progression

    Time: Up to Day 29
    452 Antiviral Effects of Tranexamic Acid (TXA) as a Preventative Treatment Following COVID-19 Exposure

    A recent report in Physiolological Reviews proposed that the endogenous protease plasmin acts on SARS-CoV-2 by cleaving a newly inserted furin site in the S protein portion of the virus resulting in increased infectivity and virulence. A logical treatment that might blunt this process would be the inhibition of the conversion of plasminogen to plasmin. Fortunately, there is an inexpensive, commonly used drug, tranexamic acid, TXA, which suppresses this conversion and could be re-purposed for the treatment of COVID-19. TXA is a synthetic analog of the amino acid lysine which reversibly binds four to five lysine receptor sites on plasminogen. This reduces conversion of plasminogen to plasmin, and is normally used to prevent fibrin degradation. TXA is FDA approved for the outpatient treatment of heavy menstrual bleeding (typical dose 1300 mg p.o. TID x 5 days) and off-label use for many other indications. TXA is used perioperatively as a standard-of-care at UAB for orthopedic and cardiac bypass surgeries. It has a long track record of safety such that it is used over-the-counter in other countries as an antiviral and for the treatment of cosmetic dermatological disorders. Given the potential benefit and limited toxicity of TXA it would appear warranted to perform randomized, double-blind placebo controlled exploratory trial at UAB as a prophylactic antiviral treatment following exposure to COVID-19 in order to determine whether it reduces infectivity and virulence of the SARS-CoV-2 virus as hypothesized. Involvement of each patient is only for 7 days before primary endpoints and 30 days for final data collection.

    NCT04550338
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tranexamic acid
    2. Drug: Placebo

    Primary Outcomes

    Description: RNA testing of nasopharyngeal swabs

    Measure: Conversion from negative to positive COVID-19 test

    Time: Repeat testing after 7 days
    453 The Safety and Efficacy Outcome of Ivermectin Plus Doxycycline in Treatment of RT-PCR Positive Adult Mild Covid-19 Cases: a Randomized Double Blind Placebo Controlled Trial

    A randomized double blind control trial will be done. Total 188 Covid-19 patients will be enrolled in this trial who are RT-PCR confirmed case of mild cases. Before enrollment, base line investigations will be done and as per eligibility criteria 188 (one hundred eighty eight) patients of mild symptoms will be selected by random sampling. Ninety four diagnosed patients (Group-A) of Covid-19 will be in the experimental group and 94 Covid-19 diagnosed patients (Group-B) will be in the control group. Group -A will be given combination treatment of Tab Ivermectin and Cap Doxycycline along with standard therapy and Group -B will be treated by standard therapy with placebo. Follow up will be done every day in both group with all the parameters as stated above and will be documented. On 5th day of treatment, if fever subsides final outcome will be measured by result of RT-PCR test preferably from one designated lab with sample of nasal swab for all. Subject to RT-PCR test negative result again on 6th day another RT-PCR test will be done at 24 hours apart. But if RT-PCR test result remain positive on 5th day, again on 10th day same test is to be done and also on 11th day subject to test result as negative on 10th day. Death of the patients will be documented as well. Regarding safety issues of the drugs we shall monitor for any SAE and would report to the DSMB for proper management guideline

    NCT04551755
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin and Doxycycline
    2. Other: Placebo

    Primary Outcomes

    Description: Outcome measure of symptoms associated with covid, fever and cough

    Measure: Time to outcome measure of fever (<100.40F)and cough

    Time: 10 days

    Description: If the result of RT-PCR test is negative, then 24 hours apart another RT-PCR test will be done. Subject to 2 consecutive negative tests patient will be declared as cured

    Measure: Negative RT-PCR test on day 5 of treatment

    Time: 10 days
    454 A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Patients WithMild-to-Moderate COVID-19

    The primary objective of this study is to investigate the safety and tolerability of BGB-DXP593 administered intravenously as a single dose in participants with mild-to-moderate COVID-19.

    NCT04551898
    Conditions
    1. Covid19
    Interventions
    1. Drug: BGB-DXP593
    2. Drug: Placebo

    Primary Outcomes

    Measure: Change from baseline to Day 8 in SARS-CoV-2 viral shedding as measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal swab samples

    Time: Up to 8 days

    Secondary Outcomes

    Measure: Time-weighted average change in viral shedding as measured by RT-qPCR in nasopharyngeal swab samples

    Time: Baseline to Day 15

    Measure: Change from baseline to Day 15 in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasopharyngeal swab samples

    Time: Baseline to Day 15

    Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples

    Time: Up to 15 days

    Measure: Number of participants requiring hospitalization due to worsened COVID-19

    Time: Up to 29 days

    Measure: Time to resolution of all COVID-19-related symptoms

    Time: Up to 29 days

    Measure: All-cause mortality rate at Day 29

    Time: Up to 29 days

    Measure: Number of participants experiencing Adverse Events (AEs)

    Time: Up to 85 days

    Measure: Number of participants experiencing Serious Adverse Events (SAEs)

    Time: Up to 85 days
    455 A Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Safety and Efficacy of Rayaldee (Calcifediol) Extended-release Capsules to Treat Symptomatic Patients Infected With SARS-CoV-2 (REsCue)

    This is a phase 2, single or multi-center, randomized, double-blind placebo-controlled study to evaluate the safety and efficacy of Rayaldee (CTAP101 Capsules) to treat adult subjects with mild to moderate COVID-19 who test positive for SARS-CoV-2 via nasopharynx swab and subsequent reverse transcription polymerase chain reaction (RT-PCR).

    NCT04551911
    Conditions
    1. Covid19
    2. Coronavirus
    3. SARS-CoV-2 Infection
    Interventions
    1. Drug: Rayaldee 30Mcg Extended-Release (ER) Capsule
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: The FLU- PRO© questionnaire was specifically designed and validated to evaluate in clinical trials the presence, severity and duration of symptoms associated with viral infections. It contains 32 items (eg, felt hot, sweating, headache), grouped into 6 domains, that provide a comprehensive evaluation of such symptoms, using 5-point scales (values ranging from 0 to 4) with higher scores indicating worse symptoms.

    Measure: Severity and duration of disease as evidenced by COVID-19 symptoms using the FLU-PRO© questionnaire.

    Time: 42 days

    Measure: Concentration of serum total 25-hydroxyvitamin D maintained at or above 50 ng/mL.

    Time: 28 days
    456 Prospective, Three-armed, Randomised, Double-blind Study to Evaluate the Efficacy and Safety of the Treatment of Mild and Moderate Actinic Keratosis With a 5% Potassium Hydroxide Solution (Solcera, Medical Device) Versus Placebo and Investigator-blinded Comparison With 3% Diclofenac Gel (Solaraze, Medicinal Product) (Regulated by the Laws for Both Medical Devices and Medicinal Products)

    The KOHDIAK study is a prospective, three-armed, randomised, double-blind study to evaluate the efficacy and safety of the treatment of mild and moderate actinic keratosis with a 5% potassium hydroxide solution (Solcera, medical device) versus placebo and investigator-blinded comparison with 3% diclofenac gel (Solaraze, medicinal product). It is performed in accordance with both the laws in force for clinical trials with medical devices and those with medicinal products.

    NCT04552327
    Conditions
    1. Actinic Keratosis
    Interventions
    1. Device: Solcera
    2. Device: Placebo
    3. Drug: Solaraze
    MeSH:Keratosis, Actinic Keratosis

    Primary Outcomes

    Description: Treatment success, defined as complete, dermatoscopically confirmed remission of all initial actinic keratosis (AK) lesions identified at treatment start that have been treated with the investigational product ("Complete Clearance")

    Measure: Treatment success

    Time: At the control visit at the end of treatment ("EOT", i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60)

    Secondary Outcomes

    Description: Treatment success, defined as complete, dermatoscopically confirmed remission of all initial AK lesions identified at treatment start that have been treated with the investigational product ("Complete Clearance")

    Measure: Treatment success

    Time: For Solaraze at day 90

    Description: (Healing) status of AK lesions (number of proliferating lesions, unchanged/stable lesions, lesions being in remission or showing partial remission, lesions with complete remission, and relapses; overall and grouped by localisation and size (0-5 mm, 6-10 mm, 11-15 mm, 16-20 mm)); analysed for a) initial AK lesions identified at treatment start that have been treated with the investigational product, b) new AK lesions appearing in the treated area after treatment start, c) all AK lesions (i.e. a) + b))

    Measure: (Healing) status of AK lesions

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Overall number of initial AK lesions identified at treatment start that have been treated with the investigational product (i.e. without AK lesions with complete remission)

    Measure: Overall number of AK lesions

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Mean size of initial AK lesions identified at treatment start that have been treated with the investigational product (lesion size determined by largest diameter)

    Measure: Mean size of AK lesions

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Treatment success (complete, dermatoscopically confirmed remission of lesions) analysed for a) initial AK lesions identified at treatment start that have been treated with the investigational product, b) new AK lesions appearing in the treated area after treatment start, c) all AK lesions (i.e. a) + b))

    Measure: Treatment success

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Number of patients with "partial clearance" (i.e. all patients with at least 75% of the initial AK lesions identified at treatment start being assessed with "complete remission")

    Measure: Partial clearance

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Reduction of AK lesion number per patient (in % compared to the number of initial AK lesions identified at treatment start) analysed for initial AK lesions identified at treatment start that have been treated with the investigational product

    Measure: Reduction of AK lesion number

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Clinical response, i.e. the number of patients with at least one AK lesion being assessed with "complete remission"

    Measure: Clinical response

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Number of initial AK lesions identified at treatment start that have been treated with the investigational product, which showed "complete remission" at least once between treatment start and EOT

    Measure: Lesion-based treatment success (without consideration of relapses)

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Number of initial AK lesions identified at treatment start that have been treated with the investigational product, which showed "complete remission" at the respectively analysed visit

    Measure: Lesion-based treatment success (with consideration of relapses)

    Time: At all control/follow-up visits with evaluation of lesions (i.e. for Solcera/Placebo 8 weeks (+ potentially 16 weeks) and 24 weeks after treatment start; for Solaraze Day 30, Day 60, Day 90, 24 weeks)

    Description: Number of patients with at least one initial AK lesion being assessed as "relapse" after previous "Complete Clearance" (definition see above), analysed for the time period between treatment start and the follow-up visit after 24 weeks and analysed in reference to a) the number of all patients and b) the number of those patients with previous "Complete Clearance"

    Measure: Patients with relapse

    Time: Analysed at the follow-up visit 24 weeks after treatment start for the time period between treatment start and the follow-up visit

    Description: Number of initial AK lesions being assessed as "relapse", analysed for the time period between treatment start and the follow-up visit after 24 weeks and analysed in reference to a) the number of all initial lesions and b) the number of those initial lesions with previous "complete remission"

    Measure: Lesions with relapse

    Time: Analysed at the follow-up visit 24 weeks after treatment start for the time period between treatment start and the follow-up visit

    Description: Assessment of the efficacy (scale based on school grades 1-6) by the treating physician

    Measure: Efficacy assessment by physician

    Time: At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start

    Description: Assessment of the efficacy (scale based on school grades 1-6) by the patient

    Measure: Efficacy assessment by patient

    Time: At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start

    Description: Assessment of the tolerability (scale based on school grades 1-6) by the treating physician

    Measure: Tolerability assessment by physician

    Time: At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start

    Description: Assessment of the tolerability (scale based on school grades 1-6) by the patient

    Measure: Tolerability assessment by patient

    Time: At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start

    Description: Overall assessment (scale based on school grades 1-6) by the treating physician

    Measure: Overall assessment by physician

    Time: At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start

    Description: Overall assessment (scale based on school grades 1-6) by the patient

    Measure: Overall assessment by patient

    Time: At EOT (i.e. for Solcera/Placebo at the end of cycle 1, 2 or 3 (each cycle is 56 days, number of cycles depends on course of remission), for Solaraze day 60) and at the follow-up visit 24 weeks after treatment start

    Description: Number and frequency of Adverse Events, Serious Adverse Events and Adverse Reactions

    Measure: Adverse Events, Serious Adverse Events, Adverse Reactions

    Time: In the time period between start of treatment and the follow-up visit (24 weeks after treatment start)

    Description: All dropouts (incl. specification of reason and date)

    Measure: Dropouts

    Time: In the time period between start of treatment and the follow-up visit (24 weeks after treatment start)

    Description: Compliance of the patients with the application schedule of the respective investigational product (based on entries in the patient diary and only overruled by the weight of returned investigational products in case of clear discrepancies)

    Measure: Compliance

    Time: Analysed for the respective time period of scheduled product application, i.e. Day 0 until Day 60 for Solaraze and 1-3x 28 days (depeding on number of cycles) for Solcera/Placebo
    457 Effects of Nitazoxanide Administration to Patients in the Initial Phase of COVID-19

    Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms. Population: 392 Patients with COVID-19 (Coronavirus Disease-19), confirmed by RT-PCR (Real Time polymerase chain reaction), symptomatic in the early phase of the disease. Experimental group: 196 patients, nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: 196 patients, placebo 8/8 hours for 5 days.

    NCT04552483
    Conditions
    1. Covid19
    2. Coronavirus
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Reduction in the duration of fever of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of information with the patient; quantified by the number of days that presented the symptom.

    Measure: Days with fever

    Time: Day8

    Description: Reduction in the duration of cough of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of information with the patient; quantified by the number of days that presented the symptom.

    Measure: Days with cough

    Time: Day8

    Description: Reduction in the duration of asthenia of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of information with the patient; quantified by the number of days that presented the symptom.

    Measure: Days with asthenia

    Time: Day8

    Secondary Outcomes

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 1; verified using the RT-PCR technique; quantified by the absolute number

    Measure: SARS-COV-2 viral load - absolute number

    Time: Day1

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 8; verified using the RT-PCR technique; quantified by the absolute number.

    Measure: SARS-COV-2 viral load - absolute number

    Time: Day8

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 1; verified using the RT-PCR technique; quantified by the percentage change between the two groups.

    Measure: SARS-COV-2 viral load - percentage

    Time: Day 1

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 8; verified using the RT-PCR technique; quantified by the percentage change between the two groups.

    Measure: SARS-COV-2 viral load - percentage

    Time: Day 8

    Description: Compare the hospital admission rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 8 days; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Hospital admission rate - absolute number

    Time: Day8

    Description: Compare the hospital admission rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 8 days; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Hospital admission rate - percentage

    Time: Day8

    Description: Compare the levels of inflammatory mediators: (interleukin [IL] -6 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-6

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: (interleukin [IL] -6 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-6

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: IL-1-beta from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-1-beta

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: IL-1-beta from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-1-beta

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: IL-8 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-8

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: IL-8 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-8

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: tumor necrosis factor (TNF)-alfa from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum tumor necrosis factor (TNF)-alfa

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: tumor necrosis factor (TNF)-alfa from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum tumor necrosis factor (TNF)-alfa

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: interferon-gamma from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum interferon-gamma

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: interferon-gamma from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum interferon-gamma

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: monocyte chemoattractant protein (MCP)-1 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum monocyte chemoattractant protein (MCP)-1

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: monocyte chemoattractant protein (MCP)-1 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum monocyte chemoattractant protein (MCP)-1

    Time: Day 8

    Description: Evaluate evolution of complete blood count with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Complete blood count

    Time: Day 3

    Description: Evaluate evolution of complete blood count with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Complete blood count

    Time: Day 8

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein - absolute number

    Time: Day 3

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein - absolute number

    Time: Day 8

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the percentage between the two group.

    Measure: C-reactive protein - percentage

    Time: Day 3

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by laboratory tests and expressed by the percentage between the two groups.

    Measure: C-reactive protein - percentage

    Time: Day 8

    Other Outcomes

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Adverse events - percentage

    Time: Day 8

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Adverse events - absolute number

    Time: Day8

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Treatment discontinuation rate - absolute number

    Time: Day8

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Treatment discontinuation rate - percentage

    Time: Day8
    458 A Pilot, Randomized, Placebo-Controlled Trial of GC4419 (Avasopasem Manganese) in Patients With Critical Illness Due to SARS-CoV-2 Infection (COVID-19)

    A Trial of GC4419 in Patients with Critical Illness due to COVID-19

    NCT04555096
    Conditions
    1. Covid19
    2. SARS-CoV-2 Infection
    Interventions
    1. Drug: GC4419
    2. Drug: Placebo
    MeSH:Infection Critical Illness

    Primary Outcomes

    Measure: 28 day all-cause mortality

    Time: 28 days
    459 A Prospective, Open-label, Randomized, Multi-center, Phase 2a Study to Evaluation the Dose Response, Efficacy and Safety of Hyper-Ig (Hyper-immunoglobulin) GC5131 in Patients With COVID-19

    The objective of this study is to evaluate the efficacy and safety of 5131A for hospitalized patients of COVID-19.

    NCT04555148
    Conditions
    1. Covid19
    Interventions
    1. Biological: GC5131
    2. Other: Placebo

    Primary Outcomes

    Description: The percent of participants reduced by 2 points or more

    Measure: Ordinal scale outcome

    Time: 7, 14, 21, 28 days

    Secondary Outcomes

    Description: The percents of negative patients for COVID-19 virus

    Measure: Viral negative

    Time: 1, 3, 5, 7, 10 days

    Description: The change of NEWS from baseline

    Measure: Change in NEWS

    Time: 7, 14, 21, 28 days

    Description: The percent of participants

    Measure: mortality

    Time: 28 days
    460 A Phase 2a Randomised, Double Blind, Multi-centre Study to Assess the Effect on Glucose Homeostasis of Two Dose Levels of AZD9567, Compared to Prednisolone, in Adults With Type 2 Diabetes

    The study is intended to assess the effect on glycaemic control of AZD9567, as measured by the glucose AUC(0-4) versus baseline following a standardised mixed meal tolerance test (MMTT), compared to prednisolone in adults with type 2 diabetes mellitus (T2DM). The study will also evaluate the safety, tolerability, and pharmacokinetics (PK) of AZD9567.

    NCT04556760
    Conditions
    1. Diabetes Mellitus, Type 2
    Interventions
    1. Drug: AZD9567
    2. Drug: Prednisolone
    3. Other: Placebo
    MeSH:Diabetes Mellitus Diabetes Mellitus, Type 2
    HPO:Diabetes mellitus Type II diabetes mellitus

    Primary Outcomes

    Description: The change from baseline in glucose AUC(0-4) will be analysed using a mixed model repeated measures (MMRM) with baseline included as covariate.

    Measure: Change in glucose AUC(0-4) versus baseline compared to prednisolone following a standardised MMTT

    Time: On Days -1, 4, 27, and 31

    Secondary Outcomes

    Description: The mean daily glucose will be analysed using a MMRM analysis with baseline as covariate.

    Measure: Mean daily glucose at 48 - 72 hours treatment as determined from multiple measures via the Continuous Glucose Monitoring (CGM) system

    Time: On Days -2, 3, 26 and 30

    Description: The mean daily glucose will be analysed using an MMRM analysis with baseline as covariate.

    Measure: Rise in mean daily glucose over 24-hour periods from start of IMP dosing (0 - 24 hours, 24 - 48 hours, 48 - 72 hours)

    Time: On Days 1, 2, 3, 28, 29, 30

    Description: Pharmacodynamic effects of AZD9567 will be evaluated as compared to prednisolone.

    Measure: Change from baseline in fasting glucose

    Time: On Days -1, 4, 27, and 31

    Description: Effects on insulin, glucagon, GLP-1 and GIP of AZD9567 following MMTT in comparison to prednisolone will be assessed.

    Measure: Change from baseline AUC(0-4) on hormones related to glucose homeostasis

    Time: On Days -1, 4, 27, and 31

    Description: Pharmacodynamic effects of AZD9567 on glucose homeostasis through a MMTT in comparison to prednisolone will be assessed.

    Measure: Change from baseline in AUC(0-4) on C-peptide

    Time: On Days -1, 4, 27, and 31

    Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

    Measure: MMTT derived first phase insulin response

    Time: On Days -1, 4, 27, and 31

    Description: The concentration of potassium in urine will be measured over 24 hours.

    Measure: 24-hour potassium concentration

    Time: On Days -1, 3, 27 and 30

    Description: The concentration of sodium in urine will be measured over 24 hours.

    Measure: 24-hour sodium concentration

    Time: On Days -1, 3, 27 and 30

    Description: AUClast will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Area under the plasma concentration versus time curve from zero to the last quantifiable concentration (AUClast)

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: AUC(0-24) will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Area under the plasma concentration versus time curve from zero to 24 hours post-dose [AUC(0-24)]

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: AUC(0-6) will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Area under the plasma concentration versus time curve from zero to 6 hours post-dose [AUC(0-6)]

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: Cmax will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Maximum observed drug concentration (Cmax)

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: Tmax will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Time to reach maximum observed drug concentration (tmax)

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: t½λz will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Terminal elimination half-life (t½λz)

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: CL/F will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Apparent total body clearance of drug from plasma after extravascular (CL/F)

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: Vz/F will be derived using standard non-compartmental methods using WinNonLin version 8.1 or higher (Certara).

    Measure: Apparent volume of distribution following extravascular administration (Vz/F)

    Time: On Days 3, 4, 30, and 31 (Pre-dose, Post-dose 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 30 hours)

    Description: Relationship between AZD9567 exposure and inhibition of LPS-stimulated TNFα release for high and low dose comparison (Cohort 1 and Cohort 2) will be assessed.

    Measure: TNFα concentrations

    Time: On Days 3 and 30 (Pre-dose, Post-dose 1, 2, 4, 8, 12, and 24 hours

    Description: Pharmacodynamic effects of AZD9567 will be evaluated following a MMTT compared to prednisolone.

    Measure: Change in free fatty acids

    Time: On Days -1, 4, 27, and 31

    Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

    Measure: Homeostatic model assessment- insulin resistance (HOMA-IR)

    Time: On Days -1, 4, 27, and 31

    Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

    Measure: HOMA-insulin sensitivity

    Time: On Days -1, 4, 27, and 31

    Description: Pharmacodynamic effects of AZD9567 on derived measures of beta cell function from the MMTT compared to prednisolone will be evaluated.

    Measure: Modified Matsuda index

    Time: On Days -1, 4, 27, and 31

    Description: Safety and tolerability will be assessed using variables like AEs/SAEs, vital signs, ECGs, changes in clinical chemistry/haematology parameters, morning serum cortisol, and adrenocorticotropic hormone.

    Measure: Safety and tolerability of AZD9567 by assessing the number of participants with adverse events

    Time: From screening up to 79 days
    461 A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Cenobamate Adjunctive Therapy in Subjects With Partial Onset Seizures, With Optional Open-Label Extension

    This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, adjunctive therapy study in subjects with POS, with optional OLE. The study consists of 4 periods as follows: An 8-week of Screening/Baseline Period, 24-week of Double-blind Treatment Period (including a 18-week Titration Phase and 6-week Maintenance Phase), 52-week of Open-label Extension (OLE) Period (applicable for subjects who participate in the OLE) and up to 5-week of End of Study (EOS) Follow-up Period. The purpose of this study is to evaluate the efficacy and safety of 100, 200 and 400 mg/day of cenobamate as adjunctive therapy compared with placebo in subjects with partial onset seizures (POS). The study will also evaluate the long-term safety and tolerability of cenobamate adjunctive therapy in subjects with POS who have completed the double-blind treatment period.

    NCT04557085
    Conditions
    1. Partial Seizure
    2. Focal Seizure
    Interventions
    1. Drug: Cenobamate
    2. Drug: Placebo
    MeSH:Seizures
    HPO:Bilateral tonic-clonic seizure Focal-onset seizure Generalized-onset seizure Seizure

    Primary Outcomes

    Measure: Percent change from baseline in seizure frequency (seizure rate per 28-day interval) of all simple partial motor, complex partial, or secondarily generalized seizures during the Maintenance Phase.

    Time: per 28 days during 6 week maintenance phase
    462 Dose-ranging Study of Labisia Pumila Aqueous Ethanolic Standardized Extract (SKF7™) for Obesity: a Randomized, Double-blind, Placebo-controlled, Phase-2 Study

    This study has been designed as a randomized, double blinded, multi-centric, placebo controlled, and phase II dose-ranging study. The herbal drug contains bioactive ingredients from Labisia pumila plant and it is an aqueous ethanolic standardized extract (SKF7™).

    NCT04557267
    Conditions
    1. Obesity
    Interventions
    1. Drug: low-dose
    2. Drug: Middle-dose
    3. Drug: Higher-dose
    4. Drug: Placebo
    MeSH:Obesity
    HPO:Obesity

    Primary Outcomes

    Description: Percentage of subjects whose Body Weight is lowered

    Measure: Change in body weight

    Time: 12 weeks

    Description: Change in waist and hip circumference

    Measure: Change in waist and hip circumferences

    Time: 12 weeks

    Description: Change in waist-hip ratio and waist-height ratio

    Measure: Change in the waist-hip and waist-height ratios

    Time: 12 weeks

    Description: Change in BMI in kg/m^2

    Measure: Change in Body Mass Index (BMI)

    Time: 12 weeks

    Secondary Outcomes

    Description: The change of body fat percentage

    Measure: Body fat percentage

    Time: 12 weeks

    Description: The amount of lean body mass will be calculated from body fat percentage

    Measure: Lean Body Mass

    Time: 12 weeks

    Other Outcomes

    Description: Abnormality of vital signs and laboratory test results

    Measure: Incidence of abnormal vital signs and of abnormal laboratory test results

    Time: 12 weeks

    Description: The incidence and percentage of Adverse events and serious adverse events

    Measure: Incidence of Adverse Events

    Time: 12 weeks
    463 A Phase III, Randomized, Placebo-controlled, Clinical Trial to Evaluate the Efficacy and Safety of Co-administered Niclosamide in Patients Treated With an Established Regimen for Novel Coronavirus Infectious Disease (COVID-19)

    This study aims to investigate the potential antiviral efficacy and safety of a novel formulation of Niclosamide; a well-known antihelmintic agent, together with an established COVID-19 treatment regimen in patients. The aim of this study is to evaluate the safety and efficacy profile of niclosamide from the test product (Niclosamide 200 mg/10 mL Suspension) in patients treated for the novel coronavirus infectious disease (COVID-19) in a placebo controlled phase III trial. Both treatment groups will receive an established treatment regimen against COVID-19 together with either niclosamide or placebo. The efficacy and safety of the molecule is well-known and the properties of novel formulation is well-established. The promising in vitro results of niclosamide as an antiviral compound is well documented and make it an ideal candidate as a therapy against SARS-CoV 2 infection. A good safety profile is expected with solid antiviral activity.

    NCT04558021
    Conditions
    1. Covid19
    Interventions
    1. Drug: Niclosamide suspension
    2. Other: Placebo

    Primary Outcomes

    Description: The physician will check for the following symptoms: Fever: axillary temperature ≤36.6°C or oral temperature ≤37.2 °C; Respiratory rate: ≤24/minute on room air; Oxygen saturation: >94% on room air; Cough: mild or absent on a patient reported scale of severe, moderate, mild, absent.)

    Measure: Physician's judgment on clinical recovery from the time of admission

    Time: Day 1 to day 19

    Secondary Outcomes

    Description: (National Early Warning Score 2) to 0 to 3 (Improvement in fever, respiratory rate, oxygen saturation,alleviation of cough scores to 3 points to 0 in 72 hours)

    Measure: Clinical improvement in NEWS2

    Time: 3 days from admission

    Description: An elevated D-dimer,ferritin, thrombocyte, PT, aPTT, troponine and fibrinogen were associated with a poor outcome in COVID19. These parameters will be checked on day 1 and day 3.

    Measure: Improvement in serum biomarkers

    Time: Day 1 to day 3

    Description: Requirement for indotracheal intubation is a key outcome for unsuccesful treatment

    Measure: Requirement for indotracheal intubation

    Time: Day 1 to day 19

    Description: Occurrence of Macrophage Activation Syndrome(MAS) will alert the physician that the patients condition is worsening.

    Measure: Occurrence of Macrophage Activation Syndrome(MAS)

    Time: Day 1 to day 19

    Description: Occurrence of Coagulopathy will alert the physician that the patients condition is worsening.

    Measure: Occurrence of Coagulopathy

    Time: Day 1 to day 19

    Other Outcomes

    Description: The assessment of safety will be based on CTCAE v4.0

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time: Day 1 to day 19
    464 A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Phase I Clinical Study to Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

    A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Phase I Clinical Study to Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

    NCT04561076
    Conditions
    1. COVID 19
    Interventions
    1. Drug: HLX70
    2. Other: Placebo

    Primary Outcomes

    Measure: Number of participants with adverse events, serious adverse event and infusion-related reactions as assessed by CTCAE v5.0

    Time: up to 92 days

    Description: The proportion of subjects undergoing DLT events

    Measure: Safety evaluation- proportion of subjects undergoing DLT events

    Time: Days 1 to 7

    Secondary Outcomes

    Measure: PK parameters-Areas under the concentration-time curves

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Maximum measured concentration

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Time from dosing to maximum measured concentration

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Terminal phase elimination rate constant

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Terminal phase elimination half life

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Clearance

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Volume of distribution during terminal phase and at steady state

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Mean residence time

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Description: The number of presence subjects that develop of anti-durg antibody (immunogenicity)

    Measure: Anti-drug antibody

    Time: pre-infusion and Days 15, day 29, day 57, and day 92
    465 Nitazoxanide for Moderate to Severe COVID-19 Pneumonia: a Multicenter, Randomized, Placebo-controlled, Double-Blind Clinical Trial

    Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms. Population: 500 Hospitalized patients with pneumonia derived from COVID-19 (Coronavirus Disease-19), either confirmed by RT-PCR (Real Time polymerase chain reaction), or suggested by typical findings on the computed tomography scan symptomatic. Experimental group: nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: placebo 8/8 hours for 5 days.

    NCT04561219
    Conditions
    1. Covid19
    2. Corona Virus Infection
    3. Pneumonia, Viral
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Compare the intubation rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by percentage.

    Measure: Orotracheal intubation rate

    Time: 14 days

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed free of mechanical ventilation, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Mechanical ventilation free days

    Time: 14 days

    Secondary Outcomes

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the hospital, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Hospitalisation days

    Time: 14 days

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the ICU, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: ICU days

    Time: 14 days

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed with the support of oxygen nasal cannula, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Intranasal oxygen support days

    Time: 14 days

    Description: Compare the mortality rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Mortality rate

    Time: 14 days

    Description: Reduction in the duration of fever of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

    Measure: Days with fever

    Time: 14 days

    Description: Reduction in the duration of cough of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

    Measure: Days with cough

    Time: 14 days

    Description: Reduction in the duration of dyspnea of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

    Measure: Days with dyspnea

    Time: 14 days

    Description: Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Radiologic findings

    Time: Day1

    Description: Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Radiologic findings

    Time: Day7

    Description: Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Cardiologic findings

    Time: Day1

    Description: Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Cardiologic findings

    Time: Day7

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein - absolute number

    Time: Day 1

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein serum levels

    Time: Day 3

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein serum levels

    Time: Day 7

    Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Lactate dehydrogenase (LDH) serum levels

    Time: Day 1

    Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Lactate dehydrogenase (LDH) serum levels

    Time: Day 3

    Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Lactate dehydrogenase (LDH) serum levels

    Time: Day 7

    Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Troponin serum levels

    Time: Day 1

    Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Troponin serum levels

    Time: Day 3

    Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Troponin serum levels

    Time: Day 7

    Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Electrolytes serum levels

    Time: Day 1

    Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Electrolytes serum levels

    Time: Day 3

    Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Electrolytes serum levels

    Time: Day 7

    Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Glucose serum levels

    Time: Day 1

    Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Glucose serum levels

    Time: Day 3

    Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Glucose serum levels

    Time: Day 7

    Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Renal function

    Time: Day 1

    Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Renal function

    Time: Day 3

    Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Renal function

    Time: Day 7

    Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Coagulogram

    Time: Day 1

    Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Coagulogram

    Time: Day 3

    Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Coagulogram

    Time: Day 7

    Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Liver function panel

    Time: Day 1

    Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Liver function panel

    Time: Day 3

    Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Liver function panel

    Time: Day 7

    Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Ferritin

    Time: Day 1

    Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Ferritin

    Time: Day 3

    Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Ferritin

    Time: Day 7

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: D-dimer

    Time: Day 1

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: D-dimer

    Time: Day 3

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: D-dimer

    Time: Day 7

    Description: To evaluate blood cell count of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, for 7 days; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Blood cell count

    Time: 7 days

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Inflammatory mediators

    Time: Day 1

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Inflammatory mediators

    Time: Day 3

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Inflammatory mediators

    Time: Day 7

    Other Outcomes

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Adverse events - percentage

    Time: Day 14

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Adverse events - absolute number

    Time: Day 14

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Treatment discontinuation rate - absolute number

    Time: Day 14

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Treatment discontinuation rate - percentage

    Time: Day 14
    466 Randomized, Double-blind, Parallel Group, Phase 2b Dose-finding, Efficacy and Safety Study of 12-week Twice Daily Oral Administration of BAY 1817080 Compared to Placebo in the Treatment of Refractory and/or Unexplained Chronic Cough (RUCC)

    Researchers in this study want to find the optimal therapeutic dose of drug BAY1817080 for patients with long-standing cough with or without clear causes (refractory and/or unexplained chronic cough, RUCC). Study drug BAY1817080 is a new drug under development for the treatment of long-standing cough. It blocks proteins that are expressed by the airway sensory nerves which are oversensitive in patients with long-standing cough. This prevents the urge to cough. Researchers also want to learn the safety of the study drug and how well it works in reducing the cough frequency, severity and urge-to-cough. Participants in this study will receive either the study drug or placebo (a placebo looks like the test drug but does not have any medicine in it) tablets twice daily for 12 weeks. Observation for each participant will last about 18 weeks in total. Participants will be asked to wear a digital device to record the cough and to complete questionnaires every day to document the symptoms. Blood samples will be collected from the participants to monitor the safety and measure the blood level of the study drug.

    NCT04562155
    Conditions
    1. Refractory and/or Unexplained Chronic Cough
    Interventions
    1. Drug: BAY1817080
    2. Drug: Placebo
    MeSH:Cough
    HPO:Cough

    Primary Outcomes

    Measure: Change from baseline in 24-hour cough count (measured by cough recording digital wearable monitoring device) after 12 weeks of intervention

    Time: From baseline up to 12 weeks

    Secondary Outcomes

    Measure: Percentage of participants with a ≥30% reduction from baseline in 24-hour cough count after 12 weeks of intervention (measured by cough recording digital wearable monitoring device)

    Time: From baseline up to 12 weeks

    Measure: Change from baseline in 24-hour cough count after 2, 4, and 8 weeks of intervention (measured by cough recording digital wearable monitoring device)

    Time: From baseline up to 2 weeks, 4 weeks and 8 weeks

    Measure: Change from baseline in awake cough frequency per hour after 2, 4, 8 and 12 weeks of intervention (measured by cough recording digital wearable monitoring device)

    Time: From baseline up to 2 weeks, 4 weeks, 8 weeks and 12 weeks

    Measure: Change from baseline in cough related quality of life (measured by Leicester Cough Questionnaire [LCQ]) after 12 weeks of intervention

    Time: From baseline up to 12 weeks

    Measure: Change from baseline in cough severity after 12 weeks of intervention (measured by Cough Severity Visual Analogue Scale [VAS])

    Time: From baseline up to 12 weeks

    Measure: Percentage of participants with a ≥30 scale units reduction from baseline after 12 weeks of intervention (measured by cough Severity VAS)

    Time: From baseline up to 12 weeks

    Measure: Percentage of participants with a ≥1.3-point increase from baseline after 12 weeks of intervention (measured with LCQ Total Score)

    Time: From baseline up to 12 weeks

    Measure: Frequency and associated severity of treatment-emergent adverse events (TEAEs)

    Time: From the start of study intervention administration until 14 days after the last study medication intake
    467 A Randomized, Double-Blind, Study Comparing the Efficacy, Safety, and Tolerability of Oral Administration of Ribavirin (RBV) and Nitazoxamide (NTZ)Versus Placebo in SARS-CoV-2 Virus Infected Participants (DuACT)

    This is a single center, randomized, double-blind, 2-arm, parallel-group study of DuACT in participants with clinical symptoms of COVID-19 that have begun within the past 48 hours prior to testing.

    NCT04563208
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Drug: Placebo
    2. Drug: DuACT
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Rate of decline in viral load over the 10 days after randomization between participants treated with RBV and NTZ for COVID-19 and placebo

    Measure: Rate of decline in viral load

    Time: 10 days

    Secondary Outcomes

    Description: Time to resolution of viral load, defined by reduction of virus below LLOQ and maintaining it for 2 days.

    Measure: Time to resolution of viral load

    Time: 28 days

    Description: Comparison of proportion of subjects who are asymptomatic and symptomatic at day 10

    Measure: Comparison of proportion of subjects who are asymptomatic and symptomatic

    Time: 10 days

    Description: To assess the rate of decline in viral load over days 3 and 6 after randomization

    Measure: Rate of decline in viral load

    Time: Days 3 and 6

    Description: Assess change in modified National Early Warning System-2 items on a scale of 0 to 20. HIgher scores meaning greater clinical risk.

    Measure: Change in modified NEWS-2

    Time: 28 days

    Description: Proportion of subjects with treatment emergent adverse events leading to study drug discontinuation

    Measure: Proportion of subjects with treatment emergent adverse events

    Time: 28 days
    468 A Study to Evaluate the Effect of Therapeutic and Supratherapeutic Oral Doses of GSK3640254 on Cardiac Conduction as Assessed by 12-Lead Electrocardiogram Compared to Placebo and a Single Oral Dose of Moxifloxacin in Healthy Adult Participants

    This study will aim to evaluate the effect of therapeutic and supratherapeutic oral doses of GSK3640254 on cardiac conduction compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. The study has 2 parts: Part 1 will determine the supratherapeutic dose for Part 2, which will be the main corrected QT interval (QTc) study. Part 1 consists of 2 sequential cohorts: Sentinel Cohort 1 will evaluate once daily (QD) dosing of GSK3640254 or placebo for 7 days and Sentinel Cohort 2 will evaluate twice daily (BID) dosing of GSK3640254 or placebo for 7 days. Part 2 will investigate the safety, tolerability and Pharmacokinetics (PK) of GSK3640254 doses on cardiac conduction as compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. Moxifloxacin will be included as a positive control. All doses of study intervention will be administered under fed conditions and will receive a moderate-fat meal 30 minutes prior to dosing. The total duration of the study is approximately 91 days. Approximately 58 participants will be enrolled in the study.

    NCT04563845
    Conditions
    1. HIV Infections
    Interventions
    1. Drug: GSK3640254
    2. Drug: Placebo
    3. Drug: Moxifloxacin
    MeSH:HIV Infections

    Primary Outcomes

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 1: Area under the plasma concentration-time curve from time zero to time t (AUC[0-t]) of GSK3640254

    Time: Up to Day 9 of each cohort

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 1: AUC from time zero to the end of the dosing interval at steady state (AUC[0-tau]) of GSK3640254

    Time: Up to Day 9 of each cohort

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 1: Maximum observed concentration (Cmax) of GSK3640254

    Time: Up to Day 9 of each cohort

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 1: Plasma concentration at the end of the dosing interval (Ctau) of GSK3640254

    Time: Up to Day 9 of each cohort

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 1: Time of maximum observed concentration (Tmax) of GSK3640254

    Time: Up to Day 9 of each cohort

    Description: Blood samples will be collected for measurement of plasma concentrations of GSK3640254 and its major metabolite.

    Measure: Part 1: Plasma concentrations of GSK3640254 and its major metabolite

    Time: Up to Day 9 of each cohort

    Description: All AEs and SAEs will be assessed.

    Measure: Part 1: Number of participants with adverse events (AEs) and serious AEs (SAEs)

    Time: Up to Day 9 of each cohort

    Description: Blood samples will be collected for the assessment of hematology and chemistry parameters.

    Measure: Part 1: Number of participants with abnormal laboratory parameters

    Time: Up to Day 9 of each cohort

    Description: Urine samples will be collected for the assessment of urinalysis parameters.

    Measure: Part 1: Number of participants with abnormal urinalysis parameters

    Time: Up to Day 9 of each cohort

    Description: Number of participants with abnormal ECG parameters will be assessed.

    Measure: Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters

    Time: Up to Day 9 of each cohort

    Description: Number of participants with abnormal vital signs will be assessed.

    Measure: Part 1: Number of participants with abnormal vital signs

    Time: Up to Day 9 of each cohort

    Description: Placebo-corrected change from Baseline in QTcF will be analyzed.

    Measure: Part 2: Placebo-corrected change from Baseline in QT interval corrected for heart rate using Fridericia's formula (QTcF) following administration of GSK3640254 (Milliseconds [ms])

    Time: Baseline (Day -1) and up to Day 51

    Description: Blood samples will be collected for measurement of plasma concentrations of GSK3640254 and its major metabolite.

    Measure: Part 2: Plasma concentrations of GSK3640254 and its major metabolite

    Time: Up to Day 51

    Secondary Outcomes

    Description: Change from Baseline in heart rate will be analyzed.

    Measure: Part 2: Change from Baseline in heart rate (HR) (Beats per minute [bpm])

    Time: Baseline (Day -1) and up to Day 51

    Description: Change from Baseline in QTcF, PR interval and QRS interval will be analyzed.

    Measure: Part 2: Change from Baseline in QTcF, PR interval and QRS interval (ms)

    Time: Baseline (Day -1) and up to Day 51

    Description: Placebo-corrected change from Baseline in HR will be analyzed.

    Measure: Part 2: Placebo-corrected change from Baseline in HR (bpm)

    Time: Baseline (Day -1) and up to Day 51

    Description: Placebo-corrected change from Baseline in QTcF, PR interval and QRS interval will be analyzed.

    Measure: Part 2: Placebo-corrected change from Baseline in QTcF, PR interval and QRS interval (ms)

    Time: Baseline (Day -1) and up to Day 51

    Description: Number of participants with abnormal HR, QTcF, PR interval and QRS interval will be assessed.

    Measure: Part 2: Number of participants with abnormal HR, QTcF, PR interval and QRS interval

    Time: Up to Day 51

    Description: Number of participants with treatment emergent changes of T-wave morphology will be evaluated.

    Measure: Part 2: Number of participants with treatment emergent changes of T-wave morphology

    Time: Up to Day 51

    Description: Number of participants with presence of U-wave will be evaluated.

    Measure: Part 2: Number of participants with presence of U-wave

    Time: Up to Day 51

    Description: Placebo-corrected change from Baseline in QTcF will be analyzed.

    Measure: Part 2: Placebo-corrected change from Baseline in QTcF following administration of Moxifloxacin (ms)

    Time: Baseline (Day -1) and up to Day 51

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 2: AUC(0-t) of GSK3640254

    Time: Up to Day 51

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 2: AUC(0-tau) of GSK3640254

    Time: Up to Day 51

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 2: Cmax of GSK3640254

    Time: Up to Day 51

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 2: Ctau of GSK3640254

    Time: Up to Day 51

    Description: Blood samples will be collected at the indicated time points for PK analysis of GSK3640254.

    Measure: Part 2: Tmax of GSK3640254

    Time: Up to Day 51

    Description: Blood samples will be collected at the indicated time points for PK analysis of Moxifloxacin.

    Measure: Part 2: Cmax of Moxifloxacin

    Time: Up to Day 51

    Description: Blood samples will be collected at the indicated time points for PK analysis of Moxifloxacin.

    Measure: Part 2: Tmax of Moxifloxacin

    Time: Up to Day 51

    Description: All AEs and SAEs will be assessed.

    Measure: Part 2: Number of participants with AEs and SAEs

    Time: Up to Day 51

    Description: Blood samples will be collected for the assessment of hematology and chemistry parameters.

    Measure: Part 2: Number of participants with abnormal laboratory parameters

    Time: Up to Day 51

    Description: Urine samples will be collected for the assessment of urinalysis parameters.

    Measure: Part 2: Number of participants with abnormal urinalysis parameters

    Time: Up to Day 51

    Description: Number of participants with abnormal ECG parameters will be assessed.

    Measure: Part 2: Number of participants with abnormal ECG parameters

    Time: Up to Day 51

    Description: Number of participants with abnormal vital signs will be assessed.

    Measure: Part 2: Number of participants with abnormal vital signs

    Time: Up to Day 51
    469 Сlinical Trial of Efficacy, Safety and Immunogenicity of Combined Vector Vaccine Gam-COVID-Vac in SARS-СoV-2 Infection Prophylactic Treatment in Republic of Belarus

    Randomized, double-blind (blinded for the trial subject and the study physician), placebo controlled, multi-center clinical trial in parallel assignment of efficacy, immunogenicity, and safety of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection in adults in the SARS-СoV-2 infection prophylactic treatment.

    NCT04564716
    Conditions
    1. Covid19
    Interventions
    1. Biological: Gam-COVID-Vac
    2. Other: Placebo

    Primary Outcomes

    Description: Demonstrate the superiority of Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the second dose of the study drug/placebo, as confirmed with the method of polymerase chain reaction (PCR)

    Measure: percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose

    Time: through the whole study, an average of 180 days

    Secondary Outcomes

    Description: Assess the efficacy of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus compared to placebo, based on the severity of the clinical course of COVID-19

    Measure: the severity of the clinical course of COVID-19

    Time: through the whole study, an average of 180 days

    Description: Assess the immunogenicity of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the geometric mean titer of SARS-CoV-2 glycoprotein-specific antibodies

    Measure: Changing of antibody levels against the SARS-CoV-2 glycoprotein S

    Time: day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose

    Description: Incidence of adverse events in trial subjects compared to placebo

    Measure: Incidence of adverse events in trial subjects

    Time: through the whole study, an average of 180 days

    Description: Severity of adverse events in trial subjects compared to placebo

    Measure: Severity of adverse events in trial subjects

    Time: through the whole study, an average of 180 days
    470 A Randomized, Double-blind, Dose-ranging, Placebo Controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 (INTEGRIS-ARDS)

    Evaluation of the safety, tolerability, and pharmacokinetics of PLN-74809 in participants with acute respiratory distress syndrome (ARDS) associated with at least severe COVID-19

    NCT04565249
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. SARS-CoV-2
    Interventions
    1. Drug: PLN-74809
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events and laboratory abnormalities, assessed by CTCAE V5.0

    Time: Up to 90 days

    Secondary Outcomes

    Measure: Assessment of PLN-74809 plasma concentrations

    Time: up to 14 days

    Other Outcomes

    Measure: Number of participants alive and free of invasive mechanical ventilation

    Time: up to 28 days

    Measure: Number of participants alive and discharged from hospital

    Time: Up to 28 days

    Measure: Number of participants alive and discharged from hospital

    Time: Up to 90 days
    471 A Randomized, Double Blind, Placebo-controlled, Phase 2 Clinical Trial to Investigate the Efficacy and Safety of 2 Doses of NuSepin® Intravenous Infusion in COVID-19 Pneumonia Patients

    A randomized, double blind, placebo-controlled, phase 2 clinical trial to investigate the efficacy and safety of 2 doses of NuSepin® intravenous infusion in COVID-19 pneumonia patients

    NCT04565379
    Conditions
    1. COVID19 Pneumonia
    Interventions
    1. Drug: NuSepin® 0.1 mg
    2. Drug: NuSepin® 0.2 mg
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Difference in Time to Clinical Improvement (TTCI) between the 2 treatments and the placebo group (in days)

    Time: Day 29

    Secondary Outcomes

    Measure: Percentage of patients with CRP < 10 mg/L or < 30% decreases from baseline

    Time: Day 15 and Day 29

    Description: Minimum value being 1, Maximum value being 6. Smaller the number, better the clinical status & outcome

    Measure: Clinical Status assessed by the six-category ordinal scale at fixed time points

    Time: Day 1, 4, 9, 15 and 29

    Measure: Time to complete clinical remission OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours

    Time: Up to Day 29

    Measure: All-cause mortality

    Time: Up to Day 29

    Measure: Duration (days) of mechanical ventilation

    Time: Up to Day 29

    Measure: Duration (days) of extracorporeal membrane oxygenation

    Time: Up to Day 29

    Measure: Duration (days) of supplemental oxygenation

    Time: Up to Day 29

    Measure: Length of hospital stay (days)

    Time: Up to Day 29

    Measure: Length of ICU stay (days)

    Time: Up to Day 29

    Measure: Number of incidence of treatment emergent adverse events (TEAEs) in 3 treatment groups

    Time: Day 15 and Day 29

    Other Outcomes

    Measure: Serum level of TNF-α in pg/ml

    Time: Day 0, 4, 9, 15 and 29

    Measure: Serum level of IL-1β in pg/ml

    Time: Day 0, 4, 9, 15 and 29

    Measure: Serum level of IL-6 in pg/ml

    Time: Day 0, 4, 9, 15 and 29

    Measure: Serum level of IL-8 in pg/ml

    Time: Day 0, 4, 9, 15 and 29
    472 A Phase 1 Study in Healthy Participants to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single -Ascending and Multiple Doses of an Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Chicken Egg Antibody (IgY)

    The primary objective of Part 1 (Single Ascending Dose) is to assess the safety and tolerability of anti-SARS-CoV-2 IgY when given as single-ascending doses administered intranasally to healthy participants. The primary objective of Part 2 (Multiple Dose) is to assess the safety and tolerability of anti-SARS-CoV-2 IgY when given as multiple doses administered intranasally to healthy participants. A secondary objective is to assess the pharmacokinetics of anti-SARS-CoV-2 IgY when given as multiple doses administered intranasally to healthy participants. Safety will be evaluated using adverse event (AE), physical examination (including vital signs), electrocardiogram, and clinical laboratory data. Pharmacokinetics will be evaluated by serum anti-SARS-CoV-2 IgY concentration.

    NCT04567810
    Conditions
    1. Covid19
    Interventions
    1. Drug: anti-SARS-CoV-2 IgY
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: up to 21 days

    Secondary Outcomes

    Measure: Number of Participants With Vital Sign Findings Reported as TEAEs

    Time: up to 21 days

    Description: Clinically significant in the judgement of the investigator.

    Measure: Number of Participants With Clinically Significant Findings in Physical Examinations

    Time: up to 21 days

    Description: Clinically significant in the judgement of the investigator.

    Measure: Number of Participants With Clinically Significant Changes From Baseline in ECG Data

    Time: up to 21 days

    Description: Clinically significant in the judgement of the investigator.

    Measure: Number of participants with Clinically Significant Changes from Baseline in Clinical Laboratory Parameters

    Time: up to 21 days

    Measure: Number of Participants with Presence of Serum anti-SARS-CoV-2 IgY

    Time: up to 21 days
    473 Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of EC-18 in Preventing the Progression of COVID-19 Infection to Severe Pneumonia or ARDS

    A trial of EC-18 in patients with mild/moderate pneumonia due to COVID-19

    NCT04569227
    Conditions
    1. Covid19 Pneumonia
    Interventions
    1. Drug: EC-18
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Proportion of patients alive and free of respiratory failure through at Day 28

    Time: 28 days

    Secondary Outcomes

    Measure: Probability of progression of mild pneumonia patients to severe pneumonia or ARDS within 28 days

    Time: 28 days

    Measure: Assessment of all-cause mortality

    Time: 28 days

    Description: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20L/min with a fraction of delivered oxygen ≥ 0.5) Non-invasive positive pressure ventilation Extracorporeal membrane oxygenation

    Measure: Respiratory failure defined based on resource utilization requiring at least 1 of the following:

    Time: 28 days

    Measure: Proportion of patients alive and free of invasive mechanical ventilation at a pre-specified timepoint

    Time: 28 days

    Measure: Proportion of patients alive and discharged from the hospital at a pre-specified timepoint

    Time: 28 days

    Measure: Lengths of ICU stay

    Time: 28 days

    Measure: Lengths of alive and respiratory failure-free days

    Time: 28 days

    Measure: Proportion of patients with objective measures of improvement (returning to room air) at time points (days 7, 14, and 28)

    Time: 7, 14, and 28 days

    Description: o Check for changes in symptoms on a daily basis for 28 days compared to the baseline at day 1

    Measure: Confirmation of changes in subject's subjective clinical symptoms (e.g., patient questionnaire)

    Time: 28 days
    474 A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Safety and Immunogenicity of V590 in Healthy Adults

    The primary objectives of this study is to evaluate the safety and tolerability of V590 versus placebo and to assess the immunogenicity of V590 on Day 28. The primary hypothesis is that at least one well-tolerated dose of V590 increases the geometric mean titers (GMTs) of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike serum neutralizing antibody, as measured by plaque reduction neutralization test (PRNT), compared to placebo.

    NCT04569786
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Biological: V590
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs (redness, swelling, and tenderness/pain) will be assessed.

    Measure: Percentage of Participants with at Least 1 Solicited Injection Site Adverse Event

    Time: Up to 5 days post-vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs (muscle pain, joint pain, headache, tiredness, fatigue, rash, nausea, joint swelling, oral lesions, and sweating more than usual) will be assessed.

    Measure: Percentage of Participants with at Least 1 Solicited Systemic Adverse Event

    Time: Up to 28 days post-vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Unsolicited AEs will be assessed.

    Measure: Percentage of Participants with at Least 1 Unsolicited Adverse Event

    Time: Up to 28 days post-vaccination

    Description: A medically attended adverse event (MAAE) is an AE in which medical attention is received during an unscheduled, non-routine outpatient visit, such as an emergency room visit, office visit, or an urgent care visit with any medical personnel for any reason. Any MAAE will be assessed.

    Measure: Percentage of Participants with at Least 1 Medically Attended Adverse Event

    Time: Up to 180 days post-vaccination

    Description: A serious adverse event is "life threatening," requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. Any SAE will be assessed.

    Measure: Percentage of Participants with at Least 1 Serious Adverse Event

    Time: Up to 365 days post-vaccination

    Description: Serum samples will be collected and the presence of serum neutralization antibodies (SNAs) will be assessed using plaque reduction neutralization test (PRNT).

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by Plaque Reduction Neutralization Test (Panels A - H)

    Time: Day 28 post-vaccination

    Secondary Outcomes

    Description: Serum samples will be collected and the presence of SNAs will be assessed using PRNT.

    Measure: Geometric Mean Titers for SNAs as Measured by PRNT (Panels A-H)

    Time: Days 7, 14, 90, 180, 270, and 365 post-vaccination

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using enzyme-linked immunosorbent assay (ELISA).

    Measure: Geometric Mean Concentration of Total Anti-SARS-CoV-2 Spike SNAs as Measured by Enzyme-Linked Immunosorbent Assay (Panels A-H)

    Time: Days 7, 14, 28, 90, 180, 270, and 365 post-vaccination

    Description: The percentage of participants with viremia detected by reverse transcription polymerase chain reaction (RT-PCR) of blood specimens will be assessed.

    Measure: Percentage of Participants with Vaccine Viremia as Measured by Reverse Transcription-Polymerase Chain Reaction

    Time: Days 1, 2, 3, 4, 5, 6, 7, 14 and 28 post-vaccination

    Description: The percentage of participants with viral shedding detected by RT-PCR in urine or saliva specimens will be assessed.

    Measure: Percentage of Participants with Vaccine Shedding in Saliva or Urine as Measured by RT-PCR

    Time: Days 1, 2, 3, 4, 5, 6, 7, 14, and 28 post-vaccination

    Description: The percentage of participants with vaccine shedding in stool as measured by RT-PCR will be assessed. Total of 2 stool samples collected if produced: one sample on Days 2 to 4; one sample on Days 5 to 7.

    Measure: Percentage of Participants with Vaccine Shedding in Stool as Measured by RT-PCR

    Time: Days 2-4, 5-7 post-vaccination
    475 Prospective, Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Intravenous L-Citrulline to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 (SARS-CoV-2) Illness

    Prospective, Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Intravenous L-Citrulline to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients with COVID-19 (SARS-CoV2) Illness. To evaluate safety and efficacy of a bolus loading dose and continuous intravenous infusion of L-Citrulline compared to placebo in patients hospitalized with COVID-19 infection (SARS-CoV-2).

    NCT04570384
    Conditions
    1. Acute Hypoxemic Respiratory Failure
    Interventions
    1. Drug: L-Citrulline
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: The primary biochemical objective of this trial is to evaluate the effects of intravenous L-Citrulline on plasma levels of citrulline and arginine in patients admitted to the hospital with COVID-19 infection (SARS-CoV2) and acute hypoxemic respiratory symptoms requiring oxygen therapy. An association of plasma amino acid levels to clinical outcomes may serve as surrogate marker for response. Also measured is time on vent and time in ICU along with hospital stay

    Measure: Primary Biochemical Objective to measure levels of citrulline and arginine in the Blood

    Time: Day 1 through Day 60 Follow up

    Description: Hemodynamic measurements will be converted to a vasopressor dependency index (VDI) for analysis through day 10

    Measure: The primary safety objective is a beneficial effect of intravenous L-Citrulline on hemodynamic status.

    Time: Day 1 through Day 10

    Description: The primary clinical objective is to evaluate the difference in the length of time to an intubation event in hours from the start of study infusion between the study arms.

    Measure: Primary Clinical Objective

    Time: Day 1 through day 60 Follow-up

    Secondary Outcomes

    Description: To evaluate the safety of intravenous L-Citrulline compared to placebo as measured by incidence of reported adverse events.

    Measure: Evaluate the Safety of L-Citrulline

    Time: Day 1 through Day 60 Follow-up

    Description: To evaluate the effect of intravenous L-Citrulline compared to placebo as measured by the total length of all mechanical ventilation, including non-invasive modalities such as high flow nasal cannula and BiPAP and oxygen therapy.

    Measure: Evaluate the effect of intravenous L-Citrulline compared to placebo as measured by the total length of all mechanical ventilation

    Time: Dat 1 through Day 12

    Description: To evaluate the effect of intravenous L-Citrulline compared to placebo on Hospital all-cause mortality

    Measure: Evaluate the Effect of IV L-Citrulline to Placebo for Hospital all cause mortality

    Time: Day 1 through day 12

    Description: To evaluate the effect of intravenous L-Citrulline compared to placebo on lengths of ICU and hospital stay

    Measure: Evaluate the Effect of IV L-Citrulline to Placebo on length of ICU and Hospital Stay

    Time: Day 1 through Day 12 (DC)

    Description: To evaluate overall difference in intubation rates

    Measure: Evaluate overall difference in intubation rates

    Time: Day 1 to Day 10

    Description: To evaluate overall duration of mechanical ventilation from consent and post-infusion

    Measure: Evaluate overall duration of mechanical ventilation from consent and post-infusion

    Time: Day 1 through day 10
    476 Pilot Randomized Controlled Trial: Fluoxetine to Reduce Hospitalization From COVID-19 Infection (FloR COVID-19)

    The current research is a pilot study to determine the feasibility of recruiting and retaining 40 participants diagnosed with COVID-19. The purpose is to observe the early use of fluoxetine (commonly known as Prozac) to reduce the severity of the COVID-19 illness. Fluoxetine is a drug that has been approved by the U.S. Food and Drug Administration (FDA) since 1987 for various mental health disorders.

    NCT04570449
    Conditions
    1. Covid19
    Interventions
    1. Drug: Fluoxetine
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Measures number of subjects hospitalized for COVID-19 symptoms

    Measure: Rate of hospitalization

    Time: 8 weeks

    Description: The 23-item daily symptom checklist measures the presence or absence of COVID-related symptoms (e.g. shortness of breath, fever, chills) and other possible symptoms (e.g. ear pain, vomit, seizures).

    Measure: Physical symptoms assessed through daily checklist

    Time: 8 weeks

    Secondary Outcomes

    Description: Measures number of subjects intubated for COVID-19 symptoms

    Measure: Rate of intubation

    Time: 8 weeks

    Description: Measures number of subjects who die from COVID-19 symptoms

    Measure: Rate of death

    Time: 8 weeks

    Description: Measured using the 9-item Patient Health Questionnaire (PHQ-9) each item rated on a scale of 0-3, where 0=no depressive symptoms and 3=depressive symptoms present nearly every day. A high score indicates severe depression.

    Measure: Depressive symptoms assessed weekly

    Time: 8 weeks

    Description: Measured using the 4-item SPAN assessment rated on a scale from 0-4 where 0=not at all distressing and 4=extremely distressing. A score greater than 5 indicates the presence of PTSD.

    Measure: Post traumatic stress disorder symptoms assessed weekly

    Time: 8 weeks

    Description: Measured using the 7-item General Anxiety Disorder Scale (GAD-7) rated from 0-3, where 0=no anxiety symptoms and 3=anxiety symptoms present nearly ever day. A high score indicates severe anxiety.

    Measure: Anxiety symptoms assessed weekly

    Time: 8 weeks

    Description: Measured using the 6-item Columbia-Suicide Severity Rating Scale (C-SSRS), a semi-structured interview on the presence or absence of suicidal ideation.

    Measure: Suicidality assessed daily

    Time: 8 weeks
    477 A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Angiotensin (1-7) for the Treatment of COVID-19 in Hospitalized Patients

    The primary objective is to evaluate the safety and efficacy of intravenous (IV) infusion of Ang (1-7) compared to placebo with respect to time to recovery, disease severity, need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO), and mortality in patients with COVID 19.

    NCT04570501
    Conditions
    1. Covid19
    Interventions
    1. Drug: Angiotensin-(1-7)
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities

    Measure: Time to recovery

    Time: Up to 29 days

    Secondary Outcomes

    Measure: Incidence of mortality at Day 29

    Time: 29 days

    Measure: Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose

    Time: Up to 29 days

    Measure: Number of participants requiring mechanical ventilation or ECMO, or dying, through Day 29

    Time: Up to 29 days

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 8

    Time: Day 8

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 15

    Time: Day 15

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 22

    Time: Day 22

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 29

    Time: Day 29
    478 A Phase II, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of MEDI3506 in Adult Participants With Uncontrolled Moderate-to-severe Asthma

    Study D9181C00001 is a Phase II, randomised, double-blind, placebo-controlled, parallel group, proof of concept study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of MEDI3506 in adult participants with uncontrolled moderate to severe asthma on standard of care (SOC). Up to approximately 80 sites globally will participate in this study. Approximately 228 participants will be randomized to 3 treatment groups in a 1:1:1 ratio to receive MEDI3506 dose 1, MEDI3506 dose 2, or placebo.

    NCT04570657
    Conditions
    1. Asthma
    Interventions
    1. Biological: MEDI3506
    2. Drug: Placebo
    MeSH:Asthma
    HPO:Asthma

    Primary Outcomes

    Description: To assess the effect of MEDI3506 compared with placebo on lung function, in adult participants with uncontrolled moderate-to-severe asthma.

    Measure: Change from baseline to Week 16 in pre-BD FEV1 (L)

    Time: From Baseline to Week 16

    Secondary Outcomes

    Description: To assess the PK of MEDI3506 in adult participants with uncontrolled moderate-to-severe asthma

    Measure: Serum MEDI3506 concentration-time profiles from Study Day 1 until Study Day 169

    Time: from Study Day 1 to Study Day 169 for a total of 24 weeks

    Description: To assess the immunogenicity of MEDI3506 in adult participants with uncontrolled moderate-to-severe asthma.

    Measure: ADA during the intervention and follow-up periods

    Time: from Study Day 1 to Study Day 169 for a total of 24 weeks

    Description: To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe asthma.

    Measure: Change from baseline to Week 16 in ACQ-6 score.

    Time: Baseline to Week 16

    Description: To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe

    Measure: Proportion of participants with a decrease in ACQ-6 score of ≥ 0.5 from baseline to Week 16

    Time: Baseline to Week 16

    Description: To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe

    Measure: Proportion of participants achieving ACQ-6 well controlled status (defined as ACQ-6 score ≤ 0.75 at Week 16)

    Time: Week 16

    Description: To assess the effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma.

    Measure: Change from baseline in SGRQ at Week 16

    Time: Baseline to Week 16

    Description: To assess the effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma.

    Measure: Proportion of participants with a decrease in SGRQ total score of ≥ 4 points from baseline to Week 16.

    Time: Baseline to Week 16

    Description: To further assess the effect of MEDI3506 compared with placebo on lung function, in adult participants with uncontrolled moderate-to-severe asthma

    Measure: Change from baseline to Weeks 8 and 16 in post-BD FEV1 (L)

    Time: From baseline to Weeks 8 and 16

    Description: To assess the effect of MEDI3506 compared with placebo on CompEx in adult participants with uncontrolled moderate-to-severe asthma

    Measure: Time to first CompEx event based on the period from baseline to Week 16

    Time: Baseline to Week 16

    Description: To assess the effect of MEDI3506 compared with placebo on CompEx in adult participants with uncontrolled moderate-to-severe asthma.

    Measure: Annualised CompEx event rate

    Time: Baseline to Week 16

    Description: To assess the effect of MEDI3506 compared with placebo on concentration of FeNO in adult participants with uncontrolled moderate-to-severe asthma

    Measure: Percent change from baseline to Week 16 in concentration of FeNO in exhaled breath

    Time: From baseline to Week 16
    479 Phase 1, Randomized, Blinded, Placebo-Controlled, Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Dapirolizumab Pegol (BIIB133) in Healthy Japanese and Caucasian Study Participants

    The primary objective of the study is to assess the safety and tolerability of a single intravenous (IV) dose of dapirolizumab pegol (DZP) in Japanese healthy study participants compared with those of Caucasian healthy study participants. The secondary objectives of the study are to assess the pharmacokinetic(s) (PK) of a single IV dose of DZP in Japanese and Caucasian healthy study participants, to evaluate ethnic sensitivity on the PK of DZP between body weight- and gender-matched Japanese and Caucasian healthy study participants and to evaluate the immunogenicity of a single IV dose of DZP in Japanese and Caucasian healthy study participants.

    NCT04571424
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: BIIB133 (Dapirolizumab pegol)
    2. Drug: Placebo

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect.

    Measure: Number of Participants with Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time: Up to Day 120

    Secondary Outcomes

    Measure: Plasma BIIB133 Concentration

    Time: Up to Day 120

    Measure: Area under Concentration-Time Curve from Time 0 to Infinity (AUCinf) of BIIB133

    Time: Up to Day 120

    Measure: Area under Concentration-Time Curve from Time 0 to Time t (AUC0-t) of BIIB133

    Time: Up to Day 120

    Measure: Maximum Observed Concentration (Cmax) of BIIB133

    Time: Up to Day 120

    Measure: Time to Reach Maximum Observed Concentration (Tmax) of BIIB133

    Time: Up to Day 120

    Measure: Elimination Half-life (t½) of BIIB133

    Time: Up to Day 120

    Measure: Clearance (CL) of BIIB133

    Time: Up to Day 120

    Measure: Volume of Distribution (Vd) of BIIB133

    Time: Up to Day 120

    Measure: Percentage of AUCinf Obtained by Extrapolation (AUCextr%) of BIIB133

    Time: Up to Day 120

    Measure: Area under Concentration-Time Curve from Time 0 to Infinity Normalized by Dose (AUCinf/Dose) of BIIB133

    Time: Up to Day 120

    Measure: Area under Concentration-Time Curve from Time 0 to Time t Normalized by Dose (AUC0-t/Dose) of BIIB133

    Time: Up to Day 120

    Measure: Maximum Observed Concentration Normalized by Dose (Cmax/Dose) of BIIB133

    Time: Up to Day 120

    Measure: Plasma Polyethylene Glycol (PEG) Concentration

    Time: Up to Day 120

    Measure: AUCinf of PEG

    Time: Up to Day 120

    Measure: AUC0-t of PEG

    Time: Up to Day 120

    Measure: Cmax of PEG

    Time: Up to Day 120

    Measure: Tmax of PEG

    Time: Up to Day 120

    Measure: t½ of PEG

    Time: Up to Day 120

    Measure: AUCextr% of PEG

    Time: Up to Day 120

    Measure: AUCinf/Dose of PEG

    Time: Up to Day 120

    Measure: AUC0-t/Dose of PEG

    Time: Up to Day 120

    Measure: Cmax/Dose of PEG

    Time: Up to Day 120

    Measure: Urine PEG Concentration

    Time: Up to Day 120

    Measure: Ratio of AUCinf of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of AUC0-t of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of Cmax of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of t½ of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of CL of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of Vd of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of AUCinf/Dose of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of AUC0-t/Dose of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Ratio of Cmax/Dose of BIIB133 between Japanese and Caucasian Participants

    Time: Up to Day 120

    Measure: Number of Participants with Anti-BIIB133 Antibodies

    Time: Up to Day 120

    Measure: Plasma Concentration of Anti-BIIB133 Antibodies

    Time: Up to Day 120

    Measure: Number of Participants with Anti-PEG Antibodies

    Time: Up to Day 120

    Measure: Plasma Concentration of Anti-PEG Antibodies

    Time: Up to Day 120
    480 A Pilot Phase Study Evaluating the Effects of a Single Mesenchymal Stem Cell Injection in Patients With Suspected or Confirmed COVID-19 Infection and Healthcare Providers Exposed to Coronavirus Patients

    This double blind, placebo controlled, multi-arm, multi-site study investigates the safety and efficacy of stem cell therapy for the treatment of patients admitted to hospital suffering complications from COVID-19 and the treatment of healthy subjects (healthcare providers) for prophylactic effect following those patients.

    NCT04573270
    Conditions
    1. Covid19
    2. Prophylaxis
    Interventions
    1. Biological: PrimePro
    2. Other: Placebo

    Primary Outcomes

    Description: Survival Rate in COVID-19 infected patients admitted to hospital for complications

    Measure: Survival Rates

    Time: 30 Days

    Description: Contraction Rate of COVID-19 in healthy healthcare workers following patients admitted to hospital for complications due to COVID-19

    Measure: Contraction Rates

    Time: 30 Days
    481 Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19

    Based on Chinese studies, cardiac injury occurs in 20-30% of hospitalized patients and contributes to 40% of deaths. There are many possible mechanisms of cardiac injury in COVID-19 patients and increased myocardial oxygen demand and decreased myocardial oxygen supply are likely contributors to increased risk of myocardial infarction and heart failure. Interventions reducing the risk of cardiac injury are needed. Ketone bodies, such as 3-hydroxybutyrate and acetoacetate, can maintain ATP production in the heart and brain during starvation. It has been suggested that ketone bodies are more efficient substrates of energy metabolism than glucose, with a lower oxygen consumption per ATP-molecule produced. In addition, the reduction in hospitalizations due to heart failure observed in type 2 diabetes patients treated with sodium-glucose cotransporter 2 inhibitors, is suggested to be partly attributable to increased levels of 3-hydroxybutyrate. Infusion with 3-hydroxybutyrate reaching a plasma level of approximately 3 mM had acute beneficial hemodynamic effects in patients with heart failure and in healthy controls in a study by Nielsen et al. Improved haemodynamics and reduced systemic oxygen consumption might be of great benefit in patients with COVID-19. The primary endpoint is left ventricular ejection fraction. Secondary endpoints are conventional echocardiography parameters, peripheral blood oxygen saturation, venous blood oxygen saturation and urine creatinine clearance. The study population are twelve hospitalized patients with COVID-19 The study design is a randomized placebo-controlled double-blinded crossed-over acute intervention study.

    NCT04573764
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Description: Echocardiography

    Measure: Left Ventricular ejection fraction

    Time: 1 hour

    Secondary Outcomes

    Description: Echocardiography

    Measure: Global longitudinal strain

    Time: 1 hour

    Description: Echocardiography

    Measure: Cardiac output

    Time: 1 hour

    Description: Pulse oximetry

    Measure: Peripheral blood oxygen saturation

    Time: 5 minutes

    Description: blood gas analysis

    Measure: Venous blood oxygen saturation

    Time: 5 minutes

    Description: Urine will be collected during the two cross-over sessions and urine creatinine will be measured on these two volumes. Creatinine clearance in ml/min/1.73m2 will then be estimated and compared with plasma creatinine for estimating kidney function.

    Measure: Urine creatinine clearance

    Time: 12 hours
    482 A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

    The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.

    NCT04574869
    Conditions
    1. Acute Lung Injury
    2. ALI
    3. COVID-19
    Interventions
    1. Drug: RLS-0071
    2. Drug: RLS-0071
    3. Drug: Placebo
    4. Drug: RLS-0071
    5. Drug: RLS-0071
    6. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
    HPO:Pneumonia

    Primary Outcomes

    Measure: Frequency and severity of Adverse Events, including Serious Adverse Events, by treatment group and dose level, including the frequency of premature discontinuation of study intervention due to Adverse Events.

    Time: Through study completion at Day 28 following last dose.

    Secondary Outcomes

    Measure: Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

    Time: Through study completion at Day 28 following last dose.

    Measure: Overall survival.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence of progression to respiratory failure requiring mechanical ventilation.

    Time: Days on ventilation while in the hospital through study completion at Day 28.

    Measure: Incidence of transfer to the ICU.

    Time: Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.

    Measure: Duration of hospitalization after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

    Time: Through study completion at Day 28 following last dose.

    Measure: Duration of requirement for supplemental oxygen after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: PaO2/FiO2

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Description: Dialysis will be assessed by the investigator with CTCAE's latest version.

    Measure: Incidence and duration after treatment (days) of dialysis.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Levels of complement activity (eg, CH50).

    Time: Through study completion at Day 28 following last dose.

    Measure: Levels of C1q (free and bound to RLS-0071).

    Time: Through study completion at Day 28 following last dose.
    483 A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

    The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.

    NCT04574869
    Conditions
    1. Acute Lung Injury
    2. ALI
    3. COVID-19
    Interventions
    1. Drug: RLS-0071
    2. Drug: RLS-0071
    3. Drug: Placebo
    4. Drug: RLS-0071
    5. Drug: RLS-0071
    6. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
    HPO:Pneumonia

    Primary Outcomes

    Measure: Frequency and severity of Adverse Events, including Serious Adverse Events, by treatment group and dose level, including the frequency of premature discontinuation of study intervention due to Adverse Events.

    Time: Through study completion at Day 28 following last dose.

    Secondary Outcomes

    Measure: Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

    Time: Through study completion at Day 28 following last dose.

    Measure: Overall survival.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence of progression to respiratory failure requiring mechanical ventilation.

    Time: Days on ventilation while in the hospital through study completion at Day 28.

    Measure: Incidence of transfer to the ICU.

    Time: Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.

    Measure: Duration of hospitalization after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

    Time: Through study completion at Day 28 following last dose.

    Measure: Duration of requirement for supplemental oxygen after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: PaO2/FiO2

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Description: Dialysis will be assessed by the investigator with CTCAE's latest version.

    Measure: Incidence and duration after treatment (days) of dialysis.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Levels of complement activity (eg, CH50).

    Time: Through study completion at Day 28 following last dose.

    Measure: Levels of C1q (free and bound to RLS-0071).

    Time: Through study completion at Day 28 following last dose.
    484 The CRISIS2 Study: A Phase 2, Randomized, Double Blind, Placebo-controlled, Multi-center Study Assessing the Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Out-patient Adults With SARS-CoV-2

    This study will assess the efficacy and safety of DHODHi (brequinar) as an antiviral via 5 days of treatment of participants with positive COVID-19 and at least one symptom of COVI019 in an out-patient setting. The study is multi-center, randomized, and placebo-controlled.

    NCT04575038
    Conditions
    1. COVID-19 Infection
    Interventions
    1. Drug: Brequinar
    2. Drug: Placebo

    Primary Outcomes

    Description: Quantitative SARS-CoV-2 viral load

    Measure: SARS-CoV-2 viral load

    Time: Day 29

    Secondary Outcomes

    Description: Safety measured by rates of AEs and SAEs including laboratory assessments

    Measure: Rates of AEs and SAEs including laboratory assessments

    Time: Day 29

    Description: Duration of viral shedding

    Measure: Viral shedding duration

    Time: Day 29

    Description: Percentage of subjects requiring admission as an inpatient for >24 hours

    Measure: Hospital Admission

    Time: Day 29
    485 A Phase 2/3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MK-4482 in Hospitalized Adults With COVID-19

    This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the rate of sustained recovery through Day 29.

    NCT04575584
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Drug: Molnupiravir
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Sustained recovery is defined as: the participant is alive and not hospitalized; or the participant is alive and medically ready for discharge as determined by the investigator.

    Measure: Time-to-sustained recovery

    Time: Up to 29 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants with an adverse event (AE)

    Time: Up to 19 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants who discontinued study intervention due to an AE

    Time: Up to 6 days

    Secondary Outcomes

    Description: All-cause mortality is death due to any cause

    Measure: Percentage of participants with all-cause mortality

    Time: Up to 29 days

    Description: Pulmonary score is a score on an ordinal scale which focuses on respiratory sequalae based on oxygen requirements using 7 mutually exclusive categories. The score ranges from 1 to 7 with a higher score indicating more severe respiratory sequalae.

    Measure: Pulmonary score on a scale

    Time: Up to 29 days

    Description: Pulmonary+ score is a score on an ordinal scale which is a 7-category assessment that captures the range of disease severity, including coagulation-related complications and respiratory dysfunction. The score ranges from 1 to 7 with a higher score indicating more severe sequalae.

    Measure: Pulmonary+ score on a scale

    Time: Up to 29 days

    Description: The National Early Warning Score assesses a participant's degree of illness as assessed by clinical risk prediction categories for poor clinical outcomes including mortality within 24 hours of a set of vital sign measurements. There are 7 physiological parameters, of which 6 are assigned a point value ranging from 0 to 3, and 1 is assigned a point value ranging from 0 to 2. The total aggregate score may range from 0 to 20 with an increasing aggregate score indicating increasing clinical risk.

    Measure: National Early Warning Score on a scale

    Time: End of Treatment (EOT) (Up to 6 days)

    Description: The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 to 10 with higher score indicating clinical progression.

    Measure: WHO 11-point outcomes score on a scale

    Time: Up to 29 days
    486 A Phase 2/3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MK-4482 in Non-Hospitalized Adults With COVID-19.

    This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the percentage of participants who are hospitalized and/or die through Day 29

    NCT04575597
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Drug: Molnupiravir
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Hospitalization (all cause) is ≥24 hours of acute care in a hospital or similar acute care facility. Death is due to any cause.

    Measure: Percentage of participants who are hospitalized and/or die

    Time: Up to 29 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants with an adverse event (AE)

    Time: Up to 19 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants who discontinued study intervention due to an AE

    Time: Up to 6 days

    Secondary Outcomes

    Description: The number of days from randomization to the first day on or before study Day 29 by which the targeted self-reported signs/symptoms improve or resolve.

    Measure: Time to improvement or resolution of targeted COVID-19 signs/symptoms

    Time: Up to 29 days

    Description: The number of days from randomization to the first day on or before study Day 29 by which the targeted self-reported signs/symptoms are newly reported or worsen.

    Measure: Time to progression of targeted COVID-19 signs/symptoms

    Time: Up to 29 days

    Description: The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 to 10 with higher score indicating clinical progression.

    Measure: WHO 11-point outcomes score on a scale

    Time: Up to 29 days
    487 Investigation of IRAK4 Inhibition to Mitigate the Impact of COVID-19 in Severe SARS-CoV-2 (I-RAMIC)

    The purpose of this study is to assess the efficacy of PF-06650833 in addition to standard-of-care compared to standard-of-care treatment alone in improving outcomes in patients with COVID-19.

    NCT04575610
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PF-06650833
    2. Drug: Placebo

    Primary Outcomes

    Description: All-cause mortality at Day 29 (end of planned treatment period).

    Measure: All-cause mortality at Day 29

    Time: Up to 29 days

    Secondary Outcomes

    Description: Proportion of patients alive, extubated, and receiving no more than low flow oxygen supplementation by nasal cannula or face mask (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 2 point decrease in the NIAID ordinal scale. The NIAID scale is as follows: Not hospitalized, no limitations on activities Not hospitalized, limitations on activities and/or requiring home oxygen Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high-flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Proportion of patients alive, extubated, and receiving no more than low flow oxygen supplementation by nasal cannula or face mask (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 2 point decrease in the NIAID ordinal scale (1 = not hospitalized, no limitations on activities, and 8 = death) at Day 61.

    Measure: Disease Severity (8 point scale)

    Time: 61 days

    Description: Proportion of patients alive, extubated, and receiving any level oxygen supplementation, including non-invasive positive pressure ventilation or high flow oxygen device (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 1-point decrease in the NIAID ordinal scale (1 = not hospitalized, no limitations on activities, and 8 = death) at Day 29.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Proportion of patients alive, extubated, and receiving any level oxygen supplementation, including non-invasive positive pressure ventilation or high flow oxygen device (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 1-point decrease in the NIAID ordinal scale (1 = not hospitalized, no limitations on activities, and 8 = death) at Day 61.

    Measure: Disease Severity (8 point scale)

    Time: 61 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 8. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 8 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 15. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 15 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 22. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 22 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 29. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 61. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 61 days

    Description: Mortality rate at day 61

    Measure: Mortality

    Time: 61 days

    Description: Time to a 1-point decrease in the NIAID 8-point ordinal scale of disease severity (1 = not hospitalized, no limitations on activities, and 8 = death).

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Time to a 2-point decrease in the NIAID 8-point ordinal scale of disease severity.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 3.

    Measure: Disease Severity (8 point scale)

    Time: 3 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 5.

    Measure: Disease Severity (8 point scale)

    Time: 5 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 8.

    Measure: Disease Severity (8 point scale)

    Time: 8 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 11.

    Measure: Disease Severity (8 point scale)

    Time: 11 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 15.

    Measure: Disease Severity (8 point scale)

    Time: 15 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 22.

    Measure: Disease Severity (8 point scale)

    Time: 22 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 29.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)

    Measure: P/F ratio

    Time: Up to 29 days

    Description: The SOFA evaluates 6 variables, each representing an organ system (one for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems), and scored from 0 (normal) to 4 (high degree of dysfunction/failure). Thus, the maximum score may range from 0 to 24.

    Measure: Change of the SOFA score.

    Time: Up to 29 days

    Description: The duration is days spent on mechanical ventilation.

    Measure: Duration (days) of mechanical ventilation

    Time: Up to 29 days

    Description: The number of days hospitalized not on a ventilator.

    Measure: Ventilator free days.

    Time: Up to 29 days

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time: Up to 29 days
    488 A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetic Profile of Voriconazole Inhalation Powder in Adult Subjects With Asthma

    This is a Phase 1b, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability, and pharmacokinetic profiles of voriconazole inhalation powder in adult subjects with well-controlled asthma. This study will involve 2 cohorts.

    NCT04576325
    Conditions
    1. Asthma
    Interventions
    1. Drug: Voriconazole Inhalation Powder
    2. Drug: Placebo
    MeSH:Asthma
    HPO:Asthma

    Primary Outcomes

    Description: Frequency of AEs, SAEs, and discontinuations due to AEs

    Measure: Number of participants who experience Adverse Events (AEs), Serious Adverse Events (SAEs) and withdrawals due to AEs

    Time: Through study completion, an average of 14 days

    Description: Number of participants with potentially clinically significant vital sign values

    Measure: Number of participants who experience vital sign abnormalities

    Time: Baseline through study completion, an average of 14 days

    Description: Number of participants with potentially clinically significant pulse oximetry values

    Measure: Number of participants who experience pulse oximetry abnormalities

    Time: Baseline through study completion, an average of 14 days

    Description: Spirometry used to measure FEV1 lung function

    Measure: Mean change from baseline in forced expiratory volume (FEV1)

    Time: Baseline through study completion, an average of 14 days

    Description: Spirometry used to measure FVC lung function

    Measure: Mean change from baseline in forced vital capacity (FVC)

    Time: Baseline through study completion, an average of 14 days

    Description: Spirometry used to measure FVC and FEF25-75% lung function

    Measure: Mean change from baseline in forced expiratory flow over the middle 1/2 of the FVC (FEF25-75%)

    Time: Baseline through study completion, an average of 14 days

    Description: Spirometry used to measure FEV1 and FVC lung function

    Measure: Mean change from baseline in FEV1/FVC ratio

    Time: Baseline through study completion, an average of 14 days

    Description: Number of participants with potentially clinically significant ECG values

    Measure: Mean change from baseline in QTcF changes via ECG

    Time: Baseline through study completion, an average of 14 days

    Description: Number of participants with potentially clinically significant physical examination findings

    Measure: Number of participants who experience physical examination abnormalities

    Time: Baseline through study completion, an average of 14 days

    Description: Number of participants with potentially clinically significant laboratory test results

    Measure: Number of participants who experience laboratory test abnormalities

    Time: Baseline through study completion, an average of 14 days

    Secondary Outcomes

    Description: Blood samples will be collected for plasma analysis

    Measure: PK of VIP in plasma: Area under the plasma-concentration time curve (AUC)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Area under the plasma-concentration time curve over the first 12 hours after dosing (AUC0-12)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Area under the concentration time curve, from time 0 to the last observed non-zero concentration (AUC0-tlast)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Area under the concentration time curve from time 0 extrapolated to infinity (AUC∞)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Maximum observed concentration (Cmax)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Time to maximal observed concentration (tmax)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Termination elimination half-life (t½)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Apparent total body clearance (CL/F)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)

    Description: Blood samples will be collected for analysis

    Measure: PK of VIP in plasma: Apparent volume of distribution during the terminal elimination phase (Vz/F)

    Time: Predose Day 1 and through 12 hours post last dose (day 4)
    489 The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE) Study - a Randomized Controlled Trial

    The aims of this vaccine trial are: (1) to measure humoral and selected cellular immune responses to repeated influenza vaccination with Flublok, including these responses' associations with age, birth year, and prior vaccination history; (2) to identify the characteristics of study participants who are vaccinated but still become infected with influenza virus ("vaccine failures") and participants who have poor immune responses to vaccination; and (3) to predict how influenza vaccinations and infections shape immunity.

    NCT04576377
    Conditions
    1. Influenza, Human
    Interventions
    1. Biological: FluBlok
    2. Other: Placebo
    MeSH:Influenza, Human

    Primary Outcomes

    Description: The proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days (the targeted rise in antibody titre is defined as the proportion of participants with a four-fold or greater rise in titer, i.e. either a pre-vaccination hemagglutination inhibition titer <10 and a post-vaccination hemagglutination inhibition titre ≥20, or a pre- vaccination hemagglutination inhibition titer ≥10 and at least a four-fold rise in post-vaccination hemagglutination inhibition antibody titer)

    Measure: Immune response to vaccination (4-fold rise in titer at day 30)

    Time: 30 days after vaccination

    Description: The geometric mean titer (GMT) ratios between the vaccine group and the comparator group (placebo) against each of the vaccine strains at 30 days and 182 days

    Measure: Immune response to vaccination (GMT ratio at day 30 and 182)

    Time: 30 days and 182 days after vaccination

    Secondary Outcomes

    Description: The proportion of participants who achieve an HAI titer ≥40 after each vaccination (or neutralization assay for H3N2 and any other non-hemagglutinating strains).

    Measure: Immune response to vaccination (antibody titer >=40 at day 30 and 182)

    Time: 30 days and 182 days after vaccination

    Description: The vaccine-induced influenza-specific CD4+ and CD8+ T cell responses 7 and 30 days post-vaccination, including cytokine production evaluated by Intracellular Cytokine Staining (ICS) assay. Responses for these and other relevant biomarkers are compared to the corresponding pre-vaccination values for each participant.

    Measure: Immune response to vaccination (cell-mediated immunity)

    Time: 7 days and 30 days after vaccination

    Description: The fine-grained specificity and phenotypes of antibodies and influenza-positive B and T cell populations before and after vaccination and natural infection.

    Measure: Immune response to vaccination (antibody specificity)

    Time: 30 days and 182 days after vaccination

    Description: The rate of adverse events within 30 days after receipt of vaccination or placebo

    Measure: Incidence of reactions after vaccination [Safety]

    Time: 30 days after vaccination

    Description: The rate of polymerase chain reaction (PCR)-confirmed influenza virus infection.

    Measure: Incidence of laboratory-confirmed influenza after vaccination (vaccine failure)

    Time: One year after vaccination

    Description: The occurrence of other respiratory infections, including COVID-19 infections, in participants, determined by PCR or serology

    Measure: Incidence of other respiratory infections

    Time: One year after vaccination
    490 A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of GLPG3970, Administered Orally for 6 Weeks in Adult Subjects With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate

    The primary objective of this study is to evaluate the effect of GLPG3970 compared to placebo on the signs and symptoms of Rheumatoid Arthritis (RA) in participants with moderately to severely active RA and an inadequate response to methotrexate (MTX).

    NCT04577781
    Conditions
    1. Arthritis, Rheumatoid
    Interventions
    1. Drug: GLPG3970
    2. Drug: Placebo
    MeSH:Arthritis Arthritis, Rheumatoid
    HPO:Arthritis Polyarticular arthritis Rheumatoid arthritis

    Primary Outcomes

    Measure: Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) (C-reactive protein [CRP]) at Week 6

    Time: Baseline and Week 6

    Secondary Outcomes

    Measure: Incidence of Treatment-emergent Adverse Events (TEAEs) by Severity

    Time: Screening up to Follow-up (Week 11)

    Measure: Observed Plasma Trough Concentration (Ctrough) of GLPG3970

    Time: Predose (within 30 minutes prior to dosing) on Days 15, 29 and 43
    491 A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of GLPG3970, Administered Orally for 6 Weeks in Adult Subjects With Moderately to Severely Active Ulcerative Colitis

    The primary objective of this study is to evaluate the effect of GLPG3970 compared to placebo on the signs and symptoms of Ulcerative Colitis (UC) in participants with moderately to severely active UC.

    NCT04577794
    Conditions
    1. Colitis, Ulcerative
    Interventions
    1. Drug: GLPG3970
    2. Drug: Placebo
    MeSH:Colitis Colitis, Ulcerative Ulcer
    HPO:Colitis Ulcerative colitis

    Primary Outcomes

    Description: Mayo score is an instrument designed to measure disease activity of UC. Total Mayo score consists of 4 sub-scores: stool frequency, rectal bleeding, flexible sigmoidoscopy and physician's global assessment, each graded from 0 to 3. These scores are summed to give a total score range of 0 to 12, with higher total scores indicating more severe disease.

    Measure: Change From Baseline in Total Mayo Clinical Score (MCS) at Week 6

    Time: Baseline and Week 6

    Secondary Outcomes

    Measure: Incidence of Treatment-emergent Adverse Events (TEAEs) by Severity

    Time: Screening up to Follow-up (Week 13)

    Measure: Observed Plasma Trough Concentration (Ctrough) of GLPG3970

    Time: Predose (within 30 minutes prior to dosing) on Days 15, 29 and 43
    492 A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase III Study to Evaluate the Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients

    The study is designed as a multicenter, randomized , double-blind, placebo controlled study to demonstrate the superiority of LNP023 at a dose of 200 mg b.i.d. compared to placebo on top of maximally tolerated ACEi or ARB on reduction of proteinuria and slowing renal disease progression in primary IgA Nephropathy patients.

    NCT04578834
    Conditions
    1. IgA Nephropathy
    Interventions
    1. Drug: Placebo
    2. Drug: LNP023
    MeSH:Kidney Diseases Glomerulonephritis, IGA
    HPO:Abnormality of the kidney IgA deposition in the glomerulus Nephropathy

    Primary Outcomes

    Description: Evaluated at interim analysis - To demonstrate superiority of LNP023 vs. placebo in the change of proteinuria at 9 months by measuring Urine Protein to Creatinine Ratio sampled from a 24h urine collection.

    Measure: Ratio to baseline in Urine Protein to Creatinine Ratio (sampled from 24h urine collection) at 9 months

    Time: Baseline and 9 months

    Description: Evaluated at the final analysis - to demonstrate superiority of LNP023 vs. placebo in slowing renal disease progression measured by the annualized total slope of Estimated Glomerular Filtration Rate (eGFR) change over 24 months.

    Measure: Annualized total Estimated Glomerular Filtration Rate (eGFR) slope estimated over 24 months).

    Time: Baseline and 24 months

    Secondary Outcomes

    Description: Evaluated at interim analysis - To assess the effect of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of Urine Protein To Creatinine Ratio (sampled from 24h urine collection) at 9 months.

    Measure: Proportion of participants reaching Urine Protein To Creatinine Ratio <1g/g at 9 months, without receiving Corticosteroids/Immunosuppressant or other newly approved drugs for treatment of IgAN or initiating Renal Replacement Therapy.

    Time: Baseline and 9 months

    Description: Evaluated at interim analysis - To evaluate the effect of LNP023 vs. placebo on slowing renal disease progression measured by the annualized total slope of Estimated Glomerular Filtration Rate change over 1 year.

    Measure: Annualized total Estimated Glomerular Filtration Rate slope estimated over 12 months

    Time: Baseline and 12 months

    Description: Evaluated at interim analysis - To assess the effect of LNP023 vs. placebo on the change from baseline to 9 months in fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.

    Measure: Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire

    Time: Baseline and 9 months

    Description: Evaluated at final analysis - To demonstrate the superiority of LNP023 vs. placebo on delaying the time to first occurrence of a composite renal endpoint of reaching either at least 30% change in Estimated Glomerular Filtration Rate, End-Stage Renal Disease or renal death.

    Measure: Time from randomization to first occurrence of composite renal endpoint event, defined as reaching either ≥30% decline in Estimated Glomerular Filtration Rate (eGFR) relative to baseline, or End Stage Renal Disease (ESRD), or renal death

    Time: Up to 24 months

    Description: Evaluated at final analysis - To demonstrate superiority of LNP023 vs. placebo in the change of proteinuria at 9 months by measuring Urine Protein To Creatinine Ratio sampled from a 24h urine collection.

    Measure: Ratio to baseline in Urine Protein-To-Creatinine Ratio (sampled from 24h urine collection) at 9 months

    Time: Baseline and 9 months

    Description: Evaluated at final analysis - To demonstrate the superiority of LNP023 vs. placebo on the proportion of study participants reaching proteinuria below 1g/g of Urine Protein To Creatinine Ratio (sampled from 24h urine collection) at 9 months.

    Measure: Proportion of participants reaching Urine Protein-To-Creatinine Ratio <1g/g at 9 months without receiving Corticosteroids/Immunosuppressant Therapy or other newly approved drugs for treatment of IgAN or initiating renal replacement therapy

    Time: Baseline and 9 months

    Description: Evaluated at final analysis - To demonstrate the superiority of LNP023 vs. placebo on the change from baseline to 9 months in the fatigue scale measured by Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.

    Measure: Change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.

    Time: Baseline and 9 months
    493 A Phase II Study Evaluating Fostamatinib for Hospitalized Adults With COVID-19

    Background: COVID-19 is a new disease caused by SARS-CoV-2 that was identified in 2019. Some people who get sick with COVID-19 become ill requiring hospitalization. There are some medicines that may help with recovery. Researchers want to see if a drug called fostamatinib may help people who are hospitalized with COVID-19. Objective: To learn if fostamatinib is safe in patients who are hospitalized with COVID-19 and gain earlier insight into whether it improves outcomes. Eligibility: Adults age 18 and older who are hospitalized with COVID-19. Design: Participants will be screened with a physical exam, including vital signs and weight. They will have a blood test and chest x-ray. They will have a COVID-19 test as a swab of either the back of the throat or the back of the nose. They will take a pregnancy test if needed. Participants will be randomly assigned, to take either fostamatinib pills or a placebo twice daily for up to 14 days in addition to standard of care for COVID-19. If they can swallow, they will take the pills by mouth with water. If they cannot swallow or are on mechanical ventilation, the pills will be crushed, mixed with water, and given through a tube placed through the nostril, or placed in the mouth, down the esophagus, and into the stomach. Blood samples will be taken daily. Participants will return to the Clinical Center for safety follow-up visits. At these visits, they will have a physical exam and blood tests. If they cannot visit the Clinical Center, they will be contacted by phone or have a telehealth visit. Participation will last for about two months

    NCT04579393
    Conditions
    1. Coronavirus Disease 2019
    Interventions
    1. Drug: Placebo
    2. Drug: fostamatinib
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: The safety primary endpoint is cumulative incidence of SAEs through day 29

    Measure: Cumulative Incidence of SAEs

    Time: Day 29

    Secondary Outcomes

    Measure: Number of days in the ICU

    Time: entire hospitalization

    Measure: Change in CRP, IL-6, d-dimer, ferritin, fibrinogen, absolute lymphocyte count, absolute neutrophil count, and platelet count from baseline

    Time: day 3, 5, 8, 11, 15, 29

    Measure: Ordinal scale

    Time: day 15, 29

    Measure: Days of hospitalization

    Time: entire hospitalization

    Measure: Time to recovery

    Time: day 29

    Measure: Number of days free of mechanical ventilation [entire hospitalization cohort 1]

    Time: entire hospitalization

    Measure: Number of days on oxygen

    Time: entire hospitalization

    Measure: Change in SOFA score from baseline

    Time: day 3, 5, 8, 11, 15, 29

    Measure: Days free of renal failure

    Time: entire hospitalization

    Measure: Clinically relevant deep vein thrombosis

    Time: entire hospitalization

    Measure: Relative change in PaO2/FiO2 or SpO2/FiO2 ratio

    Time: day 1,3,5,8,15,22 and 29

    Measure: Mortality

    Time: day 14, 18

    Measure: Grade 3 and 4 AE

    Time: through day 60
    494 A Pragmatic, Individually Randomised, Double-blind, Placebo-controlled Trial of Triazavirin (TZV) for the Treatment of Mild-moderate SARS-CoV-2 Infection A Phase II and III Clinical Trial

    A) Phase II: Early viral responses to triazavirin In hospitalised patients with mild-moderate COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days, the slope of increase of the Ct values of serial nasopharyngeal swabs to 12 days after initiation of treatment will be ≥24% higher than in hospitalised patients receiving standard of care treatment only. B) Phase III: Efficacy of triazavirin to improve clinical outcomes In hospitalised patients with mild-moderate laboratory proven COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days will reduce a composite outcome - death; ICU admission or mechanical ventilation; or prolonged duration of admission- by ≥29% when compared to the composite outcome in hospitalised patients receiving standard of care therapy only.

    NCT04581915
    Conditions
    1. Covid19
    Interventions
    1. Drug: Triazavirin (Riamilovir)
    2. Other: Placebo

    Primary Outcomes

    Description: To ascertain that indeed there is a biological effect of Triazavirin, we will compare slope of cycle threshold (Ct) values of nasopharyngeal swabs taken from all patients in the Phase II part of the trial. We require at least a 24% difference in slope.

    Measure: To compare the slope of cycle threshold(Ct) values of nasopharyngeal swabs in people receiving Triazavirin versus placebo

    Time: 11 days per patient

    Description: We have selected a composite measure including three adverse outcomes, all of which have serious implications for the patient and the health system. We will combine: deaths; ICU admissions or mechanical ventilation; and prolonged hospital stays -defined in this study as >14 days.

    Measure: To assess the proportion of patients who progress to severe COVID-19 and the proportion who need ICU or die.

    Time: 1 month per patient

    Description: We will compare rates of grade 3 and worse adverse events that occur whilst on treatment, and for up to 30 days after randomisation. We will also report on tolerability, by comparing the proportions by arm of those who had placebo/Triazavirin withheld permanently.

    Measure: To determine the proportion of patients who develop grade 3 or grade 4 adverse events on treatment

    Time: 1 month per patient

    Description: We will report on tolerability by comparing the proportions by arm who had placebo/Triazavirin withheld permanently.

    Measure: To determine the proportion of patients who stop taking either placebo/Triazavirin

    Time: 1 month per patient
    495 A Randomized, Double Blind, Placebo Controlled, Combined Phase 1/2 Single Dose and Multiple Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of NGM621 in Healthy Volunteers and the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Subjects With Confirmed SARS-CoV-2 Infection

    This study is a combined Phase 1 and Phase 2 study with IV infusion of NGM621 to evaluate the safety, tolerability, and PK in healthy volunteers (Part 1), and safety, tolerability, PK and efficacy in subjects with confirmed SARS-CoV-2 infection (Part 2).

    NCT04582318
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Biological: NGM621
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: TEAEs in subjects receiving NGM621 compared to placebo

    Measure: Treatment emergent adverse events - Part 1

    Time: 85 days

    Description: TEAEs in subjects receiving NGM621 compared to placebo

    Measure: Treatment emergent adverse events - Part 2

    Time: 91 days

    Description: Clnical status (on an 8-point ordinal scale) in NGM621 group versus placebo group

    Measure: Clinical status at Day 15 and Day 29 - Part 2

    Time: 29 days

    Secondary Outcomes

    Measure: Maxiumum Serum Concentration [Cmax]

    Time: 91 days

    Measure: Mortality at Day 29

    Time: 29 days

    Measure: Duration of Supplemental Oxygen Requirement

    Time: 91 days

    Measure: Change in Hemolytic Assays (CH50 and AH50) from Baseline

    Time: 91 days
    496 Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial For Evaluation of Efficacy and Safety of SARS-CoV-2 Vaccine (Vero Cell), Inactivated

    This study is a randomized, double-blinded, and placebo controlled phase III clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the experimental vaccine in healthy adults aged 18~59 Years.

    NCT04582344
    Conditions
    1. COVID-19
    Interventions
    1. Biological: CoronaVac
    2. Biological: Placebo

    Primary Outcomes

    Description: The protection rate of a two-dose of SARS-CoV-2 (Vero Cell) vaccine against RT-PCR confirmed symptomatic COVID-19

    Measure: Protection Indexes of Two Vaccine Doses For Symptomatic COVID-19

    Time: 2 weeks after the second dose of vaccination

    Secondary Outcomes

    Description: The protection rate of, at least, one dose of SARS-CoV-2 (Vero Cell) vaccine against RT-PCR confirmed symptomatic COVID-19 Two weeks after the last dose vaccination.

    Measure: Protection Indexes of One Vaccine Dose For Symptomatic COVID-19

    Time: 2 weeks after the second dose of vaccination

    Description: The protection rate of a two-dose of SARS-CoV-2 (Vero Cell) vaccine against rates of hospitalization, disease severity/and death two weeks after the second dose of vaccination

    Measure: Protection Indexes of Second Vaccine Dose For Hospitalization, Disease Severity/and Death

    Time: 2 weeks after the second dose of vaccination

    Description: The protection rate of a two dose of SARS-CoV-2 (Vero Cell) vaccine against RT-PCR confirmed SARS-CoV-2 infection two weeks after the second dose of vaccination

    Measure: Protection Indexes of Two Vaccine Doses For SARS-CoV-2 infection

    Time: 2 weeks after the second dose of vaccination

    Description: The incidence of adverse reactions from the day of first vaccination to 28 days after the second dose of vaccination.

    Measure: Safety indexes of adverse reactions in 28 days

    Time: 28 days after the second dose of vaccination

    Description: The incidence of adverse reactions within 7 days after each dose of vaccination

    Measure: Safety indexes of adverse reactions in 7 days

    Time: 7 days after each dose of vaccination

    Description: The incidence of SAEs from the first vaccination to one year after the second dose vaccination

    Measure: Safety indexes of serious adverse events in 1 year

    Time: 1 year after second dose of vaccination

    Description: The seroconversion rate, seropositivity rate 14 days after each dose vaccination

    Measure: Immunogenicity parameters (seroconversion rate, seropositivity rate) in 14 days

    Time: 14 days after each dose vaccination

    Description: The seroconversion rate, seropositive rate 28 days after the second dose vaccination

    Measure: Immunogenicity parameters (seroconversion rate, seropositivity rate) in 28 days

    Time: 28 days after the second dose vaccination

    Description: GMT and GMI of neutralizing antibody and IgG 14 days after each dose vaccination

    Measure: Immunogenicity parameters (GMT and GMI of neutralizing antibody and IgG) in 14 days

    Time: 14 days after each dose vaccination

    Description: GMT and GMI of neutralizing antibody and IgG 28 days after the second dose vaccination

    Measure: Immunogenicity parameters (GMT and GMI of neutralizing antibody and IgG) in 28 days

    Time: 28 days after the second dose vaccination
    497 A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of HLX71 in Healthy Adult Subjects

    A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of HLX71 in Healthy Adult Subjects

    NCT04583228
    Conditions
    1. COVID 19
    Interventions
    1. Drug: HLX71
    2. Other: Placebo

    Primary Outcomes

    Measure: Number of participants with adverse events, serious adverse event and infusion-related reactions as assessed by CTCAE v5.0

    Time: up to 28 days

    Measure: The proportion of subjects undergoing DLT events in each dose cohorts during the DLT observation period

    Time: Days 1 to 7

    Secondary Outcomes

    Measure: PK parameters-Peak concentration

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Time to peak

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Areas under the concentration-time curves

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Terminal elimination rate constant

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Elimination half-life

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Clearance (CL)

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Volume of distribution

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: The concentration-time curves of plasma Ang1-10

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma Ang1-9

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma Ang1-8

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma Ang1-7

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma aldosterone

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: ADA positive rate

    Time: Day 15 and 29

    Measure: NAb positive rate

    Time: Day 15 and 29
    498 A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rilematovir in Infants and Children (≥28 Days to ≤5 Years of Age) and Subsequently in Neonates (<28 Days of Age), Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV)

    The purpose of the study is to evaluate the efficacy of rilematovir compared to placebo treatment with respect to the clinical outcome on the RSV Recovery Scale (RRS).

    NCT04583280
    Conditions
    1. Respiratory Tract Infections
    Interventions
    1. Drug: Rilematovir
    2. Drug: Rilematovir X mg/kg
    3. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: The RRS is an ordinal scale assessing a participant's clinical status.

    Measure: Respiratory Syncytial Virus (RSV) Recovery Scale (RRS)

    Time: Up to Day 8

    Secondary Outcomes

    Description: Clinical resolution is defined by free of oxygen supplementation, and free of supplemental feeding, and no medical need for intensive care unit (ICU), and key RSV Signs/Symptoms resolved to absent or mild as per the Pediatric RSV Electronic Severity and Outcome Rating Scale (PRESORS) Clinician Rated Outcome (ClinRO) Signs/Symptoms questionnaire.

    Measure: Percentage of Participants with Clinically Resolved RSV Disease as Assessed by ClinRO Sign/Symptoms Questionnaire

    Time: Up to Day 8

    Description: Time from first study dose to resolution of key RSV Signs/symptoms (absent or mild) will be assessed based on parent's/caregiver's PRESORS Observer Rated Outcome (ObsRO) signs/symptoms and supplementation free (oxygen and feeding/hydration).

    Measure: Time From First Study Dose to Resolution of key RSV Signs/Symptoms Based on ObsRO

    Time: Up to Day 21

    Description: Time from discharge to resolution of key RSV Signs/symptoms will be assessed based on PRESORS ObsRO Sign/Symptoms (only including participants who did not reach resolution before first discharge).

    Measure: Time From Discharge to Resolution of key RSV Signs/Symptoms based on ObsRO Sign/Symptoms Questionnaire

    Time: Up to Day 21

    Description: Time from first dosing to end of oxygen supplementation will be assessed (only including participants who were receiving oxygen supplementation at the time of first dosing).

    Measure: Time From First Dosing to end of Oxygen Supplementation

    Time: Up to Day 35

    Description: Number of participants with post-baseline RSV-related complications will be assessed.

    Measure: Number of Participants with Post-baseline RSV-Related Complications

    Time: Up to Day 35

    Description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.

    Measure: Number of Participants with Adverse Events

    Time: Up to Day 35

    Description: Number of participants with abnormalities in Clinical laboratory values (Hematology, Clinical chemistry, and routine urinalysis) will be assessed.

    Measure: Number of Participants with Abnormalities in Clinical Laboratory Values

    Time: Up to Day 35

    Description: Number of participants with ECG abnormalities will be assessed.

    Measure: Number of Participants with Abnormalities in Electrocardiograms (ECG)

    Time: Up to Day 35

    Description: Number of participants with vital signs (Temperature, pulse/heart rate, and peripheral capillary oxygen saturation [SpO2]) abnormalities will be assessed.

    Measure: Number of Participants with Abnormalities in Vital Signs

    Time: Up to Day 35

    Description: Time to resolution of signs/symptoms (absent or mild) of RSV disease as assessed by PRESORS ObsRO signs/symptoms questionnaire.

    Measure: Time to Resolution of Signs/symptoms of RSV Disease as Assessed by ObsRO Signs/Symptoms Questionnaire

    Time: Up to Day 21

    Description: PRESORS ObsRO Signs/Symptoms Questionnaire Scores will be assessed. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease.

    Measure: PRESORS ObsRO Signs/Symptoms Questionnaire Scores

    Time: Up to Day 21

    Description: Change from baseline in PRESORS ObsRO Signs/Symptoms questionnaire scores over time will be assessed. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease.

    Measure: Change From Baseline in PRESORS ObsRO Signs/Symptoms Questionnaire Scores Over Time

    Time: Baseline up to Day 21

    Description: Time to improvement on PRESORS ObsRO GHQ will be assessed. ObsRO GHQ contains questions which are used to record the caregiver's general impression of the child's RSV disease severity, change in RSV disease severity, and overall health status.

    Measure: Time to Improvement in ObsRO General Health Questions (GHQ)

    Time: Up to Day 21

    Description: Time to resolution of signs/symptoms of RSV disease as assessed by ClinRO signs/symptoms questionnaire will be reported.

    Measure: Time to resolution of Signs/Symptoms of RSV Disease as Assessed by ClinRO Signs/Symptoms Questionnaire

    Time: Up to Day 21

    Description: PRESORS ClinRO signs/symptoms questionnaire score will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease.

    Measure: PRESORS ClinRO Signs/Symptoms Questionnaire Scores

    Time: Up to Day 21

    Description: Change from baseline in PRESORS ClinRO signs/symptoms questionnaire scores over time will be assessed.

    Measure: Change From Baseline in ClinRO Signs/Symptoms Questionnaire Scores

    Time: Baseline up to Day 21

    Description: Percentage of participants with clinically resolved RSV disease based on PRESORS ClinRO signs/symptoms will be assessed.

    Measure: Percentage of Participants with Clinically Resolved RSV Disease Based on ClinRO Signs/symptoms

    Time: Day 2 to 8

    Description: Change from baseline in ClinRO GHQ score over time will be assessed. ClinRO GHQ contains questions which are used to record the caregiver's general impression of the child's RSV disease severity, change in RSV disease severity, and overall health status.

    Measure: Change from Baseline in ClinRO GHQ Score Over Time

    Time: Baseline up to Day 21

    Description: Time to hospital discharge from start of dosing will be assessed.

    Measure: Time to Hospital Discharge From Start of Dosing

    Time: Up to Day 35

    Description: Time to readiness of participants for hospital discharge (as evaluated by the investigator) will be assessed.

    Measure: Time to Readiness for Hospital Discharge

    Time: Up to Day 35

    Description: Percentage of participants requiring ICU stay will be assessed.

    Measure: Percentage of Participants Requiring Intensive Care Unit (ICU) Stay

    Time: Up to Day 35

    Description: Duration of requiring ICU stay will be assessed.

    Measure: Duration of Requiring ICU Stay

    Time: Up to Day 35

    Description: Percentage of participants requiring re-hospitalization for respiratory/other reasons will be assessed.

    Measure: Percentage of Participants Requiring Re-hospitalization for Respiratory/other Reasons

    Time: Up to Day 35

    Description: Time to end of oxygen supplementation will be assessed.

    Measure: Time to end of Oxygen Supplementation

    Time: Up to Day 35

    Description: Percentage of participants requiring oxygen supplementation will be assessed.

    Measure: Percentage of Participants Requiring Oxygen Supplementation

    Time: Up to Day 35

    Description: Duration of oxygen supplementation will be assessed.

    Measure: Duration of Oxygen Supplementation

    Time: Up to Day 35

    Description: Time to end of supplemental feeding/hydration will be assessed.

    Measure: Time to end of Supplemental Feeding/hydration

    Time: Up to Day 35

    Description: Percentage of participants requiring hydration and/or feeding by IV administration or nasogastric tube will be assessed.

    Measure: Percentage of Participants Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube

    Time: Up to Day 35

    Description: Duration of supplemental feeding/hydration will be assessed.

    Measure: Duration of Supplemental Feeding/hydration

    Time: Up to Day 35

    Description: Time to end of supplemental oxygen and/or feeding/hydration will be assessed.

    Measure: Time to end of Supplemental Oxygen and/or Feeding/hydration

    Time: Up to Day 35

    Description: Number of participants with medical care encounters and treatments (including physician or emergency room visits, tests and procedures, and medications, surgeries and other procedures) will be reported.

    Measure: Number of Participants with Medical Encounters and Treatments

    Time: Up to Day 35

    Description: Number of participants with antibiotic treatment episodes will be assessed.

    Measure: Number of Participants with Antibiotic Treatment Episodes

    Time: Up to Day 35

    Description: Number of participants with systemic or inhaled corticosteroids and bronchodilators use will be assessed.

    Measure: Number of Participants with Systemic or Inhaled Corticosteroids and Bronchodilators use

    Time: Up to Day 35

    Description: RSV viral load area under the RSV viral load-time curve [AUC] will be assessed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assay of nasal swabs.

    Measure: RSV Viral Load Area Under the RSV Viral Load-time Curve [AUC]) From Immediately Prior to First Dose of Study Intervention (Baseline) Through Day 3, Day 5, and Day 8

    Time: Baseline, Day 3, 5 and Day 8

    Description: RSV viral load over time will be assessed by qRT-PCR assay in the mid-turbinate nasal swab specimens.

    Measure: RSV Viral Load Over Time

    Time: From Baseline to Day 21

    Description: Change From baseline in RSV viral load over time will be assessed by qRT-PCR assay in the mid-turbinate nasal swabs specimens.

    Measure: Change From Baseline in RSV Viral Load Over Time

    Time: Baseline to Day 21

    Description: Percentage of participants with undetectable RSV viral load will be assessed.

    Measure: Percentage of Participants with Undetectable RSV Viral Load

    Time: Up to Day 21

    Description: Number of participants with post-baseline changes in the RSV F-gene compared with baseline sequences will be assessed.

    Measure: Number of Participants with Post-baseline Changes in the RSV F-gene Compared with Baseline Sequences

    Time: Up to Day 21

    Description: Plasma concentration of rilematovir will be assessed.

    Measure: Plasma Concentration of Rilematovir

    Time: Post-dose (Day 1) and pre-dose (Day 2)

    Description: Acceptability and palatability of the rilematovir formulation will be assessed through a questionnaire completed by parent(s)/caregiver(s).

    Measure: Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s)

    Time: Day 8
    499 A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy of Camostat Mesilate for Treatment of COVID-19 in Outpatients

    This is a randomized, double-blind, placebo-controlled study of camostat mesilate in ambulatory patients with confirmed COVID-19 with at least one risk factor for severe illness.

    NCT04583592
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Camostat Mesilate
    2. Drug: Placebo

    Primary Outcomes

    Description: Disease progression will be defined as the proportion of participants requiring hospitalization (including emergency room visit) or who die due to any cause within 28 days of randomization.

    Measure: Disease Progression at Day 28

    Time: 28 days

    Secondary Outcomes

    Description: The overall survival rate (the proportion of randomized participants who survive up to Day 15 and Day 28).

    Measure: Survival Rate

    Time: Up to Day 15 and Day 28

    Description: Time (in hours) from initiation of study treatment until normalization of fever (≤ 37.2 °C oral or tympanic) and sustained for at least 72 hours only assessed in participants who experienced a fever within 24 hours of enrollment up to Day 28.

    Measure: Time to Fever Resolution

    Time: Up to 28 days

    Description: Time to disease progression is defined as the time from randomization to either hospitalization or death up to Day 28.

    Measure: Time to Disease Progression

    Time: Up to 28 days

    Description: Proportion of participants with no viral shedding (yes/no) using reverse transcriptase-polymerase chain reaction (RT-PCR) at Day 7, Day 15, and at early termination.

    Measure: Resolution of Viral Shedding

    Time: Day 1, Day 7 and Day 15

    Description: Incidence of adverse events (AEs) and serious adverse events (SAEs) of any grade from randomization up to Day 28.

    Measure: Rate of Adverse Events and Serious Adverse Events

    Time: 28 days

    Description: Cumulative incidence of grade 3 and 4 AEs from randomization up to Day 28.

    Measure: Cumulative Rate of Grade 3 and 4 Adverse Events

    Time: 28 days

    Description: Incidence of discontinuation from study due to an AE/SAE (discontinued participants will be followed up to Day 28).

    Measure: Rate of Discontinuation

    Time: 28 days

    Description: Change from baseline in clinical laboratory value of platelet count.

    Measure: Change in Laboratory Parameter - Platelet Count

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of potassium level.

    Measure: Change in Laboratory Parameter - Potassium Level

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of AST.

    Measure: Change in Laboratory Parameter - Aspartate Aminotransferase (AST)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of ALT.

    Measure: Change in Laboratory Parameter - Alanine Aminotransferase (ALT)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of ALP.

    Measure: Change in Laboratory Parameter - Alkaline Phosphatase (ALP)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of GGT.

    Measure: Change in Laboratory Parameter - Gamma-Glutamyl Transferase (GGT)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of albumin.

    Measure: Change in Laboratory Parameter - Albumin

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of bilirubin.

    Measure: Change in Laboratory Parameter - Bilirubin

    Time: Day 1 and Day 15

    Description: Change from baseline in heart rate.

    Measure: Change in Vital Signs - Heart Rate

    Time: Day 1, Day 7 and Day 15

    Description: Change from baseline in blood pressure.

    Measure: Change in Vital Signs - Blood Pressure

    Time: Day 1, Day 7 and Day 15

    Description: Change from baseline in SpO2.

    Measure: Change in Vital Signs - Peripheral Capillary Oxygen Saturation (SpO2)

    Time: Day 1, Day 7 and Day 15
    500 A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

    This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with COVID-19. BET is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 40 sites throughout the US. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 100 subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

    NCT04583956
    Conditions
    1. COVID-19
    Interventions
    1. Other: Placebo
    2. Drug: Remdesivir
    3. Biological: Risankizumab

    Primary Outcomes

    Description: Clinical status assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Clinical efficacy in adults hospitalized with COVID-19 according to clinical status on an 8-point ordinal scale.

    Time: Day 8

    Secondary Outcomes

    Measure: Change from baseline in C-reactive protein (CRP) concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in ferritin concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in fibrinogen concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in troponin concentration

    Time: Day 1 through Day 29

    Measure: Change in alanine aminotransferase (ALT) over time

    Time: Day 1 through Day 29

    Measure: Change in aspartate aminotransferase (AST) over time

    Time: Day 1 through Day 29

    Measure: Change in creatinine over time

    Time: Day 1 through Day 29

    Measure: Change in hemoglobin over time

    Time: Day 1 through Day 29

    Measure: Change in international normalized ratio (INR) over time

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Measure: Change in platelets over time

    Time: Day 1 through Day 29

    Measure: Change in total bilirubin over time

    Time: Day 1 through Day 29

    Measure: Change in white blood cell (WBC) count with differential over time

    Time: Day 1 through Day 29

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.

    Measure: Clinical efficacy, as assessed by time to recovery

    Time: Day 1 through Day 29

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 60

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 60

    Description: For any reason.

    Measure: Discontinuation or temporary suspension of study product administration

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use during the study

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of non-invasive ventilation/high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Supplemental oxygen concentration or flow rate will be measured.

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Mean change in the ordinal scale

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Oxygenation use

    Time: Day 1 through Day 29

    Description: A subject who is "alive and without respiratory failure" is defined as meeting any one of the following five categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3)Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen.

    Measure: Proportion of subjects alive and without respiratory failure

    Time: Day 1 to Day 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 29-day mortality

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Measure: Time to death

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of < / = 2 and maintained for 24 hours, whichever occurs first

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Ventilator/ extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29
    501 A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

    This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with COVID-19. BET is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 40 sites throughout the US. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 100 subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

    NCT04583969
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Lenzilumab
    2. Other: Placebo
    3. Drug: Remdesivir

    Primary Outcomes

    Description: Clinical status assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Clinical efficacy in adults hospitalized with COVID-19 according to clinical status on an 8-point ordinal scale

    Time: Day 8

    Secondary Outcomes

    Measure: Change from baseline in C-reactive protein (CRP) concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in ferritin concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in fibrinogen concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in lactate dehydrogenase (LDH) concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in troponin concentration

    Time: Day 1 through Day 29

    Measure: Change in alanine aminotransferase (ALT) over time

    Time: Day 1 through Day 29

    Measure: Change in aspartate aminotransferase (AST) over time

    Time: Day 1 through Day 29

    Measure: Change in creatinine over time

    Time: Day 1 through Day 29

    Measure: Change in hemoglobin over time

    Time: Day 1 through Day 29

    Measure: Change in international normalized ratio (INR) over time

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Measure: Change in platelets over time

    Time: Day 1 through Day 29

    Measure: Change in total bilirubin over time

    Time: Day 1 through Day 29

    Measure: Change in white blood cell (WBC) count with differential over time

    Time: Day 1 through Day 29

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.

    Measure: Clinical efficacy, as assessed by time to recovery

    Time: Day 1 through Day 29

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 60

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 60

    Description: For any reason.

    Measure: Discontinuation or temporary suspension of study product administration

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use during the study

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of non-invasive ventilation/high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Supplemental oxygen concentration or flow rate will be measured.

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Incidence of ventilator/ extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Mean change in the ordinal scale

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Oxygenation use

    Time: Day 1 through Day 29

    Description: A subject who is "alive and without respiratory failure" is defined as meeting any one of the following five categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3)Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen.

    Measure: Proportion of subjects alive and without respiratory failure

    Time: Day 1 through Day 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 29-day mortality

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Measure: Time to death

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of < / = 2 and maintained for 24 hours, whichever occurs first

    Time: Day 1 through Day 29
    502 A Phase 3, Randomised, Observer-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in Adult Participants 18-84 Years of Age in the United Kingdom

    This is a study to evaluate the effectiveness, immune response, and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in adults aged 18-84 years in the United Kingdom. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in the study population. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study. Approximately 9,000 participants will take part in the study. The first 400 participants who meet additional criteria will receive a flu vaccine, in addition to the SARS-CoV-2 rS vaccine or placebo, as part of a sub-study. An effort will be made to enroll a target of at least 25% of participants who are ≥ 65 years of age, as well as prioritizing other groups that are most affected by COVID-19, including racial and ethnic minorities.

    NCT04583995
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: SARS-CoV-2 rS/Matrix M1-Adjuvant
    2. Other: Placebo
    3. Biological: Licensed seasonal influenza vaccine

    Primary Outcomes

    Description: Number of participants, testing serologically negative for SARS-CoV-2 at baseline, with first occurrence of positive (+) polymerase chain reaction (PCR)-confirmed SARS-CoV-2 illness with symptomatic COVID-19 with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic COVID-19

    Time: From Day 28 to Day 386

    Description: Number of participants, testing serologically negative for SARS-CoV-2 at baseline with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic Moderate or Severe COVID-19

    Time: From Day 28 to Day 386

    Secondary Outcomes

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic COVID-19 assessed from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic COVID-19

    Time: From Day 28 to Day 386

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, or serologically confirmed, SARS-CoV-2 illness with asymptomatic or symptomatic COVID-19 with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Asymptomatic or Symptomatic COVID-19

    Time: From Day 28 to Day 386

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with COVID-19 with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with COVID-19 requiring Hospitalization, Intensive Care Unit (ICU), or Mechanical Ventilation

    Time: From Day 28 to Day 386

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild COVID-19 (with no progression to moderate or severe COVID-19 during the course of the COVID-19 episode) with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic Mild COVID-19

    Time: From Day 28 to Day 386

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMEUs (Geometric mean ELISA unit) at Day 0 (baseline), Day 21 (21 days after first study vaccination), and Day 35 (14 days after second study vaccination).

    Measure: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMEUs

    Time: Day 0 to Day 35

    Description: Numbers and percentages (with 95% CI) of participants with SAEs (Serious Adverse Events) and MAAEs (Medically Attended Adverse Events) through End of Study by MedDRA classification, severity score and relatedness.

    Measure: Participants with SAEs and MAAEs

    Time: 386 days
    503 A Randomized, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) in Outpatients With COVID-19 Who Are Asymptomatic or Have Mild Symptoms

    This is a randomized, placebo-controlled study to assess the safety, PK profile, and efficacy of COVI-AMG in subjects with COVID-19.

    NCT04584697
    Conditions
    1. Covid19
    Interventions
    1. Biological: COVI-AMG
    2. Drug: Placebo

    Primary Outcomes

    Description: Safety as assessed by incidence of adverse events by type, frequency, severity, and causality

    Measure: Incidence of adverse events by type, frequency, severity, and causality (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of treatment-emergent adverse events by type, frequency, severity, and causality

    Measure: Incidence of treatment-emergent adverse events by type, frequency, severity, and causality (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of serious adverse events by type, frequency, severity, and causality

    Measure: Incidence of serious adverse events by type, frequency, severity, and causality (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of dose-limiting toxicities

    Measure: Incidence of dose-limiting toxicities (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of clinically meaningful laboratory abnormalities

    Measure: Incidence of clinically meaningful laboratory abnormalities (safety)

    Time: Randomization through study completion at Day 60

    Description: Viral load as assessed using plasma and salivary samples at various timepoints correlated with nasopharyngeal testing

    Measure: Viral load as assessed using plasma and salivary samples at various timepoints

    Time: Randomization through study completion at Day 60

    Description: Time from onset of COVID-19 symptoms to treatment (Day 1)

    Measure: Time from onset of COVID-19 symptoms to treatment (Day 1)

    Time: Day 1

    Description: Presence and levels of anti-drug antibodies directed to COVI-AMG

    Measure: Presence and levels of anti-drug antibodies directed to COVI-AMG

    Time: Randomization through study completion at Day 60

    Description: Cytokine levels post-treatment including EGF, IFNγ, IL-1β, IL-6, IL-8, IL-10, and TNFα will be measured by ELISA

    Measure: Cytokine levels post-treatment

    Time: Randomization through study completion at Day 60

    Secondary Outcomes

    Description: Area under the serum concentration-time curve (AUC) of COVI-AMG

    Measure: AUC of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60

    Description: Maximum observed serum concentration (Cmax) of COVI-AMG

    Measure: Cmax of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60

    Description: Time to Cmax (Tmax) of COVI-AMG

    Measure: Tmax of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60

    Description: Apparent serum terminal elimination half life (t½) of COVI-AMG

    Measure: t½ of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60
    504 A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Adults Age ≥65 Years

    The proposed trial will obtain preliminary data on the feasibility of studying RTB101 as compared to placebo for COVID-19 post-exposure prophylaxis in adults age ≥ 65 years to inform the design of a subsequent pivotal trial.

    NCT04584710
    Conditions
    1. Covid19
    Interventions
    1. Drug: RTB101
    2. Drug: Placebo

    Primary Outcomes

    Description: The number of days from the date of receipt of a positive SARS-CoV-2 swab test result to the date of first dose of study drug in asymptomatic subjects who: have SARS-CoV-2 detected on a surveillance nasal or nasopharyngeal swab OR live in the same house or apartment as someone who has laboratory-confirmed symptomatic COVID-19

    Measure: To determine the length of time from date of receipt of a positive SARS-CoV2 test result to date of first dose of study drug in asymptomatic adults age ≥ 65 years

    Time: Beginning of randomization through Week 2

    Secondary Outcomes

    Description: Study drug compliance determined from the number of capsules of study drug taken by the subject based on data reported in an eDiary

    Measure: To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population

    Time: Beginning of randomization through Week 2

    Description: Study drug compliance determined from the number of capsules of study drug taken by the subject based on data from twice weekly phone calls

    Measure: To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population

    Time: Beginning of randomization through Week 2

    Description: Study drug compliance determined from the number of capsules of study drug taken by the subject based on a pill count done by phone when subjects complete study drug treatment

    Measure: To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population

    Time: Beginning of randomization through Week 2

    Description: Incidence and severity of COVID-19 symptoms based on data reported in an eDiary

    Measure: To determine the feasibility of using an eDiary to assess COVID-19 symptoms in the study population

    Time: From time of first dose through Week 3

    Description: Incidence and severity of COVID-19 symptoms based on data from twice weekly phone calls

    Measure: To determine the feasibility of using an eDiary to assess COVID-19 symptoms in the study population

    Time: From time of first dose through Week 3

    Description: Safety and tolerability will be assessed by report of AE/SAEs from first dose of study drug through Week 3

    Measure: To assess the incidence of treatment-emergent of AEs and SAEs in subjects assigned to RTB101 as compared to placebo

    Time: From time of first dose through Week 3

    Description: The percentage of subjects who have SARS-CoV-2 detected on nasal or nasopharyngeal swab and who develop 2 or more concurrent symptoms of COVID-19 from first dose of study drug through Day 14

    Measure: To determine the percentage of subjects treated with RTB101 as compared to placebo who develop symptomatic laboratory-confirmed COVID-19 from first dose through Day 14

    Time: From time of first dose through Week 2

    Description: The percentage of subjects who die from any cause from first dose of study drug through Day 14 and 21

    Measure: To determine the percentage of subjects treated with RTB101 as compared to placebo who die from any cause from first dose of study drug through Day 14 and 21

    Time: From time of first dose through Week 3

    Description: The percentage of subjects who develop laboratory-confirmed COVID-19 from first dose of study drug through Day 14 and are subsequently hospitalized for any reason through Day 21

    Measure: To determine the percentage of subjects treated with RTB101 as compared to placebo who develop laboratory-confirmed COVID-19 from first dose through Day 14 and are subsequently hospitalized for any reason through Day 21

    Time: From time of first dose through Week 3

    Description: The percentage of subjects who have SARS-CoV-2 detected on nasal or nasopharyngeal swab regardless of symptoms from first dose of study drug through Day 7, 14, and 21 among subjects who are not SARS-CoV-2 positive at screening or baseline

    Measure: To determine the percent of subjects treated with RTB101 or placebo who have laboratory-confirmed SARS-CoV-2 infection regardless of symptoms from first dose of study drug through Days 7, 14, 21.

    Time: From time of first dose through Week 3
    505 Study to Evaluate the Safety, Tolerability and Immunogenicity of INO-4700 for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Healthy Volunteers

    The purpose of this Phase 2a, randomized, blinded, placebo-controlled, multi-center study is to evaluate the safety, tolerability and immunogenicity of INO-4700 administered by intradermal (ID) injection followed by electroporation (EP) using the CELLECTRA™ 2000 device in healthy adult volunteers for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. This study is divided into 2 parts: Part 1- dose finding stage and Part 2- dose expansion stage.

    NCT04588428
    Conditions
    1. Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
    Interventions
    1. Drug: INO-4700
    2. Drug: Placebo
    3. Device: CELLECTRA™ 2000
    MeSH:Coronavirus Infections Syndrome

    Primary Outcomes

    Measure: Frequency of Adverse Events in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Percentage of Participants with Adverse Events in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Frequency of Injection Site Reactions in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Percentage of Participants with Injection Site Reactions in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Frequency of Adverse Events of Special Interest (AESIs) in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Percentage of Participants with Adverse Events of Special Interest (AESIs) in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Geometric Mean Titers (GMTs) of MERS-CoV Antigen Specific Binding Antibodies in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Percentage MERS-CoV Antigen Specific Neutralizing Antibodies in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Percentage Antigen Specific Cellular Immune Response in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Percentage of Seroconverted Participants in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Percentage of Participants with Overall Immune Response in Part 1

    Time: Part 1: baseline up to Week 48

    Measure: Frequency of Adverse Events in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Percentage of Participants with Adverse Events in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Frequency of Injection Site Reactions in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Percentage of Participants with Injection Site Reactions in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Frequency of Adverse Events of Special Interest (AESIs) in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Percentage of Participants with Adverse Events of Special Interest (AESIs) in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Geometric Mean Titers (GMTs) of MERS-CoV Antigen Specific Binding Antibodies in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Percentage MERS-CoV Antigen Specific Neutralizing Antibodies in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Percentage Antigen Specific Cellular Immune Response in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Percentage of Seroconverted Participants in Part 2

    Time: Part 2: baseline up to Week 68

    Measure: Percentage of Participants with Overall Immune Response in Part 2

    Time: Part 2: baseline up to Week 68
    506 A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, AND OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A SARS-COV-2 RNA VACCINE CANDIDATE AGAINST COVID-19 IN HEALTHY JAPANESE ADULTS

    This is a Phase 1/2, randomized, placebo-controlled, and observer-blind study in healthy Japanese adults. The study will evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 RNA vaccine candidate against COVID-19: - As 2 doses, separated by 21 days - At a single dose level - In adults 20 to 85 years of age

    NCT04588480
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: BNT162b2
    2. Other: Placebo

    Primary Outcomes

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: Percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: Percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: Percentage of participants reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants reporting serious adverse events

    Time: From dose 1 through 12 months after the last dose

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with abnormal hematology and chemistry laboratory values

    Time: 1 day after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 2

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 1 day after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 7 days after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between before dose 2 and 7 days after dose 2

    Description: As measured at the central laboratory

    Measure: SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs

    Time: 1 month after dose 2

    Description: As measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 serum neutralizing titers

    Time: From before vaccination to 1 month after dose 2

    Description: as measured at the central laboratory

    Measure: SARS-CoV-2 S1-binding IgG levels, expressed as GMCs

    Time: 1 month after dose 2

    Description: as measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 S1-binding IgG levels

    Time: From before vaccination to 1 month after dose 2

    Secondary Outcomes

    Description: As measured at the central laboratory

    Measure: SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs

    Time: Through 1 year after dose 2

    Description: As measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point

    Time: Through 1 year after dose 2 from baseline

    Description: As measured at the central laboratory

    Measure: SARS-CoV-2 S1-binding IgG levels, expressed as GMCs

    Time: Through 1 year after dose 2

    Description: As measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 S1-binding IgG levels from before vaccination to each subsequent time point

    Time: Through 1 year after dose 2 from baseline

    Description: As measured at the central laboratory

    Measure: GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 S1-binding IgG levels

    Time: Through 1 year after dose 2
    507 A Ph 1, Rndmzd, Dbl-Blinded, Pbo-Controlled, 3-Part Study to Eval the Safety, Tolerability, PK, and PD of TD-1058 Admin by Inhalation of Single (A) and Multiple (B) Ascending Doses in Healthy Subjs and Subjs With IPF (C)

    This is a Phase 1, 3-part, randomized, double-blinded, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-1058 inhaled solution. Part A is a SAD study in healthy subjects, Part B is a MAD study in healthy subjects, and Part C is a multiple-dose study in subjects with IPF.

    NCT04589260
    Conditions
    1. Idiopathic Pulmonary Fibrosis (IPF)
    Interventions
    1. Drug: TD-1058
    2. Drug: Placebo
    MeSH:Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Number and severity of treatment emergent adverse events

    Measure: Part A (SAD) - Adverse Events

    Time: Part A (SAD) Day 1 to Day 8

    Description: Number and severity of treatment emergent adverse events

    Measure: Part B (MAD) - Adverse Events

    Time: Part B (MAD) Day 1 to Day 21

    Description: Number and severity of treatment emergent adverse events

    Measure: Part C (IPF) - Adverse Events

    Time: Part C (IPF) Day 1 to Day 35

    Secondary Outcomes

    Description: Multiple PK variables of TD-0903 will be assessed during Part A, B and C and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

    Measure: Pharmacokinetics (PK) of TD-1058: AUC

    Time: Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35

    Description: Multiple PK variables of TD-0903 will be assessed during Part A, B and C and may include, but are not limited to: Maximum observed concentration (Cmax)

    Measure: Pharmacokinetics (PK) of TD-1058: Cmax

    Time: Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35

    Description: Multiple PK variables of TD-0903 will be assessed during Part A, B and C and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

    Measure: Pharmacokinetics (PK) of TD-1058: Tmax

    Time: Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35
    508 A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose First-in-Human Study Investigating the Safety, Tolerability, and Pharmacokinetics of Intravenously Administered HFB30132A, a Monoclonal Antibody Directed Against SARS-CoV-2, in Healthy Adult Subjects

    The purpose of this study is to test the safety and tolerability of HFB30132A when it is given by intravenously to healthy participants. Blood tests will be done to check how much HFB30132A is in the bloodstream and how long the body takes to eliminate it. Participation may include up to ten visits to the study center.

    NCT04590430
    Conditions
    1. Healthy
    Interventions
    1. Drug: HFB30132A
    2. Other: Placebo

    Primary Outcomes

    Description: Number of participants experiencing TEAEs

    Measure: Number of participants with treatment emergent serious adverse events (TESAEs)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Description: Safety and tolerability will be evaluated in terms of number of participants with TEAEs of special interest (hypersensitivity / anaphylactic reaction / local tolerability)

    Measure: Number of participants with treatment emergent adverse events (TEAE) of special interest

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Description: Safety and tolerability will be evaluated in terms of number of participants with TEAE

    Measure: Number of participants with treatment-emergent adverse events (TEAE)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Maximum observed serum concentration (Cmax)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Minimum observed serum concentration (Cmin)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Time of maximum serum concentration (Tmax)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Area under the concentration vs. time curve (AUC0-last), AUC0-∞)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Terminal half-life (T1/2)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Systemic clearance (CL)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Steady-state volume of distribution (Vss)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Secondary Outcomes

    Description: Safety and tolerability will be evaluated in terms of number of participants with TEAEs

    Measure: Number of participants with treatment-emergent adverse events (TEAEs)

    Time: From Day 1 to up to last follow-up day (Day 270)

    Description: Safety and tolerability will be evaluated in terms of number of participants with TESAEs

    Measure: Number of participants with treatment-emergent serious adverse events (TESAEs)

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Maximum observed serum HFB30132A concentration (Cmax) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Minimum observed serum HFB30132A concentration (Cmin) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Time of maximum serum HFB30132A concentration (Tmax) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Area under the concentration vs. time curve (AUC0-last), AUC0-∞) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Terminal half-life (T1/2) of HFB30132A in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Systemic clearance (CL) of HFB30132A in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Steady-state volume of distribution (Vss) of HFB30132A in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Description: Presence or absence of antibodies against HFB30132A over time

    Measure: HFB30132A Anti-drug antibodies

    Time: From Day 1 to up to last follow-up day (Day 270)
    509 Safety, Tolerability and Efficacy of GLS-1027 in the Prevention of Severe Pneumonitis Caused by SARS-CoV-2 Infection

    This clinical trial will evaluate the safety, tolerability and efficacy of GLS-1027 in the prevention of severe pneumonitis caused by SARS-CoV-2 infection

    NCT04590547
    Conditions
    1. Pneumonitis
    2. SARS-CoV Infection
    Interventions
    1. Drug: GLS-1027
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Incidence of serious adverse events relative to treatment group

    Time: 56 days

    Measure: Incidence of progression to WHO Classification of ≥6 to include intubation with mechanical ventilation, need for ECMO, or death relative to treatment group

    Time: 56 days

    Secondary Outcomes

    Measure: Assess the number of days requiring ICU care relative to treatment group

    Time: 56 days

    Measure: Assess the number of days of mechanical ventilation relative to treatment group

    Time: 56 days
    510 Industry Alliance Platform Trial to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients

    The primary objective of this study is to evaluate the time to confirmed clinical recovery in participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for efficacy and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.

    NCT04590586
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Standard of care
    2. Drug: Apremilast
    3. Drug: Placebo

    Primary Outcomes

    Description: Confirmed clinical recovery means the participant is fit for discharge from hospital. Fit for discharge is defined by achieving a score of 6, 7, or 8 on the 8-point ordinal scale of clinical severity status, without being re-hospitalized prior to Day 29. 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high-flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Time to confirmed clinical recovery

    Time: Up to Day 29

    Secondary Outcomes

    Description: Oxygen-free recovery is defined as participants who are alive, discharged, and not receiving supplement oxygen

    Measure: Number of participants who achieve oxygen-free recovery at Day 29

    Time: Day 29

    Description: Fit for discharge is defined by achieving a score of 6, 7, or 8 on the 8-point ordinal scale of clinical severity status, without being re-hospitalized prior to Day 29. 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high-flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Number of participants who experience ≥2-point improvement from baseline or assessed as fit-for-discharge on the ordinal scale at Day 29

    Time: Baseline to Day 29

    Measure: Incidence of all-cause mortality

    Time: Up to Day 29

    Description: 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Distribution of participants across the 8-point ordinal scale of clinical severity status scores at Day 8, Day 15 and Day 29

    Time: Day 8, Day 15 and Day 29

    Description: 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Worst post-baseline score on the 8-point ordinal scale of clinical severity status

    Time: Up to Day 29

    Measure: Number of intensive care unit (ICU) days

    Time: Day 1 to Day 29

    Measure: Number of invasive mechanical ventilator days

    Time: Day 1 to Day 29

    Description: Clinical recovery is defined by achieving a score of 6, 7 or 8 on the 8-point ordinal scale of clinical severity status. 8-point ordinal scale of clinical severity status scores are Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Number of participants who achieve clinical recovery at Day 8, Day 15, and Day 29

    Time: Day 8, Day 15, and Day 29

    Description: Sustained clinical recovery is defined by achieving a score of 6, 7 or 8 on the 8-point ordinal scale of clinical severity status at follow-up visit (Day 60). 8-point ordinal scale of clinical severity status scores are Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Number of participants who achieve sustained clinical recovery at Day 60

    Time: Day 60

    Measure: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more serious adverse events (SAEs)

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade 3 or higher

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more adverse events (AEs) leading to dose modification

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more adverse events (AEs) leading to discontinuation

    Time: Baseline to Day 60
    511 A Randomized, Double-blind, Placebo- and Active Comparator-controlled, Crossover Trial to Examine the Effect of Multiple Doses of CVL-865 on Panic Symptoms Induced by Carbon Dioxide Inhalation in Healthy Subject

    The purpose of this study is to determine anxiolytic effect of multiple doses of CVL-865 using an experimental medicine model of carbon dioxide (CO2) inhalation in healthy volunteers.

    NCT04592536
    Conditions
    1. Panic Disorder
    Interventions
    1. Drug: CVL-865 High dose
    2. Drug: Alprazolam 1mg XR
    3. Drug: Placebo
    4. Drug: CVL-865 low dose
    MeSH:Panic Disorder

    Primary Outcomes

    Description: Change in Panic Symptom List -IV (PSL-IV), a questionnaire including 13 symptoms, each with intensity rating from 0 (not at all) to 4 (very intense), from pre-CO2 to Post CO2 challenge value

    Measure: PSL-IV score

    Time: up to Day 8

    Secondary Outcomes

    Description: Change in Visual Analog Scale (VAS) value for fear, consisting of a horizontal line 100 mm in length with 0 corresponding to "no fear" and 100 corresponding to "the most fear possible", from pre-CO2 to Post CO2 challenge

    Measure: VAS Fear score

    Time: up to Day 8

    Description: Change from pre-CO2 to post-CO2 challenge values in Finapres NanoCore Physiological Measurements

    Measure: CO2 challenge

    Time: Screening, Day 1, Day 8

    Description: Treatment-emergent AEs

    Measure: Treatment-emergent AEs

    Time: From screening to Follow-up Visit

    Description: Suicidality assessed using Columbia - Suicide Severity Rating Scale (C-SSRS) with no/yes (0/1) to each interview question on the occurrence of suicide events or ideation.

    Measure: Suicidality assessed using Columbia - Suicide Severity Rating Scale (C-SSRS)

    Time: Screening, Day -1, Day 8

    Measure: CVL-865 (and alprazolam, if appropriate) concentrations

    Time: Day 8

    Description: Psychodynamic effects of CVL-865 will be assessed by means of the NeuroCart test battery (including saccadic eye movements, adaptive tracking, body sway, Quantitative EEG)

    Measure: Change From Baseline in NeuroCart test battery Score

    Time: Screening, Day 1, Day 8

    Description: Visual Analogue Scale (VAS) is made up of 16 pairs of alternative descriptors of mood and attention at either end. The Bond-Lader of a 10 cm line. Participants will rate their feelings at the time of assessment by indicating the point on the line which best represent their mood. Each item is scored by measuring the position relative to the left hand end of the line and levels of anxiety, sedation, and dysphoria are then calculated from the combined scores of selected items. The score ranges from 0 to 100, with a high score reflecting a high level of anxiety, sedation or dysphoria.

    Measure: Change from Baseline in Bond & Lader Visual Analogue Scale (VAS)

    Time: Day 1, Day 8
    512 A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Immunogenicity of ADM03820 in Adults

    ADM03820 is indicated for the treatment and prevention of SARS-CoV-2 (COVID-19) in adults. The primary purpose of this study is to assess the safety of ADM03820 in healthy male and female subjects compared to placebo.

    NCT04592549
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Drug: ADM03820
    2. Other: Placebo

    Primary Outcomes

    Measure: The number of participants with Serious Adverse Events following administration of ADM03820 to the final visit

    Time: 180 days

    Measure: The number of participants with AEs from administration of ADM03820 to the final visit

    Time: 180 days

    Secondary Outcomes

    Measure: The assessment of Peak Plasma Concentration (Cmax) for total antibodies of ADM03820 as measured by enzyme-linked immunosorbent assay (ELISA) methods designed for total monoclonal antibody in the Drug Product.

    Time: 180 days

    Measure: The assessment of Tmax for total antibodies of ADM03820 as measured by enzyme-linked immunosorbent assay (ELISA) methods designed for total monoclonal antibody in the Drug Product.

    Time: 180 days

    Measure: The assessment of the Area under the plasma concentration (AUC(0-t)) for total antibodies of ADM03820 as measured by enzyme-linked immunosorbent assay (ELISA) methods designed for total monoclonal antibody in the Drug Product.

    Time: 180 days

    Measure: To assess the anti-drug antibody levels

    Time: 180 days
    513 A Phase 1, Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending-Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB107 in Healthy Adult Participants

    The primary objective is to determine the safety and tolerability of single and multiple ascending subcutaneous (SC) doses and single ascending intravenous (IV) doses of BIIB107 in healthy adult participants. The secondary objectives are to characterize the single-dose pharmacokinetic (PK) of SC and IV BIIB107 in healthy adult participants and to characterize the multiple-dose PK of SC BIIB107 in healthy adult participants.

    NCT04593121
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: BIIB107
    2. Drug: Placebo

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event.

    Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Single Ascending Dose (SAD)

    Time: Day -1 up to Day 84

    Description: An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event.

    Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs): Multiple Ascending Dose (MAD)

    Time: Day -1 up to Day 117

    Secondary Outcomes

    Measure: Area Under the Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUCinf): SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Maximum Observed Concentration (Cmax): SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Time to Reach Maximum Observed Concentration (Tmax): SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Terminal Half-Life (t1/2): SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Total Body Clearance (CL) for IV Doses: SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Apparent Clearance (CL/F) of SC Doses: SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Volume of Distribution During the Terminal Phase (Vss) for IV Doses: SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) for SC Doses: SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Bioavaibility of SC Doses: SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Absorption Rate Profile of SC Doses: SAD

    Time: Day 1 pre-dose and multiple time-points up to Day 84

    Measure: Maximum Observed Concentration (Cmax): MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117

    Measure: Time to Reach Maximum Observed Concentration (Tmax): MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117

    Measure: Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau): MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117

    Measure: Trough Concentration (Ctrough): MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117

    Measure: Terminal Half-Life (t1/2): MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117

    Measure: Accumulation Ratio (R): MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117

    Measure: Apparent Clearance (CL/F) of SC Doses: MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117

    Measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) for SC Doses: MAD

    Time: Day 1 pre-dose and multiple time-points up to Day 117
    514 A Multicentre, SAD, and MAD Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IV Treatment of CALY-002 in Healthy Subjects and Subjects With Celiac Disease and Eosinophilic Esophagitis

    This is a single and multiple ascending study to characterize the safety, PK, PD and clinical effect in healthy volunteers and participants with Celiac Disease and Eosinophilic Esophagitis.

    NCT04593251
    Conditions
    1. Eosinophilic Esophagitis
    2. Celiac Disease
    Interventions
    1. Biological: CALY-002
    2. Biological: Placebo
    MeSH:Esophagitis Celiac Disease Eosinophilic Esophagitis
    HPO:Celiac disease Esophagitis Gluten intolerance

    Primary Outcomes

    Measure: Incidence of treatment-emergent adverse event

    Time: through study completion, an average of 3 months post last dose
    515 A Randomized, Double-blind, Placebo-controlled Safety and Clinical Outcomes Study of Disulfiram in Subjects With Moderate COVID-19

    This clinical trial evaluates the safety, efficacy, and biomarker levels of FDA-approved drug disulfiram in the treatment of adult subjects hospitalized with moderate COVID-19. Disulfiram may limit the hyperinflammatory response associated with COVID-19 and reduce the risk of progression to severe illness. Subjects will be screened and randomized to receive either daily administration of oral disulfiram or placebo for 14 days. Subjects will be followed up on Day 28.

    NCT04594343
    Conditions
    1. Covid19
    Interventions
    1. Drug: Disulfiram
    2. Drug: Placebo

    Primary Outcomes

    Measure: Change from baseline to day 7 for cytokine IL-18

    Time: Baseline to Day 7

    Secondary Outcomes

    Measure: Percentage of subjects that do not require invasive mechanical ventilation

    Time: 14 Days

    Measure: Mean number of days of invasive mechanical ventilation for those subjects requiring invasive mechanical ventilation

    Time: 14 Days

    Measure: Mean number of days of non-invasive ventilation for those subjects requiring non-invasive ventilation

    Time: 14 Days

    Measure: Mean number of days of supplemental oxygen

    Time: 14 Days

    Measure: Percentage of subjects that deteriorate 1 or more points in the 7-point WHO Ordinal Scale from baseline to Day 14

    Time: Baseline to Day 14

    Measure: Percentage of subjects that are not admitted to the Intensive Care Unit (ICU)

    Time: 14 Days

    Measure: 28-day mortality

    Time: At Day 28

    Other Outcomes

    Measure: Percent change in neutrophil count from baseline to Day 7 and 14

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Percent change in total lymphocyte count from baseline to Day 7 and 14

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for neutrophil-derived circulating free DNA (cf-DNA/NETs)

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for Cytokine TNF-α

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-1β

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-1RA

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-6

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-8

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-10

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for Lactate Dehydrogenase (LDH)

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for D-dimer

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 14 for cytokine IL-18

    Time: Baseline to Day 14
    516 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib Administered Once Daily for 52 Weeks in Subjects With Non-Cystic Fibrosis Bronchiectasis - The ASPEN Study

    The primary objective of this study is to evaluate the effect of brensocatib at 10 mg and 25 mg compared with placebo on the rate of pulmonary exacerbations (PEs) over the 52-week treatment period.

    NCT04594369
    Conditions
    1. Non-Cystic Fibrosis Bronchiectasis
    Interventions
    1. Drug: Brensocatib 10 mg
    2. Drug: Brensocatib 25 mg
    3. Drug: Placebo
    MeSH:Bronchiectasis Fibrosis
    HPO:Bronchiectasis

    Primary Outcomes

    Measure: Rate of Pulmonary Exacerbations (PEs)

    Time: 52 Weeks

    Secondary Outcomes

    Measure: Time to First Pulmonary Exacerbation (PE)

    Time: 52 Weeks

    Measure: Percentage of Participants who are Pulmonary Exacerbation (PE) Free

    Time: 52 Weeks

    Measure: Change from Baseline in Postbronchodilator Forced Expiratory Volume in 1 second (FEV1) Measurements

    Time: Baseline to Week 52

    Measure: Rate of Severe Pulmonary Exacerbations (PEs)

    Time: 52 Weeks

    Measure: Change from Baseline to Week 52 in Quality of Life Questionnaire - Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score

    Time: Baseline to Week 52

    Measure: Incidence and severity of treatment-emergent adverse events

    Time: Up to Week 56
    517 A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of GLPG3667 in Subjects With Moderate to Severe Plaque Psoriasis

    The purpose of this research study is to assess the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of GLPG3667 in multiple daily oral doses in subjects with moderate to severe plaque psoriasis.

    NCT04594928
    Conditions
    1. Plaque Psoriasis
    Interventions
    1. Drug: GLPG3667
    2. Drug: Placebo
    MeSH:Psoriasis
    HPO:Palmoplantar pustulosis Psoriasiform dermatitis

    Primary Outcomes

    Description: To evaluate the safety and tolerability of GLPG3667 compared to placebo in subjects with moderate to severe plaque psoriasis.

    Measure: Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuation in subjects with moderate to severe plaque psoriasis.

    Time: From screening through study completion, an average of 3 months

    Description: To evaluate signs of clinical efficacy of GLPG3667 compared to placebo in subjects with moderate to severe plaque psoriasis.

    Measure: Psoriasis Area and Severity Index (PASI) % change

    Time: At week 4

    Secondary Outcomes

    Description: To characterize the pharmacokinetics (PK) of GLPG3667 in subjects with moderate to severe plaque psoriasis.

    Measure: Observed GLPG3667 plasma trough concentrations (Ctrough).

    Time: Between Day 1 pre-dose and Day 30

    Description: To evaluate blood pharmacodynamics (PD) markers in response to administration of GLPG3667 in subjects with moderate to severe plaque psoriasis.

    Measure: Change from baseline in interleukin 17 [IL-17] levels between treatment groups and time points.

    Time: Between Day 1 pre-dose and Day 60
    518 A Phase 2b, Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Study to Evaluate the Efficacy, Safety and Tolerability of Oral AZD9977 and Dapagliflozin Treatment in Patients With Heart Failure With Left Ventricular Ejection Fraction (LVEF) Below 55% and Chronic Kidney Disease

    The purpose of the study is to evaluate the efficacy and safety of AZD9977 alone and AZD9977 in combination with dapagliflozin and to assess the dose-response relationship of placebo, AZD9977 alone, dapagliflozin alone and 3 doses of AZD9977 combined with dapagliflozin on urinary albumin to creatinine ratio (UACR). The study will be conducted in participants with heart failure (HF) with left ventricular ejection fraction (LVEF [below 55%]) and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR [between 20 and 60 mL/min, with at least 30% of participants with eGFR <30 mL/min and a maximum of 25% of participants with eGFR >45 mL/min]), including at least 40% of participants with type 2 diabetes mellitus (T2DM).

    NCT04595370
    Conditions
    1. Heart Failure
    2. Chronic Kidney Disease
    Interventions
    1. Drug: AZD9977
    2. Drug: Dapagliflozin
    3. Drug: Placebo
    MeSH:Kidney Diseases Renal Insufficiency, Chronic Heart Failure
    HPO:Abnormal left ventricular function Abnormality of the kidney Chronic kidney disease Congestive heart failure Nephropathy Right ventricular failure

    Primary Outcomes

    Description: Evaluating the effect of AZD9977 and dapagliflozin in combination and alone compared with placebo on UACR.

    Measure: Percent change from baseline in UACR at 12 weeks

    Time: Baseline (Day 1) until Week 12 (Day 85)

    Secondary Outcomes

    Description: Assessment of the dose-response relationship of placebo, AZD9977 (Dose C) alone, dapagliflozin (10 mg) alone and 3 doses of AZD9977 (A, B or C) combined with dapagliflozin (10 mg) on UACR.

    Measure: Percent change from baseline in UACR at 12 weeks to assess dose-response relationship

    Time: Baseline (Day 1) until Week 12 (Day 85)

    Description: Assessment of the general safety and tolerability of AZD9977 and dapagliflozin in combination and alone compared with placebo.

    Measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    Time: From baseline (Day 1) until Day 113 (Safety Follow-up)

    Description: Assessment of the effect of AZD9977 and dapagliflozin in combination and alone compared with placebo on serum potassium.

    Measure: Absolute value of serum potassium over time

    Time: Days 1, and 3 until Day 85

    Description: Assessment of the effect of AZD9977 and dapagliflozin in combination and alone compared with placebo on serum potassium.

    Measure: Change from baseline in serum potassium over time

    Time: From baseline (Day 1), Day 3 until Day 85

    Description: Assessment of the effect of AZD9977 and dapagliflozin in combination and alone compared with placebo on eGFR.

    Measure: Absolute value of eGFR over time

    Time: Days 1, and 3 until Day 85

    Description: Assessment of the effect of AZD9977 and dapagliflozin in combination and alone compared with placebo on eGFR.

    Measure: Change from baseline in eGFR over time

    Time: From baseline (Day 1), Day 3 until Day 85
    519 A Randomized Double-Blind, Placebo-Controlled Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy

    This is one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. Approximately 105 patients, stratified as to the presence or absence of tophi, will be randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment with one of two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each trial (SEL-212/301 and SEL-212/302). Analysis of efficacy will be performed at Day 28 of Treatment Period 6. Safety will be monitored throughout the study.

    NCT04596540
    Conditions
    1. Chronic Gout
    Interventions
    1. Drug: SEL-212A
    2. Drug: SEL-212B
    3. Other: Placebo
    MeSH:Gout
    HPO:Gout

    Primary Outcomes

    Description: The percentage of patients who achieve and maintain reduction in serum uric acid (sUA) < 6mg/dL for at least 80% of the time during month 6 in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

    Measure: Serum uric acid control during Month 6

    Time: 6 months

    Secondary Outcomes

    Description: To assess changes in number of tender and swollen joints in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

    Measure: Tender and Swollen Joint Counts

    Time: 6 months

    Description: To assess change in tophus burden by photographic area assessments in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

    Measure: Tophus burden

    Time: 6 months

    Description: To assess change in Patient Reported Outcomes (PROs) including assessments of activity limitation (HAQ-DI) in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

    Measure: HAQ-DI

    Time: 6 months

    Description: To assess change in Patient Reported Outcomes (PROs) including assessments of patients' quality of life (QoL) (SF-36) in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

    Measure: SF-36

    Time: 6 months

    Description: To assess changes in gout flare incidence in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

    Measure: Gout flare Incidence

    Time: 6 months
    520 Favipiravir for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

    Double-blinded, placebo controlled, randomized, phase 3 trial evaluating the antiviral drug favipiravir as potential therapy for mild to moderate COVID-19 in adult outpatients who are not requiring hospitalization and who have had a recently positive COVID-19 test prior to study enrollment.

    NCT04600895
    Conditions
    1. Covid19
    Interventions
    1. Drug: Favipiravir
    2. Drug: Placebo

    Primary Outcomes

    Description: The endpoint will be considered to have been met at the earliest time point at which the associated symptoms over a continuous period of 48 hours.

    Measure: Time to sustained clinical recovery

    Time: From Day 0 to Day 21

    Secondary Outcomes

    Description: Time (number of days) to negative conversion of detectable SARS-CoV-2 viral RNA in negative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assays of saliva

    Measure: Time of Negative Conversion of SARS-CoV2 RNA

    Time: From Day 0 to Day 10

    Description: Proportion of patients showing negative conversion of detectable SARS-CoV-2 viral RNA in saliva

    Measure: Proportion of Negative Conversion of SARS-CoV2 RNA

    Time: Day 2, 4, 6, 8 and 10

    Description: Proportion of patients showing Alleviation of Symptoms fever, chills, cough, sore throat, malaise, headache, muscle pain, diarrhea, vomiting, shortness of breath

    Measure: Proportion of patients showing Alleviation of Symptoms

    Time: Day 4, 7, 10, 14 and 21

    Description: Progression to severe COVID-19 (severe COVID-19 defined as O2 saturation of <94% at rest, all cause hospitalization, or death)

    Measure: Proportion of patients that progress to severe COVID-19

    Time: Day 21

    Description: Proportion of patients dying a. from any cause, b. from a COVID-19 associated complication

    Measure: Reduction in Death Related to COVID-19

    Time: Day 21

    Description: Proportion of patients hospitalized: a. from any cause, b. from a COVID-19 associated complication

    Measure: Reduction in Patient Hospitalization

    Time: Day 21

    Description: Incidence of hospitalization for respiratory distress or O2 saturation <93%

    Measure: Reduction in incidence of hospitalization for respiratory distress or O2 saturation

    Time: Day 21

    Other Outcomes

    Description: Number (and proportion) of patients reporting treatment emergent adverse events by MedDRA system organ class and preferred term

    Measure: Safety / Adverse Events

    Time: Day 21

    Description: Changes of parameters for heart rate (beats per minutes) at each assessment during the study/follow-up period, compared to baseline

    Measure: Vitals (Heart rate)

    Time: Day 21

    Description: Changes of parameters for body temperature (°C) at each assessment during the study/follow-up period, compared to baseline

    Measure: Vitals (Body Temperature)

    Time: Day 21

    Description: Changes of parameters for oxygen saturation (%) at each assessment during the study/follow-up period, compared to baseline

    Measure: Vitals (Oxygen Saturation)

    Time: Day 21
    521 Pilot Study: The Evaluation of Nitric Oxide Generating Lozenges on Outcome in Newly Diagnosed COVID-19 Patient of African American Origin

    This study is a multi-center, randomized, double blinded, prospective, placebo controlled study. Patients upon diagnosis of COVID-19 (Corona Virus Disease-19) will be eligible to participate in the study. The purpose of this study is to find out the side effects and ability to take the study drug, Nitric Oxide (NO) lozenges when taken twice daily by mouth. If this study shows that the drug has no or few, acceptable side effects, it will then include up to 840 participants to find out if the drug can reduce bad outcomes of COVID-19 infection (hospitalization, ICU admission, death). In each part of the study, half of the subjects will receive the study drug and the other half will be given a placebo (inactive pill).

    NCT04601077
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitric Oxide lozenges, 30 mg
    2. Drug: Placebo

    Primary Outcomes

    Description: Blood pressure under 90 mmHg

    Measure: Low blood pressure

    Time: 30 days

    Description: Incidence of self reported dizziness

    Measure: dizziness

    Time: 30 days

    Secondary Outcomes

    Description: The effects of NO therapy on incidence of hospitalization, intubation, ICU admission, dialysis and death in treated patients vs. those receiving placebo therapy.

    Measure: Incidence of hospitalization, ICU admission, intubation, dialysis and death

    Time: 30 Days
    522 PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

    This is a multi-center study conducted at 13 sites in 3 countries (Singapore, New Zealand, and the United Kingdom). Approximately 360 patients with an acute myocardial infarction (AMI) will be randomized in a ratio of 1:1 ratio to receive AZD5718 125 mg or placebo for 12 months.

    NCT04601467
    Conditions
    1. Acute Coronary Syndrome
    Interventions
    1. Drug: AZD5718
    2. Drug: Placebo
    MeSH:Acute Coronary Syndrome Syndrome

    Primary Outcomes

    Description: Percent change in NCPV (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment

    Measure: Change in noncalcified coronary artery plaque volume (NCPV)

    Time: Baseline (before treatment) and after 12 months of treatment

    Secondary Outcomes

    Description: To assess whether AZD5718 reduces coronary inflammation

    Measure: Change in CT pericoronary adipose tissue (PCAT)

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: Percent change in total plaque volume (in mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment

    Measure: Change in total plaque volume (mm3)

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: Percent change in LVEF (%), as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment

    Measure: Echocardiographic assessment: Change in left ventricular ejection fraction (LVEF)

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: To assess the PK of AZD5718 after repeated oral dosing for 12 months

    Measure: Plasma concentrations of AZD5718

    Time: 12 month

    Description: To assess the pharmacodynamics (PD) effect of AZD5718 by assessment of u-LTE4 in AMI patients

    Measure: Change in levels of urinary LTE4 (u-LTE4)

    Time: 12 months

    Other Outcomes

    Description: Percent change in low attenuation (<30 HU) plaque volume (mm3), as assessed by CT coronary angiography, from baseline (before treatment) to after 12-month of treatment

    Measure: Change in low attenuation plaque burden

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: To assess the effect of AZD5718 on LTB4 levels in ex vivo stimulated human plasma by liquid chromatography-tandem mass spectrometry

    Measure: Change in levels of ex vivo stimulated plasma leukotriene B4 (LTB4)

    Time: 12 months

    Description: To assess the changes in circulating hs-CRP concentrations from baseline (before treatment) to after 12-month of treatment

    Measure: Change in plasma hs-CRP concentration

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: To assess the changes in circulating troponin concentrations from baseline (before treatment) to after 12-month of treatment

    Measure: Change in plasma troponin concentration

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: To assess the changes in circulating NT-proBNP concentrations from baseline (before treatment) to after 12-month of treatment

    Measure: Change in plasma NT-proBNP concentration

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: Percent change in LV global longitudinal strain, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment

    Measure: Echocardiographic assessment: Change in LV global longitudinal strain

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: Percent change in global circumferential strain, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment

    Measure: Echocardiographic assessment: Change in global circumferential strain

    Time: Baseline (before treatment) and after 12 months of treatment

    Description: Percent change in longitudinal early diastolic strain rate, as assessed by 2D echocardiography, from baseline (before treatment) to after 12-month of treatment

    Measure: Echocardiographic assessment: Change in longitudinal early diastolic strain rate

    Time: Baseline (before treatment) and after 12 months of treatment
    523 Ivermectin in Adults With Severe COVID-19. Double-blind Randomized Clinical Trial

    Since the onset of the disease, more than 40.5 million people have been diagnosed with COVID-19 and nearly 1.2 million people have died (October 21, 2020). There is no complete understanding of the pathogenesis of SARS-CoV-2 infection and to this day there is no specific therapy or vaccine available. Thus, patient care is based on symptomatic therapy and treatment of complications. Ivermectin has been used for more than 30 years for the treatment of several diseases. More than one million doses of the drug are administered daily, particularly in low- and middle-income countries. Due to the low prevalence of adverse events with the use of this drug, ivermectin is considered to have a good safety profile and its potential benefit in other diseases is currently under investigation. An in vitro study of ivermectin in SARS-CoV-2 in Australia showed a significant reduction of viral load in infected cells. Subsequently, a descriptive study of 704 critical patients with COVID-19 showed a reduction in mortality, hospitalization, and intensive care unit length-of-stay in those patients who received the drug. Unfortunately, this study was withdrawn by its authors, leaving more questions than answers. Some countries in Latin America have authorized its use for the management of patients with COVID-19 even in the absence of solid evidence, and several other countries are conducting clinical trials to evaluate its efficacy for the treatment of moderate and severe disease. Since there is no specific treatment for COVID-19 and the therapeutic options are scarce, the researchers believe it is completely plausible, urgent, and necessary to evaluate if ivermectin use reduces the risk of admission to an intensive care unit (ICU) in hospitalized adults with severe COVID-19. The proposal is a randomized, double-blind clinical trial, conducted at CES Clinic, Medellin-Colombia. The investigators will randomize 100 patients with severe, non-critical illness, into two groups, one group will receive ivermectin in addition to standard management and the other group will receive placebo plus standard management. Clinical outcomes to evaluate will be ICU admission, need for mechanical ventilation, length of hospital stay, days in the ICU and mechanical ventilation, and finally, the incidence of adverse events related to the intervention. The estimated time to complete the study is approximately five months.

    NCT04602507
    Conditions
    1. Covid19
    2. Severe Acute Respiratory Syndrome
    Interventions
    1. Drug: Ivermectin
    2. Other: Placebo
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections

    Primary Outcomes

    Description: Cumulative incidence of ICU admission.

    Measure: Admission to the intensive care unit.

    Time: 21 days

    Secondary Outcomes

    Description: Duration of hospitalization (days).

    Measure: Hospital length of stay.

    Time: 21 days

    Description: 21-day mortality.

    Measure: Mortality rate.

    Time: 21 days

    Description: Number of days in ICU.

    Measure: ICU length of stay.

    Time: 21 days

    Description: Number of days with mechanical ventilator.

    Measure: Length of stay in ventilator time.

    Time: 21 days

    Description: Cumulative incidence of adverse effects: headache, rash, pruritus, arthralgia, tachycardia, dizziness, hypotension, uveitis, Steven Johnson Syndrome.

    Measure: Adverse effects of ivermectin.

    Time: 21 days
    524 A Phase 2/3 Randomized and Placebo-Controlled Study of ANA001 in Moderate COVID-19 Patients

    Study of ANA001 in Moderate COVID-19 Patients

    NCT04603924
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Niclosamide
    2. Drug: Placebo

    Primary Outcomes

    Description: Incidence of treatment emergent adverse events (TEAE's)

    Measure: Safety and Tolerability of ANA001 as measured by the incidence of treatment emergent adverse events (TEAE's) (Part 1 and Part 2)

    Time: Randomization to Day 28

    Description: Median time to hospital discharge

    Measure: Efficacy as measured by median time to hospital discharge (Part 2)

    Time: Randomization to Day 60

    Secondary Outcomes

    Description: Median time to hospital discharge

    Measure: Efficacy as measured by median time to hospital discharge (Part 1)

    Time: Randomization to Day 60

    Description: Plasma concentrations of ANA001

    Measure: Pharmacokinetics (PK) of ANA001 as measured by plasma concentrations (Part 1)

    Time: Day 1, 2, 3 or 4

    Description: Mean change from baseline in National Early Warning Score (NEWS 2) score

    Measure: Efficacy of ANA001 as measured by mean change from baseline in the National Early Warning Score (NEWS 2) (Part 2)

    Time: Day 8, Day 15

    Description: Mean number of days on rescue therapy

    Measure: Efficacy of ANA001 as measured by mean number of days on rescue therapy (Part 2)

    Time: Within 15 days after enrollment
    525 BI 764198 Efficacy and Safety in Prevention/Progression of ARDS and ARDS-related Complications Secondary to COVID-19 (ACTION ON COVID-19)

    This study is open to adults with COVID-19 infection who are in hospital and receive oxygen. Participants need to be 50 years of age or older and need to be at risk of further worsening of their condition. The purpose of the study is to find out whether a medicine called BI 764198 helps people with COVID-19 infection and breathing problems. BI 764198 may prevent cell death and swelling of the lung tissue and therefore help patients with COVID-19 infection. Participants are put into 2 groups by chance. One group of participants gets BI 764198 capsules and the other group gets placebo capsules. The placebo capsules look exactly like the BI 764198 capsules but do not contain any medicine. Participants take 1 capsule per day. Participants are in the study for about a month. At study end, doctors compare the 2 groups for the number of patients that are alive and do not need mechanical breathing support. During the study, the doctors collect information on any health problems of the participants.

    NCT04604184
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BI 764198
    2. Drug: Placebo

    Primary Outcomes

    Measure: Patients alive and free of mechanical ventilation

    Time: At Day 29

    Secondary Outcomes

    Measure: Patients alive and discharged free of oxygen

    Time: At Day 29

    Measure: Patients with occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation

    Time: At Day 29

    Description: Clinical improvement of at least 2 points (from randomisation) on the World Health Organization Clinical Progression Scale, discharge from the hospital, or considered fit for discharge (a score of 0, 1, 2, or 3 on the Clinical Progression Scale), whichever comes first. The scale provides a measure of illness severity across a range from 0 (not infected) to 10 (dead).

    Measure: Time to response

    Time: Up to Day 29

    Measure: Number of ventilator free days

    Time: Up to Day 29

    Measure: Mortality

    Time: At Day 15, 29, 60 and 90
    526 A Randomised, Double-blind, Placebo Controlled, Parallel Group Phase III Study to Assess the Clinical Efficacy and Safety of 100 mg SC Mepolizumab in Adults With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) / Eosinophilic Chronic Rhinosinusitis (ECRS) MERIT: Mepolizumab in Eosinophilic Chronic RhinosinusITis Study

    This is a randomized, double blind, placebo controlled, parallel group phase III study designed to assess the clinical efficacy and safety of 100 milligrams (mg) subcutaneous (SC) mepolizumab treatment in adults with CRSwNP/ECRS for the purpose of registration in Japan and China. Approximately 160 participants will be randomized in a 1:1 ratio to receive either 100 mg SC mepolizumab or placebo SC. The study will include a 4-week run-in period followed by randomization to a 52-week treatment period, where participants will be administered 4-weekly doses of mepolizumab or placebo via a pre-filled safety syringe device (SSD) injection.

    NCT04607005
    Conditions
    1. Nasal Polyps
    Interventions
    1. Drug: Mepolizumab
    2. Drug: Placebo
    3. Drug: Standard of care
    MeSH:Nasal Polyps Polyps
    HPO:Nasal polyposis

    Primary Outcomes

    Description: NP score is graded and based on NP size recorded as the sum of the right and left nostril scores with a range of 0-8; higher scores indicate worse status. Individual score ranges from 0 (no polyps) to 4 (large polyps causing almost complete congestion/ obstruction of the inferior meatus) within each nostril.

    Measure: Change from Baseline in total endoscopic NP score at Week 52 (scores on a scale)

    Time: Baseline (Day 0) and at Week 52

    Description: Participant will be asked to indicate on a VAS the severity of 5 nasal polyposis symptoms (one VAS for each symptom) and symptoms overall: 1. nasal obstruction; 2. nasal discharge; 3. mucus in the throat; 4. loss of smell; 5. Facial pain; 6. overall VAS symptoms score. The left-hand side of the scale (0) represents "None" and the right-hand side of the scale (100) represents "As bad as you can imagine". The participant selects a point on the line that represents their current state on the continuum. VAS will be collected using an electronic Diary, suitably pixilated to allow the selection of all integers from 0 to 100.

    Measure: Change from Baseline in mean nasal obstruction visual analogue scale (VAS) score (scores on a scale)

    Time: Baseline (Day 0) and up to 52 weeks

    Secondary Outcomes

    Description: SNOT-22 is a 22-item measure of disease specific health related quality of life (HRQoL). Participants will be asked to rate the severity of their condition on each of the 22 items over the previous 2 weeks using a 6-point rating scale of 0-5 including: 0 =Not present/no problem; 1 =Very mild problem; 2 = Mild or slight problem; 3 = Moderate problem; 4 = Severe problem; 5=Problem as "bad as it can be". The total score range for the SNOT-22 is 0-110, where higher scores indicate greater disease impact.

    Measure: Change from Baseline in sino-nasal outcome test (SNOT)-22 total score at Week 52 (scores on a scale)

    Time: Baseline (Day 0) and at Week 52

    Description: Participant will be asked to indicate on a VAS the severity of 5 nasal polyposis symptoms (one VAS for each symptom) and symptoms overall: 1. nasal obstruction; 2. nasal discharge; 3. mucus in the throat; 4. loss of smell; 5. Facial pain; 6. overall VAS symptoms score. The left-hand side of the scale (0) represents "None" and the right-hand side of the scale (100) represents "As bad as you can imagine". The participant selects a point on the line that represents their current state on the continuum. VAS will be collected using an electronic Diary, suitably pixilated to allow the selection of all integers from 0 to 100.

    Measure: Change from Baseline in mean overall VAS symptom score (scores on a scale)

    Time: Baseline (Day 0) and up to 52 weeks

    Description: Participant will be asked to indicate on a VAS the severity of 5 nasal polyposis symptoms (one VAS for each symptom) and symptoms overall: 1. nasal obstruction; 2. nasal discharge; 3. mucus in the throat; 4. loss of smell; 5. Facial pain; 6. overall VAS symptoms score. The left-hand side of the scale (0) represents "None" and the right-hand side of the scale (100) represents "As bad as you can imagine". The participant selects a point on the line that represents their current state on the continuum. VAS will be collected using an electronic Diary, suitably pixilated to allow the selection of all integers from 0 to 100.

    Measure: Change from Baseline in the mean composite VAS score [combining VAS scores for nasal obstruction, nasal discharge, mucus in the throat and loss of smell] (scores on a scale)

    Time: Baseline (Day 0) and up to 52 weeks

    Description: The LMK CT scoring system is based on localization with points given for degree of opacification: 0 =normal, 1 = partial opacification, 2 = total opacification. These points are then applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side. The osteomeatal complex (OC) is graded as 0 = not occluded, or 2 = occluded deriving a maximum score of 12 per side. The range for the LMK CT score is therefore 0-24 when summed across both sides.

    Measure: Change from Baseline in Lund Mackay (LMK) computed tomography (CT) score at Week 52 (scores on a scale)

    Time: Baseline (Day 0) and at Week 52

    Description: Participant will be asked to indicate on a VAS the severity of 5 nasal polyposis symptoms (one VAS for each symptom) and symptoms overall: 1. nasal obstruction; 2. nasal discharge; 3. mucus in the throat; 4. loss of smell; 5. Facial pain; 6. overall VAS symptoms score. The left-hand side of the scale (0) represents "None" and the right-hand side of the scale (100) represents "As bad as you can imagine". The participant selects a point on the line that represents their current state on the continuum. VAS will be collected using an electronic Diary, suitably pixilated to allow the selection of all integers from 0 to 100.

    Measure: Change from Baseline in mean individual VAS symptom score for loss of smell (scores on a scale)

    Time: Baseline (Day 0) and up to 52 weeks

    Description: NP surgery is defined as any procedure involving instruments resulting in incision and removal of tissue from the nasal cavity (for example polypectomy). Additionally, the number of courses of systemic steroids and reason for treatment will be recorded throughout the study.

    Measure: Time to first nasal surgery or course of systemic corticosteroids (CS) for CRSwNP/ECRS up to Week 52

    Time: Up to 52 weeks
    527 A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of the HIV-1 CH505 Transmitted/Founder gp120 Adjuvanted With GLA-SE in Healthy, HIV-exposed Uninfected Infants

    This study will evaluate the safety and immune response in healthy HIV-exposed and uninfected infants to the protein vaccine, CH505TF gp120, adjuvanted with GLA-SE.

    NCT04607408
    Conditions
    1. HIV Infections
    Interventions
    1. Biological: CH505TF gp120
    2. Biological: GLA-SE adjuvant
    3. Biological: Placebo
    MeSH:HIV Infections

    Primary Outcomes

    Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

    Measure: Local reactogenicity signs and symptoms

    Time: Measured through week 55

    Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

    Measure: Systemic reactogenicity signs and symptoms

    Time: Measured through week 55

    Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

    Measure: Frequency of adverse events (AEs)

    Time: Measured through week 106

    Description: Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

    Measure: Frequency of serious adverse events (SAEs)

    Time: Measured through week 106

    Description: Measured by Binding antibody multiplex assay (BAMA)

    Measure: Magnitude of HIV-1 specific serum IgG binding antibodies

    Time: Measured at week 56

    Description: Measured by flow cytometry

    Measure: Quantification of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site

    Time: Measured at week 18

    Description: Measured by flow cytometry

    Measure: Quantification of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site

    Time: Measured at week 56

    Description: Measured by flow cytometry

    Measure: Phenotypic characterization of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site

    Time: Measured at week 18

    Description: Measured by flow cytometry

    Measure: Phenotypic characterization of peripheral B cells capable of binding HIV-1 Env gp120, the CD4 binding site (including differential binding to the IΔ371 mutant) and the V1V2 binding site

    Time: Measured at week 56

    Secondary Outcomes

    Description: Measured by Pediatric Vaccine Multiplex Assay (PVMA)

    Measure: EPI vaccine-specific antibody responses

    Time: Measured at week 56

    Description: Measured by TZM-bl assay

    Measure: Magnitude of serum neutralization of vaccine-matched viral isolates, and viruses engineered to detect precursors of CD4 binding site and V1V2 antibodies

    Time: Measured at week 56

    Description: Measured by TZM-bl assay

    Measure: Serum neutralization of vaccine-matched viral isolates, and viruses engineered to detect precursors of CD4 binding site and V1V2 antibodies

    Time: Measured at week 56

    Description: Measured by BAMA

    Measure: Response rate of vaccine-elicited serum binding antibodies to FcR proteins

    Time: Measured at week 56

    Description: Measured by BAMA

    Measure: Magnitude of vaccine-elicited serum binding antibodies to FcR proteins

    Time: Measured at week 56

    Description: Measured by flow cytometry and/or luciferase assays

    Measure: Response rate of serum Antibody-dependent cellular cytotoxicity (ADCC)

    Time: Measured at week 56

    Description: Measured by flow cytometry and/or luciferase assays

    Measure: Magnitude of serum Antibody-dependent cellular cytotoxicity (ADCC)

    Time: Measured at week 56

    Description: Measured by flow cytometry

    Measure: Response rate of serum Antibody-dependent cellular phagocytosis (ADCP)

    Time: Measured at week 56

    Description: Measured by flow cytometry

    Measure: Magnitude of serum Antibody-dependent cellular phagocytosis (ADCP)

    Time: Measured at week 56
    528 A Phase 1b/2, Randomised, Placebo-controlled, Dose-ranging Study to Evaluate Safety, Tolerability and Immunogenicity of a Chimpanzee Adenovirus (ChAdOx1)-Vectored Multigenotype High Risk Human Papillomavirus (hrHPV) Vaccine and Modified Vaccinia Ankara (MVA)-Vectored Multigenotype hrHPV Vaccine in Women With Low-grade HPV-related Cervical Lesions

    A Phase 1b/2 multi-centre study evaluating the safety, efficacy and immunogenicity of prime-boost vaccines ChAdOx1-HPV and MVA-HPV in women with HPV related low grade cervical lesions.

    NCT04607850
    Conditions
    1. HPV
    Interventions
    1. Biological: ChAdOx1-HPV
    2. Biological: MVA-HPV
    3. Biological: Placebo

    Primary Outcomes

    Description: Measure of adverse events, serious adverse events (SAEs), ≥Grade 3 study vaccine-related adverse events reported.

    Measure: Incidence of adverse events to measure safety and reactogenicity

    Time: 3 months for the lead-in and 12 months for the main phase

    Secondary Outcomes

    Description: Measurement of the highest multi-parameter index made of CD4+ magnitude, CD4+ avidity and CD8+ magnitude at peak timepoint

    Measure: Determine the dose of ChAdOx1-HPV plus MVA-HPV vaccines for further development

    Time: 3 months for lead in phase and 12 months for main phase

    Description: The percentage of hrHPV infection clearance

    Measure: Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on the clearance of high risk HPV infection

    Time: 12 months for main phase only

    Description: The percentage of cervical lesions cleared as determined by colposcopy

    Measure: Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on cervical intraepithelial neoplasia (CIN)

    Time: 12 months for main phase only

    Other Outcomes

    Description: This will be assessed by measuring the individual phenotypic subsets of CD4+ and CD8+ T cells induced by vaccination

    Measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines

    Time: 3 months for lead in phase and 12 months for main phase

    Description: This will be assessed by measuring the innate immune response after vaccination compared to baseline

    Measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines

    Time: 3 months for lead in phase and 12 months for main phase

    Description: This will be assessed by measuring the T cell breadth of response to the components of the ChAdOx1-HPV plus MVA-HPV vaccines

    Measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines

    Time: 3 months for lead in phase and 12 months for main phase

    Description: Immune responses after prime and boost vaccinations in cytobrush samples compared to baseline

    Measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines

    Time: 3 months for lead in phase and 12 months for main phase
    529 Phase-II Randomized Clinical Trial to Evaluate the Effect of Pirfenidone Compared to Placebo in Post-COVID19 Pulmonary Fibrosis

    Study population: Patients with fibrotic lung sequelae after recovery from acute phase of severe COVID19 pneumonia Objectives: To evaluate the effect of pirfenidone administered for 24 weeks in patients who have pulmonary fibrotic changes after suffering severe COVID19 pneumonia, analysed by - % change in forced vital capacity (FVC) - % fibrosis in high resolution computed tomography (HRCT) of the lung

    NCT04607928
    Conditions
    1. Fibrotic Pulmonary Sequelae Post-COVID19 Infection
    Interventions
    1. Drug: Pirfenidone
    2. Drug: Placebo
    MeSH:Pulmonary Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: To investigate the effect of pirfenidone administered for 24 weeks measuring the number of patients who have pulmonary fibrotic changes from baseline after suffering severe COVID19 pneumonia, analysed by Change From Baseline in % in forced vital capacity (FVC) Change From Baseline % fibrosis in high resolution computed tomography (HRCT) of the lung

    Measure: To investigate the effect of pirfenidone on fibrotic signs induced by COVID19 infection

    Time: 24 weeks

    Secondary Outcomes

    Description: Number of patients who show maintenance of stability or functional improvement: stability will be considered when the FVC does not increase more than 10% or does not decrease more than 10% and the DLCO does not increase more than 15% or decreases more than 15%. An increase in% FVC greater than 10% or in DLCO greater than 15% will be considered significant improvement.

    Measure: Maintenance of stability or functional improvement FVC

    Time: 24 weeks

    Description: Rate of decreased oxygen requirement for physical activity in patients

    Measure: Decreased oxygen requirement for physical activity

    Time: 24 weeks

    Description: Number of patients who have improved exercise capacity (> 50 meter improvement or less decrease in% oxygen saturation) in the TM6m

    Measure: Improved exercise capacity (> 50 meter improvement or less decrease in% oxygen saturation) in the TM6m

    Time: 24 weeks

    Description: Number of Hospitalizations (general and due to respiratory problems)

    Measure: Hospitalizations (general and due to respiratory problems)

    Time: 24 weeks

    Description: Number of Visits to the Emergency or Day Hospital for respiratory causes

    Measure: Visits to the Emergency or Day Hospital for respiratory causes

    Time: 24 weeks

    Description: Number of patients who need Lung transplantation

    Measure: Lung transplantation

    Time: 24 weeks

    Description: Number of patients who die

    Measure: Death

    Time: 24 weeks
    530 A Multicenter Randomized Trial to Evaluate the Efficacy and Safety of Camostat Mesylate for the Treatment of SARS-CoV-2 Infection - COVID-19 in Ambulatory Adult Patients (CAMOVID)

    The overall objective of the study is to determine the therapeutic effect and tolerance of Camostat mesylate, compared to placebo in adult patients with ambulatory COVID-19 disease, presenting with risk factors of severe COVID-19. Camostat mesylate is a serine protease TMPRSS2 (Transmembrane Serine Protease 2) inhibitor which has been successfully and safely used to treat pancreatitis-associated pain and post-operative reflux oesophagitis in Japan. More recently, it has been shown to inhibit SARS-CoV-2 viral entry and reduce infection of human primary pneumocytes and lung cell lines. Camostat mesylate or placebo will be administered to consenting adult patients with virologically confirmed COVID-19, not requiring initial hospitalization. All patients will receive standard of care along with randomized treatments. Outcomes of included patients will be compared between the 2 groups.

    NCT04608266
    Conditions
    1. Covid19
    Interventions
    1. Drug: Camostat Mesylate
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Proportion of patients hospitalized for COVID-19 deterioration or who died without hospitalization

    Measure: Hospitalization for COVID-19 deterioration or death without hospitalization

    Time: Day 21

    Secondary Outcomes

    Description: Number of patients with at least one adverse event

    Measure: Adverse events

    Time: Day 21

    Description: Number of patients with at least one serious adverse event

    Measure: Serious adverse events

    Time: Day 21

    Description: Number of patients who discontinued the investigational medication

    Measure: Investigational medication discontinuation

    Time: Day 21

    Description: Proportion of patients hospitalized for COVID-19 deterioration (reviewed by independent adjudication comitter) or who died without hospitalization

    Measure: Hospitalization for COVID-19 deterioration or death without hospitalization, evaluated by independent adjudication comittee

    Time: Day 21

    Description: WHO clinical scale: Uninfected - No clinical or virological evidence of infection: 0; Ambulatory - No limitation of activities: 1; Ambulatory - limitation of activities: 2; Hospitalized - no oxygen therapy: 3; Hospitalized - oxygen by mask or nasal prongs: 4; Hospitalized; oxygen by non invasive ventilation or High flow: 5; Intubation and Mechanical ventilation: 6; Mechanical ventilation + additional organ support (pressors, Renal replacement therapy, ECMO):7; Dead: 8

    Measure: Clinical improvement using the Word Health Organization (WHO) COVID-19 scale

    Time: Day 7, 14, 21

    Description: Proportion of patients admitted to an intensive care unit

    Measure: Need for intensive care

    Time: Day 21

    Description: Number of days alive without hospitalization up to day 21

    Measure: Duration of hospitalization

    Time: Day 21

    Description: Proportion of patients with initiation of invasive mechanical ventilation

    Measure: Need for invasive mechanical ventilation for severe COVID-19

    Time: Day 21

    Description: Proportion of patients with initiation of oxygen therapy

    Measure: Need for oxygen therapy for COVID-19

    Time: Day 21

    Description: Proportion of patients alive at day 90

    Measure: Overall survival

    Time: Day 90

    Description: Number of days alive without symptoms at day 21

    Measure: Duration of symptoms

    Time: Day 21

    Description: By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasal swab and droplet quantification of SARS-CoV2 ribonucleic acid-emia (RNAemia)

    Measure: SARS-CoV-2 virological assessment

    Time: Day 7, 14, 21

    Description: SARS-CoV2 antibodies quantification in blood

    Measure: SARS-CoV-2 serological assessment

    Time: Day 7, 14, 21 and 90

    Description: Peripheral blood lymphocyte phenotyping with telomere length measurement

    Measure: Peripheral blood lymphocyte phenotyping

    Time: Day 1, 14, 90

    Description: Acute kidney failure defined as at least serum creatinine increase of 0.3mg/dl or 1.5-1.9 times baseline and/or oliguria < 0.5ml/kg/h

    Measure: Acute kidney failure

    Time: Day 21

    Description: estimated glomerular filtration rate

    Measure: Renal function

    Time: Day 7, 14 and 21

    Description: Uricemia in mmol/L or mg/dL

    Measure: Concentration of urea in blood

    Time: Day 7, 14 and 21

    Description: Kaliemia in mmol/L

    Measure: Concentration of potassium in blood

    Time: Day 7, 14 and 21

    Description: Liver transaminases dosage on blood sample

    Measure: Liver function

    Time: Day 7, 14 and 21

    Description: Gamma-glutamyl transferase (gamma-GT) dosage on blood sample

    Measure: Liver function (2)

    Time: Day 7, 14 and 21

    Other Outcomes

    Description: Biobanking of blood samples for predictive biomarker assessment

    Measure: Biobanking for biomarker assessment

    Time: Day 1, 7, 14, 21, 90
    531 A Single-center, Double-blind, Randomized, Placebo-controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects

    A safety and tolerability study in healthy subjects including examination of how the body takes up, distributes, and gets rid of ACT-1014-6470

    NCT04608513
    Conditions
    1. Healthy
    Interventions
    1. Drug: ACT-1014-6470
    2. Drug: Placebo

    Primary Outcomes

    Measure: Safety profile including incidence of treatment-emergent adverse events.

    Time: Safety and tolerability assessments will be performed at predefined time points from Day 1 to Day 4 in Part A and Day 1 to Day 10 in Part B (total duration: max. 50 days).

    Secondary Outcomes

    Measure: Part A - Single ascending dose (SAD): Area under the plasma concentration-time curve (AUC) from zero to time t of the last measured concentration above the limit of quantification (AUC0-t).

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).

    Measure: Part A - Single ascending dose (SAD): Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf).

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).

    Measure: Part A - Single ascending dose (SAD): Maximum plasma concentration (Cmax).

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).

    Measure: Part A - Single ascending dose (SAD): Time to reach Cmax (tmax).

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).

    Measure: Part A - Single ascending dose (SAD): Terminal half-life (t½).

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).

    Measure: Part B - Multiple ascending dose (MAD): AUC during a dosing interval (AUCτ) following the first and the last dose.

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).

    Measure: Part B - Multiple ascending dose (MAD): Cmax of the first and the last dosing interval.

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).

    Measure: Part B - Multiple ascending dose (MAD): tmax of the first and the last dosing interval.

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).

    Measure: Part B - Multiple ascending dose (MAD): t½ after last dose administration.

    Time: Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).
    532 A Phase 2b Double-blind, Randomized, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of Norketotifen (NKT) in the Treatment of Acute Uncomplicated Influenza-like Illness (ILI)

    This is a Phase 2b, multi-center, double-blind, randomized, placebo-controlled, parallel-group study of NKT versus placebo in otherwise healthy adults presenting with acute uncomplicated ILI due to influenza or other respiratory viruses in a community setting.

    NCT04610047
    Conditions
    1. Influenza
    2. Influenza -Like Illness
    Interventions
    1. Drug: Norketotifen
    2. Drug: Placebo
    MeSH:Influenza, Human

    Primary Outcomes

    Description: Time to alleviation of the symptoms of ILI (headache, feverishness/chills, muscle/joint pain, fatigue, cough, sore throat, nasal congestion)

    Measure: Time to alleviation of symptoms

    Time: 14 days

    Secondary Outcomes

    Measure: Time to resolution of fever (body temperature equal to or less than 37ºC)

    Time: 14 days

    Measure: Proportion of subjects whose symptoms have been alleviated at each time point through Day 14

    Time: 14 days

    Measure: Change from baseline in composite symptom score at each time point through Day 14

    Time: 14 days

    Measure: Body temperature at each time point through Day 14

    Time: 14 days

    Measure: Time to alleviation of individual symptoms (headache, feverishness/chills, muscle/joint pain, fatigue, cough, sore throat, nasal congestion)

    Time: 14 days

    Measure: Time to resumption of normal activity

    Time: 14 days

    Measure: Use of rescue medication (acetaminophen)

    Time: 14 days

    Measure: Time to alleviation of symptoms by confirmed viral pathogen (influenza vs non influenza)

    Time: 14 days

    Measure: Time to resolution of fever by confirmed viral pathogen (influenza vs non influenza)

    Time: 14 days
    533 A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of ZnAg Liquid Solution to Treat COVID-19 in Acutely Symptomatic Non-Hospitalized Participants

    This is a multi-site, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of ZnAg liquid solution in symptomatic participants with acute COVID-19 that are not hospitalized at the time of enrollment.

    NCT04610138
    Conditions
    1. Covid19
    Interventions
    1. Drug: CNM-ZnAg
    2. Drug: Placebo

    Primary Outcomes

    Description: Confirmed symptom resolution over a continuous period ≥ 48 hours, defined as PGI-Severity of 'Normal' in Participants whose Baseline PGI-Severity value was 'Mild'; or, a PGI-Severity of 'Normal' or 'Mild' in participants whose Baseline PGI-Severity value was 'Moderate' or 'Severe'.

    Measure: Time to substantial alleviation of COVID-19 symptoms

    Time: Up to 28 days.

    Secondary Outcomes

    Description: Hospitalization will be determined by Investigator's clinical judgement. Where applicable, Investigators should follow local recommendations for hospitalization of patients with COVID-19 within their institution.

    Measure: The proportion of participants who require COVID-19 related hospitalization, are hospitalized for COVID-19 related medical support, or are deceased within 28-days following randomization.

    Time: Up to 28 days.

    Other Outcomes

    Description: Days from baseline participant remains alive.

    Measure: Number of alive hospital free days at Day 28.

    Time: 28 days

    Description: Cycle Thresholds assessed by RT-qPCR.

    Measure: Mean change from Baseline to Day 14, Day 21, and Day 28 in SARS-CoV-2 viral load.

    Time: Up to 28 days

    Description: Oxygen saturation will be obtained after the participant has been resting for 5 minutes.

    Measure: Change from Baseline to Day 8, Day 14, Day 21, and 28 in the slope of oxygen saturation levels (SpO2) assessed per protocol.

    Time: up to 28 days

    Description: Measured by changes in participant rated Clinical Global Impression.

    Measure: Clinical Global Impression (CGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.

    Time: Up to 28 days

    Description: Measured by changes in participant rated Patient Global Impression.

    Measure: Patient Global Impression (PGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.

    Time: Up to 28 days

    Description: Summary measure integrating semi-daily serial assessments of a subject's symptom count and severity over the duration of the study.

    Measure: Change in the area under the curve for Net Symptom Burden from Baseline to Day 8, Day 14, Day 21, and 28.

    Time: Up to 28 days

    Description: Assessed by the Clinical Status Ordinal Scale established in the remdesivir ACTT study. Scale is 1-8, with 1 being the least severe and 8 being the most severe (death).

    Measure: Change in clinical status from Baseline to Day 8, Day 14, Day 21, and Day 28.

    Time: Up to 28 days

    Description: Rate of deceased participants at day 28.

    Measure: All-cause mortality rate at Day 28.

    Time: 28 days
    534 A Randomized, Placebo-Controlled, Participant- and Investigator-Blind, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of LY3832479 Administered Subcutaneously to Healthy Participants

    The purpose of this study is to test the safety and tolerability of LY3832479 when it is given by injection just under the skin to healthy participants. Blood tests will be done to check how much LY3832479 is in the bloodstream and how long the body takes to eliminate it. Participation could last up to 16 weeks and may include up to six visits to the study center, with a one-week overnight stay.

    NCT04611789
    Conditions
    1. Healthy
    Interventions
    1. Drug: LY3832479
    2. Drug: Placebo

    Primary Outcomes

    Description: PK: AUC(0-inf)

    Measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time 0 to Infinity (AUC[0-inf]) of LY3832479

    Time: Day 1 through Day 85

    Description: PK: Cmax of LY3832479

    Measure: PK: Maximum Concentration (Cmax) of LY3832479

    Time: Day 1 through Day 85
    535 A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in Adult Participants ≥ 18 Years

    This is a study to evaluate the effectiveness, immune response, and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in adults 18 years of age and older in the United States and Mexico. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in the study population. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study. Up to 30,000 participants will take part in the study.

    NCT04611802
    Conditions
    1. SARS-CoV Infection
    2. Covid19
    Interventions
    1. Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Number of participants with first occurrence of positive (+) polymerase chain reaction (PCR)-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)

    Time: Day 28 to Day 750

    Secondary Outcomes

    Description: Number of participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic Moderate or Severe COVID-19

    Time: Day 28 to Day 750

    Description: Number of participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with any symptomatic COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Any Symptomatic COVID-19

    Time: Day 28 to Day 750

    Description: Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0, 35 and Month 3.

    Measure: Neutralizing Antibody Activity Expressed as Geometric Mean Titers (GMTs)

    Time: Day 0 to Day 105

    Description: Neutralizing antibody activity as detected by MN as expressed as GMFRs at Days 0, 35 and Month 3.

    Measure: Neutralizing Antibody Activity Expressed as Geometric Mean Fold Rises (GMFRs)

    Time: Day 0 to Day 105

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs at Days 0, 35 and Month 3.

    Measure: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs

    Time: Day 0 to Day 105

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0, 35 and Month 3.

    Measure: Serum IgG Antibody Levels Expressed as GMFRs

    Time: Day 0 to Day 105

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMTs at Days 0, 35 and Month 3.

    Measure: Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as GMTs

    Time: Day 0 to Day 105

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMFRs at Days 0, 35 and Month 3.

    Measure: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs

    Time: Day 0 to Day 105

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Months 6, 12, 18, and 24.

    Measure: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs at Later Time Points

    Time: Day 165 to Day 750

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Months 6, 12, 18, and 24.

    Measure: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMFRs at Later Time Points

    Time: Day 165 to Day 750

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMTs at Months 6, 12, 18, and 24.

    Measure: hACE2 Receptor Binding Inhibition Assay Expressed as GMTs at Later Time Points

    Time: Day 165 to Day 750

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMFRs at Months 6, 12, 18, and 24.

    Measure: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs at Later Time Points

    Time: Day 165 to Day 750

    Description: Neutralizing antibody activity as detected by MN as expressed as GMTs at Months 6, 12, 18, and 24.

    Measure: Neutralizing Antibody Activity Expressed as GMTs at Later Time Points

    Time: Day 165 to Day 750

    Description: Neutralizing antibody activity as detected by MN as expressed as GMFRs at Months 6, 12, 18, and 24.

    Measure: Neutralizing Antibody Activity Expressed as GMFRs at Later Time Points

    Time: Day 165 to Day 750

    Description: Description of course, treatment and severity of COVID-19 reported after a PCR-confirmed case via the Endpoint Form.

    Measure: Description of Course, Treatment and Severity of COVID-19

    Time: Day 28 to Day 750

    Description: Reactogenicity incidence and severity (mild, moderate or severe) recorded by all participants on their electronic patient-reported outcome diary application (eDiary) on days of vaccination and subsequent 6 days (total 7 days after each vaccine injection).

    Measure: Reactogenicity Incidence and Severity

    Time: Day 0 to Day 27

    Description: Number of participants with mild, moderate, or severe MAAEs through Day 49.

    Measure: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49.

    Time: Day 0 to Day 49

    Description: Number of participants with mild, moderate, or severe AEs through Day 49.

    Measure: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49.

    Time: Day 0 to Day 49

    Description: Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through Month 12.

    Measure: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Month 12.

    Time: Day 0 to Day 375

    Description: Number of participants with mild, moderate, or severe SAEs through Month 12.

    Measure: Incidence and Severity of Serious Adverse Events (SAEs) Through Month 12.

    Time: Day 0 to Day 375

    Description: Number of participants with mild, moderate, or severe AESIs through Month 12.

    Measure: Incidence and Severity of Adverse Events of Special Interest (AESIs) Through Month 12.

    Time: Day 0 to Day 375

    Description: Number of participants with mild, moderate, or severe SAEs from Month 12 to Month 24.

    Measure: Incidence and Severity of SAEs from Month 12 to Month 24.

    Time: Day 360 to Day 750

    Description: Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine from Month 12 to Month 24.

    Measure: Incidence and Severity of MAAEs Attributed to Study Vaccine from Month 12 to Month 24.

    Time: Day 360 to Day 750

    Description: Number of participants with mild, moderate, or severe AESIs attributed to study vaccine from Month 12 to Month 24.

    Measure: Incidence and Severity of AESIs from Month 12 to Month 24.

    Time: Day 360 to Day 750

    Description: Number of participants who died during the study due to any cause.

    Measure: Deaths Due to Any Cause

    Time: Day 0 to Day 750

    Description: Number of participants with antibodies to SARS-CoV-2 NP at Days 0 and 35, or Months 3, 6, 12, 18 and 24 to determine natural infection and to determine the incidence of asymptomatic infection acquired during study follow-up.

    Measure: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specific Time Points

    Time: Day 0 to Day 750

    Description: Number of participants with antibodies to SARS-CoV-2 NP, regardless of whether the infection was symptomatic.

    Measure: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Any Time Point

    Time: Day 0 to Day 750
    536 A Phase 2, Multi-Center, Randomized, Placebo-Controlled, Dose-Finding Study Evaluating Efficacy, Safety and Tolerability of Different Doses and Regimens of Allocetra-OTS for the Treatment of Organ Failure in Adult Sepsis Patients

    A phase II, multi-center (approximately 10 sites in Israel), randomized, placebo-controlled, dose- finding study comparing the efficacy, safety and tolerability of different dosing regimens of Allocetra-OTS, in up to 160 adult sepsis patients with organ sysfunction.

    NCT04612413
    Conditions
    1. Sepsis
    2. Community-acquired Pneumonia
    3. Organ Dysfunction Syndrome
    Interventions
    1. Drug: ALLOCETRA-OTS
    2. Other: Placebo
    MeSH:Sepsis Toxemia Pneumonia
    HPO:Pneumonia Sepsis

    Primary Outcomes

    Description: Number and severity of AEs and SAEs throughout 28 days follow up period

    Measure: To compare the safety of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients

    Time: 28 days

    Description: Change from baseline in SOFA score throughout 28 days

    Measure: To compare the efficacy of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients

    Time: 28 days

    Secondary Outcomes

    Description: Vasopressor-free days over 28 days.

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Ventilator-free days over 28 days

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients.

    Time: 28 days

    Description: Days without renal replacement therapy (dialysis).

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Time in ICU and time in hospital

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Number of days with creatinine ≤ Baseline levels +20%.

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: All-cause mortality at Day 28 following first dose

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Changes in CRP levels

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Number and severity of AEs and Serious Adverse Events (SAEs) throughout 12 months follow up period

    Measure: Assess long term safety follow up

    Time: 12 months
    537 A Randomized, Double-blind, Open for Active Comparator, Parallel-group, Multicenter Phase 2b Study to Assess the Efficacy and Safety of Three Different Doses of P2X3 Antagonist (BAY1817080) Versus Placebo and Elagolix 150 mg in Women With Symptomatic Endometriosis

    The purpose of this study is to assess safety and efficacy of BAY1817080 compared to elagolix and placebo in women with symptomatic endometriosis. Study details include: - Study duration: 155 up to 285 days - Treatment duration: 84 days - Visit frequency: approximately once a month

    NCT04614246
    Conditions
    1. Endometriosis
    Interventions
    1. Drug: BAY1817080
    2. Drug: Elagolix
    3. Drug: Placebo
    MeSH:Endometriosis
    HPO:Endometriosis

    Primary Outcomes

    Description: Endometriosis associated pelvic pain (EAPP) will be measured daily on the numerical rating scale (NRS) ranging from 0 to 10 by item 1 of the Endometriosis Symptom Diary (ESD). The higher number indicates a higher level of pain experience

    Measure: Absolute change in mean worst EAPP from baseline to end of intervention

    Time: At baseline (last 28 days before start of study drug) and at day 57-84 (+3)

    Secondary Outcomes

    Description: Any event arising or worsening after the start of study drug administration until 14 days after the last study medication intake

    Measure: Number of participants with treatment-emergent adverse events

    Time: Up to 98 days
    538 A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older

    The study will enroll up to 30,000 participants in order to evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical coronavirus disease-2019 (COVID-19), as compared to placebo, in adult participants.

    NCT04614948
    Conditions
    1. Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 at Different Stages of the Protocol
    Interventions
    1. Biological: Ad26.COV2.S
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in Food and Drug Administration (FDA) guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Secondary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus

    Time: 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus

    Time: 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline

    Time: 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline

    Time: 14 days after the 1st vaccination (Day 15) to end of study (2 years and 3 months)

    Description: Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), linked to objective measures such as decreased oxygenation, X-ray, computed tomographic [CT] findings) linked to any molecularly confirmed COVID-19 at least 14 days after the second vaccination will be reported.

    Measure: Number of Participants with First Occurrence of COVID-19 Requiring Medical Intervention

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: The viral load of SARS-CoV-2 will be assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs will be used to detect and/or quantify SARS-CoV-2.

    Measure: SARS-CoV-2 Viral Load as Assessed by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) in Participants with Molecularly Confirmed, Moderate to Severe/Critical COVID-19

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Molecularly confirmed mild COVID-19 is defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Mild COVID-19 includes: Fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, or chills, without shortness of breath or dyspnea.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Mild COVID-19

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Molecularly confirmed moderate and severe/critical COVID-19 defined as a positive SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case definition at the time of finalization of this protocol: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.

    Measure: Number of Participants with First Occurrence of Molecularly confirmed COVID-19 Defined by the US FDA Harmonized Case Definition

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate, or severe/critical COVID-19 case.

    Measure: Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Serologic conversion between baseline (Day 1) and 14 days, 6 months, and 1 year after the 2nd vaccination using an ELISA and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein will be reported.

    Measure: Serologic Conversion Between Baseline (Day 1) and 14 days, 6 months, and 1 year after the 2nd vaccination Using an Enzyme-linked Immunosorbent Assay (ELISA)

    Time: Between baseline (Day 1) and 14 days, 6 months, and 1 year after the 2nd vaccination

    Description: Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 14 days after second vaccination (Day 71) to end of Study (2.3 years) will be reported.

    Measure: Number of Participants with First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed)

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

    Measure: Number of Participants with Serious Adverse Events (SAEs)

    Time: Up to 2 years and 3 months

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs.

    Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs)

    Time: 6 months after second vaccination (Up to 34 weeks)

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs.

    Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs) Leading to Study Discontinuation

    Time: Up to 2 years and 3 months

    Description: Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post each vaccination (day of each vaccination and the subsequent 7 days).

    Measure: Number of Participants with Solicited Local Adverse Events (AEs) During 7 Days Following Each Vaccination

    Time: Up to Day 8 (7 days after first vaccination on Day 1), up to Day 64 (7 days after second vaccination on Day 57)

    Description: Participants will be instructed on how to record daily temperature using a thermometer provided for home use. Participants should record the temperature in the e-Diary in the evening of the day of each vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement is made on any given day, the highest temperature of that day will be recorded in the e-Diary. Fever is defined as endogenous elevation of body temperature >= 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily basis for 7 days post each vaccination (day of each vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.

    Measure: Number of Participants with Solicited Systemic AEs During 7 Days Following Each Vaccination

    Time: Up to Day 8 (7 days after first vaccination on Day 1), up to Day 64 (7 days after second vaccination on Day 57)

    Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Number of Participants with Unsolicited Local Adverse Events (AEs) During 28 Days Post-vaccination

    Time: Up to Day 29 (28 days after first vaccination on Day 1), up to Day 85 (28 days after second vaccination on Day 57)

    Description: SARS-CoV-2 binding antibodies as assessed ELISA to measure humoral immune response will be reported.

    Measure: SARS-CoV-2 Binding Antibodies Assessed by ELISA

    Time: Up to 2 years and 3 months

    Description: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported

    Measure: SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA)

    Time: Up to 2 years and 3 months
    539 Double-blind, Randomized, Controlled, Clinical Trial to Assess the Efficacy of Allogenic Mesenchymal Stromal Cells in Patients With Acute Respiratory Distress Syndrome Due to COVID-19

    A double-blind, randomized, controlled, clinical trial to evaluate the efficacy and safety of MSC (mesenchymal stromal cells) intravenous administration in patients with COVID-induced ARDS compared to a control arm.

    NCT04615429
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. COVID-19 Pneumonia
    Interventions
    1. Biological: Mesenchymal stromal cells
    2. Other: Placebo
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Primary endpoint

    Measure: Change in the PaO2/FiO2* ratio from baseline to day 7 of treatment administration

    Time: 7 days

    Secondary Outcomes

    Description: Secondary endpoint

    Measure: All-cause mortality

    Time: Days 7, 14, and 28 after treatment

    Description: Secondary endpoint

    Measure: Time to PaO2/FiO2 ratio greater than 200 mmHg

    Time: 12 months

    Description: Secondary endpoint. Categories: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities. Hospitalized, not requiring supplemental oxygen. Hospitalized, requiring supplemental oxygen. Hospitalized, on non-invasive ventilation or high flow oxygen devices. Hospitalized, on invasive mechanical ventilation or ECMO . Death.

    Measure: Clinical status on the World Health Organization ordinal scale

    Time: Baseline, daily until day 14, and on day 28 after treatment

    Description: Secondary endpoint

    Measure: PaO2/FiO2 ratio

    Time: Baseline and days 2, 4, 14 and 28 after treatment

    Description: Secondary endpoint Sequential Organ Failure Assessment score (0-24)

    Measure: SOFA score

    Time: Baseline and days 2, 4, 7, 14 and 28 after treatment

    Description: Secondary endpoint

    Measure: Oxygen therapy-free days

    Time: Day 28

    Description: Secondary endpoint

    Measure: Duration of hospitalization

    Time: 12 months

    Description: Secondary endpoint

    Measure: Duration of ICU admission

    Time: 12 months

    Description: Secondary endpoint Proportion of patients with non-invasive ventilation

    Measure: Incidence of non-invasive ventilation

    Time: Day 28

    Description: Secondary endpoint Proportion of patients with invasive mechanical ventilation

    Measure: Incidence of invasive mechanical ventilation

    Time: Day 28

    Description: Secondary endpoint (number of days)

    Measure: Duration of non-invasive ventilation

    Time: Day 28

    Description: Secondary endpoint (number of days)

    Measure: Duration of invasive mechanical ventilation

    Time: Day 28

    Description: Secondary endpoint

    Measure: Mechanical ventilation-free days

    Time: Day 28

    Description: Secondary endpoint

    Measure: Survival rate

    Time: 3 and 12 months.

    Description: Secondary endpoint

    Measure: Cumulative incidence SAEs, Grade 3 and 4 AEs, ADR and AEs of special interest.

    Time: 12 months

    Other Outcomes

    Description: Exploratory endpoint Analytical markers (e.g., neutrophil and lymphocyte counts). Changes from baseline to set time points will be calculated.

    Measure: Analytical endpoints

    Time: Baseline and days 2, 4, 7, 14 and 28 after treatment
    540 Study to Evaluate the Efficacy and Safety of CardiolRx™ in Patients With COVID-19 and Cardiovascular Disease or Risk Factors A Double-blind, Placebo-controlled Trial

    Non-critical patients, hospitalized within the previous 24 hours who tested positive for COVID-19 and have a prior history of cardiovascular disease (CVD) and/or significant risk factors for CVD will be treated for 28 days.

    NCT04615949
    Conditions
    1. COVID-19
    2. Cardiovascular Diseases
    3. Cardiovascular Risk Factor
    Interventions
    1. Drug: Cannabidiol, pharmaceutically produced with < 5 ppm THC
    2. Drug: Placebo
    MeSH:Cardiovascular Diseases
    HPO:Abnormality of the cardiovascular system

    Primary Outcomes

    Description: proportions of patients not surviving

    Measure: All-cause mortality

    Time: 28 days post randomization

    Description: Proportions of patients needing ICU admission and/or ventilatory support

    Measure: Requirement for ICU admission and/or ventilatory support

    Time: 28 days post randomization

    Description: HF, AMI, myocarditis, new sustained arrhythmia or stroke

    Measure: CV complications

    Time: 28 days
    541 First-in-human, Randomised, Double-blind, Placebo-controlled, Dose-escalation Study in Healthy Young Adults Evaluating the Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Candidate for Prevention of COVID-19

    This is the first study of COVI-VAC in humans. The purpose of the study is to evaluate the safety and immune response of COVI-VAC (a live attenuated vaccine to prevent COVID-19) in healthy adults aged 18 to 30 years. Approximately 48 participants will be enrolled into 1 of 3 dose groups (low, medium, high). Within each of these dose groups, participants will be assigned randomly to receive either 2 doses of COVI-VAC 28 days apart, 2 doses of placebo (saline), or 1 dose of COVI-VAC and 1 dose of placebo. COVI-VAC or placebo is administered by drops into each nostril. Neither the participants nor the researchers will know whether COVI-VAC or placebo has been received. To assess the safety of the vaccine, each participant will record symptoms and oral temperature in a diary daily for 14 days after each dose. Safety laboratory tests, physical exams, ECGs, and a chest X-ray will also be performed, and peak expiratory flow and vital signs will be measured. Adverse events and medication use will be recorded. Blood samples and intranasal samples will be collected to assess the immune response from the vaccine.

    NCT04619628
    Conditions
    1. COVID-19
    Interventions
    1. Biological: COVI-VAC
    2. Other: Placebo

    Primary Outcomes

    Description: Percentage of subjects with reactogenicity events

    Measure: Reactogenicity

    Time: 14 days after each dose

    Description: Percentage of subjects with adverse events

    Measure: Adverse events

    Time: Days 1 through 57

    Description: Percentage of subjects with serious adverse events

    Measure: Serious adverse events

    Time: Days 1-400

    Secondary Outcomes

    Description: IgG titre measured by ELISA in serum collected on Days 1, 15, 29, 43, 57, 120, 210, and 400

    Measure: IgG titre

    Time: Days 1, 15, 29, 43, 57, 120, 210, and 400

    Description: Neutralising antibody level measured by microneutralisation assay in serum

    Measure: Neutralizing antibody titre

    Time: Days 1, 15, 29, 43, 57, 120, 210, and 400
    542 Early Nintedanib Deployment in COVID-19 Interstitial Fibrosis

    This is a collaborative study between Icahn School of Medicine at Mount Sinai and Boehringer Ingelheim Pharmaceuticals to determine the effect of Nintedanib on slowing the rate of lung fibrosis in patients who have been diagnosed with COVID-19, and have ongoing lung injury more than 4 weeks out from their diagnosis.

    NCT04619680
    Conditions
    1. Pulmonary Fibrosis
    2. Interstitial Lung Disease
    3. Respiratory Disease
    Interventions
    1. Drug: Nintedanib
    2. Drug: Placebo
    MeSH:Lung Diseases Pulmonary Fibrosis Lung Diseases, Interstitial Respiration Disorders Respiratory Tract Diseases Fibrosis
    HPO:Abnormal lung morphology Interstitial pneumonitis Interstitial pulmonary abnormality Pulmonary fibrosis

    Primary Outcomes

    Description: Change in Forced Vital Capacity (FVC) at 180 days as compared to baseline. Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible, as measured by spirometry.

    Measure: Change in Forced Vital Capacity (FVC)

    Time: Baseline and 180 days

    Secondary Outcomes

    Description: Death within 90 days and 180 days from enrollment due to a respiratory cause

    Measure: Number of deaths due to respiratory cause

    Time: within 90-180 days

    Description: Quantitative Change in chest CT visual score graded by blinded chest radiologists. Data driven texture analysis (DTA) is a patented deep learning method to quantify lung fibrosis. DTA score is reported in percentage ranging from 0% to 100%. A minimally clinical important difference when comparing CT scans from the same subject is 4%. A higher percentage suggests worsening lung injury.

    Measure: Chest CT visual score

    Time: 180 days

    Description: The Saint George's Respiratory Questionnaire (SGRQ) is a self-reported disease-specific, health-related quality of life (QOL) questionnaire. 50-item instrument. Scores range from 0 to 100, with higher scores indicating more limitations.

    Measure: St. George's Respiratory Questionnaire (SGRQ)

    Time: Day 90

    Description: The Saint George's Respiratory Questionnaire (SGRQ) is a self-reported disease-specific, health-related quality of life (QOL) questionnaire. 50-item instrument. Scores range from 0 to 100, with higher scores indicating more limitations.

    Measure: St. George's Respiratory Questionnaire (SGRQ)

    Time: Day 180

    Description: The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of health-related quality of life, comprising 15 items with three domains (Psychological (KBILD-P), Breathlessness and activities (KBILD-B), and Chest symptoms (KBILD-C)) combined in a total score (KBILD-T). The KBILD domain and total score ranges are 0-100; 100 represents best health status.

    Measure: King's Brief Interstitial Lung Disease (KBILD)

    Time: Day 90

    Description: The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of health-related quality of life, comprising 15 items with three domains (Psychological (KBILD-P), Breathlessness and activities (KBILD-B), and Chest symptoms (KBILD-C)) combined in a total score (KBILD-T). The KBILD domain and total score ranges are 0-100; 100 represents best health status.

    Measure: King's Brief ILD (KBILD)

    Time: Day 180

    Description: The LCQ is a 19 item questionnaire that assesses cough-related QOL. It has 3 domains (physical, psychological and social). The domain scores range from 1-7 and total score range is 3-21 with a higher score indicating a better quality of life.

    Measure: Leicester Cough Questionnaire (LCQ)

    Time: Day 90

    Description: The LCQ is a 19 item questionnaire that assesses cough-related QOL. It has 3 domains (physical, psychological and social). The domain scores range from 1-7 and total score range is 3-21 with a higher score indicating a better quality of life.

    Measure: Leicester Cough Questionnaire

    Time: Day 180

    Description: The (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status. Scores range from 0 - 100, with higher scores indicating less disability.

    Measure: Short Form (SF) 36 Health Survey

    Time: Day 90

    Description: The (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status. Scores range from 0 - 100, with higher scores indicating less disability.

    Measure: SF 36 Health Survey

    Time: Day 180

    Description: Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression. 14-items scale with responses scored from 0-3, scores for each subscale from 0 (normal) to 21 (severe symptoms). Scores for the entire scale is 0 to 42, with higher score indicating more distress.

    Measure: Hospital Anxiety and Depression Scale (HADS)

    Time: Day 90

    Description: Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression. 14-items scale with responses scored from 0-3, scores for each subscale from 0 (normal) to 21 (severe symptoms). Scores for the entire scale is 0 to 42, with higher score indicating more distress.

    Measure: Hospital Anxiety and Depression Scale (HADS)

    Time: Day 180

    Description: Number of participants with Increase in liver transaminases

    Measure: Number of participants with Increase in liver transaminases (AST and ALT) > 3 times the upper limit of normal

    Time: day 90

    Description: Number of participants with Increase in liver transaminases

    Measure: Number of participants with Increase in liver transaminases (AST and ALT) > 3 times the upper limit of normal

    Time: day 180

    Description: Number of participants with Thrombotic events: venous or arterial thrombosis

    Measure: Number of participants with Thrombotic events

    Time: day 90

    Description: Number of participants with Thrombotic events: venous or arterial thrombosis

    Measure: Number of participants with Thrombotic events

    Time: day 180

    Description: Number of participants with 10% weight loss

    Measure: Number of participants with 10% weight loss over 90 days

    Time: day 90

    Description: Number of participants with 10% weight loss

    Measure: Number of participants with 10% weight loss over 90 days

    Time: day 180

    Description: Number of participants with Nausea/emesis/diarrhea not responsive to anti-emetics and anti-motility agents

    Measure: Number of participants with GI events

    Time: day 90

    Description: Number of participants with Nausea/emesis/diarrhea not responsive to anti-emetics and anti-motility agents

    Measure: Number of participants with GI events

    Time: day 180
    543 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase IIA Study of FSD201 (Ultramicronized PEA) + Standard of Care (SOC) Vs SOC in the Treatment of Hospitalized Patients With COVID-19

    This study will measure the effect of FSD201 (ultramicronized PEA) + SoC vs placebo + SoC on Day 28, on disease progression in the confirmed coronavirus disease 2019 (COVID-19) patient population.

    NCT04619706
    Conditions
    1. COVID-19
    Interventions
    1. Drug: FSD201
    2. Drug: Placebo

    Primary Outcomes

    Description: Disease progression will be defined as the percentage of participants who are not alive or who have respiratory failure. Respiratory failure will be defined as the need for invasive or non-invasive mechanical ventilation, high-flow oxygen, or extracorporeal membraneoxygenation (ECMO).

    Measure: Percentage of Participants With Disease Progression at Day 28

    Time: Day 28

    Secondary Outcomes

    Description: Disease resolution will be defined as participants alive and not requiring supplemental oxygen (at home or in the hospital).

    Measure: Percentage of Participants With Disease Resolution at Day 28

    Time: Day 28

    Measure: Percentage of Participants Requiring Invasive Mechanical Ventilation or ExtraCorporeal Membrane Oxygenation (ECMO) or who are not Alive on Day 28

    Time: Day 28

    Description: Oxygen use will be assessed by change in the type of oxygen use between the following categories: no oxygen, supplemental oxygen, non-invasive mechanical ventilation or high-flow oxygen, invasive mechanical ventilation/ECMO.

    Measure: Change From Baseline in Oxygen use

    Time: Baseline, Day 15, and Day 28

    Measure: Change From Baseline in Saturation of Oxygen (SpO2) percent (%)

    Time: Baseline through Day 28

    Description: Clinical status will be measured with the 9-point ordinal scale ranging (1-9; 1 being death and 9 being not hospitalized, not requiring supplemental home oxygen, and no limitations on activities).

    Measure: Change From Baseline in Clinical Status Related to COVID-19

    Time: Baseline, Day 15, and Day 28

    Description: Mortality rate will be defined as the percentage of participants who die.

    Measure: Percentage of Participants who Die (Mortality Rate) at Day 28

    Time: Day 28

    Description: COVID-19 testing by standard standard reverse transcription-polymerase chain reaction (RT-PCR) assay or equivalent test.

    Measure: Percentage of Participants Testing Negative for COVID-19 at Day 28

    Time: Day 28

    Description: Number of participants with AEs and SAEs will be summarized and reported by seriousness, severity, relationship to the study medication, outcome, and duration.

    Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time: From the signing of the informed consent to Day 60 (approximately 9 months)

    Description: The number of participants with clinically significant changes in vital signs, laboratory parameters and electrocardiogram findings, and physical findings will be reported.

    Measure: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters, Electrocardiogram Findings and Physical Examination Findings

    Time: Baseline through Day 28

    Description: Plasma concentrations will be measured in participants who give optional consent will be collected relative to the first dose on Day 1 and the first dose on Day 14. Samples on Day 1 and Day 14 will be collected predose (within 10 minutes before the first daily dose) and post dose at 2 hours (±30 minutes), 12 hours (±30 minutes) (before the evening dose), and 24 hours (±30 minutes)(before the next morning dose).

    Measure: Plasma Concentrations of FSD201

    Time: Day 1 and Day 14

    Description: Cmax is defined as maximum observed plasma concentration.

    Measure: Maximum Observed Plasma Concentration (Cmax) of FSD201

    Time: Day 1 and Day 14

    Description: Area under the concentration-time curve (AUC).

    Measure: Area Under the Concentration-Time Curve (AUC) of FSD201

    Time: Day 1 and Day 14

    Description: Elimination half-life (t1/2) of FSD201.

    Measure: Elimination Half-Life (t1/2)

    Time: Day 1 and Day 14

    Description: CL/F is the apparent total body clearance of FSD201 in plasma.

    Measure: Apparent Total Body Clearance (CL/F) of FSD201

    Time: Day 1 and Day 14

    Description: Vz/F is the apparent volume of distribution of FSD201 in plasma.

    Measure: Apparent Volume of Distribution (Vz/F) of FSD201

    Time: Day 1 and Day 14

    Description: Cav is average plasma concentration over a dosing interval.

    Measure: Average Observed Plasma Concentration at Steady State (Cav) of FSD201

    Time: Day 1 and Day 14

    Related HPO nodes (Using clinical trials)

    HP:0005162: Abnormal left ventricular function
    Genes 88
    TBX20 MFAP5 SDHA ELN TRNS2 LDLR SDHAF1 TLL1 APOB GATA4 TRNC TNNT2 MYH11 SMAD3 MYPN TRNF TGFBR1 COX2 TOP3A TRNK MYH7 GTPBP3 PRDM16 FBN1 MYH11 TGFB3 POLG PPCS TRNV MYH11 PCSK9 MYLK LDB3 ZMPSTE24 KIF20A ND5 EYA4 GATA6 PRKG1 FOXE3 GDF1 SGCG POMT1 TGFBR2 TGFB2 RYR2 CITED2 LMNA LMNA TNNI3 ND6 TBX20 ABCG8 ND1 MAT2A COX3 CYTB FKRP DYSF TRDN FLNC VHL CASQ2 LAMA2 POMT2 DMPK TTN TAB2 NKX2-5 TRNL1 ABCG5 SDHD POLG2 COX1 MYH6 POMT2 LDLRAP1 SLC25A4 SMAD4 ACTC1 TWNK ACTA2 TRNS1 TRNQ RRM2B TRNW LOX SDHB
    Protein Mutations 0
    SNP 0
    HP:0002088: Abnormal lung morphology
    Genes 1393
    CDC45 SMARCA4 TBC1D24 ELN SNX10 SLC1A4 GRHL3 CFAP298 RSPH4A EDNRB TMEM94 CARD11 LPIN2 CD3E COG4 PGM3 ECM1 GNPTAB LIMK1 HLA-DRB1 CFTR CD247 PDGFRA LMNA FBN1 NTRK1 SOS2 PSAT1 ZBTB24 GP1BB MANBA CLEC7A IL2RG TARS1 DNAAF2 NSD2 SEC24C DNAJB13 DNAAF3 EXOSC9 DYNC2LI1 NELFA EDARADD NPHP3 STING1 GDF1 COL2A1 MAP3K20 CTRC HLA-DPB1 OFD1 SMARCD2 ABCA12 ERCC6 FGF20 LZTR1 SCNN1G SLC25A24 BLNK NKX2-5 TRIP13 SOX10 GAS2L2 TYK2 HELLS TTC21B FOXH1 DNAAF6 INPPL1 ITGA8 PERP EIF2AK4 OCRL GPR35 GTF2E2 NEB FOXC2 MASP2 STAT5B COL11A2 FBXW11 MYO5A CTLA4 LBR FCGR2A PRKCD RANBP2 HYLS1 IL21R DGCR8 BMPER GATA4 NSD1 TSC2 FLCN LTBP3 CYBA SPINK5 ATP5F1A CTLA4 FLT4 TERC KCNJ6 FOXH1 TCF4 NAGLU GUSB SHROOM4 EVC LIPN RNU4ATAC TPM3 PTPN11 CDT1 MUSK HERC2 NEK1 FLNB EPG5 GAS1 FBLN5 NRAS ACP5 MCIDAS MAN2B1 TIMM8A COL13A1 BCOR MYLK PTPN22 SLC35A1 SLC46A1 HGSNAT RASGRP1 LYST ZNF341 XIAP LRRC56 FGFR1 IGH NODAL WDR19 LETM1 TRIP4 EFEMP2 NCF1 MCM4 SFTPC SOS1 STRA6 RSPH4A IL2RB RAG2 RAC1 DISP1 PHGDH WRAP53 PSMC3IP RBM10 PANK2 PEX1 TNFRSF13C GLI3 WNT3 ARID2 SBDS NPAP1 ACTA1 BLM CD40LG BRAF ICOS FASLG PRKN CCDC103 SNORD116-1 FOXP3 MEFV PTEN TDGF1 IL6R CIITA SLC2A10 CYTB ENG GLI2 FGF8 DNAJB13 CCDC39 STAT6 INVS IDUA GATA4 RPS15A NOP10 IFNG HLA-DRB1 FLNA JAG1 HABP2 VANGL1 GNPTAB MYBPC3 TBX6 MKRN3 SNORD115-1 LACC1 ELANE SMN1 DYNC2H1 KIF20A RPL10 ARHGAP31 PGM3 PEX13 CDON IL7R RAF1 SCNN1A STAG2 PLEC FLI1 CITED2 SIX3 TCIRG1 ETFA MITF MST1 ZNHIT3 LAMA2 IFT81 PDGFRB CYP4F22 DNAAF4 HLA-B FAT4 ZIC2 CALCRL KMT2E HFE CSF2RB CD55 IGH TTC37 DICER1 NFKB2 PEPD GPC6 TNFRSF13B FGF8 RAF1 ABCA3 STK36 RFX5 DPP9 RYR1 SFTPA1 SHH SKIV2L IRF1 LAT DCLRE1C SON SLC25A22 TLL1 AP3D1 TGFBR1 NODAL AGT ZMYND10 SOX18 NOS1 TPM2 BUB1B TRIP11 ERAP1 TNFRSF1B REST ZIC2 CTCF RAC2 CTLA4 PLP1 GAS1 EFL1 FMO3 TRIP4 RYR1 CIITA DLL3 AP3B1 PRTN3 PIGN TBX1 ABCA3 EFEMP2 AGA CHRND PCNT PKHD1 RSPH1 ZAP70 PAX3 NDN CHRNG NHLRC1 ACE DNAH1 KRAS IL12A KEAP1 ALDH18A1 SCNN1G ACADVL DCTN4 IRF5 TRAPPC4 CCN2 PTCH1 DKC1 GMNN TNFRSF13B GLI2 MCIDAS SCN11A ROR2 IVNS1ABP TRPV4 TSC1 FANCB ZEB2 RPL10 ODAD1 MESP2 CHST14 IL23R SLC12A6 MGP CFAP300 SMAD3 RSPH9 UMPS DHCR7 KRAS SFTPC COL13A1 SNRPN BUB3 FAM13A GAS8 WDR35 MFAP5 CACNA1B ZCCHC8 NTNG1 FLCN AK2 INPPL1 CHAT CCDC40 IL2RG CDC42 DYNC2H1 CD3G TASP1 SLC18A3 DGCR6 HOXD13 SCNN1G WT1 KAT6B WT1 MAP3K8 STAT1 ACTA1 TGFB3 MUC5B PRKAG2 SMN1 TAP1 SMAD4 ABL1 MED25 CHD7 TERT COG4 LMNA SULT2B1 GBA SPEF2 RREB1 SDR9C7 CEP57 CFI IDUA FUCA1 FLCN TBX1 HPS4 PIGT SAMD9L FLNC ESS2 NCF4 LRBA DRC1 DYNC2I2 RFXAP KIAA0586 DNAH5 DOCK8 PTEN MAN2B1 ZMPSTE24 TP53 ATM LAMC2 ACTL6A TRAF3IP2 POLR3H RELA TBX5 PARN CR2 IRF5 MED13 NUP88 GALNS TAP2 AFF4 UNG DNAAF4 RFC2 BCL11B NCF1 HPS1 CD3D RELB PTPN11 ODAD4 TDGF1 KAT6B PMM2 CYP2A6 RUNX2 POLA1 SGSH RIPPLY2 SERPINA1 WAS NDUFAF6 MMP21 SPP1 GLDN NSDHL ZFPM2 IL17F IL6ST IRAK4 KAT6B ACTL6B LRRC8A TAPBP CCNO GLI3 PLCG2 HK1 BMP15 TMEM260 MYL2 LEP ERCC3 TRPV3 IGLL1 EPM2A CCDC65 PRKCD SLC18A3 TAPT1 BMPR2 CD79B SLC7A7 FLNA FAM20C HLA-DRB1 SLCO2A1 CD46 XIAP DKC1 CYBB MYT1L CD3E AFF4 MESP2 VHL POLE BCOR FOXH1 BMP2 HYDIN TNNI3 RARA MAT2A EOGT NFIX MEFV DVL3 PTH1R BCL10 RNF168 CBL ITGA8 NEU1 KRAS CEP55 MYD88 NPM1 IGLL1 TP53 RSPO2 RRAS TRIP11 TGIF1 WAC ADA PKD1L1 UNC119 ACTA2 PSMD12 ACTA1 STRA6 PIGN GAA CD8A BCOR NEK9 TERT DHCR7 IKZF1 TSC2 LEPR SLC35A1 MUSK ARSB COG6 VPS51 COLQ WDR1 RASA2 TTC7A LTBP4 BTK GPC3 STAT3 GAS1 RUNX1 TTC12 WASHC5 INTU CD3D WT1 STAT3 BPTF CRTAP SLC2A10 COL2A1 COMT CCDC40 ASAH1 LIFR MEFV ACVRL1 MYH3 FAT4 DNAI2 LAMB3 PIEZO2 FOXE3 GRIP1 NFKB2 PIGL PTCH1 TGFBR2 ATP6V1E1 COL6A3 IL1RN PAFAH1B1 FOXH1 TP53 CRELD1 MBTPS2 RYR1 TNFRSF13B GRIP1 TGIF1 CLCN7 SP110 CC2D2A COL6A1 STN1 APC2 ITPR1 TCTN3 SMARCC2 PNP SLC11A1 GLUL PKHD1 ALPL BLM ACP5 WDR19 ASCC1 TDGF1 TFRC MGP DLL1 WNT4 IFT140 CCN2 SHH SMAD3 TGIF1 PRKAR1A EHMT1 EP300 CASP8 TGFBR1 ITGA7 AARS2 ERF DNMT3B FGFR1 IRF2BP2 CHRNG HLA-DQB1 SPAG1 SRP54 UBE2A CCNQ TINF2 BUB1 LFNG CARD11 DHCR24 ARID1B SELENON RMRP WAS NEK10 MAPK1 GATA6 SCNN1B TRIM28 DHCR24 SYT2 DOCK6 USB1 B3GLCT DLL1 CCR1 POLR3A PRPS1 HIRA RSPH1 SLC26A2 TNFSF12 PIK3R1 IER3IP1 GSN TINF2 NME8 SVBP LIG4 IL7R ALB COL11A2 COL3A1 NHLRC2 KIAA0319L TGFB1 DLL1 IFNGR1 LAMTOR2 DNAAF5 NXN CTLA4 CEP57 HLA-DRB1 MINPP1 CASP10 PTPN22 TBX20 RAB3GAP2 ALOXE3 ZIC2 NUP107 HES7 LRRC56 HLA-DQA1 KIF1A GAS8 TERT PSAP DNAI2 NOTCH2 DPM2 CD81 NODAL DNAH9 NABP1 PRKAR1A NUMA1 TBC1D23 NFKB2 DLL4 ORC6 FANCB SMARCB1 FCGR2B SIX3 GBA GATA4 MDM2 LAMA3 DSP KIF11 MLXIPL HLA-DRB1 NOTCH2 ADGRG6 DNAH5 SLC26A2 DYNC2I1 ATP6V0A2 EGFR ZBTB24 LYST ODAD4 CACNA1C CYBB RNF125 DPF2 RIT1 CITED2 RLIM WDR35 DYNC2I2 GATA6 RTEL1 IRF8 DISP1 GAS1 ABCA12 TRIP13 GPC3 ODAD3 DNAAF2 MECP2 BIRC3 SFTPB ELN CFTR NOTCH3 SCNN1A KMT2D DIS3L2 MDM4 IL17RA EPHB4 CCDC39 FBLN5 SPIDR TCF20 KLHL41 WNT3 IL17RA FCGR3A JMJD1C VPS33A UFD1 ODAD1 IKBKB CHEK2 FADD RSPH3 ZMIZ1 CREBBP TNFSF11 SCNN1B FREM2 CCR6 AGA SCNN1A ADA RAG1 RAG1 LMNA BRCA2 TGM1 TSC1 DLL1 SIX3 CARMIL2 GTF2I AKT1 CCDC65 ARID1A FGF20 RIPK4 ALG9 CFB RAG2 SCNN1G APOE SOX4 RAB27A MUC5B EWSR1 NECTIN1 ZMYND10 SGCG DNAAF6 CDON TAF1 IGHM LMNA LAMB2 LEP CSF2RA CD79A CFTR HPS6 DOK7 RCBTB1 CCBE1 FIP1L1 COQ7 SERPINF2 PWAR1 RPGR VPS33A ELN SPECC1L TET2 BTK SCNN1A RLIM IL7R EPG5 HLA-DRB1 TGFB2 PIK3CD GLA NBN HYDIN PSMB8 VAMP1 SDCCAG8 TINF2 FCGR2A SHH ARHGAP31 RAC2 CD19 DSE DDX6 HLA-B SERPINH1 GLI2 FLNA MARS1 ALMS1 SCNN1B ITCH SPAG1 DISP1 DNAAF5 IDUA TGFB2 FGF8 MSN SMARCE1 CHST14 WRN BCR FGFR3 SERPINA1 WDFY3 RAG1 PRPS1 FASLG DNASE1 NIPBL KLHL40 RAG2 MRAS RHOH ZAP70 TK2 FGFR1 CREBBP MYRF ALOX12B NOD2 RFXANK MYH11 EVC2 DYNC2LI1 ZEB2 IFIH1 RARB GBA USP9X IKBKB ABCA3 MYOD1 GATA6 CCNO CSPP1 TBCE GBA RARB NAA10 TSC1 FAS WNT4 PLCG2 ETFDH G6PC3 MS4A1 SPINK1 CD19 UBAC2 FLCN EXTL3 GUSB DYNC2I2 ATP11A NGLY1 SAMD9 NME8 TRAIP RRAS2 PYROXD1 SIK1 SLC26A2 RAG1 MYOD1 ALMS1 NKX2-5 IL21 FOXP1 PUF60 LAMTOR2 BCL2 SMAD4 TBL1XR1 ACTC1 FOXJ1 ARID1B HELLPAR SCNN1B DGCR2 DOCK3 FSHR MIF CYBC1 SNAI2 CSPP1 CCBE1 SMARCD1 IRAK1 JAK3 STAG2 PCGF2 CXCR4 LEPR DDR2 BCL6 POLA1 TRMT1 PTCH1 RPGR GATA6 CSF2RB CHRNA1 ASAH1 ASAH1 RAG2 NAB2 TERT MYSM1 BTK FRAS1 DCLRE1C BTNL2 CFTR NOP10 KNSTRN FOXJ1 PEPD TERT NR5A1 CDON MARS1 BRAF TCF3 NKX2-1 ICOS ZMPSTE24 DNAH11 OSTM1 ALG12 KATNIP AGTR1 PPP1CB BMPR2 CAV1 TGFB1 KPTN ADA TPP2 MKRN3-AS1 SLC25A1 FARSB GPC4 FUZ MYH6 HLA-DPA1 FBLN5 SRP54 TNFSF12 IGHM NEK10 RSPH3 TTC12 CRKL RASGRP1 SELENON PTPN22 DLL3 CLPB DOCK8 GLI3 HPGD THOC2 LOX RBPJ PIGN SMC1A DCLRE1C DNAL1 RIPK1 ZBTB16 CFH BTNL2 GLE1 SFTPC FOXF1 KLRC4 CCND1 CD79A EGFR TNNT2 DNAJC21 IL12A-AS1 IFT80 TSC1 CTSC USP9X MKKS SFTPA2 PIK3R1 CHRNG CITED2 TNFRSF13C ELN ADAMTS2 NR2F2 RSPO2 CFTR SCARB2 NKX2-5 SOX18 ADNP DNMT3B CCR6 TCIRG1 PAX6 STAT4 SETD2 DRC1 CFAP221 C11ORF95 TSC2 IFT172 TNFRSF13C FBN1 ARVCF RNF168 NFKBIA NFKB1 BAP1 NEPRO SLC52A3 PRSS1 SLC26A2 CLIP2 MKS1 GLI1 CRELD1 FGFR3 SFTPC FCN3 NCF2 SIM1 CD28 BAZ1B P4HTM DNAAF3 GAS2L2 CCDC103 UGP2 CEP120 GATA2 ETFB DICER1 IL6 ICOS CDCA7 CDKN2A SIX3 JAGN1 SFTPB DNASE1L3 PPP2R1B MBTPS2 CLCA4 STX1A KIAA0586 AGGF1 BNC1 POU6F2 MYH3 PHGDH STAT3 HRAS SFTPA2 DNAH11 LRRC6 SLC35C1 CDON IL17RC ASXL1 TRIM28 COL3A1 CD79B KDM6A UBB NHP2 NAA10 NCF4 CCDC22 MAGEL2 TBC1D24 PARN NRAS MTHFD1 MYH7 MIR140 BLNK LCK NFE2L2 CSF2RA MYSM1 DNAI1 MYT1L RAG2 CAV1 ZIC2 PRKG1 HACD1 MPLKIP TLL1 PIK3CA NSMCE3 IL10 PRSS2 SMPD1 IFT80 NLRC4 COL6A2 FLNB OFD1 PARN RB1 SCN9A MCTP2 FGF8 MAGEL2 FANCF CORO1A PIK3R1 PRKDC CR2 GBA EP300 TGFBR2 PIK3CD CASP8 CRLF1 PLVAP RAPSN NOTCH1 H19 PTCH1 NCF2 SH3KBP1 CR2 ERBB2 DNAAF1 AGRN RFXANK TDGF1 LGI4 GLE1 IL2RA SOX11 IL2RG MEFV ATM STAT3 ODAD3 SERPINF2 CYBC1 SNAP25 SMPD1 TRPS1 REN SHH ELP1 GLI2 CHRM3 IL2RG PNP GREB1L BACH2 SRSF2 NPHP3 CREBBP RIT1 BGN SH2D1A WIPF1 GATA6 DDR2 CTC1 FAS DYNC2I1 KITLG TBX1 TGIF1 RFX5 DCLRE1C CFAP410 GTF2IRD1 GPKOW FAS DONSON CCNQ ELN FADD SLC5A7 GDF1 ERCC2 TERC CBL ADAMTS3 TBX20 ODAD2 STAT4 SLC29A3 FOXE1 CBL FBN1 DVL3 MALT1 IFT43 DSG1 TECPR2 RTEL1 IPW NGLY1 CYBA PIEZO1 NHP2 EP300 TNFRSF11A DZIP1L CCND1 TLR4 CD81 FAM111B LRRC6 RTEL1 BCORL1 PORCN RAG1 SLC34A2 COPA DICER1 FRAS1 DNAI1 TERC MYPN NFKB1 ODAD2 ITCH TBCD ELANE NPM1 CXCR4 PWRN1 TNFRSF1A FOXP1 MYO9A DNAAF1 TGFB1 RFXAP C4A PML RAG1 TREX1 SMPD1 CREBBP SLC22A18 ELN TSC2 A2ML1 FSHR SETBP1 USB1 NADK2 MS4A1 CHAMP1 TERT NKX2-1 PTPRC SCN10A NEK8 CEP120 SMO CFI LMOD3 ELP1 NAA10 POLR2A NODAL GFI1 PLG RNF113A HSPG2 TBL2 EMG1 SFTPB STK11 SLC7A7 RSPH9 MRPS22 TERC CFAP298 WT1 CD19 RET JAK3 AICDA GLB1 GTF2H5 NIPAL4 PLOD1 MESP2 DYNC2I1 RNU4ATAC ZEB2 TANC2 ITGA3 NBN GNS FOXN1 STAT1 DISP1 B2M
    Protein Mutations 11
    A105G A118G D299G G551D G719A L858R L861Q R753Q S1009A T399I T790M
    SNP 6
    rs1051730 rs1800470 rs1828591 rs25331 rs4129267 rs7103572
    HP:0001626: Abnormality of the cardiovascular system
    Genes 4365
    NR2E3 ND4 MMUT EDNRB NDUFS6 TMEM94 LPIN2 COG4 VEGFC PGM3 GATA1 PDE11A KIAA1549 SLMAP LBR CD247 RHBDF2 AGK ABCD3 SEMA5A GP1BB HS6ST1 FANCC SEC61A1 SEC24C PROM1 CALM1 TRNL1 ANK2 NELFA HPS3 STING1 GDF1 MMP14 APOE PEX11B POLR1A OFD1 ABCA12 FGF20 ABCG8 CCDC141 NSD2 CYTB HGD KRAS NKX2-5 JUP KCNH2 TRIP13 FEZF1 PERP IKBKG BTD LDB3 GDF1 RAD51 ERCC4 FGB NDP SLC25A4 ASXL1 CTLA4 ABCC9 LBR FLT4 KCNJ2 SEC31A ATP6 USH2A FLNC GATA4 MYH6 PLEC NSD1 FHL1 GLB1 TSC2 LMNA CAVIN1 TNFRSF4 FLT4 GUSB AIP EVC C12ORF57 RET RNU4ATAC PPP2R1A TPM3 XYLT2 COQ2 FBLN5 HBA1 LZTFL1 ACP5 NUP188 IL7 MAP2K1 ROBO4 MYLK PUF60 FKRP TPM2 TTR TSFM TMEM67 FGFR2 SPOP IGH KDSR DNAJC21 LETM1 ACTN2 POMGNT1 PTDSS1 MYF6 CD70 SOS1 ATP6V1A GJB6 NPPA ACADM GATB TERF2IP GLI3 G6PD HNF4A MGMT COA6 RERE KLLN IFNG ARNT2 FANCM WT1 PDE11A FOXP3 USP45 MYCN UBR1 MYOT IARS1 ENG PLEKHM1 GJA1 GLI2 DNAJB13 PRKAG2 FLT1 INVS IDUA CCDC174 NOTCH3 HPGD HIBCH CAV1 IFNG HLA-DRB1 JAG1 ARL13B GFM2 HOXA13 COL4A1 GBE1 SALL4 CFHR1 TBXAS1 DDX58 TGIF1 MKS1 LACC1 DNAJB11 ND5 RPS19 H19-ICR BLOC1S3 CDON PRPF6 PLCB4 GPD1 SLC18A2 FGFR1 EVC2 NEDD4L BAP1 RPGR THPO MST1 LAMA2 HPS5 ADAMTSL2 PEX14 RAB23 NDUFA6 MYH7 ESR1 EDA VCP KCNE3 ZIC2 KMT2E HFE SDHD C2 ITGA2B TET2 CAV3 ALDH3A2 PEPD FGF8 RAF1 SHH XYLT2 PSMB4 SON HMBS TLL1 DTNBP1 ABCD4 FHL2 MMEL1 NODAL JAK2 HEPHL1 TAZ HAAO BUB1B ERAP1 ADAMTSL1 CSTA SMC1A ZNF148 LZTR1 MIB1 CLRN1 FMO3 TMEM231 PRTN3 PIGN CHRND TRNF LRP6 TDGF1 NDUFB11 COL1A1 SCARF2 PTPN22 UBE3B DPF2 ANKS6 DNM2 XK KRAS HEXB IDH2 MYH6 IRF5 HLA-DQB1 ERBB3 DUX4 TBX19 SIX3 IDH3B MTHFR FANCB TERT EPB42 TRNL1 ZEB2 ODAD1 NECTIN1 COX1 ARCN1 COL1A2 LDLRAP1 TP63 SMAD3 F13A1 CAV1 GJA1 VPS33B CASR WDR35 LIG4 LARP7 CCDC40 CUL7 DDRGK1 IL2RG PLOD1 HAND2 PRRX1 SACS SCN5A WT1 CD96 WT1 TGFB3 PRPF3 ACTA2 BBIP1 SLC4A1 HAMP LMNA GBA CYP11B1 SGCG IDUA TRNL1 CTSK KLF1 ABCC6 SIM1 SETD5 SAMD9L SF3B1 ESS2 NCF4 DRC1 FERMT1 TPI1 NFU1 NDUFS2 COX7B SCAPER DNAH5 SAMHD1 MAN2B1 KCNJ18 FXN AGXT ZMPSTE24 ALDH18A1 ACTL6A GFI1B D2HGDH EOGT GP9 CEP290 HCCS SMARCB1 PIGV GMPPB TRIM32 DNAAF4 HPS1 KIF15 ODAD4 SPECC1L TDGF1 PMM2 SGSH WAS SOX9 DCAF8 HAVCR2 ND5 CDKN2A ARX GNPTAB SEMA3E IL17F SCN10A LRRC8A SLC35A2 CCNO LMNA MYL2 SOX2 NKX2-5 NOS3 SETD1A NEXN BMPR2 CDK8 POMT1 ERGIC1 TMEM127 NCKAP1L CC2D2A JAK2 HNF1A BAP1 DKC1 CYBB COL1A1 PAFAH1B1 VHL SCN5A TTC7A FOXH1 NDUFAF5 TNNI3 SLC25A11 PAFAH1B1 ND1 ITGA8 GLMN MYD88 EIF4G1 ARF1 KCNJ5 SLC20A2 PRNP RRAS XPA GATA4 AKAP9 STRA6 SDHA FGF17 FANCC TRNW ARMC5 COA8 PSAP DHCR7 PTCH1 CALM3 MEN1 CLCNKB MAB21L1 PROK2 CKAP2L CC2D2A F7 BPTF COX10 MGME1 TKFC ADAM17 CRYAB PLAGL1 ABL1 NDUFS1 WASHC5 SMARCE1 INTU ERCC5 ACTN4 STAT3 DYNC2LI1 TRNV HGD HYMAI WNK4 LIFR SHH AEBP1 MEFV DNAI2 AKT1 ND4L NFIX NFKB2 DCDC2 PIGL TGFBR2 ATP6V1E1 XYLT1 CRELD1 PTPN11 DLST MYH7 FOXF1 SDHAF1 TGFBR3 GDF2 LARS2 GDNF RPS6KA3 PROKR2 APC2 TNFRSF1B CTNS SMARCC2 FGFR1 PQBP1 COX15 PPOX F10 PNP GLUL PKHD1 NKX2-5 HYLS1 CAV1 BLM ASCC1 MYH6 MEIS2 KCNJ11 TFRC IDH1 PEX6 RPS26 COL6A3 CIB1 SOS2 RPL18 DVL1 RHO TGFBR1 RPGRIP1L TRNK CEP120 EPB41 CYP7B1 FECH SF3B4 UBE2A CRYAB MNS1 FGFR2 MEOX1 VAMP7 LMNB1 GP1BA ARL6 JAK2 NDUFAF1 SRY CFC1 DNMT3A EPAS1 KCNQ1OT1 WNT10A TANGO2 GATA6 TNFSF4 DYRK1B GATA6 BSCL2 RUNX1 ATP5F1A AKR1D1 DHCR24 OFD1 ABCC9 USB1 TSHR HTRA1 THSD1 SMC1A SVBP GYG1 ALB F8 COL2A1 TFAP2B COL3A1 ABCG5 ALDOB DLL1 IFNGR1 SDHB TNFRSF11A CEP57 CASP10 PTPN22 RAB3GAP2 ABCA4 TERT POGZ F8 CA2 PIGP PEX11B NOTCH2 COL5A1 NRXN1 CD81 NODAL MYBPC3 ANKRD11 SDCCAG8 F13B PPARG NDUFA2 CSGALNACT1 SF3B4 STXBP1 BCOR HADHA SNCA DNMT3A ARL2BP DSP KIF11 WRN SLC37A4 GNAQ SCN9A AGXT EDNRA AVPR2 CCND1 RYR1 ATP6V0A2 XYLT2 MYL3 NBEAL2 ODAD4 CACNA1C FGF8 RIT1 RLIM GATA1 TFAP2B TMEM43 F9 MEF2A DISP1 CNGA3 GPC3 TCTN3 PRF1 ETV6 SLC29A3 CLCF1 NPHP3 TCF20 IL17RA CANT1 LMNA FREM2 RAG1 FRA16E LMNA LMNA CPLANE1 DLL1 EIF2AK3 AKT1 HSPG2 FAN1 G6PC NFIX MUC5B EWSR1 ZMYND10 ACTG2 SDHC DHODH SGCG PTCH1 CD79A ARL6 COL5A2 FIP1L1 PBX1 LRP5 SMARCA2 SOX9 RPGR SCO1 SPECC1L GINS1 GLRX5 TGFB2 PIK3CD PHOX2B BRAF ALAS2 TCTN1 SLURP1 EBP ECHS1 NF1 ARHGAP31 GATA4 IDH3B CDH2 CSNK2A1 GLI2 PROS1 ALMS1 PEX26 SIX3 FGFR2 ATRX TGFB2 FGF8 PSAP ACAD8 BCHE NPHP1 AP1S1 CHST14 POLG WDFY3 LRIG2 DCX NDP DNASE1 NIPBL POU1F1 CEP41 OPA1 ARMC9 TULP1 SDHA IFIH1 TWIST1 RNF135 GATAD1 ND3 MYRF ND1 BRCA2 APP IFIH1 ND5 FXN FOXE3 APP BRCA1 FIBP NXN PEX3 ATPAF2 CIZ1 EYA4 ALDOA ORAI1 MTAP CD19 COX1 CEP104 LMNA RAI1 GUSB LRP5 GNE NGLY1 TMCO1 SAMD9 SDHA F13A1 POMP GMPPB GUCA1B PKP2 NPHP4 HDAC8 TRAPPC11 ALDH18A1 PUF60 PTCH2 SMAD4 RANBP2 KIAA1549 MPL SCN5A OCLN THBD DOCK3 SUMF1 SNAI2 MYL2 PIK3CA CYTB FAH STAG2 POLR3A KRT83 SEC23B GATA6 FOXC1 MYSM1 SERPINC1 SARS2 GJA1 CDKN2A ABCC8 CPT2 CBS TET2 PRPH2 ZMPSTE24 SDCCAG8 NR3C2 TCF3 RPL11 NKX2-1 NDUFA4 ZMPSTE24 TCAP PACS1 ALG12 KMT2D RPL15 TGFB1 IGF2 CKAP2L CASR CCDC47 GGCX NOTCH1 RRAS2 PDE6H ADCY5 MYOZ2 HLA-DPA1 CHD7 RPGRIP1 RSPH3 GNAQ SELENON RYR1 CLPB PIGN ND3 SMC1A TGFBR1 IDH1 PADI4 CFH HSD3B2 TRNN SUFU MRPL3 FOXF1 KLRC4 COG7 B3GALT6 SMAD6 WWOX USP9X ATP2C1 PDCD10 PIGU KRT5 KCNJ2 NDUFAF6 CITED2 NLRP3 ESCO2 RPL5 ZFPM2 ELN JAK1 ZFPM2 NR2F2 FGF8 TKT WASHC5 HLA-B CTU2 SETD2 PNPLA2 ATP6V1B2 ARHGEF18 FBN1 JAG1 MEN1 BMPR1A KIAA0753 ATP6V0A2 ZNF423 STK4 GCH1 AKT3 PMS1 C8ORF37 CPN1 RHAG POGZ DSP NDUFS2 F12 JAK2 ATRX TTN BRAT1 FUCA1 CFH ADAR KCNE2 JAK2 NLRP3 CCDC103 CEP120 HBA1 AGK SMARCE1 ERCC5 CLCC1 GPD1L GUCY1A1 PRCD AGGF1 DOLK DCHS1 TRDN CALM1 FSCN2 FAM161A TNNI3K MRPS22 KRIT1 FGFR1 DMXL2 DNAH11 IL17RC FLNA FCGR2C NSMF NAA10 GNAS KDSR KIZ MKKS LDB3 DNAI1 AGTR1 ERCC2 BRF1 IGH LRRK2 GLI2 FGG SNRPB IL10 FZD2 QRSL1 SLC4A1 STEAP3 SLC26A2 OFD1 GJB3 PEX13 SCN9A MCTP2 ANK2 FGF8 PIK3R1 EP300 SCNN1B CASP8 KCNE5 EFTUD2 RP1L1 SCN1B PLVAP FOXH1 IMPG2 SDHAF1 DNAAF1 CDH23 TDGF1 IL2RA MAP3K7 COL4A4 FGA PDE3A USP8 REN AMER1 CC2D2A TERT GJB3 ZIC2 ARID1A WDR35 PRKAR1A PRDM16 RIT1 BGN WIPF1 GNA11 SF3B4 F2 NF2 SLC29A3 SLC19A3 FAS RNASEH2A DYNC2I1 TGIF1 FLNA DCLRE1C SMAD4 BBS1 PALB2 GTF2IRD1 CFI TET2 KDR FADD APOA1 COX7B AKT2 TAB2 PDX1 SLC39A4 MYLK SMC3 FKRP SLC29A3 PLIN1 FLNA FOXE1 SPARC GBA GATA3 COL6A2 PCARE KLF13 BANF1 ESCO2 MYH11 SCN4A FBN2 DCAF17 RTEL1 RPGRIP1L LIPC SBDS KRT9 HMCN1 CACNA1D FANCE KRAS TLR4 ETHE1 GPD1L PEX19 XPR1 TRNC FANCA ODAD2 NEK9 FBN1 IFNG SDHD ANTXR1 ELANE CXCR4 COL4A3 CENPE BBS4 DMD C4A IFT88 UROS KANSL1 MMP1 FMR1 KRT16 F13A1 PCCB TSC2 NR3C1 PRPF8 SETBP1 USB1 LAMP2 TET2 BPGM MVK NKX2-1 SLC17A5 CTCF PNKP DDX3X RRM2B GFI1 RNF113A CLIC2 MAF DDC ALG9 KAT8 TMEM237 NEBL STK11 IL10 SLC7A7 MED12 CDKN2B LONP1 ERBB3 RET JAK3 PEX10 OTX2 SYNE2 AICDA GLB1 GTF2H5 ZFPM2 PLOD1 RPS28 PRDM16 COL3A1 IKBKG ITGA3 ITPA CIITA GBA DOCK6 ACTC1 JAK2 KIT CDC45 CARD11 GALE CFAP298 PEX5 DCC COL7A1 TRPM4 WNT5A SHANK3 MTHFR TRAF7 MAP2K2 LIMK1 NRAS HLA-DRB1 EXT2 LMNA FBN1 SOS2 HBB PSAT1 FANCI MITF TNNI3 SALL1 PAX8 TARS1 NSD2 DNAAF3 DAXX DYNC2LI1 NLRP3 NPHP3 NPC1 HJV TNFRSF1A HLA-DPB1 SYNE2 DSG4 RINT1 LZTR1 SLC25A11 COL1A2 TRAF3IP1 TRPM4 MPIG6B VHL POMK GANAB TCAP NLRC4 EIF2AK4 RPSA GPR35 POMT2 CLRN1 LRP2 STAT5B FBXW11 NLRP3 CHRNA7 KRAS FCGR2A KIAA1109 CNGB3 SELENOI MYOC ATP8B1 CYBA ERCC6 SF3B1 PLN GNA14 FOXH1 MDM2 CAT TCF4 THOC6 PET100 ACTG1 ITGB3 NOTCH2NLC IL12RB1 CYP11B2 ATP6V0A2 CACNA1D PITX2 PKLR TCOF1 GAS1 ERCC4 PLN STAG2 TRNH KIF1B PTPN22 SPTA1 POMGNT1 HGSNAT F10 SLC2A1 ERCC3 IDUA HLA-B COL5A2 GM2A NDUFV2 TWIST1 MIPEP EFEMP2 NCF1 ADA2 RPS15A HESX1 KMT2A F2 IL2RB ERCC4 DISP1 CSRP3 ATP6AP2 BCR RBM10 PEX1 FGFR2 WNT3 COL1A1 AP1B1 GATA1 NR5A1 ACTA1 HCRT PDGFRB FASLG SMAD4 DMPK CYSLTR2 ROM1 CCDC103 CACNA2D1 HBA2 PEX5 ATAD3A FGF8 CCDC39 NEU1 COQ2 POU3F4 LMNA RPS15A NKX2-5 HBA2 PSAP HSD11B2 GJB4 ITGB3 MDH2 CA4 RP9 BBS2 PITX2 KCNE3 PALB2 RAF1 KCNN4 LMBR1 CFB WDR11 PEX2 WAC ARL6IP6 GNAS PLEC FLNA TCIRG1 TP63 NF1 SON PIK3CA NKX2-5 LMNA CHD7 CUL3 NMNAT1 KCND3 SLC4A1 BCS1L CAPN5 CD55 TTC37 LONP1 SHOC2 GJA8 HTRA1 GPC6 ABCA3 STK36 LMNA OFD1 PALB2 TECRL HLA-A SURF1 FGFR2 FMR1 APOB TFAP2A AP3D1 ACTA2 DHPS PEX6 AGT ZMYND10 SOX18 TGM5 TPM2 REST ZIC2 SNRNP200 SC5D PTEN TBX22 CTCF PRRX1 RAC2 CTLA4 PLP1 MEGF8 FGFR2 ZIC2 TAF2 EFL1 TTC8 DDB2 B9D2 PEX16 EFEMP2 PTEN PCNT NEUROG3 CFHR1 PDSS2 PIK3R2 FGFR2 SPIB TGFB3 FANCB USH2A TNXB MYH7 PRPH2 SCNN1G UMPS ACVR2B TRAPPC4 XPNPEP2 PTCH1 LEMD3 CRLF1 TNFRSF13B MYH8 COL1A2 MYPN MCIDAS F2 GNAT2 YWHAE CYP11B2 IVNS1ABP NSUN2 CHRM3 COL1A2 SLC25A4 STIM1 DHCR7 KRAS TMC8 RBM10 DPH1 LYZ KDM6B FAM13A MFAP5 CWC27 TBX3 MRAS MAN2B1 KRAS KRAS SH2B1 ANO5 TUB CDH2 CYP27A1 CBS NODAL IFT122 ACAT1 RBM20 NDUFB3 ROR2 COL4A1 MUC5B USP8 LIPN RTTN CRPPA SMAD4 HBG1 MED25 CCND2 SELENON COG4 RREB1 JUP PROP1 CEP57 DLL4 SH3PXD2B DES CEP41 TBX1 CEP164 RNASEH1 ADCY5 ERMARD NRAS GJA1 GPIHBP1 ZNF408 COLGALT1 PTEN AMMECR1 SDHC ATM DPH1 SLC25A4 AKT1 CYP21A2 FLNA NR2F2 TBX5 GCDH ATP2C1 STAG2 MED13 GATA6 GALNS ACTC1 IDH2 UNG MRPS16 CTLA4 KAT6B SMAD4 CLCN7 POLA1 SCN2A HBG2 RPS7 TNNI3 MMP21 GLB1 SCN4B NDUFS3 PIGL AKAP9 WDPCP ADA2 COL4A1 KAT6B VANGL2 SCN3B ACTL6B EED GLI3 PLCG2 ADAMTSL4 FGFR1 BRIP1 ZNF513 KCNE1 ERCC3 PTPN11 TRPV3 PRKCD FBN1 RIN2 CD79B ALOX5AP TECRL ABHD5 CD46 RAI1 MYT1L GP6 COL3A1 MAP3K7 ARID2 HDAC8 SPATA5 KAT6A BCOR DGUOK CACNA1C DVL3 BCL10 ABCB4 TP63 HLCS TRPS1 NEU1 ACADL BMPR1A RSPO2 NADSYN1 POLG2 GDF6 MAX SOX2 TRIP11 ARID1B SLFN14 POLG2 GAA UBE3A FKTN SNTA1 FGG CSPP1 TERT GDF6 ARFGEF2 DES UBE2T GALNT3 CSRP3 KYNU HCCS KCNMB1 HMGA2 LMNA CPT2 TMPO TTC7A SLC25A24 SKI STAT3 NRAS TTC12 RPS24 INPP5E BPTF FLNA TFAP2A RPL35 SLC2A10 RPS17 SDHA CYP17A1 INPP5E NLRP3 CCDC40 ASAH1 POLR1A CTNND2 MYH3 MVK NOS3 BRAF ATRX KCNJ5 APRT PRPF31 PIEZO2 MED13L KCNQ1OT1 NDUFS8 DTNA CCM2 PHKA2 NKX2-5 GJA5 POU2AF1 SNAP29 PAFAH1B1 FOXH1 SLC40A1 SULT2B1 HADH MBTPS2 FLII FN1 NRL PDE6G RBP3 PHKG2 ARPC1B CDKL5 SMARCA4 SP110 HCN4 TCTN2 ITPR1 FANCA PMM2 RASA1 ROR2 COX3 CEP290 ALPL POLG STAT3 DNMT3B PEX26 MGP ABCC9 OTX2 DLL1 KCNE1 SHH COQ2 ABCA1 EP300 DDRGK1 CLIC2 ITGA7 SCN9A IRF2BP2 CCNQ TNNC1 RIN2 ADGRE2 ALKBH8 NF1 CPOX OTC DHCR24 ARID1B MAK RMRP LIPT1 NEK10 SGCA FGFR2 MICOS13 SOX5 NEXN SYNE1 BIN1 TGM1 PSTPIP1 COL7A1 FOXE3 EDN3 IGF2 H19-ICR B3GLCT TUBB MYCN TNFSF12 PIK3R1 RASA1 F5 SARDH GSN SH2B3 DSP KIAA0319L SLC52A2 CDKN1B LIPA TELO2 SSR4 GJC2 DACT1 TRPM4 GYG1 FIBP RBM8A ZIC2 CDC42 LRRC56 LMNA TNNT2 DNAI2 NONO FAT4 PPCS ERCC8 USP18 VWF SALL4 PQBP1 GBA GJB2 GATA4 PDE6B GATA4 MYH11 HFE EED CDON PROC STRADA TTR SLC26A2 BMP2 WWOX BVES C8ORF37 CALM3 TPM2 CITED2 PTEN DYNC2I2 COX3 SNRPB MTO1 DHX37 SLX4 LOX ACTA1 IRF8 XRCC4 TRIP13 CDC73 ODAD3 DNAAF2 MANBA CFTR SCNN1A PPP2R5D WARS2 CCDC39 PKD2 TNNT2 PRKCH SMAD9 RYR1 ELOVL4 JMJD1C TRNT1 VPS33A ODAD1 ZMIZ1 CREBBP DIS3L2 AGA SETX SGCD BAP1 COX2 SLC25A20 KIAA0586 GTF2I POT1 EFTUD2 ALG9 KIF3B TRDN LMNA ACTG1 ALX4 COX1 ACAD8 ATP6 TRPC6 LMNA LAMB2 ERCC4 GTPBP3 PDE6A HPS6 GATA1 OTUD6B COQ7 LRP5 BEST1 MPI CALR CCM2 HBB VPS33A GDF3 CYP11B2 OTC SEC23B RPE65 ANKRD26 TET2 SCNN1A RLBP1 EPG5 DSP POLR1C SIX3 KRT5 GLA MTHFR HBB RPL35A ND1 FGG SDHD MARS2 CYP26C1 ANTXR1 APOB HLA-B TRMT10C ATP6V1E1 TRNE UVSSA CPOX CDHR1 SLC20A2 RBCK1 TWNK AKAP9 APOC2 NDUFAF3 SAA1 HBA2 KCNQ2 TAF1A NBAS DBH SMAD6 TEK EXT2 ABCC6 FZD4 NKX2-6 RAG1 LIPT1 F8 BAP1 NCAPG2 YY1 LPL TMEM107 DUSP6 SLC25A3 AHI1 PRKACA PNPLA6 RHOH FGFR1 PLAGL1 SNCA CREBBP SCN5A MYH11 EVC2 LDB3 GBA PRDM5 GATA6 WFS1 ND4 NDP SLC25A26 GBA SLC19A2 ND1 NEXN RARB NDUFAF1 ATP7A F5 DCHS1 GJA1 APOE ELN GNAS MAF PLCG2 HLA-DQB1 HBB TCIRG1 RAF1 EXTL3 ATP11A ND6 PCCA TPI1 SOX10 KIT NPPA APP GNAI3 NKX2-5 VAC14 PDGFB BIN1 LIPA TGFBR2 SPTA1 NDUFS7 FOXJ1 NEK1 RPL10 SCNN1B ECE1 KIT ATP7A FSHR CYBC1 SEMA3A SMARCD1 PRKAR1A JAK3 CD109 SPTB PCGF2 LIG4 FERMT1 MYH7 LZTFL1 SGCD IRF5 PTCH1 CA2 SYNE1 NTRK1 CHRNA1 FGA RSPRY1 KCNJ8 FRAS1 ERCC6 RNASEH2B P2RY11 NEU1 GP1BA MYH7 BTNL2 NDUFA9 KIF23 ND2 HSPA9 PIGA MEIS2 CACNA1S DNAH11 GCLC ACVRL1 POMT1 AGTR1 DMD POLG MSL3 PLCB3 GP1BB CAV1 KCNH2 TPP2 FARSB UCP2 IRF6 SALL4 PACS1 GLI2 AHI1 SHOC2 FUZ MAP3K1 MYH6 SRP54 IGHM CRKL C1QBP IL10RA COX15 SLC12A3 DLL3 RPS26 FERMT3 LOX RBPJ RB1 ZBTB16 LCAT CYP11B1 GIGYF2 SFTPC HSD3B7 IL12A-AS1 RECQL4 SIK3 MKKS SFTPA2 ABCA1 BNC2 IFT172 LMX1B SDHB SCARB2 RNF6 PARS2 XYLT1 CALR GP1BA GLI1 CRELD1 FGFR3 FANCF RAF1 SFTPC MPL PRKCSH ODC1 ALG10B IARS2 GPC6 GJA1 BAZ1B BRAF METTL5 JAK2 ATP6 DNAAF3 WDR19 CALM2 EBP STOX1 ICOS CALM2 DCTN1 SIX3 FKRP TMEM231 DNASE1L3 TTN SPRY2 TMEM70 FASTKD2 KIAA0586 ATF6 TRNF PLEKHM1 POU6F2 MYPN NBEAL2 SRD5A3 LRRC6 MIR17HG FGA KCNE1 B2M COG4 NHP2 CCDC22 TBC1D24 IGF2 KCNA5 CORIN TNXB MYT1L RAG2 MYL4 NDUFS8 DCAF17 PRKG1 NLRP3 FGA FOXRED1 MPLKIP TLL1 HESX1 NSMCE3 CCDC22 HADHB RPL35A EXT2 SCN1B NDUFB10 VPS35 NDUFS4 C8ORF37 ACTA1 HBB GABRD TGFBR2 APC BRCA1 AIP SNX14 SGO1 NDNF SCN5A NOTCH1 SDHD NCF2 FOXRED1 KIF5A HRAS TRNS2 ADNP PEX16 SDHD IL2RG MEFV TULP1 ATM ODAD3 RYR1 NDUFB11 CYBC1 SMPD1 CDON FIG4 DMD TREX1 ELP1 C2CD3 TWNK PNP BACH2 CRX TXNL4A CCDC115 KISS1R FUT8 ROM1 SUGCT PPA2 FAS CCNQ ERCC2 COG6 CBL PIGL GPC4 COG8 DSP NOD2 ODAD2 RAI1 CBL TGFBR2 CC2D2A MALT1 COL4A3 KDM1A SIK1 TAB2 TMEM237 SEMA4A PPARG SLC12A1 SLC37A4 VPS13A MYH7 TERT FAS TNFRSF11A COL1A2 ATOH7 DSG2 DZIP1L BCORL1 COPA AKT1 FRAS1 NSD1 LTBP4 YARS2 NPM1 DLEC1 ND6 TACR3 TMEM237 PML ND2 POLG IL12B MYMK NDE1 DISP1 ND5 TTC8 RPS10 KDM3B NODAL KIT PLG INTU CD46 HSPG2 AIPL1 RGR RSPH9 TERC CD19 CEP55 NOS3 RDH5 KCNH1 VHL GPR101 PMS2 HSD11B2 MCCC2 ANAPC1 B9D1 PGM1 TTN SLC26A3 IFT140 RNU4ATAC LMAN1 CRYAB GNS GNAO1 ABCC8 PLEC SDHB SMARCA4 RPS19 GPR101 RSPH4A AEBP1 RNASEH2C OBSL1 PEX1 LAMA4 PRPH2 FANCB ND2 POMT1 LIPA SPTB TERC CTNNB1 NR3C2 PDGFRA NTRK1 KCTD1 ANGPTL6 ASS1 ENPP1 SH3PXD2B IL2RG KRT14 RET PTGIS MED13L TRIP11 PAH PRKAR1A CNBP KCNQ1 COL2A1 CHN1 ELAC2 COG2 TMEM43 FLT4 RYR2 DBH FBXL4 ATP5F1D UNC13D SOX10 CACNA1S KCNH1 RNU4ATAC FOXH1 CDH23 PIEZO1 SOX4 JAK2 COL1A1 GTF2E2 FOXC2 NF1 PRF1 GPI GFI1B POLG AKAP10 DVL3 IGSF3 PSTPIP1 CRYAB RHO DGCR8 SMCHD1 MLH3 SIN3A SCN5A ERCC2 GATA4 SPINK5 FANCL NDUFA1 NOTCH1 NAGLU DLD STX3 MCCC1 ND2 GNPTG SDHB NEK1 POLH TMEM67 BRAF DSG2 MAN2B1 ARSA CALR HJV BRAF MYLK COL4A5 HADHB PAX3 SEMA3E RASGRP1 KIF7 LYST TKT H19 XIAP APP LRRC56 CITED2 COL4A1 FKBP14 WDPCP MCM4 RAG2 FAM149B1 PEX19 PHGDH PRKAG2 TNFRSF13C RPL26 SBDS POMT2 COL6A1 KIF7 MEFV PTEN TGFBR2 SLC2A10 OSGEP ELOVL4 SVBP VPS13B FTO RNASEH1 ALB COL1A1 GAS1 GATA4 NT5E PLN KRT14 HIC1 ANKRD11 SURF1 SIX6 RRM2B TACO1 TRNK ZFP57 VANGL1 LMNA GNPTAB FANCG TBX6 RAD51C ATN1 ELANE CASK PIGO SHH MYPN F8 KIF20A ARHGAP31 IDH2 MERTK KCNQ1 RAF1 SCNN1A PRKAR1A SIX3 CYP27A1 MUC1 DST MITF SMARCB1 RPL27 NKAP TOR1A RAI1 TRNV RBP4 RB1 DNAAF4 HPSE2 TCIRG1 FAT4 CYP3A5 CALCRL CSF2RB ALDH18A1 BMPR1A SAMD9 LPL CLDN1 NFKB2 MYD88 SELENON POLR1D STAT2 SFTPA1 TPM1 SKIV2L COL18A1 LAT TPM1 SKI KCNJ5 SEC23A LORICRIN XPC MTFMT SGCD GAS1 ATP6 STAC3 TRIP4 KCNJ2 ARX FLNA TBX1 ABCA3 GATA1 PKHD1 ZAP70 HTRA2 PAX3 VIPAS39 DYRK1A BCOR RAB23 FLCN CYP24A1 FGF23 CHRNG ACE NSD1 PIGQ TSR2 IL12A SGCB ALDH18A1 CDKN1A CCN2 ARL3 DKC1 FBN2 CASQ2 BAP1 ALX1 DSE SCN11A ROR2 HAVCR2 NDUFV2 DGUOK RIPK4 COQ2 TAB2 RPL10 PRKCD F2 CLCN2 C1S PEX7 SLC22A5 SH2B3 BUB3 GAS8 NTNG1 GNAS CYP17A1 RPGRIP1 LDLRAP1 TMEM127 ARL3 KRT1 DYNC2H1 TREX1 HOXA1 NR3C1 FGB LCAT KCNE5 PLOD3 COA3 SCNN1G TGFB3 SDHAF2 SDHD SLC39A13 STAT1 RDH12 PHOX2B TMEM237 FBN1 NRXN1 ABL1 CHD7 GP9 CTSA ERCC6 MMP2 CDAN1 CERKL PQBP1 NDUFS7 CYP11A1 LIMS2 XPA PDGFRA OFD1 VHL CDK13 FLNC LRBA TTC8 GDF2 TNNC1 PRG4 LAMC2 MMUT TRAF3IP2 KCNQ1 KATNIP FANCD2 GBA PYGL APP CR2 PIK3R2 IRF5 VPS45 PDGFRB CYP11A1 TRNQ RRM2B DSP CTSB RFC2 BCL11B NCF1 ALG1 CD3D PRCD STEAP3 MEOX1 SLC7A14 WT1 TANGO2 TLL1 TRNS1 SPTB MLYCD CASQ2 CTSA CST3 DDX59 NAGS TMEM260 ETHE1 NLRP3 PEX19 RAD21 TAPT1 MYH6 SLC7A7 INS MED12 CENPF HLA-DRB1 MAP2K1 NDUFAF4 NFIA PPA2 AFF4 POLE SMG9 MGME1 BMP2 RARA EOGT DYSF PTH1R PTH1R CACNA2D1 CBL ACTA2 GJB4 NAXD NDUFS4 NPM1 PTEN SMAD4 MTTP SOX3 TMEM216 CASK CEP290 FGA SP7 NOTCH1 PKD1L1 ACTA2 AIRE PHKG2 NDUFB8 WFS1 IFIH1 KRAS PEX1 PEX12 FBP1 CYLD VCL ZNF423 BRCC3 SLC35A1 ARSB MMP1 COLQ AGBL5 RPL27 WDR1 RHAG APOE SCNN1B AVPR2 OTULIN PIK3CA LMNA MID1 GPC3 PALLD GAS1 SOS1 AQP5 GALC MYH9 ABCC6 CRTAP RERE MKS1 PRKCSH CACNA1C KBTBD13 MKS1 ACVRL1 MPL FAT4 DOLK RIPK1 TGM5 FOXE3 DEAF1 NDUFAF8 HADHA CALM1 MRPS14 PSAP PEX12 ITGA2B PRDM6 ABCA4 LRP5 TNFRSF13B POMT2 PDE4D GRIP1 PIGW TGIF1 CLCN7 LAMP2 SMC3 MECP2 TCTN3 ATAD3A JAG1 PET100 MAPT RANGRF IL12A KRT18 TDGF1 GUCY1A1 CERKL TRNW STRADA PROS1 CDSN TGIF1 PRKAR1A ZNF687 NOTCH3 EHMT1 NOS1AP TGDS POR ANO10 TCIRG1 SDHB SPAG1 ATP6AP1 LFNG INSR CEP290 LRP1 IDUA WDR26 KRAS PHYH SDHB WNT5A SCNN1B CISD2 TRIM28 CFAP53 KRT5 POLR3A RSPH1 AKR1D1 FGFR1 TFR2 LIG4 IL7R TPM3 RMRP GNB5 DNAAF5 NXN GP1BB DNAH1 ENG KDM6A IQCB1 MINPP1 TBX20 HES7 LMOD1 TRNT GLIS3 FOXH1 TRNL1 DNAH9 DNAJC13 ALX4 ANTXR2 PRPF4 PLD1 GSN SMCHD1 RP2 ENPP1 SMARCB1 VHL TOPORS MLXIPL NKX2-5 HLA-DRB1 ADK MYH7 DNAH5 CPS1 TF CACNB2 EYA4 ND1 CPLX1 ITGB3 RYR1 CHST3 CYBB DPF2 BBS2 TP63 ERCC8 KRAS CDK10 SUFU MSX2 PEX13 GAS1 RPGRIP1L SFTPB DSP FBN1 ASCL1 GATA5 FBLN5 ISG15 GJA5 UFD1 TNFSF11 SCNN1B SERPINA6 NKX2-5 FHL1 TSC1 TXNRD2 APC PIK3CA YY1AP1 MMP2 CCDC65 GNB5 GATA6 ARID1A CACNA1S WAS SCNN1G NDUFA11 RAD21 KRT1 RAB27A MSH2 HLA-DRB1 CYP7B1 MAFB CDON PDCD10 ALX3 TBX1 TMEM67 INPP5E MYORG CCBE1 ITK LRP2 NPHP1 SCNN1A NPHP3 SCN4B PIK3C2A TMTC3 REEP6 GATA6 ELN TTC37 BTK RS1 RLIM IL7R ISCU HLA-DRB1 ACTB POMT1 LHX4 PSMB8 SAG CALM2 FANCE FCGR2A ADAMTS10 AKT3 CFHR3 RAD21 GPC4 COL11A1 UROS RAC2 CD19 NAGA CP ARL6 AIP CPT1A INVS NFIX FANCI FBN1 BAG3 DISP1 PRDM16 DNAAF5 FLRT3 NF1 FGD1 AIRE TNNC1 WNK1 PIK3CA SMARCE1 WRN BCR KCNQ1 SRCAP GP1BA TRNS2 SDHB GJA1 PCNT MRAS SGCB CASR DPM1 IDUA TOP3A ZAP70 MEN1 CYTB MYH7 NOD2 GNE ZEB2 ATP5F1E NODAL F13B LETM1 USP9X KRAS MAFB RORC PSMB9 PLAU FLT4 WNT4 TBCK ZNF469 FMR1 COX6B1 UBAC2 NKX2-5 LBR NME8 TRAC HEXA CRB2 PEX1 SLC26A2 HABP2 RERE ALMS1 AQP2 SERPING1 FOXP1 EYS RUNX1 TRNK FLT4 ASAH1 SNTA1 ACTC1 ARID1B HELLPAR KRAS DGCR2 MIF PROKR2 ABCA1 CCBE1 TSPYL1 MOG BBS5 TRPM4 STX11 IRAK1 CPLANE1 AAAS EVC PEX6 DDR2 ECE1 TMC6 FGFR2 PPP2CA RET MKKS B3GAT3 RAG2 C1R HYMAI PIBF1 TERT HMGCL ANTXR1 NDUFA11 IRX5 BTK HSD17B10 CAV3 GNAI2 RPS6KA3 CYP11B2 FTL CITED2 NDUFA12 SDHD TTN CSPP1 KCNJ2 KNSTRN TMEM216 CDON BRAF FLAD1 FZD4 ICOS TMEM126A KCNN4 FHL1 NNT PPP1CB DHDDS BMPR2 NDUFB11 ATAD3A STN1 DSC2 MYH7 NOTCH3 ERCC4 GPC4 IL36RN CNGA1 PEX16 PTPN22 NDUFA2 GATA4 GREM1 HPGD COX7B PSEN2 COL1A1 THOC2 DCLRE1C CHCHD2 GLB1 BTNL2 FLNC CCND1 TNNT2 DNAJC21 CAV1 PCCA TSC1 TRNK MEN1 DMD TNFRSF13C EPHB2 ADAMTS2 HMBS ADA2 SLC4A1 CFTR CAVIN1 C4A GANAB GBA NKX2-5 WT1 FKBP14 CLCNKB PPP1R15B SOX18 CCR6 IFNGR1 BSCL2 TCIRG1 DDX11 STAT4 PDE8B CHST3 AMER1 TMEM216 TJP2 NDUFS1 PDGFB ARVCF PROC NFKB1 MTFMT PGAP2 SLC26A2 DNM2 RECQL4 MKS1 KCNJ11 EHMT1 POLG XRCC2 KLHL7 FH RECQL4 NCF2 RPS6KA3 GGCX NDUFS8 CD28 MYH9 NT5E SLC25A20 SDHD NDUFS2 KRIT1 COL3A1 WHCR ND4L CD2AP MAP3K7 JPH2 GATA2 TRNQ LIAS RET ESCO2 SFTPB EXT1 SPEG CYP11B1 TET2 BEST1 MBTPS2 COL2A1 NF1 OFD1 ANOS1 PHGDH HRAS TKFC TALDO1 TRIM28 TCTN2 GATA4 CD79B KDM6A TRIM8 FBN1 SLC25A13 FDFT1 POLD1 MAP2K2 NFE2L2 PIK3R2 MCFD2 CAV1 DOLK COX3 SMPD1 NLRC4 ECHS1 PIK3C2A COX8A GBA DNAJC19 PIK3CD NDUFB11 ENG ATP6 ALOXE3 ND6 DPM3 PDE6D ITGB3 SRP54 SCYL1 SOX11 EBP ERCC6 F11 IL17RD SLC30A10 EPHB4 COX2 CHRM3 MVK SDHC GREB1L DNAL1 CRB1 SH2D1A PEX3 CHRNA7 GLRX5 MAP2K2 GNE ACAD9 CD27 FN1 BSCL2 LTBP2 HNRNPU NEUROD2 GATA5 SOX9 ELN KLHL7 GDF1 MAX TDP2 LTBP3 CASQ2 ADAT3 TBX20 STAG1 STAT4 ADA2 FBN1 SMAD3 FGFR2 TCOF1 GMPPB NDUFS2 FBLN5 KDM6A RYR2 MAD2L2 SPRY4 TACO1 CLN3 MPLKIP RPGRIP1L SCNN1A RPGR RFWD3 HGSNAT CCND1 PROS1 ERCC8 UPF3B CD81 CARD9 LRRC6 PORCN MED12 DNAI1 IDH3A PKP2 SCN1B CTBP1 TNFRSF1A BRCA2 TBX1 CHRNA3 MPL STX16 ERCC1 RAG1 TREX1 SMPD1 ALG8 TBXA2R CHD7 ELN HADHA A2ML1 ENG STAMBP SDHC NEK8 PDE3A CFI ELP1 SALL4 APOA5 ESPN TBL2 EMG1 WT1 SRCAP JUP DMPK PEX5 DLD PPARG DYNC2I1 CASP10 IDS LTBP2 KDM5B IRF8 GBA TRNS1 DISP1 TRNE IVD ELN SNX10 RNASEH2A LAMA4 TRIO NDUFA10 SLC25A22 ARX LDB3 GNPTAB ERCC6 CACNA1C ALOXE3 KCNH2 SRY PIGO P2RY12 FGFR3 ABCC6 LEMD3 CLEC7A WDR37 DNAAF2 NOTCH2 CAV3 FOXRED1 ZIC3 EXT1 TNFSF15 PIGA MAP3K20 FBN1 KCTD1 DMRT3 CFAP300 PIEZO2 SLC25A24 CTNNB1 SCN10A TNNT2 GPC1 RYR2 SOX2 PSEN1 DNAAF6 FOXC2 INPPL1 ITGA8 EMD NID1 SERPIND1 IFT172 GJB6 PTF1A HBA1 MYC COL11A2 PDE6A PRKCD HYLS1 TNNI3 LYST BTD KCNQ1 EZH2 MED25 SDHC CTLA4 ADD1 RYR1 MNX1 AGL NDUFAF4 RLBP1 CD244 NAGA TUBB GATA4 PTPN11 AIP SLC25A4 FKRP FHL1 EPG5 NRAS PRKAR1A HIBCH TREX1 BCOR KCNJ1 FBP1 NEB SLC35A1 DNMT3A PDGFB MRAP PTPN14 RFWD3 CDH23 RPL15 FGFR1 RNF113A NODAL BICC1 GATA1 TTC8 GBA CST3 STRA6 RAC1 WRAP53 NR0B1 PIGM TMEM70 UQCRFS1 NDUFV1 CTSH PYGM ARID2 SEC23A IRF8 VHL BLM ACTA1 CD40LG ICOS CAV3 RPS27 CFHR3 PTEN ABCC9 COX14 THPO TDGF1 GGCX MED13L KIF7 NPHP1 NDUFA13 SELENOI PIEZO1 CYTB RP1 DDX6 BRAF WDPCP HBB ZIC3 MRPL44 NOP10 WNT10A FLNA ERCC2 CALR FHL1 ACD NEB HABP2 DPP6 PHF21A MYBPC3 NIPBL ITGA2 HYOU1 EGFR ACADS DES TPM3 RPL10 MTRR PGM3 KCNQ1 MTTP IL7R STAG2 STXBP1 PSMD12 FLI1 CITED2 TMEM43 SMAD4 PRKACG IFT81 HLA-B SPINK5 KCNQ1 RNASEH2C SP110 RBM8A TIMMDC1 ATIC BAG3 SLC39A13 IGH TOP3A DPP9 TMEM231 DCLRE1C SDHD GJA5 TGFBR1 TNFRSF1B WARS2 TNNI3 GTPBP3 ITGA2B TXNL4A AP3B1 TCTN3 GPC3 DVL1 FLNB KCNQ1 TTN NDUFAF3 AGA BBS10 FOXP3 KYNU COG5 FN1 PCSK9 TRMU SOX10 DNAH1 KCNJ18 OSTM1 HADHA AKT1 FKTN BBS2 ACADVL RPL26 DISP1 RNF213 CDKN1C SH2B3 GLI2 GLI2 COL4A2 EDN1 CYP1B1 TSC1 JUP TRRAP GATAD1 CHST14 IL23R BOLA3 MGP PLIN1 CFAP300 STIM1 SCN5A UMPS CTC1 ZMIZ1 SFTPC XPC CHD4 ND6 FRG1 ANK1 FKTN STK11 SPEG AK2 MASP1 GNAQ MYCN MYH11 LRP5 SOX3 PHYH HFE CDC42 TASP1 FOXA2 DGCR6 TEK HOXD13 B3GALT6 RPL5 SLC39A4 KAT6B NEK2 ACTA1 PRKAG2 SMN1 NLRP12 GDNF CHKB ABCG8 PEX10 MVK COG1 TP63 IFT27 SPEF2 COL2A1 ABCA4 ND4 CFI LRAT ATP5MD RAD51C MLX SEC23B FUCA1 PKDCC FGB HPS4 PIGT JAK2 ALG1 AHCY FOXC1 SUZ12 PIK3CA VCL DOCK8 DNAH9 LOXL1 COX20 HCN4 KLHL41 RAI1 RMND1 PIK3CA HRAS AFF4 ERCC2 DHX38 PTPN11 KCNE2 IFT172 ND1 RIPPLY2 NDUFAF6 MYBPC3 GGCX FAM111A SPP1 NSDHL ZFPM2 NDUFAF2 TBX20 VCL SPECC1L CPT2 GYS1 CLCN7 PTCH1 LEP LBR IGLL1 NOTCH3 PPCS SCO2 PTCH1 OTUD6B PIK3CA NKX2-6 PORCN FLNA TK2 FLNC SLCO2A1 FAH XIAP HES7 GNAS MEGF8 CD3E ABCB6 KCNJ8 EPCAM ATP6V1A TDGF1 VWF PEX6 MAT2A NFIX PSMD12 SCN3B ZNF462 RNF168 TBX5 FYB1 CYB561 ATM NAA10 COL5A1 ATRX MPL SERPING1 ATP8 ACAD9 PTEN SLC12A3 SLC25A3 PKP1 CPT1A TGIF1 ADA PSMD12 UBR1 PIGN BCOR NEK9 IKZF1 AGT TSC2 LEPR WIPI2 RASA2 CARS1 EPB42 LTBP4 BTK STIM1 INF2 APOA1 RPS20 RUNX1 KCNA1 TNNT2 WT1 NDUFS2 COMT CDC73 SBDS SCNN1G ARL2BP POLH GLA CTSB CLCN7 BBS1 PIGV LAMB3 MTHFR TPM2 ANK1 STXBP2 CSRP3 ACTB PTCH1 CPOX C12ORF57 IL1RN TP53 CCDC28B SNX10 TGFB1 GP1BB ALPK3 SALL1 VPS13B NDUFAF5 STN1 HAMP XRCC4 PIGT NLRP1 ABCC9 SOX18 ELMO2 ACP5 TWIST1 FLNA TRIM37 RPL31 FLNB SRD5A3 EPB41 SLC4A1 DMD WNT4 SERPINC1 CCN2 HNRNPA2B1 RET SMAD3 RP1L1 SDHB TREX1 CNGA1 HSPG2 AARS2 ATP7A MSH6 F5 TALDO1 RPE65 C2CD3 GLI3 FGFR1 SIN3A EYS SRP54 TINF2 BUB1 ARL6 KCNE1 AHI1 SMAD4 SHPK ATP7B ERCC3 TXNRD2 SCN5A SELENON GATA6 WAS ACSL4 MAPK1 F7 KCNJ11 DOCK6 YY1AP1 PDE6C PIK3CA MEFV DLL1 FLI1 CCR1 TRDN COQ2 COX4I2 FSCN2 HIRA JAM2 KRT2 TBX1 GATC NHLRC2 ACADVL COQ4 PPARG CTLA4 GJA5 MKS1 LEMD3 HLA-DRB1 PYCR1 ADAMTS10 IGF1R CHST3 KRT10 SNRNP200 CACNB2 TBX3 PSAP RAF1 COL5A1 NABP1 FBN1 PRKAR1A NUMA1 FECH MYO18B DLL4 COL7A1 DDB2 TBX1 BMP2 FCGR2B SIX3 CALM3 SDHC LIG4 COA5 LAMA3 GMPPB MTOR NOTCH2 KAT6A BBS12 GNAQ NUP155 TP53 SCN1B SERPING1 SYT1 NPHP1 BMPR1A EGFR ABCC8 LYST LRP5 RNF125 GATA6 SCNN1A FGF8 PKD1 BBS7 BIRC3 ELN KMT2D DIS3L2 SMARCAL1 NR2F2 EPHB4 KLF1 IL6 TRNL1 KIF1B GNA11 KCNE2 ARMC5 FADD CCR6 KLHL3 HRAS HYLS1 LMX1B ADA RAG1 ACTN2 BRCA2 RPS17 SIX3 SDHA ABCB11 TNFRSF11B VWF APOE PCARE KYNU SOX4 SETD5 WDR19 TWNK POR TNFSF11 MGAT2 HK1 DNAAF6 IGHM DLX5 THOC6 TFAP2B OTX2 PEX2 SERPINF2 ZNF469 B4GALT7 CACNA1D BBS9 FGG PEX2 SETBP1 HOXA11 LMNA CTNNA3 WT1 KRT14 HYDIN CD40 CD28 SHH MNX1 SEMA4A MECP2 KCNK3 DSE ND6 DDX6 KIT FLNA B3GLCT KRAS ITCH SPAG1 TRDN GJB2 LMNB1 TSPYL1 IDUA DLL1 NDUFS4 ZNF513 FGFR3 KCNQ1 SLC19A2 PPP1CB MYOT RBBP8 TRNS1 CDON PRKACA RAG2 RPL11 KCND3 MAP2K1 MC4R STAR SCYL1 GYPC TBX4 SPATA7 NODAL GABRA3 RARB EDA2R HBB COX3 FGB MBTPS2 TMEM126B SUFU MYOCD NAA10 TSC1 PCCB FAS G6PC3 MS4A1 PROC LMNA KRT5 ZDHHC9 TRAIP RRAS2 MYH7 MED12 NEU1 CYP11B1 ZNF365 RAG1 NDUFA10 IGF2 PROP1 AUTS2 FANCD2 BCL2 TBL1XR1 PEX12 ACTC1 TWNK GATA5 LMNA DCDC2 MRE11 LMNA SEMA3A ABCA1 CNTNAP2 TMEM67 SLC2A1 BCL6 TRMT1 PSEN2 DLL1 LMX1B FOXC1 CNGB1 EMD GAS1 NDUFS3 TRAF7 HCN4 FKTN ANK1 PIGY HESX1 ACTN2 PGAP3 SMOC1 RPS29 TGIF1 PEPD TERT BAG3 ERCC8 FIG4 CDK4 TAF2 NUBPL SAMHD1 RBM20 ACTC1 MAPRE2 MAP3K7 SDHA KPTN KCNH2 ADA PIGY ATP7A IGFBP7 NUP107 C3 PKD1 CCDC141 FBLN5 NFKBIL1 PEX14 DSG2 TNFSF12 RASGRP1 GLI3 SDHA DNAL1 MLH1 MC2R AGPAT2 KCNN3 GMPPA KIT B2M FOS DYRK1A PEX7 KCNJ5 PAM16 EXOC6B ABCC9 SMO TBX1 CDKN1B CHRNG CYP7A1 ACTG2 CALM1 AMMECR1 DPM3 TMEM138 TNNI3 ADNP CYLD PAX6 KCNN3 NDUFV1 SCO2 CFAP221 RGR PKLR TSC2 MSX1 KDSR CD96 SCN2B SCN5A MFAP5 CLIP2 BEST1 PIGT PIGS SCN1B PDSS1 TGDS POR POMT2 CEP120 HNRNPA1 PPOX ATR GAS2L2 FASLG ALOX12B TPM3 IL6 AIP LDLR XRCC2 MTM1 CDKN2C PSEN1 MYH6 STAT3 IFT172 ANKRD1 SFTPA2 ITGA2B ATXN7 PDGFB B9D1 CDON ASXL1 CDKN2B COL3A1 TTPA PDHA1 MAGEL2 INSR PARN MAP1B NRAS NPC2 TP63 PRKG1 MYH7 PKD2 BLNK DIS3L2 DES CSF2RA SMOC1 MYPN ZIC2 SH2B3 HACD1 TBC1D24 AHCY CEP290 PCNA SUFU GPX4 PRPF3 NONO IFT80 EXT2 MYMK PARN FGFR3 SCN5A XPNPEP3 COQ9 TP53 NAGA NAGA TAZ CACNA1H SLC22A4 KCNAB2 USF3 GCK H19 HDAC4 ND5 PTCH1 SCN5A CR2 MYPN TNPO3 F5 F5 MPL HADH SERPINF2 DSP SHH HSD3B7 NDUFB11 AK2 ND4 ASXL1 GLI2 MYOC AHR TNFRSF11A SRSF2 SDHB NUP107 GATA6 TET2 SCN2B CCDC8 CTC1 KITLG NDUFV2 TBX1 IMPDH1 IGBP1 ENPP1 CFAP410 SOX6 PACS2 GPX4 BMPR1A SKI ASXL2 TERC ADAMTS3 TOPORS COG7 PUF60 CAP2 AGPAT2 MRPL12 TTN DVL3 IFT43 DSG1 SOX10 SNIP1 SCNN1G TBX2 GNB3 NGLY1 TF CYBA PIEZO1 SEC63 TMEM126B INTS1 CDIN1 FRG1 GBE1 TRNW RTEL1 PEX5 TET3 PCNA KRT8 MYPN ITCH PNPLA2 FOXP1 GNB5 MYO5B DNAAF1 PEX7 FGFRL1 AMMECR1 SUMF1 MTMR14 TPM1 FGFR2 CREBBP PDE6G NDUFAF2 CEP19 APC NDP HLA-DRB1 TERT PTPRC MC1R SCN10A GDAP1 SMO NAA10 ERCC6 SFTPB CACNA1S EPHB4 KAT6B NDUFB9 RFT1 CFAP298 ACTA2 KIF1B CPT2 IQSEC2 NSMCE2 COA8 DNAJC19 MYLK2 MESP2 ERF WDPCP ZEB2 SIM1 TANC2 LIPC TAZ FBXW11 TPK1
    Protein Mutations 20
    C807T D36Y E138K G20210A G98T H295R I349V I843S K55R L33P M235T N155H Q148H R399G R4E R506Q S49G T1405N V34L Y113H
    SNP 14
    rs1024611 rs11569562 rs11687951 rs13333226 rs2250656 rs28459296 rs3808607 rs4149056 rs4244285 rs6318 rs6841581 rs738409 rs7579240 rs867186
    HP:0000077: Abnormality of the kidney
    Genes 1793
    SMARCA4 H19 RPS19 WT1 ND4 MMUT EDNRB NDUFS6 LPIN2 PGM3 FXYD2 FANCB PGAM2 NTRK1 KCTD1 GP1BB HS6ST1 FANCC RET SEC61A1 SLC6A20 SEC24C PAH NELFA CHN1 APOE PEX11B BLK FGF20 ABCG8 CCDC141 HGD FBXL4 TRIP13 PTH1R SOX10 FEZF1 KCNH1 RNU4ATAC TTC21B CDH23 MCC FOXC2 NF1 EIF2AK3 C1QB RAD51 ERCC4 NPHP1 NSD1 TSC2 SPINK5 FANCL NDUFA1 STX3 EVC RET CFTR PPP2R1A PLCD1 APRT XYLT2 SDHB NEK1 FLNB COQ2 TMEM67 BRAF FBLN5 LZTFL1 ACP5 PAX7 MAP2K1 PUF60 COL4A5 TP63 SEMA3E RASGRP1 TKT SIX1 TTR H19 SPOP DNAJC21 LETM1 COL4A1 WDPCP SFTPC ACTG2 FAM149B1 PEX19 ADCY10 BBS12 GLI3 RPL26 HNF4A RERE NEK8 EYA1 KLLN FANCM WT1 FOXP3 MEFV MYCN UBR1 OSGEP IARS1 PDGFRL FAM20A FLT1 INVS TMEM231 SLC3A1 CPLANE1 HIC1 IFNG SURF1 HLA-DRB1 JAG1 TACO1 ZFP57 VANGL1 GBE1 SALL4 FANCG RAD51C KCNJ10 ATN1 MKS1 DNAJB11 ND5 RPS19 CASK DYNC2H1 H19-ICR F8 C1QC ATP6V0A4 ETFA MUC1 MITF ALG8 INSL3 MST1 PRDX1 TOR1A ADGRG2 TRNV PDGFRB RAB23 HPSE2 FAT4 NDUFA6 CIT PRODH WT1 ALDH18A1 PIGQ RAF1 NPHP4 STAT2 SKIV2L SON KCNJ5 HAAO BUB1B TRIP11 ERAP1 ADAMTSL1 SMC1A ZNF148 NPHS2 TMEM231 ARX PRTN3 PIGN TRNF PKHD1 TDGF1 NDUFB11 B4GAT1 VIPAS39 DYRK1A FLCN CYP24A1 ANKS6 TMEM231 ACE CTH PIGQ TSR2 IL12A CDKN1A IRF5 ERBB3 ROR2 RIPK4 FANCB ZEB2 BBIP1 NUP107 LDLRAP1 PRKCD NCAPD3 PEX7 HSD17B4 BUB3 VPS33B CASR WDR35 LIG4 GNAS PAX2 SDCCAG8 GNA11 FAN1 TMEM127 HPSE2 DYNC2H1 TREX1 LCAT MET COA3 WT1 CD96 SDHAF2 WT1 STAT1 TNXB TMEM237 BBIP1 GATM PTPRJ HPRT1 CHD7 LMNA GBA SDR9C7 PQBP1 NDUFS7 TRNL1 CIT SLC5A2 ABCC6 SLC9A3R1 OFD1 IQCB1 SETD5 GDF2 PLG AGXT TP53 LAMC2 MAGI2 BICC1 MMUT TRAF3IP2 GP9 CEP290 FANCD2 PYGL PIK3R2 APPL1 HOXA13 PPM1B PIGV TRNQ TRIM32 RFC2 ALG1 HPS1 SPECC1L PMM2 SERPINA1 WAS SOX9 WT1 TRNS1 APOL1 SEMA3E IL17F HOGA1 SHANK3 SLC35A2 DDX59 TMEM260 NUP160 PYCR2 TAPT1 DSTYK TMEM127 APC SLC7A7 INS CC2D2A FREM2 FAM20C CENPF BUB1 CEP83 DKC1 NDUFAF4 NFIA PGK1 RAD54B AFF4 VHL CLDN10 SRC SLC25A11 RARA PAFAH1B1 MEFV ND1 ITGA8 GLMN MYD88 PTEN FGF10 TP53 SMAD4 WDR19 TMEM216 CEP290 GATA4 WAC AIRE ITGA6 STRA6 NDUFB8 PLCE1 FGFR2 FGF17 FANCC WFS1 IFIH1 COA8 DHCR7 PTCH1 CDC73 LAMB2 CLCNKB ZNF423 RNF139 H19-ICR PROK2 CLCNKB RPL27 CC2D2A SCNN1B AVPR2 COX10 MGME1 GPC3 NDUFS1 WASHC5 MDM2 ACTN4 ABCC6 CRTAP DYNC2LI1 MKS1 PRKCSH SHH MEFV REN DEAF1 NDUFAF8 PIGL XYLT1 PEX12 PTPN11 SLC4A4 ITGA2B DLST FOXF1 GRIP1 PIGW PHEX CRB2 COQ6 GDNF EYA1 LIPT2 PROKR2 APC2 ARHGDIA CTNS TCTN3 SMARCC2 PPOX F10 PKHD1 ODC1 TPRKB WDR19 RAB3GAP1 KCNJ11 RPS26 TRNW STRADA RPL18 CDK5RAP2 PRKAR1A ZNF687 WDR4 EHMT1 RPGRIP1L TRNK SLC30A9 INPP5E UMOD SDHB TMEM67 SF3B4 INSR MEOX1 VAMP7 CEP290 FAT4 PTPN22 ARL6 SLC34A1 BCS1L SRY EPAS1 KCNQ1OT1 PHYH SDHB CISD2 TRIM28 PAX2 HPRT1 GCM2 LIG4 COL3A1 ABCG5 ALDOB NXN GP1BB ENG CENPJ IQCB1 MINPP1 CASP10 PTPN22 LMOD1 TRNT GLIS3 POGZ F8 CA2 FOXH1 TRNL1 PIGP NOTCH2 SDCCAG8 ALX4 PLD1 GSN ENPP1 RNU4ATAC SMARCB1 SF3B4 STXBP1 BCOR VHL GREB1L KCNJ11 MLXIPL SLC37A4 RAB18 AGXT MAPKBP1 RYR1 NPHP3 GNB1 DPF2 TP63 CEP135 HNF1B HPRT1 PEX13 GPC3 RPGRIP1L WDR19 JAM3 PRPS1 CEL TCTN3 SIX5 NPHP3 TP53RK IL17RA UFD1 CHEK2 FREM2 AAGAB MKKS TGM1 TSC1 EIF2AK3 APC AKT1 YY1AP1 ARID1A CACNA1S ITPR3 NDUFA11 RAD21 G6PC RORA MAFB SDHC PTCH1 ALG8 HNF4A TBX1 PREPL TMEM67 INPP5E CCBE1 ARL6 FIP1L1 DNA2 PBX1 NPHP1 SOX9 NPHP3 PIK3C2A SCO1 SPECC1L TTC37 TMEM216 APC PIK3CD BRAF SDCCAG8 DHDDS KIF14 FANCE FCGR2A TAF13 RAD21 LMNB2 GPC4 CEP164 ARL6 SERPINH1 CPT1A MARS1 ALMS1 INVS FANCI PEX26 FLRT3 SMARCAL1 NPHP1 SMARCE1 CHST14 WRN SRCAP LRIG2 GP1BA TRNS2 FGFR3 DNASE1 SDHB NIPBL RPGRIP1L SLC22A12 TMEM107 TMEM138 ZAP70 ND3 GNAS ALOX12B ND1 CILK1 NOD2 ZEB2 B9D1 NODAL RRM2B USP9X CLDN16 MYOD1 CSPP1 MAFB FIBP PEX3 WNT4 COX6B1 ETFDH OCRL UBAC2 COX1 HNF4A RAI1 TMCO1 BUB1B MAGED2 CRB2 PEX1 NPHP4 MMACHC RERE ALMS1 AQP2 HDAC8 TRAF3IP1 TBC1D8B PUF60 CASR ARID1B OCLN HELLPAR THBD SNAI2 CSPP1 CCBE1 MCM5 PIK3CA BBS5 IRAK1 CPLANE1 ARX POU6F2 POLR3A FGFR2 SEC23B RET TFE3 MKKS HYMAI SHH SARS2 CD151 SDHD ABCC8 CSPP1 KNSTRN TMEM216 SDCCAG8 BRAF SLC7A9 RPL11 KIF14 KMT2D SLC3A1 IGF2 NUP85 CASR PLA2G2A MLH3 GPC4 HLA-DPA1 CHD7 RPGRIP1 PEX16 PTPN22 CLPB PIGN ND3 DCLRE1C PEX1 CFH TRNN SUFU NPHS1 FOXF1 KLRC4 CCND1 COG7 IFT80 TSC1 BSND USP9X TRNK SMC1A MEN1 ADCY10 ESCO2 ZFPM2 AP2S1 JAK1 PRCC HMBS ADA2 SLC4A1 RSPO2 C4A GANAB WT1 CLCNKB PPP1R15B FGF8 CTNS WASHC5 CTU2 BSCL2 STAT4 SETD2 XDH AMER1 IFT172 TMEM216 KIAA0753 ZNF423 ARVCF AKT3 ATRX BAP1 ALDOB PGAP2 C8ORF37 RECQL4 MSH2 MKS1 EHMT1 KLHL7 FH RECQL4 MYH9 CFH NDUFS2 CD2AP FGFR2 CEP120 CDKN2A OFD1 AGGF1 FLNB ANOS1 PHGDH HRAS MRPS22 FGFR1 DMXL2 MOCOS TALDO1 IL17RC TRIM28 TCTN2 NSMF KDM6A TRIM8 CEP63 BAX WDR62 MAP2K2 MKKS CPT2 MCFD2 CAV1 BRF1 SNRPB IL10 COX3 OFD1 PAX4 TRIP13 MCTP2 CLCNKA PIK3C2A COX8A SLC34A3 EP300 DGKE SCNN1B PIK3CA KCNE5 PLVAP PDE6D CEP152 ITGB3 SRP54 SOX11 MAP3K7 COL4A4 ERCC6 IL17RD SLITRK6 FGA USP8 REN CC2D2A WT1 WDR35 CHRM3 POLE SDHC GREB1L NPHP3 WIPF1 GNA11 SF3B4 F2 HNF4A FAS DYNC2I1 LRP4 PDE6D OSGEP BBS1 HNRNPU GTF2IRD1 NEUROD2 CFI GPC4 LAGE3 LAMB2 LPIN1 SOX9 APOA1 MAX PDX1 MYLK EP300 TP53RK ADAT3 SMC3 STAG1 STAT4 SLC29A3 FOXE1 ITGB4 FGFR2 CLCN5 GATA3 ESCO2 MYH11 SLC34A1 ATP1A1 KDM6A RPGRIP1L MAD2L2 SPRY4 RPGRIP1L RFWD3 FANCE KRAS CCND1 TLR4 ERCC8 CD81 PEX19 PORCN PREPL DICER1 FANCA SCN1B ANTXR1 BRCA2 COL4A3 TBX1 BBS4 CHRNA3 C4A TREX1 KIAA0753 CAMKMT DCHS1 ANLN KANSL1 MMP1 CHD7 ELN TSC2 SETBP1 WT1 PEX10 MMUT FLNA SLC17A5 NEK8 LMX1B PNKP CFI ELP1 ALG9 TMEM237 TBL2 STK11 SLC7A7 CDKN2B WT1 RET NUP133 PEX5 PCK1 NIPAL4 RPS28 CASP10 AKT1 PRDM16 ASPM IFT27 ITGA3 NBN GCK CDKN1C TRNE SLC25A22 DCC COL7A1 WNT5A SHANK3 CFHR5 LIMK1 BBS10 FAM20A SASS6 SRY SLC34A1 PIGO FANCI LEMD3 CLEC7A SALL1 NOTCH2 NSD2 ZIC3 DYNC2LI1 BMP4 YAP1 NLRP3 NPHP3 CLDN19 OGG1 PIGA HLA-DPB1 ATP6V1B1 KCTD1 DMRT3 TRAF3IP1 PIEZO2 CTNNB1 VHL GANAB KLLN ITGA8 OCRL GPR35 TMEM67 LRP2 STAT5B NLRP3 ROBO2 HPRT1 MSH3 HYLS1 NEUROD1 BMPER MED25 FLCN SMS CTLA4 STS MDM2 TCF4 LIPN THOC6 PET100 PDX1 CACNA1D WDR73 EPG5 ERCC4 TREX1 BCOR KCNJ1 TRNH KIF1B IL6 PTPN22 DNMT3A CDC73 RFWD3 KANK2 RPL15 FGFR1 WDR19 BICC1 HNF1A EFEMP2 TTC8 ADA2 RPS15A HESX1 KMT2A STRA6 NR0B1 TMEM70 RBM10 PEX1 GATA3 WNT3 PYGM ARID2 TBX15 NR5A1 VHL BLM RPS27 FASLG CFHR3 COX14 PPP2R3C KIF7 AQP2 NPHP1 CYTB DDX6 COQ2 HBB ZIC3 POU3F4 MSH6 SCARB2 FLNA PPP3CA SLX4 LARGE1 HABP2 CLCN5 WDR73 PHF21A ITGB3 MDH2 NIPBL ITGA2 BBS2 PALB2 CFB KRT17 WDR11 MTRR PEX2 PGM3 IL7R STXBP1 ARL6IP6 FLI1 NF1 SON DSTYK CYP4F22 CHD7 HLA-B NARS2 BRCA2 APOE PAX6 RBM8A TIMMDC1 BCS1L GRIA3 TTC37 DICER1 SC5D OFD1 TMEM231 PALB2 NRAS SDHD SIX5 APOB TFAP2A HNF1B FREM1 PEX6 AGT SOX18 REST ANKLE2 SC5D TBX22 PRMT7 ZIC2 KCNJ10 TCTN3 GPC3 DVL1 B9D2 KCNQ1 NDUFAF3 HMGA2 CFHR1 SLC4A1 PDSS2 PIK3R2 BBS10 FOXP3 KYNU HNF1B FN1 PCSK9 FGFR2 SOX10 FANCB DMP1 KIF14 ENPP1 OSTM1 AKT1 KEAP1 PHC1 INS UMPS OCRL RPL26 DISP1 CDKN1C LEMD3 YWHAE CYP11B2 LRP4 NSUN2 TRRAP COLEC10 ATP7B CHST14 IL23R PTPN12 CHRM3 DHODH DHCR7 ZMIZ1 CHD4 RBM10 DPH1 LYZ KCNJ10 CWC27 OPLAH MASP1 MYCN KRAS PHYH CDC42 TMEM216 DNASE1L3 TASP1 CYP27A1 DACT1 IFT122 NDUFB3 HOXD13 RPL5 ROR2 COL4A1 USP8 RTTN MED25 PEX10 CCND2 MVK IFT27 SULT2B1 RREB1 CEP57 B9D2 CFI RAD51C COQ8B DLL4 ZNF592 PKDCC TBX1 CEP164 PIGT GEMIN4 DYNC2I2 PIK3CA KIAA0586 PTEN AMMECR1 COX20 DPH1 PEX3 FLNA GCDH RAI1 RMND1 PIK3CA MCPH1 HRAS AFF4 PTPN11 IGF2 KAT6B HNF1B IFT172 ND1 NDUFAF6 SCN2A RPS7 NDUFS3 PIGL SPP1 PLCD1 NSDHL NDUFAF2 WDPCP KAT6B TMEM67 CPT2 GLI3 FGFR1 BRIP1 CDKN1B NUP133 PRKCD POMT1 PIK3CA AHI1 PORCN FLNA CD46 FAH RAI1 TMEM67 BCOR NEU1 CYB561 CEP55 NADSYN1 NAA10 ATRX GDF6 MAX SLC12A3 CPT1A ADA C1QA UBR1 PIGN GDF6 IKZF1 UBE2T GALNT3 TSC2 CAD KYNU HMGA2 TTC21B DHX16 LTBP4 COL4A3 INF2 SKI STAT3 NRAS KCNA1 DCC RPS24 FKTN FLNA NDUFS2 TFAP2A RPL35 RPS17 SDHA COMT CDC73 SBDS SCNN1G GLA LRP5 BBS1 PIGV APRT LAMB3 PIEZO2 KCNQ1OT1 SLC36A2 ACTB NUP93 TBC1D20 SNAP29 CCDC28B ABCC8 PAX2 MBTPS2 FLII FN1 SALL1 CDKL5 SLC26A4 CC2D2A EBP NDUFAF5 XRCC4 FANCA NUP205 YAP1 PMM2 CLDN19 CEP290 ALPL ACP5 FLNA CPT2 STAT3 TRIM37 RPL31 WNT4 IFT140 CCN2 DLC1 SGPL1 NDUFAF3 SDHB EP300 HSPG2 TBCK IRF2BP2 CCNQ BUB1 MYO1E SHPK C3 PC NF1 CEP41 POMT2 DHCR24 ARID1B RMRP NUP133 PEX6 WAS ACSL4 MICOS13 KCNJ11 IGF2 H19-ICR B3GLCT CCR1 TPRKB FH HIRA LRIG2 TTC21B GSN PGK1 FOXI1 TLR2 MOCS2 CDKN1B TELO2 SSR4 CTLA4 DACT1 HLA-DRB1 FIBP SH2B1 RBM8A ALOXE3 CDC42 HNF1A TCTN2 VHL TBX3 FAT4 NABP1 FBN1 NUMA1 LMNB2 PTPRO ERCC8 LAGE3 FANCB FCGR2B SALL4 GBA DZIP1L MDM2 LAMA3 CDON NOTCH2 KAT6A AVPR2 STRADA BBS12 CLCN5 NRIP1 DYNC2I1 ARL3 NPHP1 WWOX PCK2 SI LRP5 WDR35 DYNC2I2 CTNNB1 SCNN1A SNRPB DHX37 SLX4 FGF8 ABCA12 PKD1 TRIP13 CDC73 BBS7 NPHP4 ELN NOTCH3 KMT2D DIS3L2 SMARCAL1 PKD2 TRNL1 WNT3 JMJD1C IARS1 TRNT1 VPS33A ARMC5 CREBBP CCR6 DIS3L2 LMX1B COX2 BRCA2 SLC25A20 GTF2I KNL1 AURKA ALG9 ACTG1 KYNU SOX4 GPC3 ATP6 WDR19 TRPC6 POR VDR LMNA ERCC4 THOC6 MBTPS2 GATA1 SLC1A1 COQ7 VPS33A GDF3 FH CACNA1D BBS9 PEX2 SETBP1 WT1 SIX3 FKRP GLA PEX13 RPL35A MNX1 ANTXR1 DSE ND6 HLA-B FLNA B3GLCT CPOX LEMD3 FREM1 DLL1 BBS4 NDUFAF3 SLC2A2 NDUFS4 SAA1 FGFR3 ABCC6 RBBP8 TRNS1 NCAPG2 COL14A1 YY1 RAG2 RPL11 TMEM107 DUSP6 PNPLA6 PLAGL1 MFSD2A CREBBP PDSS2 EVC2 DYNC2LI1 RARB MBTPS2 WFS1 ND4 TMEM126B NDUFAF1 MYOCD NAA10 TSC1 FAS DCHS1 SLC6A17 G6PC3 FLCN EXTL3 DYNC2I2 PAX1 PUS3 CTNS CDK6 SLC3A1 RAG1 VAC14 BUB1B ATRX IGF2 FANCD2 TBL1XR1 PEX12 ADAMTS13 DCDC2 ATP7A LMNA CYBC1 NPHP1 SEMA3A SMARCD1 MOCS1 CD109 TMEM67 LZTFL1 CA2 LMX1B GAS1 DYNC2H1 FRAS1 ERCC6 PIGY NEU1 GP1BA FANCL BTNL2 PGAP3 SMOC1 PLEC REST RPS29 ND2 TGIF1 HSPA9 PIGA ERCC8 ACVRL1 AGTR1 TCN2 MAFB NUBPL DDX59 GP1BB WNT4 WNT4 MAP3K7 ADA PIGY KLF11 NUP107 SALL4 C3 PACS1 GLI2 PKD1 LDHA CCDC141 FUZ MAP3K1 PEX14 C1QBP SLC12A3 LHX1 RPS26 GLI3 AR ZBTB16 SPART B2M AXIN2 CEP290 DYRK1A IL12A-AS1 UQCC2 MME MKKS CDKN1B STIL TP53 WDR4 BNC2 ACTG2 LMX1B ITGB4 SCARB2 ZAP70 AMMECR1 TMEM138 GNB1 NDUFV1 SCO2 HMOX1 IFT140 GRHPR CD96 CLIP2 PROKR2 PIGT GLI1 FGFR3 FANCF UMOD POR PRKCSH BAZ1B C8ORF37 WDR19 FLCN ETFB STOX1 AIP DICER1 GCM2 TMEM231 LDLR XRCC2 DNASE1L3 FGF23 SPRY2 GLIS2 HNF1A CDKN2C COLEC11 SIX1 MEN1 ATRX POU6F2 IFT172 ITGA2B SOX17 KMT2A CCDC22 TBC1D24 CEP290 INSR PKD2 INF2 DIS3L2 CORIN TNXB NDUFS8 TBC1D24 NLRP3 FOXRED1 CEP290 IFT80 EXT2 EXT2 NDUFB10 SLC2A9 COG1 XPNPEP3 CDK4 HBB CFH GABRD BRCA1 KCNAB2 USF3 GCK NDNF H19 EMP2 HDAC4 SDHD ND5 F5 SDHD IL2RG MEFV SERPINF2 RAB3GAP2 FIG4 ELP1 ASXL1 FGFR3 TXNL4A ARX NUP107 CASR KISS1R METTL5 FUT8 KITLG NDUFV2 TBX1 CLCN5 EYA1 ENPP1 IFT43 GPKOW COL4A4 FAS CCNQ NPHS1 COG6 ADAMTS3 PIGL PUF60 TRAPPC14 AGPAT2 NOD2 RAI1 HOGA1 CC2D2A IFT43 COL4A3 SIK1 TMEM237 SLC12A1 COPB2 SLC37A4 TRIM32 SEC63 TMEM126B INTS1 BMPER DZIP1L TRNW PEX5 CCND1 COPA FRAS1 NSD1 MLH1 NPM1 WDR73 FLCN FOXP1 ND6 GRHPR MYO5B TACR3 PEX7 AVIL AMMECR1 TBX18 PML ND2 CREBBP MYMK APC NADK2 TTC8 RPS10 CEP120 SMO PLG INTU CD46 ERCC6 ARNT2 SLC26A1 NDUFB9 SLC6A19 KIF1B CEP55 VHL CPT2 IQSEC2 ANOS1 HSD11B2 COA8 B9D1 LMAN1 ZEB2 UMOD GNAO1 ABCC8 FBXW11
    Protein Mutations 4
    C282T C677T K55R Y93H
    SNP 5
    rs2281135 rs2294918 rs35652124 rs738409 rs7903146
    HP:0001919: Acute kidney injury
    Genes 32
    CD46 RYR1 DZIP1L APRT LPIN1 CFH CFI CACNA1S CCND1 TCN2 CD46 FLT1 SLC22A12 SLC26A1 HPRT1 C3 CFH PYGM HNF4A DGKE CFHR1 HNF1B CFHR3 HELLPAR CFI PKHD1 THBD SAA1 STOX1 STAT2 CFB CORIN
    Protein Mutations 0
    SNP 0
    HP:0012393: Allergy
    Genes 29
    CARMIL2 PGM3 PSTPIP1 CNTNAP2 MS4A2 IL4R PGM3 TGM5 CHD1 CCDC28B COX4I2 CSTA IL6ST SIK3 CTLA4 FOXP1 SPINK5 PLCG2 ARL6 PLA2G7 JAK1 RBM8A MTOR FOXP3 NRXN1 BBS1 SOX6 FOXP3 ADA
    Protein Mutations 5
    A118G C677T G20201A L858R P12A
    SNP 2
    rs11648486 rs1761667
    HP:0002511: Alzheimer disease
    Genes 13
    HFE APOE PSEN1 MPO APP CACNA1G PLAU GATA1 APOE A2M PSEN2 ABCA7 NOS3
    Protein Mutations 5
    E280A K56M P200T R199W R38H
    SNP 10
    rs10524523 rs11870474 rs2227902 rs3742376 rs3745274 rs3796529 rs4900442 rs6971 rs7157609 rs754203
    HP:0001681: Angina pectoris
    Genes 39
    ABCC6 PIGA PMM2 LDLR LCAT APOB APOE HLA-DPB1 GLA LMNA CYP27A1 CTLA4 GATA6 ABCC6 XYLT1 ABCG8 GATA4 CYP27A1 JAK2 CRELD1 LMNA ABCG5 XYLT2 PRTN3 HLA-DPA1 NR2F2 LIPC LDLRAP1 ABCC6 ENPP1 IDUA PCSK9 TET2 GLA PTEN PTPN22 MPL LIPC ZMPSTE24
    Protein Mutations 0
    SNP 2
    rs10455872 rs3798220
    HP:0000458: Anosmia
    Genes 69
    SEMA3A SMCHD1 SHH PROK2 DCC SOX10 CHD7 PROK2 SMCHD1 IL17RD PHYH PEX7 DUSP6 SEMA3E KISS1R ANOS1 ATP13A2 SOX10 WDR11 FGFR1 TACR3 PEX7 KISS1R KISS1 NSMF NSMF OTX2 CHD7 HS6ST1 NDNF HESX1 FGF8 SOX10 DNAI1 SEMA3A SEMA3E PHYH WDR11 FEZF1 ANK1 IL17RD CCDC141 PROKR2 ARSL HESX1 GNRH1 MFN2 FEZF1 SOX10 SOX2 CHD7 FGFR1 ANOS1 FGF8 CCDC141 SOX3 CHD7 PROKR2 FGFR1 ARNT2 SPRY4 FLRT3 ADCY3 TAC3 PEX7 SCN9A NDNF FGF17 PROKR2
    Protein Mutations 0
    SNP 0
    HP:0001369: Arthritis
    Genes 269
    PADI4 AEBP1 KLRC4 IL12A-AS1 NLRP3 COL5A1 HLA-DRB1 TGFB3 NTRK1 NLRP3 FCGR2B GBA GJB2 GP1BB TRPV4 PTPN22 NLRP12 SCARB2 LEMD3 SLC37A4 ABCG8 SEC61A1 IL2RB HPRT1 SEC24C TRAPPC2 HLA-B MVK TF STAT4 FGFR3 NLRP3 RREB1 MMP2 COL2A1 FBN1 MMP14 EXT1 CFI APOE HJV ARVCF MLX STAT4 GCH1 ANKH HLA-C COL2A1 TBX1 HGD F9 ACAN HPRT1 LRBA IL2RA UMOD COMP PRPS1 MYH14 GJB6 PRG4 OCRL ADAR UFSP2 MMP13 JMJD1C UFD1 CCR6 ANKH IL6 LMX1B RAG1 HPRT1 PSTPIP1 HNF1B DNASE1L3 MATN3 KIF7 SPP1 G6PC PHEX SPTB PTPN2 LRRC8A COL9A2 PTPN22 CD244 IGHM NLRP3 CD79A IGLL1 MATN3 CD79B PRKCD HOXD10 COMP ACP5 MTHFD1 MIR140 BLNK HLA-DRB1 SLCO2A1 RASGRP1 ANKRD55 CAV1 HLA-B COL5A2 PFKM NLRP3 BTK IL10 PIK3CD GLA COL9A1 SLC4A1 MEFV FCGR2A RNF168 RAG2 COL11A1 PTPN2 GDF5 AIP COL1A1 COL5A1 SLC12A3 SLC22A4 FASLG MEFV CD247 SH3KBP1 EXT2 COL2A1 F8 CLCNKB DNASE1 MEFV STAT3 IL2RA TRPS1 HPGD CLCN7 IFIH1 BTK HLA-DRB1 KIF22 ANKRD55 NOD2 TRAPPC2 WIPF1 ACAN MATN3 HNF4A FAS HGD ASPN RNASEH2A COMT TBX1 HPGD ASAH1 LACC1 DNAJB11 PSMB9 MEFV FAS FAS COL2A1 UBAC2 LMNA LBR FRZB MUC1 SLC40A1 STAT4 STAT4 ADA2 TRPV4 SMAD3 CD247 HLA-B ACAN PHEX RNASEH2C SLC37A4 VPS13A SPTA1 ASAH1 MYD88 MIF ACP5 PSMB4 TLR4 TNFRSF11B IRAK1 CCN2 MMP13 CLCN7 CCN6 COPA ZNF687 ERAP1 TREX1 IL2RB TNFRSF1A COMP CTLA4 C4A COL2A1 TREX1 BTK UFSP2 IL12B AGA RNASEH2B DCLRE1C ATP7B LRP6 ANK1 FOXP3 HNF1B COL1A1 WAS KNSTRN PTPN22 COL11A2 ZMPSTE24 MVK COL9A1 TCF3 IL12A COL11A2 PSTPIP1 GNAS NOD2 COMP SAMHD1 IRF5 COL9A3 IL10 CCR1 SLC26A2 HIRA GHR PIK3R1 COL9A2 HPRT1 EPCAM TFR2 COL9A3 IL36RN COL2A1 EPB42 COL11A2 GPR101 COL3A1 CCN6 ATP7B IL23R NFKBIL1 SMAD3 CTLA4 PTPN22 UMOD CIITA HPGD CASP10 PTPN22 CANT1
    Protein Mutations 4
    A147T N363S R620W V600E
    SNP 10
    rs2246704 rs2853884 rs35705950 rs3747158 rs3790515 rs3828057 rs4820059 rs7291050 rs933226 rs9826
    HP:0002099: Asthma
    Genes 108
    LIG4 PTCH1 ALOX5 HNMT SUFU FOXH1 GP1BA PEX5 CARD11 VPS51 TNF PGM3 NFKB2 SIK3 CREBBP SRSF2 NOD2 RUNX1 GRHL2 NODAL JAK1 GP1BB ADRB2 COMT MTOR TBX1 CDON BBS1 PLA2G7 SHH SEC24C TBCK IL13 FLG PGM3 RREB1 STXBP1 ARVCF CBL SCN4A CCDC28B TBX1 TRAIP LRBA FGF8 ODAD3 SPINK5 ODC1 CFTR DOCK8 GTF2H5 SCGB3A2 SDHD RIC1 GP9 ELOVL4 JMJD1C UFD1 PEPD CREBBP HLA-G AFF4 FCGR2A BCL11B CARMIL2 PTGER2 ERCC2 IL4R SPINK5 USP7 CDSN NEK9 LMX1B TALDO1 FGFR1 ZIC2 GAS1 PLCG2 PLA2G7 ASXL1 LIFR TDGF1 TGIF1 TBX21 NKX2-1 NKX2-1 TET2 MS4A2 SIX3 DISP1 GP1BB TGFB1 COX4I2 CCL11 HIRA ARL6 MUC7 NSUN2 DDX41 GLI2 ALMS1 EP300 CASP8 IDS WAC ADA DLL1 DOCK8
    Protein Mutations 4
    D299G G16R Q27E T399I
    SNP 18
    rs1042711 rs1042713 rs1042714 rs1042718 rs11958940 rs11959427 rs12654778 rs12936231 rs1504982 rs17778257 rs1800888 rs1801275 rs1805010 rs2053044 rs2895795 rs324011 rs324015 rs4950928
    HP:0002621: Atherosclerosis
    Genes 86
    MFAP5 WRN ABCC6 ELN LDLR LCAT APOB LDLRAP1 ACTA2 BRCC3 GLB1 MYH11 ERCC6 LMNA GGCX SMAD3 SMPD1 ZNF687 KCNJ5 ABCA1 LMNA CYP27A1 TGFBR1 SC5D LCAT ANTXR1 ERCC8 LMNA FBN1 MYH11 CYP7A1 LMNA LMNA TGFB3 XYLT2 SMPD1 ANGPTL6 MYH11 CEP19 ASAH1 ENPP1 NPC2 ABCG8 PCSK9 MYLK AGXT CSF2RA ZMPSTE24 LMNA TNXB PRKG1 NPC1 FOXE3 APOE APOA5 TGFBR2 TGFB2 LMNA SMPD1 ABCC6 XYLT1 ABCG8 MAT2A THSD1 HGD LOX APOB GGCX ESR1 BANF1 SERPIND1 TGFBR3 ABCG5 ALMS1 CSF2RB LDLRAP1 PPARG SMAD4 ENG COL3A1 ACTA2 LIPC LMNA LOX ABCA1 ABCA1
    Protein Mutations 3
    G21210A V167F V617F
    SNP 7
    rs1024611 rs1051931 rs10757274 rs10757278 rs16874954 rs1799724 rs2383206
    HP:0007018: Attention deficit hyperactivity disorder
    Genes 377
    PRNP ZIC2 MLH1 LIG4 NTNG1 KCNA2 TRIO SETBP1 DYNC1I2 GNAQ MID2 NODAL DYRK1A HDC SH2B1 ZNF41 CDH2 RAB39B LIMK1 CIC CNKSR2 SCN8A LHCGR USP27X EEF1A2 NR2F1 CSGALNACT1 SIX3 ACTL6B PAK3 SLITRK1 GP1BB GATA4 MLXIPL IQSEC1 ADNP C12ORF4 CDK19 TKT SEC24C DHTKD1 SETD2 SYNJ1 RREB1 BMPR1A ARVCF YWHAG DMD PMS1 RLIM IQSEC2 CLIP2 SIM1 TBX1 WWOX PIEZO2 SETD5 SYNGAP1 PPP3CA DLL1 DISP1 FTSJ1 HCFC1 GAS1 ARF1 FOXH1 ODC1 ELN IKBKG SPG7 BAZ1B OCRL ACTL6A TBC1D24 METTL5 NF1 TCF20 JMJD1C STAG2 UPF3B UFD1 MED13 ZMIZ1 FBXW11 CHRNA7 RFC2 SIX3 TSC1 DLL1 AP3B2 SIX3 TDGF1 THRB GTF2I CACNA1A MLH3 NECAP1 GNB5 PRKCG NSD1 GABRB2 OPHN1 SATB2 USP7 FAN1 FGF12 STS CXORF56 SEMA3E MSH2 FOXH1 SETD5 GABRA2 ACTL6B SLC2A1 ZNF711 CDON CDON TBX1 HERC2 MED12 DLG3 NLGN1 TRAK1 GRIA4 USP9X TLK2 GAS1 RPS6KA3 SCN3A CDK8 KIF11 TIMM8A PARS2 PPM1D DRD4 PWAR1 JRK MED12 MED12L MYT1L RAI1 TKT ZIC2 MYT1L ARID2 EPCAM CRBN CACNA1H CYFIP2 NODAL NBN SMPD1 GABRG2 CACNA1B FOXH1 CLCN4 KMT2A SHH DISP1 RAD21 ABCD1 UBA5 STS DDX6 MCTP2 CSNK2A1 PANK2 TRIO PPP1R12A FGF8 MAGEL2 GLI2 PTCHD1 DYM NPAP1 PHIP TANC2 DISP1 TGIF1 WAC PSMD12 FGD1 SLC13A5 SLC6A8 SNORD116-1 SRPX2 FGF8 ARHGEF6 UBE3A MAP1B GABRA5 TDGF1 HDAC4 TGFBR2 PTCH1 BCR SH3KBP1 GDI1 WDFY3 TDGF1 TSC2 GLI2 FGF8 YY1 SHH CARS1 TUBB2B IFNG GLI2 FGFR1 SYP RPS20 DHDDS GAS1 BCORL1 BPTF RERE NIPBL MKRN3 GNE COMT SNORD115-1 TBX1 TGIF1 SPRED1 GLUD1 NDP WAC GTF2IRD1 SCN8A TSC1 TSPAN7 FMR1 CDON WAC GRIN2D NUS1 KCNA2 STAG2 DEAF1 PAH DNM1 FLI1 GABRG2 PTCH1 FGD1 SIX3 DALRD3 RAI1 GNE TMCO1 YWHAG SMC3 FOXH1 PIK3CA ZDHHC9 NKAP TAF1 RAI1 FLII CNKSR2 HOXA2 TGIF1 RERE SEMA4A ZIC2 MED13 HDAC8 KMT2E AGTR2 IPW RIC1 APC2 AUTS2 PAH ASPM GABRG2 SZT2 KRAS ALG13 DRD5 DOCK3 FGF8 SHH ARV1 TDGF1 STXBP1 UPF3B GALC DLL1 STAG2 BCORL1 PCGF2 TET3 SHH NODAL SLC1A2 TRMT1 NOP56 TGIF1 MED12 PTCH1 ZIC2 SMC1A CLTC HSPG2 MSH6 PWRN1 IGF1 CPLX1 FOXP1 GRIN2A FGFR1 GAS1 TBX1 SIN3A IL1RAPL1 NTRK2 PCNT KCNB1 ELN ALKBH8 TSC2 SLC9A7 POLA1 NDN MECP2 MAPK1 CDON PTCHD1 SOX5 ATP6V1A KDM3B NODAL HCN1 KIF14 TRAPPC4 GRIN2A KAT8 TBL2 DLL1 PTCH1 MED12 DNAJC12 HIRA GLI2 MKRN3-AS1 IQSEC2 SVBP ZNF81 NSUN2 AARS1 GABRB3 RSRC1 PMS2 DLL1 FRMPD4 GABRA1 CHD7 FGFR3 CNKSR2 CRKL ARX TANC2 DHCR7 ZMIZ1 TRAPPC14 TBL1X ACSL4 CLTC SNRPN PHF21A DISP1 DPH1 SH2B1 SMC1A
    Protein Mutations 2
    D203E G143E
    SNP 2
    rs2307227 rs71647871
    HP:0000717: Autism
    Genes 197
    WFS1 KCNA2 NFIB SHANK3 SH2B1 LIMK1 SCN8A EEF1A2 ACTL6B GP1BB NRXN1 PRKAR1A CDK19 SEC24C SYNJ1 RREB1 TBR1 ARVCF CACNA1C ZBTB20 CLIP2 TBX1 WWOX TMLHE SETD5 SYNGAP1 PPP3CA DEAF1 SOX2 EHMT1 ELN BAZ1B PLXND1 JMJD1C UFD1 CHRNA7 RFC2 TSC1 AHDC1 AP3B2 GTF2I CACNA1A NECAP1 FTSJ1 PDE4D GABRB2 SATB2 ATRX FGF12 STS NLGN4X SEMA3E GABRA2 SDHC NAGA SLC35C1 HERC2 TRAK1 OTX2 AUTS2 SCN3A PARS2 PWAR1 MECP2 GATM SNRPN CYFIP2 NONO CACNA1B EXT2 KMT2A NHS RAD21 UBA5 STS PTEN MAGEL2 NAGA GABRD PTCHD1 DYM NPAP1 SOX3 PTEN RERE REV3L KLLN KCNAB2 ARNT2 SLC13A5 USF3 SNORD116-1 UBE3A GABRA5 HDAC4 DHCR7 MED13L TSC2 SDHD YY1 ANKRD11 IFNG SKI DHDDS SLC9A6 MAOA NIPBL MKRN3 COMT SNORD115-1 TCF12 TBX1 SMAD4 NDP GTF2IRD1 GAMT TSC1 NLGN3 TBCK FMR1 NLGN3 GRIN2D NUS1 KCNA2 SCN8A MED13L PAH DNM1 ADSL PIGL DALRD3 GABRA5 GJA5 YWHAG SMC3 RAI1 MED12 CNKSR2 HDAC8 IPW ALDH5A1 FGFR1 GABRG2 GJA8 SZT2 PROKR2 IL1RAPL1 PIK3CA ARV1 MEIS2 STXBP1 CNTNAP2 FMR1 HNF1B DYRK1A SLC1A2 SEC23B GRIA3 EHMT1 EP300 SMC1A CLTC PWRN1 ALG13 TBX1 SIN3A CREBBP NTRK2 IQSEC2 CHD8 KCNB1 TSC2 HESX1 NDN BCKDK FLCN ATP6V1A SDHB AKT1 HCN1 TBL2 HIRA MKRN3-AS1 DMPK AARS1 RPL10 CHD7 PRDM16 MAN1B1 PDE4D SIM1 LHX1 DHCR7 KDM5C DPYD NLGN4X SNRPN
    Protein Mutations 1
    S1009A
    SNP 1
    rs6971
    HP:0000729: Autistic behavior
    Genes 638
    LMAN2L WFS1 KCNA2 TRIO POGZ CAMTA1 SLC25A22 PIGP NDUFS6 GPHN MID2 LSS SHANK3 LINS1 ZNF41 TBC1D23 RAB39B LIMK1 CNKSR2 SCN8A UBTF EXT2 USP27X EEF1A2 GRIN1 NR2F1 STXBP1 ACTL6B CRADD PIGO GP1BB ALG13 MTOR EGF C12ORF4 TAF1 PRKAR1A SEC24C CHD2 SYNJ1 SYT1 NOVA2 ATP1A3 CACNA1C DMD NUS1 ZBTB20 CRBN WFS1 RLIM FRMPD4 WWOX DLL1 PRKN DEAF1 FTSJ1 HCFC1 SOX2 RPS23 TM4SF20 LRRK2 MECP2 ELN PPP2R5D SCN1B DNAJC6 CXORF56 AFF2 TCF20 JMJD1C MAN1B1 UFD1 ZMIZ1 CREBBP FBXW11 C9ORF72 HECW2 ZFPM2 HNRNPH2 CHRNA7 TSC1 AHDC1 GTF2I TUBB3 NECAP1 FTSJ1 SYNGAP1 C12ORF4 NSD1 SNX14 GABRB2 SATB2 NDUFA1 NDUFA11 FOXG1 STS CXORF56 RORA NDUFAF4 SETD5 GABRA2 HERC1 MSTO1 SYN1 SDHC NAGA GABRD TCF4 HERC2 MED12 NLGN1 TRAK1 CHMP2B OTX2 USP9X TLK2 AUTS2 SCN3A JAM2 OTUD6B BCOR CDH15 PWAR1 PUF60 MECP2 GRIA2 MBOAT7 NEUROD2 GATM GFM1 CUX2 CYFIP2 CACNA1B POMT1 KMT2A SCN2A NAA15 SQSTM1 RAD21 MECP2 POU3F3 DDX6 TREM2 ZIC1 PIGG RIMS2 HIVEP2 SBDS PTCHD1 DYM NPAP1 RERE TANC2 KLLN ARNT2 KDM5B SLC13A5 NDUFAF3 SLC6A8 SNORD116-1 NDUFS4 ARHGEF6 CARS2 MAP1B GABRA5 MED13L GDI1 WDFY3 IARS1 SVBP DCX STXBP1 YY1 CHD1 PCDH19 DDX3X SCN1A ANKRD11 IFNG RNF135 SYP CREBBP ND3 HERC2 GFM2 BCORL1 SLC9A6 NIPBL MKRN3 SNORD115-1 TCF12 CDKL5 TMEM126B NDP ACOX1 CASK GAMT NDUFAF1 NAA10 TSC1 DEAF1 SLC6A1 TBCK TSPAN7 FMR1 NLGN3 WAC GRIN2D SCN8A PSMD12 DNM1 EXTL3 ADSL SLC35A3 PRODH NSUN2 B3GALNT2 RAI1 EZR MED12 NDUFA6 CDKL5 RERE ALMS1 STXBP1 HDAC8 KMT2E TIMMDC1 ALDH18A1 DCPS ASH1L TWNK PUF60 AUTS2 GRIA3 GABRG2 GJA8 CNNM2 CHD2 ST3GAL3 DOCK3 USP7 PROKR2 TMEM231 PIK3CA ARV1 STXBP1 SON CNTNAP2 FMR1 HNF1B PCGF2 SLC1A2 TRMT1 PCDH19 PPP2CA SEC23B GRIA3 SMC1A CLTC PIGP CC2D1A CTCF ALG13 PGAP1 EFL1 TRAPPC9 KCNT1 CEP85L SLC25A12 RSPRY1 MAPK8IP3 ARX AP3B2 SETD2 NTRK2 IQSEC2 RAB11B KCNB1 NDUFB11 HESX1 CNOT3 NEXMIF TECR VCP MFF PGAP3 NDN COG5 DYRK1A BCKDK MECP2 ND2 FLCN PTCHD1 PIGQ AKT1 UCHL1 MEIS2 MAPT HCN1 NUBPL TRAPPC4 FRRS1L CTNNB1 GABBR2 KPTN MKRN3-AS1 PIGY TCF4 AARS1 TRRAP PACS1 RPL10 FRMPD4 PARK7 CHD7 LHX1 DOCK7 DHCR7 ZMIZ1 ACSL4 SNRPN PHF21A THOC2 KDM6B AP2M1 NTNG1 GRIK2 NFIB AIMP1 GNAQ DNAJC21 DYRK1A ALG11 SH2B1 CDH2 ANK3 NDUFB3 GABRA1 DLG4 PINK1 PAK3 TCF20 TMEM138 ADNP NRXN1 CDK19 CDKL5 SETD2 NDUFV1 RREB1 MED25 TMEM216 TBR1 NDUFS7 ZNF423 PSEN1 ARVCF NDST1 GALNT2 KMT5B IQSEC2 PGAP2 PIGC CLIP2 SIM1 TBX1 TMLHE SETD5 SYNGAP1 PPP3CA CNTNAP2 EHMT1 SYNJ1 SIM1 SH2B1 FBXO31 BAZ1B RSRC1 ACTL6A NDUFS2 PRSS12 METTL5 PLXND1 UPF3B PIGV SLC25A1 MED13 UGP2 AP1S2 RFC2 TUSC3 AP3B2 CACNA1A POLA1 ND1 PDE4D SCN2A PODXL OPHN1 USP7 ATRX FGF12 EP300 NDUFS3 PIGL NLGN4X NDUFAF2 RSPRY1 SEMA3E ACTL6B SHANK3 SPECC1L DMXL2 ZNF711 SLC35C1 GATAD2B CLCN4 DLG3 MED23 TBR1 TRIM8 OTUD6B MAGEL2 TBC1D24 RPS6KA3 CDK8 GABRA2 PARS2 PPM1D CC2D2A HNMT MED12L MYT1L NDUFS8 SCN1B NDUFAF4 SYNGAP1 MYT1L FOXRED1 SPATA5 KAT6A SMG9 SNRPN SLC6A8 VAMP2 ST3GAL3 NONO ASXL3 EXT2 FOXP2 CLCN4 ZNF462 NHS VPS13C SIN3A NDUFB10 SNCA NDUFS4 UBA5 STS SRP54 MCTP2 PTEN ACADL WASHC4 MAGEL2 NAGA GABRD EP300 SOX3 PTEN FMN2 GRN REV3L GABRG2 KCNAB2 WAC SNX14 PSMD12 CLP1 USF3 NTNG2 GABRB3 UBE3A HDAC4 DHCR7 ADNP TSC2 SDHD HCN1 SKI CLCN4 SCN2A SCN9A CREBBP DHDDS NDUFS1 FOXG1 KCNA1 NEXMIF BPTF RERE MAOA DNM1 COMT NDUFV2 TBX1 SMAD4 AGTPBP1 GTF2IRD1 NEUROD2 STAG2 PACS2 NLGN3 DEPDC5 NUS1 KCNA2 IQSEC1 MED13L NDUFAF8 PAH PIGL UBA5 DALRD3 GABRA5 SLC45A1 GJA5 SCN1A YWHAG SMC3 STAG1 IREB2 TAF1 MAPK10 DPYD NALCN PDE4D SIK1 CNKSR2 PIGW TMEM237 MEF2C KMT2C CDKL5 MED13 AGTR2 TBX2 IPW NDUFAF5 APC2 AP2M1 ALDH5A1 FGFR1 SZT2 CLIP1 CUX2 ALG13 EP300 INTS1 CACNA2D2 IL1RAPL1 MEIS2 TNIK SCN9A METTL23 BCORL1 DYRK1A SLC35A3 TET3 NDUFAF3 EHMT1 SCN1B EP300 ADGRV1 PWRN1 FOXP1 TBX1 HCN1 SIN3A IL1RAPL1 SRP54 MEF2C NDUFA13 CREBBP CHD8 SARS1 GABRG2 EDC3 TSC2 CEP290 SLC9A7 POLA1 ARID1B WDR26 SRY IQSEC2 MICOS13 ATP6V1A SDHB CTCF NTNG1 PNKP NAA10 RARS1 KDM3B POLR2A MECP2 SCN1A KAT8 TBL2 HIRA ZC3H14 NDUFB9 NTRK2 SVBP DMPK STX1B ZNF81 GNB5 PRDM16 TMEM106B CHD2 MAN1B1 MBOAT7 ARX PDE4D SIM1 TANC2 KDM5C HTRA2 ARFGEF2 DPYD GNAO1 NLGN4X FBXW11 SH2B1
    Protein Mutations 1
    S1009A
    SNP 1
    rs6971
    HP:0002069: Bilateral tonic-clonic seizure
    Genes 298
    AP2M1 ND4 KCNMA1 SLC1A4 KCNQ3 TRNL1 PSAP SLC25A22 PIGP GPHN MID2 MICAL1 ZNF41 RAB39B CNKSR2 USP27X GABRA1 STXBP1 PAK3 KCNQ2 PIGO SCN8A FA2H GABRA1 SLC2A1 GNB1 SLC25A19 KCNQ2 SETD2 CHD2 RELN CNTN2 PSEN1 CILK1 DMD IQSEC2 PGAP2 COX3 CYTB PIGT ADGRG1 FTSJ1 HCFC1 ATP1A2 SCN1A EFHC1 SCN1B TBC1D24 SIK1 EFHC1 TRNL1 ALDH7A1 PSPH UPF3B PIGV SLC9A6 C9ORF72 STX1B TRNQ TRNQ GABRD COX2 ASPA KCNJ11 SCN2A NHLRC1 NSD1 TBC1D24 PRPS1 FOXG1 PIGL TRNF CXORF56 KCNQ3 HERC1 ZNF142 ATP6 SLC2A1 DMXL2 GABRD ZNF711 GYS1 LBR MED12 DLG3 EPM2A CACNA1D COQ2 CHMP2B TRIM8 TXN2 USP9X SETD1A EFHC1 TBC1D24 RPS6KA3 TRNH INS JRK GRIA2 KCNMA1 CACNA1D SCN1B SLC22A5 FIG4 EPM2A SPATA5 CACNA1H CUX2 COX3 GPT2 VAMP2 GABRG2 ND1 GRIN2A CLCN4 SCN2A SQSTM1 ND1 GPAA1 ATP6AP2 POLG ACADM ND6 CACNB4 TREM2 YEATS2 SCN8A SCN2A PIGG NIPA1 SCN2A ST3GAL5 GRN CLTCL1 GABRG2 WAC GABRD GCK SRPX2 GABRB3 ARHGEF6 TRNW ND5 SCN1B TRNS2 GDI1 GRIN2A TRNS2 TRNS1 CSTB HCN1 PCDH19 SCN1A COX2 DHX16 CLCN4 SAMD12 SYP ND1 TRNK SCN2A SCN9A GABRG2 KCNA1 KCTD7 LAMC3 CLCN2 DNM1 TRNV ND4 HNRNPU ND5 NEUROD2 CASK GAMT SLC6A1 AFG3L2 TSPAN7 GABRG2 PDX1 COX1 CLN8 GABRA5 SCN1A ND6 SLC12A5 BUB1B PUS3 KCNMA1 PHGDH TRNV MAPK10 TRAPPC11 SIK1 DHDDS SCN2A PIGW SLC12A5 LGI1 KCNQ3 CERS1 CDKL5 STARD7 STXBP1 SP110 AGTR2 VPS13A JRK APC2 AP2M1 GRIA3 ALDH5A1 NEK1 EFHC1 SLC2A1 ALG13 CACNB4 TUBA8 STAT3 TRNW SRPX2 AP3D1 TRNW TRNC SCN9A CERT1 PCDH19 SCN1B ADGRV1 TRNK CLN8 ASAH1 TBCD PCDH19 CPLX1 ND6 GRIN2A IL1RAPL1 CLCN2 CEP85L ALDH5A1 ARX ND2 TRNF GABRG2 PDSS2 SLC9A7 VCP PGAP3 DNM1L DYRK1A WDR26 TMX2 HACE1 MECP2 ND5 NHLRC1 TANGO2 PTCHD1 PIGQ PNKP MARCHF6 MAPT KCNJ11 SCN1A RORB PYCR2 SCN2A PCYT2 SARDH PIGY MTHFR STX1B ZNF81 TRNL1 GABRB3 RPL10 SCN9A COX1 FRMPD4 GABRA1 CPA6 STXBP1 TMEM106B CHD2 ADGRV1 ARX PRRT2 TRNS1 RNF13 ATP6AP2 ACSL4 GNAO1 ABCC8 THOC2 ND3 AFG3L2
    Protein Mutations 0
    SNP 0
    HP:0002110: Bronchiectasis
    Genes 175
    GAS8 DNAL1 RIPK1 CR2 LRRC56 GAS8 BTNL2 DNAAF1 TERT CFAP298 CCDC40 RSPH4A DNAI2 DNAJB13 CCDC39 ATM ODAD3 CD81 DNAH9 WDR1 PGM3 HLA-DRB1 DNAL1 BACH2 TTC12 TNFRSF13C STAT1 DSP CFTR TAP1 CCNO CCDC40 DNAH5 DNMT3B DNAAF2 DNAJB13 DNAAF3 DRC1 DNAI2 CFAP221 SPEF2 PGM3 MS4A1 NFKB2 CD19 ODAD4 NFKB1 OFD1 ATP11A CFAP300 NME8 ODAD2 SCNN1G SLC29A3 LRBA IRF8 DRC1 GAS2L2 ODAD3 DNAAF4 SFTPC TNFRSF13B DNAAF6 DNAH5 CFTR SCNN1A RTEL1 CCDC39 STN1 CR2 DNAAF3 NFKB2 FOXJ1 GAS2L2 CCDC103 ODAD1 RSPH3 SCNN1B TAP2 SCNN1A DNAAF4 ABCA3 ICOS STK36 BLM DPP9 FCGR2A PRKCD SFTPA1 ODAD4 CARMIL2 IL21R CCDC65 LRRC6 CXCR4 ZMYND10 SCNN1G DNAI1 ODAD2 IL6ST MUC5B CXCR4 RAC2 LRRC8A ZMYND10 CTLA4 SFTPA2 TAPBP DNAAF6 DNAH11 DNAAF1 CCNO LRRC6 IGHM SPAG1 CD79A IGLL1 CD79B CCDC65 RSPH1 MCIDAS RIN2 BTNL2 CFTR PARN BLNK NCKAP1L FOXJ1 NEK10 RPGR DNAI1 DNAH1 TCF3 ICOS ZNF341 DNAH11 LRRC56 HYDIN HYDIN TGFB1 TNFRSF13B RSPH9 RSPH1 TERC TNFSF12 RSPH4A PIK3R1 CFAP298 MCIDAS CD19 TNFRSF13C ARHGEF1 PIK3R1 ODAD1 PIK3CD SCNN1B TNFSF12 IGHM SPAG1 CFAP300 NEK10 ICOS RSPH3 TTC12 DNAAF5 DNAH1 RASGRP1 RSPH9 NBN CCDC103 HLA-DRB1 IRF9 CD8A B2M FAM13A
    Protein Mutations 1
    C19P
    SNP 0
    HP:0012387: Bronchitis
    Genes 62
    CARMIL2 CR2 SERPINA1 HLA-DQA1 GAS8 DNAAF1 CFAP298 CD79A ATM CD81 NOS1 GNPTAB RPGR ODAD2 RAC2 ZMYND10 IL2RG TAPBP LRRC6 TNFRSF13C HLA-DQB1 SPAG1 CCDC65 TAP1 CFTR CD79B DNMT3B DNAJB13 EGFR ICOS ZBTB24 MS4A1 NFKB2 CD19 CACNA1C NFKB1 HYDIN SCNN1G TNFRSF13B RNF168 TNFSF12 RSPH4A ODAD3 TNFRSF13B CD19 TNFRSF13C ALMS1 IL17RA SCNN1B MGP BLM TNFSF12 DNAAF5 ICOS CR2 CRLF1 NFKB2 NBN TAP2 SCNN1A ICOS PRKCD
    Protein Mutations 1
    G551D
    SNP 0
    HP:0002608: Celiac disease
    Genes 19
    IL12A IVNS1ABP ODC1 WAC TNPO3 IL12RB1 TNFSF15 SRCAP GPR35 STAT3 MMEL1 STAT5B ELN POU2AF1 MLXIPL IRF5 MST1 SPIB TCF4
    Protein Mutations 1
    Q65E
    SNP 0
    HP:0004469: Chronic bronchitis
    Genes 19
    CARMIL2 LRRC6 SPAG1 SERPINA1 ALMS1 ZBTB24 CFAP298 SCNN1B CCDC65 DNAAF5 CFTR ODAD2 DNMT3B SCNN1G SCNN1A RSPH4A RAC2 ODAD3 ZMYND10
    Protein Mutations 1
    G551D
    SNP 0
    HP:0012622: Chronic kidney disease
    Genes 144
    NPHP1 OSGEP LAMB2 TSC2 MMUT COL4A4 FAN1 COL7A1 CEP290 FLT1 INVS CFHR5 TTC21B IFT122 LAGE3 INF2 JAG1 NTRK1 NUP107 CLCN5 ACTN4 BNC2 CLDN16 DZIP1L RAD51C GANAB CLCN5 DNAJB11 SEC61A1 CTNS MYOCD AGXT TSC1 CLCN5 LAMB2 MAPKBP1 APRT IFT140 CLDN19 REN COQ8B NUP93 PKDCC ALDOB MUC1 CEP164 TRAF3IP1 IQCB1 NOD2 PUS3 PAX2 WDR19 IFT43 COL4A3 NPHP4 NPHP4 ALMS1 MAGI2 TRAF3IP1 PKD2 NPHP3 TBC1D8B ARHGDIA GCDH TP53RK CTNS NUP205 PPOX DCDC2 PKHD1 STOX1 CEP290 TMEM126B NPHP4 ACP5 NPHP1 CPT2 WDR19 DZIP1L HNF1B IFT172 SPRY2 GLIS2 NDUFAF6 SOX18 SGPL1 LZTFL1 KYNU APOL1 TMEM67 NPHS2 COL4A3 WDR19 TRPC6 AVIL CHRNA3 TMEM67 SARS2 TMEM231 NUP160 MYO1E CD151 ANLN MMP1 CEP290 DSTYK FN1 WT1 PKD2 INF2 SLC7A7 AHI1 COL4A5 NPHP1 NPHP3 CORIN SDCCAG8 CEP83 TMEM67 OCRL BICC1 TPRKB NUP85 PAX2 TTC21B GSN XPNPEP3 NUP133 NUP107 GATA3 PKD1 INVS CFH PYGM DGKE WDR19 NEK8 WT1 UMOD PLCE1 SAA1 IQCB1 MEFV SH2B1
    Protein Mutations 1
    C677T
    SNP 4
    rs2281135 rs2294918 rs35652124 rs738409
    HP:0012532: Chronic pain
    Genes 5
    FLVCR1 TGFB2 ATXN3 COL7A1 MMP1
    Protein Mutations 1
    K15210D
    SNP 2
    rs1042713 rs12654788
    HP:0006510: Chronic pulmonary obstruction
    Genes 34
    RREB1 CYBB SERPINA1 ARVCF HLA-DPB1 GLA CYBA CTLA4 CYBC1 MMP1 TBX1 NFKB1 HIRA NCF4 RAC2 MYH7 NCF2 WIPF1 ALMS1 PRTN3 GP1BB HLA-DPA1 COMT BLM HMOX1 TBX1 MCIDAS JMJD1C UFD1 SEC24C PTPN22 WAS DNAAF4 NCF1
    Protein Mutations 2
    A118G G551D
    SNP 6
    rs1051730 rs1800470 rs1828591 rs25331 rs4129267 rs7103572
    HP:0001394: Cirrhosis
    Genes 177
    AP1S1 UROD TERT PEX1 TRMT5 AGPAT2 SERPINA1 TNPO3 NR1H4 ENG FOS AXIN1 HSD3B7 COG4 APOE HFE HSD3B7 CC2D2A SLC30A10 TREX1 FECH DLL4 CAV1 NOP10 LIPA SFTPA2 JAG1 PPARG SRSF2 RUNX1 GBE1 HBB GLRX5 GBA PIK3CA HBB CCDC115 MUC5B TYMP CTC1 ASS1 APC SLC30A10 SCARB2 TP53 POLG BSCL2 ACVRL1 TERT BSCL2 F5 COG4 NHP2 ARHGAP31 NPHP3 TNFSF15 PIGA HJV DCDC2 COG6 TERC CBL KRT18 PHKA2 LBR POU2AF1 NGLY1 AGPAT2 MST1 GPC1 JAK2 RPGRIP1L CC2D2A IFT43 GDF2 CASP8 PHKG2 ALMS1 HFE GPR35 LIPA MET HAMP PYGL TTC37 JAK2 KRT8 IL12A KRT18 SKIV2L IL21R ABCB11 RTEL1 TFAM HFE MMEL1 IGF2R ATP8B1 KIF3B RRM2B KRT8 CAVIN1 IRF5 TERC ARG1 TERC RPGRIP1L CYP7B1 TCF4 ITCH TALDO1 TALDO1 TINF2 IL12RB1 ATP6AP1 ASXL1 TMEM67 INPP5E NHP2 AMACR ATP7B TMEM67 BCS1L TREX1 SPIB MPI ABHD5 TERT SLC40A1 TERT MARS1 FAH DKC1 TTC37 BSCL2 TET2 POLG ACVRL1 DOCK6 SLC40A1 USB1 SMPD1 DGUOK BMP2 EOGT DKC1 SLC7A7 TINF2 ABCB4 PARN AKR1D1 F5 WRAP53 SKIV2L PDGFRL TFR2 FARSB NPM1 HBB AP1B1 SMAD4 CTNNB1 ATP7B SLC25A13 ALDOB MTTP GALT PPARG CD40LG PPARG ENG PHKG2 SFTPC MPV17 ATP6AP2 NOTCH1 RBPJ
    Protein Mutations 0
    SNP 0
    HP:0100543: Cognitive impairment
    Genes 877
    SPG11 PRKRA PRDM8 KCNA2 VCP RBM12 SNCB MAPT ITGA7 RBM28 COMT PDE11A PRNP ERCC6 GRN BBS10 EEF1A2 HFE GBA2 PNKP MAPT GDNF SEC61A1 SYNJ1 TRNE SPG7 C19ORF12 SYNJ1 ATP1A3 NPC1 ATXN2 PEX11B FKRP WFS1 WWOX CYTB MFN2 AP5Z1 PRKN CHI3L1 ADH1C ACTB AUH IKBKG SCN1B DNAJC6 GDAP2 SPAST CHCHD10 POLG COASY PMPCA NPHP1 CUBN MLH3 NECAP1 PDGFB TSC2 PLA2G6 PINK1 ECM1 GABRA2 WDR45 NAGLU LIPN TRNQ NOTCH2NLC TRAK1 CSF1R COL18A1 VCP JAM2 ARSA TIMM8A HIBCH TREX1 TRNH B3GALNT2 UQCRC2 HGSNAT LYST ERCC3 ALG12 HSD17B4 GM2A MPO TSFM PRNP APP TREM2 CUX2 ADA2 CLN6 NAGS SCN2A CST3 ATP6V1A SQSTM1 PEX19 PANK2 BBS12 CTSH HNF4A GBA HCRT KLLN PCNT COL4A1 SLC13A5 CFHR3 PLP1 SLC2A1 TGFBR2 PSEN1 NRAS C12ORF65 RNASEH1 PCDH19 NOTCH3 REEP2 NR4A2 SURF1 PSAP ERCC2 TRNK CEP120 VAMP1 GNPTAB ERCC3 TBK1 DGUOK TARDBP MYO1H POLG TUBA4A ND5 LRRK2 SLC6A1 TMEM240 SPG21 SLC18A2 ARL6IP6 BAP1 PRKAR1A DNM1 CYP27A1 RAB27A GALC SMARCB1 PIK3CA PRDX1 A2M LAMA2 QDPR CYP4F22 ATP6 ABCA5 HLA-B VCP PLAA SNORD118 STXBP1 HNRNPA2B1 GABRG2 SQSTM1 HTRA1 AARS2 ABCA7 TSC1 ARV1 STXBP1 GALC FA2H DCTN1 PEX6 RRM2B ERAP1 TIMM8A CLN8 ADD3 SLC2A3 GTPBP3 SLC25A13 NDUFAF3 NTRK2 PPT1 TRNF CFHR1 MAPT B3GALNT2 VCP CHRNG NHLRC1 DNM1L HEXB IL12A AKT1 UCHL1 POLG HCN1 OCRL CYP2U1 CRLF1 HLA-DQB1 APOE STUB1 CHCHD10 MTHFR TRNL1 BBIP1 ATP7B IL23R COX1 NDUFA6 RBBP8 PARK7 NUP107 SLC25A4 CTC1 XPC GNAS PRNP LAMA1 PRNP GRN IRF6 ALG2 TMEM240 SPTBN2 TREX1 APP PDGFRB DSTYK NF2 PRNP AIFM1 EIF2B5 PRNP CDK19 GLUD2 PEX10 GJB6 SPTBN2 SULT2B1 GBA SDR9C7 IDUA PSEN1 CTSK XPA SIM1 ERF RNASEH1 SYNGAP1 PPP3CA CNTNAP2 GCH1 SNCA DAOA SPG11 SYNJ1 CYP2U1 TBK1 MAPT SPG7 SNCA ATM TBC1D24 SLC25A4 GCDH GBA APP PDGFRB DRD3 TTC19 TRNQ RRM2B SYNJ1 SPG21 BBS5 PRKCG TBP CCDC78 SPP1 KRT83 ADA2 MARS2 VCP ACSF3 PTPN22 ADAMTSL4 PHOX2B NAGS NUP133 JPH3 EPM2A CEP152 KRT81 HNF1A TK2 ROBO3 SCN1B GJC2 NFIA EPCAM TP53 EPM2A TMEM106B ALDH18A1 PRNP MATR3 VPS13C ND1 UBA5 MYD88 EIF4G1 PTEN EIF2B2 POLG2 GDF6 PRNP MTOR XPA SQSTM1 GABRG2 NDUFB8 TRNW TREM2 MEN1 BDNF GM2A PIK3CA UBA1 RNF216 RPS20 SCN9A ATXN10 KCTD7 MAOA GALC ERCC5 PRICKLE1 TRNF NDUFS2 APP TRNV TARDBP ATP1A3 MYH3 BRAF MAPT PAH CCM2 POMT2 DALRD3 PEX12 TREM2 SQSTM1 MAPK10 MBTPS2 POMT2 FA2H SDHAF1 SPAST RAB39B ATN1 SMC3 XRCC4 CTNS ARSA ATXN3 PKHD1 MAPT TPRKB POLG SCN9A HNRNPA2B1 SGPL1 COQ2 TBP NOTCH3 WDR4 SLC30A9 DNMT1 MSH6 RIN2 ITM2B MEOX1 GABRG2 APTX LMNB1 UBTF TNFSF4 ATP6V1A SDHB TREM2 CISD2 CENPJ HTRA1 ATP13A2 CCR1 ATP13A2 SMC1A PSEN1 NOS3 GSN DSG4 HEPACAM COL3A1 RMRP CHD2 KCNT1 HTRA2 TRNS2 ALOXE3 TRNS1 CAMTA1 TRNL1 TBP DNAJC13 PNPLA6 SCN8A PSEN2 ERCC8 TREM2 DDB2 FTL SNCA ACTL6B TYMP SNCA HTT GMPPB TTR CHD2 ABCC8 ITPR1 C9ORF72 CSTB COX3 MTO1 ZFYVE26 FKTN PEX13 NDP ABCA12 ATG5 LRRK2 TLR3 NKX6-2 MAPT SLC44A1 CLCF1 C12ORF65 TINF2 CREBBP C9ORF72 GMPPB BAP1 COX2 TGM1 SDHA GRID2 NHLRC1 GABRB2 FAN1 FOXG1 MSH2 SDHC TWNK GABRD CHMP2B TOMM40 GALC MAG ATRIP CHMP2B GDF5 SCN3A TRNK MATR3 CHMP2B GDF3 PEX2 TTC37 GRN DCC PPP2R2B CYFIP2 GLA NBN CACNA1B COASY ND1 SDCCAG8 CLN6 SDHD MECP2 ABCD1 DNAJC5 PDGFRB TREM2 CP PSAP SLC13A5 ATP6V1E1 SLC2A1 ATXN2 MYORG FBN1 PEX26 SLC20A2 FMR1 HLA-DQB1 TWNK FGD1 ATXN7 KATNB1 PRKCG SCARB2 PSAP GABRA5 CENPJ GRN FGFR3 TYROBP GNAS PSEN1 ATN1 POLG RNF216 SRCAP CHMP2B APOE DCX TRNS2 TRNS1 CLMP SCN1A HTT SDHA TUBB2B XPR1 ROGDI TK2 SNCA ATXN1 CREBBP SPG11 ALOX12B APP OPA1 MAPT RRM2B CACNA1G GJB2 GNAS GBA2 ITM2B C9ORF72 WFS1 ND4 PDE10A APP APOL2 GBA ATXN3 SUFU CTDP1 PEX3 AASS TBCK PANK2 UBAP1 PSEN2 GRIN2D MFSD8 UBAC2 CP COX1 PRNP SORL1 CLN8 EIF2B1 UBQLN2 GNE ND6 OPA3 HEXA MAPT PEX1 CTNS APP ZNF365 TRNH DGUOK MMACHC CENPE CERS1 ALMS1 ALDH18A1 DNAJC3 TRNK TBK1 TYROBP SOST SPR TWNK KRAS SUMF1 MOG PIK3CA IRAK1 HTT SLC1A2 LZTFL1 SEC23B TRNP CLTC ASAH1 ASAH1 CPLX1 ALG13 TRAF7 HSD17B10 GJC2 GBE1 KCNB1 P2RY11 FTL C9ORF72 PLA2G6 ERCC8 PSEN1 MAPT DMD POLG PSEN1 PLAU FBXO7 FGF14 MAPT UCP2 ERCC4 SNCAIP AARS1 LARGE1 PEX14 DISC2 ND5 PTS PEX16 EPRS1 TRNL1 FLNA AP2M1 MLH1 GLB1 SPART GIGYF2 PSAP KLRC4 VPS37A IL12A-AS1 C9ORF72 TSC1 KCNC1 ATP13A2 SMO PDCD10 SMC1A GABRA1 PINK1 PPP2R2B HMBS MAPT FA2H GRID2 PSEN1 STAT4 TRPM7 SLC5A7 SCO2 IFT140 VAMP1 BMPR1A PDGFB SYN2 ATP6V0A2 PANK2 KCND3 PMS1 MCOLN1 MTFMT ROGDI DNMT1 KCNJ11 FUS ATP1A2 SCN1A TRAIP SERPINI1 CFH HNRNPA1 SDHD VPS13C TSC2 ATP6 CSF1R PLK4 TRNQ SMARCE1 DCTN1 AP3B2 CACNA1A AP5Z1 TIMMDC1 POMT1 RTN4R PODXL FGF12 TRNF ATP13A2 KRIT1 PLEKHG4 CTSD ATXN7 PDGFB C9ORF72 ATXN3 TTPA PNKP GNAS KMT2A MAGEL2 CLN5 NPC2 PARS2 DARS2 JPH3 KMT2B ERCC2 DCAF17 HTR2A LRRK2 DOLK VCP IL10 COX3 ITPR1 ATP13A2 FAS TMEM106B SNCA VPS35 NAGA EP300 POMK GRN MTHFR DNMT1 SLC18A2 USF3 POMGNT1 GABRB3 PRDM8 KIF5A TRNS2 ATXN3 SDHAF1 LARS2 SDHD MEFV CSTB HCN1 ERCC6 TERT COX2 TWNK ERCC4 CHRM3 GBA SCN2A DHDDS EIF2B4 PRKAR1B NF2 DNM1 AFG3L2 PANK2 RBM28 OSGEP BSCL2 RNR1 SCN8A FAS AFG3L2 LAGE3 SLC25A15 NUS1 KCNA2 ATR METTL23 DNAJC6 KRT86 TP53RK SCN1A GPC4 YWHAG STAT4 PLA2G6 GBA EIF2B3 BSCL2 CNKSR2 SEMA4A CYP7B1 VPS13A STARD7 VPS13A STUB1 SZT2 CLN3 CTSF ATXN2 DZIP1L TLR4 MAPT APOL4 GBE1 FGF14 TRNW CHMP2B TRNC PORCN PEX5 EDN3 AKT1 ALG9 PEX16 ADGRV1 IBA57 LTBP4 WDR73 C12ORF65 ND6 WDR45 ATXN1 ATXN8OS SUMF1 CFAP43 C4A DARS2 POLG FMR1 LAMP2 HLA-DRB1 ND5 TTC8 TUBB4A RRM2B SCN1A ARSA NOTCH2NLC SLC7A7 ABCA7 DMPK STX1B UGT1A1 C19ORF12 PMS2 NIPAL4 TMEM106B MPDU1 TRNS1 GBA SDHB
    Protein Mutations 0
    SNP 0
    HP:0002583: Colitis
    Genes 47
    RASGRP1 CIITA CARMIL2 SKIV2L XIAP OPLAH RTEL1 PLCG2 PSTPIP1 POLA1 NLRC4 MST1 TCF4 LRBA ZAP70 ELANE FERMT1 SKIV2L BACH2 GPIHBP1 RFXANK IVNS1ABP NOD2 IL6 RFXAP STAT1 GPR35 TGFB1 FAS PRKCD MASP2 TTC37 NCF4 RFX5 MAP3K7 ZAP70 IL10RA INAVA FASLG RET TNFAIP3 IL10RB FOXP3 CYBC1 CASP10 FAS HPS1
    Protein Mutations 2
    H180Q V600E
    SNP 0
    HP:0012423: Colonic inertia
    Protein Mutations 0
    SNP 0
    HP:0001635: Congestive heart failure
    Genes 261
    TBX20 RAB3GAP2 AGPAT2 FLNC LDB3 TMEM127 FOS COG7 PHYH HFE PRKAR1A GNPTAB KCNJ5 LIMK1 TRNK RBM20 PPARG SDHAF2 HBB STAT1 HADHA VHL FGFR3 PRKAG2 ENPP1 RET CAV3 SELENON EYA4 PNPLA2 PRKAR1A SCO2 LMNA RYR1 FBN1 MYL3 HJV ELAC2 TMEM43 TRNL1 CITED2 DES ABCC6 CLIP2 COX3 CYTB JUP TPI1 ADCY5 PSEN1 FH GDF2 DSP ELN TTN IKBKG GJA1 BAZ1B HNRNPA1 GPR35 COL1A1 CCR6 TRNQ AFF4 RFC2 GTF2I TTN GATA4 CACNA1S GLB1 TNNI3 AGGF1 SF3B1 CAVIN1 PLN TRNF TNNI3K TCF4 VCL TUBB RET ATXN7 LMNA LMNA GTPBP3 XYLT2 SDHB FBLN5 HBA1 MYH7 TMEM127 KIF1B DES HADHB DNMT3A VPS33A CAV1 CDH23 TLL1 EPG5 ATP6V1A GLA BMP2 EFEMP2 SLC25A11 HADHB ACTN2 ND1 PSMB8 SCN1B CP TMEM70 MYD88 HBB SMAD4 ALMS1 MTTP MAX ACAD9 VHL SLC25A3 FGD1 NDUFB8 TRNW HBA2 SDHD BCHE WRN SLC2A10 TRNS2 CYTB ENG SDHB NDUFB11 LMNA DMD COX2 CAV1 NKX2-5 LMNA SURF1 HLA-DRB1 GATAD1 SDHC PRKAR1A TRNK PRDM16 TNNT2 GNA11 IFIH1 ABCC6 HBB MDH2 NDUFS2 TRNV SDHA ACAD9 FXN SLC25A26 SLC19A2 GTF2IRD1 RPS19 GLA PPA2 MYPN EYA4 CITED2 DTNA MAX NF1 LMNA XYLT1 ND6 SNAP29 TBX20 DSP MST1 FLNA DLST MYH7 MYH7 ADAMTSL2 MYH7 VCP SCN4A ALMS1 NKX2-5 GDNF HFE TF MECP2 BAG3 HAMP TRNK TET2 ACTC1 RASA1 LMNA LMNA MYH6 TRPM4 TRIM37 SDHD TLL1 TRNC STRADA CCN2 HNRNPA2B1 MYH7 TAZ RET CLIC2 SGCD GTPBP3 PEX7 SDHB TRIP4 MYSM1 TPM1 NDUFAF3 PTEN CEP19 SDHD NDUFAF1 FGF23 EPAS1 ND5 SLC17A5 HADHA GATA6 BSCL2 ATP5F1A ACVRL1 CLIC2 IRF5 ACTC1 TBL2 MAPRE2 JUP CASR KIF1B VHL NSMCE2 TRNL1 ADCY5 DNAJC19 DSP MYLK2 PLOD1 COX1 MYH6 COL1A2 IDS PPARG ENG SCN5A GBA TRNS1 PSEN2 SLC22A5 TRNE
    Protein Mutations 14
    C1236T C3435T C825T E161K E28A E28C E28D G2677T G308A M235T Q12H S2808A V30M V66M
    SNP 0
    HP:0002019: Constipation
    Genes 478
    ZIC2 TRIO POGZ CAMTA1 TRNL1 NRXN1 NODAL COL5A1 DNAJC13 POLG LIMK1 PRNP EXT2 COL7A1 VANGL1 SIX3 SDHC TSHR GP1BB SNCA LAMA3 HFE MAPT MLXIPL SALL1 PAX8 AVPR2 SEC24C TTR CAMK2B HNRNPK ATXN2 THRA UBE3A SCNN1A NKX2-5 PRKN DEAF1 DISP1 GAS1 SOX2 ADH1C CDC73 CACNA1S LRRK2 FOXH1 MECP2 BIRC3 ELN SCN11A MAGEL2 DNAJC6 OCRL ASCL1 JMJD1C UFD1 CREBBP HNRNPH2 TSHR COX2 DLL1 TXNRD2 SIX3 NKX2-5 GTF2I MBD5 MLH3 NSD1 FAN1 FOXG1 VPS11 RORA SLC26A4 MSH2 TG FOXH1 SETD5 DDOST KMT2A EDN3 CDON EDNRB TCF4 LHX3 OTX2 TLK2 GAS1 SMO OTUD6B KCNJ1 TRNH MRAP SLC5A5 KRT14 UFC1 RET COL5A2 TTR SPOP IGH NODAL BRAF RET LHX4 PSMB8 ACTG2 SHH DISP1 MNX1 MECP2 DSE POU1F1 NKX2-1 CSNK2A1 KIT GLI2 COL1A1 HIVEP2 TBCD RERE SCN9A TANC2 WDR26 DISP1 LMNB1 SIX3 ARNT2 POLG TWNK SLC6A8 FGF8 MEFV TDGF1 TGFBR2 CHST14 AQP2 LRIG2 TRNS2 GLI2 FGF8 TRNS1 STAT6 POU1F1 NR4A2 FGFR1 STAR CREBBP ZEB2 GABRA3 WFS1 ATN1 ND4 CDKL5 PAX8 ND5 PCCB CDON WAC STAG2 OCRL STXBP1 WASF1 FLI1 SIX3 COX1 RAI1 NGLY1 PCCA PIK3CA CAMTA1 DDOST KIT HPSE2 CTNS ZIC2 AQP2 ATRX FOXP1 PROP1 KRAS FGF8 PROKR2 SHH CNTNAP2 HMBS DHPS TH STAG2 PCGF2 NODAL SLC26A4 PTCH1 ZIC2 LMX1B NAB2 TRHR GAS1 ECE1 SLC5A5 TCF4 TRNF HESX1 FTL DUOXA2 DYRK1A UBE3B CDON DPF2 TYMP KCNJ18 UCHL1 TSHR PACS1 NNT CDKN1A MSL3 PTCH1 GLI2 SLC6A3 TCF4 TSHB SNCAIP COQ2 PACS1 ZEB2 CHST14 PARK7 SLC25A4 SLC12A3 NRTN ZMIZ1 SDHA SMC1A SCN10A CASR KRT5 CHCHD2 MLH1 NALCN MC2R KIT SPART GIGYF2 SOX3 PCCA HPSE2 FOXA2 SIK3 TRNK CDKN1B MEN1 PINK1 MRPS34 DDHD2 HMBS TCF20 PHOX2B CAVIN1 GDNF ADNP NRXN1 RET GLUD2 ABL1 MED25 SETD2 RREB1 PROP1 BMPR1A CD96 TRNL1 ARVCF ATRX GALNT2 PMS1 EDNRB ALDOB CLIP2 PDGFRA TBX1 IGHMBP2 POGZ PIGS SYNJ1 BRCA1 ODC1 BAZ1B ZSWIM6 LAMC2 PPOX LHX4 P4HTM GBA RAI1 UGP2 TRNQ RRM2B AFF4 TRH RFC2 SIX3 TDGF1 SEMA3C CDKN2C SLC6A3 PODXL USP7 ATRX HESX1 MLYCD GATAD2B CDON GDNF B2M OTUD6B MAGEL2 ALAD FDFT1 PPM1D EDN3 MED12L RAI1 GJC2 ZIC2 HESX1 LRRK2 GLI2 ARID2 EPCAM FOXE1 SPATA5 COX3 SLC6A8 FOXH1 TRIO EXT2 BCL10 VPS13C SNCA ND1 VPS35 EIF4G1 FGF8 ATRX GABRD POLG2 EP300 APC SOX3 SLC12A3 KCNAB2 TGIF1 WAC POLG2 GRIN1 DHCR7 PTCH1 DES TDGF1 CLCNKB VPS51 MMP1 SHH SCNN1B AVPR2 GLI2 CHRM3 SKI RPS20 GBA SDHB CREBBP GAS1 FOXG1 PROP1 COMT UNC80 TBX1 TGIF1 CDC73 WAC SCNN1G GTF2IRD1 MEFV PAX8 SCN11A PIGV LAMB3 IYD NFIX DEAF1 PTCH1 FGF12 ADAT3 FOXH1 RAI1 TAF1 FLII MALT1 NALCN SOX10 TGIF1 MDH2 SEMA4A SLC12A1 MED13 FLNA KCNH1 KDM1A APC2 FGFR1 PPOX ALPL EP300 TDGF1 TRNW DLL1 SHH RET TPO TGIF1 MED12 TBP PEX16 EP300 SOX10 TBCD MSH6 TNFRSF1A FOXP1 SCN9A ND6 FGFR1 ATXN8OS UBE2A SMPD1 POLG CREBBP CHD8 ELN PCCB CPOX WDR26 SDHC PAX8 DUOX2 ELP1 CISD2 NODAL COL7A1 DDC EDN3 TBL2 DLL1 COQ2 MED12 CDKN2B VPS11 HIRA LRIG2 SRCAP MITF IQSEC2 DMPK OTX2 PMS2 DLL1 PRDM16 SDHB ZEB2 DACT1 SEMA3D HTRA2 TBL1X UNC80 DISP1 SH2B1 TRNE
    Protein Mutations 2
    G1314A G1321A
    SNP 0
    HP:0001677: Coronary artery atherosclerosis
    Genes 52
    MFAP5 ELN LDLR APOB ACTA2 BRCC3 MYH11 ERCC6 LMNA SMAD3 ZNF687 KCNJ5 TGFBR1 ERCC8 LMNA FBN1 MYH11 CYP7A1 LMNA LMNA TGFB3 XYLT2 MYH11 CEP19 ABCG8 PCSK9 MYLK LMNA PRKG1 FOXE3 APOE TGFBR2 TGFB2 SMPD1 ABCC6 XYLT1 ABCG8 MAT2A LOX APOB ESR1 SERPIND1 ABCG5 LDLRAP1 PPARG SMAD4 ACTA2 LIPC LMNA LOX ABCA1 ABCA1
    Protein Mutations 3
    C282Y C825T H63D
    SNP 19
    rs10153820 rs1143623 rs1143633 rs1143634 rs12041331 rs16944 rs16969968 rs17561 rs1761667 rs2043211 rs20432111 rs2305619 rs4612666 rs4848306 rs6434222 rs7586970 rs7903146 rs8069645 rs8176528
    HP:0012735: Cough
    Genes 152
    GAS8 TERT DNAL1 ZBTB16 IKZF1 LRRC56 HLA-DQA1 VCP GAS8 TERT CCDC40 CYTB RSPH4A DNAI2 DNAJB13 CCDC39 LPIN2 ODAD3 DNAH9 NABP1 IL2RG NUMA1 WWOX TSC1 ACAT1 HLA-DRB1 SFTPA2 STAT3 TTC12 GBA MUC5B EPOR DSP CFTR RNF6 CLEC7A DNAAF2 DNAI2 CFAP221 SPEF2 ODAD4 HLA-DPB1 OFD1 ATP11A CFAP300 NME8 ODAD2 DRC1 TGFBR2 ODAD3 DNAAF4 SFTPC DNAAF6 DNAH5 SCNN1A EIF2AK4 DNAH9 SP110 RTEL1 CSF2RB TRAF3IP2 STN1 PARN TBL1XR1 IL17RA DNAAF3 FOXJ1 GAS2L2 CCDC103 ODAD1 STAT5B SCNN1B SLC11A1 ABCA3 STK36 DPP9 SFTPA1 ODAD4 DNASE1L3 CCDC65 LRRC6 TSC2 ZMYND10 CTLA4 COPA SCNN1G NOS1 PRKAR1A DNAI1 IL17F MUC5B STAT3 NPM1 LRRC8A DLEC1 SFTPA2 DNAAF6 DNAH11 DNAAF1 CCNO IRF2BP2 IGHM HLA-DQB1 IL17RC CD79A PML PRTN3 IGLL1 CD79B FIP1L1 BTNL2 PARN BLNK PTPN22 FOXJ1 NEK10 RPGR CSF2RA TERT MARS1 DNAH1 TCF3 SCNN1B SCNN1A SCNN1G LRRC56 BCOR HYDIN POMT1 RARA RSPH9 RSPH1 TERC PIK3R1 CFAP298 MCIDAS FARSB HLA-B PANK2 ODAD1 HLA-DPA1 SPAG1 CFAP300 RSPH3 DNAAF5 CRLF1 SFTPC CCDC103 HLA-DRB1 ERLIN2 PTPN22 FAM13A
    Protein Mutations 0
    SNP 0
    HP:0100280: Crohn's disease
    Genes 10
    BACH2 NOD2 PSTPIP1 IL10RA INAVA IL6 MEFV CYBC1 CTLA4 IGHM
    Protein Mutations 3
    G908R R702W V600E
    SNP 2
    rs2062305 rs2097432
    HP:0000726: Dementia
    Genes 291
    PRNP PRDM8 VCP TRNL1 GIGYF2 GRN IRF6 SNCB C9ORF72 DNAJC13 PNPLA6 MAPT APP PDGFRB PSEN2 ATP13A2 PRNP TREM2 FTL HFE PINK1 SNCA PPP2R2B GBA2 PRNP TYMP SNCA HTT MAPT MAPT PRNP GLUD2 TTR PSEN1 TRPM7 TRNE C19ORF12 GBA NPC1 ATP6V0A2 PSEN1 ATXN2 PANK2 WFS1 C9ORF72 CSTB COX3 CYTB ZFYVE26 ROGDI DNMT1 PRKN NDP FUS SNCA ADH1C LRRK2 AUH SYNJ1 TBK1 MAPT DNAJC6 SNCA SERPINI1 HNRNPA1 SDHD VPS13C GCDH GBA APP CHCHD10 ATP6 C9ORF72 TRNQ TRNQ DCTN1 COX2 SPG21 SDHA CUBN PDGFB TBP NHLRC1 PODXL PINK1 TRNF ATP13A2 WDR45 VCP CHMP2B NOTCH2NLC TOMM40 C9ORF72 JPH3 EPM2A CSF1R CHMP2B VCP ARSA NPC2 TIMM8A TREX1 TRNH MATR3 JPH3 CHMP2B LYST LRRK2 GRN MPO PRNP EPM2A APP VCP TREM2 PPP2R2B TMEM106B COX3 ALDH18A1 ND1 ADA2 PRNP CLN6 MATR3 ATP13A2 CST3 VPS13C ATP6V1A TMEM106B SQSTM1 SNCA ND1 VPS35 MECP2 ABCD1 DNAJC5 TREM2 EIF4G1 SLC13A5 ATP6V1E1 PRNP ATXN2 GBA GRN FMR1 COL4A1 HLA-DQB1 TRNW SCARB2 GRN PSEN1 TRNS2 TYROBP TREM2 PSEN1 SDHAF1 ATN1 RNF216 CHMP2B APOE TRNS2 TRNS1 NOTCH3 HTT COX2 XPR1 TWNK GM2A ROGDI ERCC4 NR4A2 RNF216 SNCA PSAP GBA TRNK ATXN10 APP PRKAR1B OPA1 KCTD7 MAPT PRICKLE1 DGUOK APP TRNV GBA2 ITM2B WFS1 TARDBP ND4 POLG APP TUBA4A TARDBP ND5 LRRK2 SPG21 PANK2 PSEN2 CP COX1 SORL1 UBQLN2 CYP27A1 ND6 TREM2 HEXA PRDX1 MAPT A2M PLA2G6 SQSTM1 MBTPS2 ATP6 APP MMACHC VCP SPAST CERS1 RAB39B VPS13A ATN1 ALDH18A1 HNRNPA2B1 TBK1 TYROBP SQSTM1 HTRA1 AARS2 ATXN3 CLN3 CTSF ATXN2 MAPT TRNW CHMP2B TRNC DCTN1 HNRNPA2B1 RRM2B TBP NOTCH3 ASAH1 DNMT1 ND6 WDR45 ATXN8OS CFAP43 ITM2B TRNF FMR1 GBE1 MAPT APTX FTL VCP C9ORF72 PLA2G6 ND5 NHLRC1 DNM1L ERCC8 UCHL1 TUBB4A TREM2 CISD2 PSEN1 POLG MAPT PSEN1 PLAU FBXO7 HTRA1 ATP13A2 NOTCH2NLC APOE ABCA7 PSEN1 NOS3 CHCHD10 SNCAIP TRNL1 ATP7B COX1 PARK7 TMEM106B HTRA2 TRNS1 GBA SDHB
    Protein Mutations 1
    V158M
    SNP 0
    HP:0000819: Diabetes mellitus
    Genes 547
    VANGL2 NR2E3 WFS1 GLIS3 FOXH1 PROK2 TRNL1 NDUFS6 PPARG PEX1 FBN1 LMNB2 LIMK1 PRPF4 RP2 CFTR PAX4 PPARG CTNNB1 HBB COL2A1 POC1A KCTD1 LIG4 PDE6B TOPORS ARL2BP ABCC8 SLC30A8 KCNJ11 MLXIPL CDON WRN PRKAR1A PROM1 TRNE NEUROD1 CNBP KCNJ11 MMP14 C8ORF37 APOE SLC16A2 CTRC ZBTB20 BBS2 WFS1 BLK WFS1 KRAS COX3 CYTB ZFYVE26 FGF8 SOX2 XRCC4 CDH23 ELN CEL GPR35 SLC29A3 FOXC2 EIF2AK3 PTF1A TCF7L2 HNF1A ARMC5 MKKS PDE6A PDX1 COX2 PSTPIP1 EIF2AK3 GTF2I NEUROD1 CNOT1 ATP6 USH2A ITPR3 LMNA NDUFA1 NDUFA11 CAVIN1 PCARE HLA-DRB1 CAT TCF4 AIP GCK PLCD1 HNF4A HERC2 PDX1 OTX2 HJV TRNH IL6 PWAR1 PAX4 TKT RPE65 REEP6 HNF4A RLBP1 SIX3 CFTR IGF2BP2 HNF1A POMGNT1 ND1 SAG GCK BLK GPD2 RAC1 AKT2 SEMA4A WRAP53 MOG CP ARL6 AIP ALMS1 SBDS NPAP1 CDHR1 ITCH BLM HNF1B NSMCE2 ARNT2 TWNK PDX1 PDX1 DLL1 ROM1 NDUFAF3 SNORD116-1 PDE11A NDUFS4 FOXP3 WRN ZMPSTE24 UBR1 ZNF513 INSR IARS1 SLC19A2 RP1 GJA1 TRNS2 TRNS1 PRKACA PCNT FLT1 NOTCH3 TULP1 LMNA MC4R PRKACA PNPLA6 CAV1 IFIH1 NOP10 NEUROD1 MEN1 PLAGL1 ND3 TRNK ZFP57 BRCA2 SPATA7 OPA1 VANGL1 DMXL2 NODAL GJB4 EDA2R HBB CA4 MKRN3 SNORD115-1 FXN GATA6 WFS1 RP9 ND4 TMEM126B NDP BRCA1 SLC19A2 ND5 HMGA1 NDUFAF1 MERTK RETN PRPF6 HLA-DQB1 SPINK1 CP COX1 HNF4A RPGR ND6 MST1 GUCA1B NDUFA6 EDA HNF1A RNASEH2C ALMS1 TIMMDC1 HFE CIDEC DNAJC3 INS KIAA1549 IRS1 LMNA PROKR2 GCK PRKAR1A HNF1B LEPR POLR3A HYMAI SNRNP200 LIPE HYMAI CNGB1 CLRN1 ZIC2 APOA5 GAS1 EFL1 PIK3R1 TTC8 SARS2 HNF1A GJA1 PTF1A RNASEH2B TRNF NEUROG3 LRP6 TDGF1 NDUFB11 HESX1 NDN FOXP3 HNF1B ABCC8 ND2 TGIF1 PRPH2 DNM1L PRSS2 BBS2 INS NUBPL LIPE SAMHD1 DISP1 DHDDS LEMD3 DKC1 MKRN3-AS1 KLF11 IDH3B TRNL1 GLI2 FUZ SMPD4 COX1 PLIN1 SLC25A4 CNGA1 LHX1 SNRPN INS AGPAT2 GNAS SUFU DNAJC21 FOS SPINK1 CAV1 ARL3 HFE TUB TRNK KLF11 AKT2 NDUFB3 PPP1R3A NEK2 STAT1 PRPF3 RDH12 USP8 IFT172 BSCL2 ABCC8 HAMP PDE8B NDUFV1 PNPLA2 CYP19A1 LMNA ARHGEF18 MMP2 ABCA4 LRAT NDUFS7 INS TRNL1 LMNA ABCC8 PAX4 PRSS1 CLIP2 BEST1 SCAPER PIK3R1 ZNF408 SIM1 KCNJ11 PTRH2 FXN TRMT10A CASR BAZ1B ATM CPA1 NDUFS2 BRAF ADAR ZFP57 APPL1 TRNQ TRNQ RRM2B DNAJC3 STOX1 RFC2 PRCD DHX38 HNF1B IRS2 SMAD4 HNF1A ND1 KCNJ11 SLC7A14 PDE4D CDKN2A IL18BP PTRH2 NDUFS3 TRNF NDUFAF2 FAM161A VANGL2 FGFR1 CISD2 ABCC8 LEP XRCC4 TTPA NHP2 NKX2-5 AMACR MAGEL2 KDSR POLD1 KIZ INS CORIN NDUFS8 DCAF17 NDUFAF4 FOXRED1 PEX6 COX3 PRSS2 MTNR1B BMP2 PEX10 PARN PAX4 NDUFB10 ND1 INSR PRSS1 TP53 NPM1 MAGEL2 HBB POLG2 SOX3 SLC12A3 AIRE UBR1 GCK IL2RA TRNW WFS1 IMPG2 TRNS2 PTCH1 LEPR KCNJ11 IL2RA CLCNKB ATM STAT3 AGBL5 CARS1 HMGA2 COX2 MAFA TTC7A TWNK GJB3 LMNA AHR PLAGL1 PALLD NDUFS1 CRX CRB1 GATA6 GLRX5 ENPP1 CEL HNF4A CTC1 TRNV RNASEH2A HYMAI NDUFV2 IMPDH1 APPL1 BBS1 PALB2 GTF2IRD1 EIF2S3 SHH AEBP1 SLC2A2 PRPF31 MTHFR KLHL7 NDUFAF8 TERC PDX1 GCK TP53 AGPAT2 CCDC28B SLC29A3 ABCC8 PLIN1 GATA3 NRL PDE6G RBP3 PDX1 DCAF17 IPW NDUFAF5 MTHFR XRCC4 CTNS GCK FGFR1 STUB1 HNF1A BLM ELMO2 STAT3 HGSNAT KCNJ11 CERKL TRNW RTEL1 TRNC CTRC KCNJ11 RHO IDH3A RP1L1 TREX1 ITCH PNPLA2 PWRN1 CNOT1 FOXP1 ND6 EYS SRP54 TINF2 INSR IFT88 POLG ARL6 AHI1 ELN PTPN22 CEP19 PRPF8 POLA1 MAPK8IP1 MAK ND5 TERT LIPC BSCL2 AR CISD2 KCNJ11 OFD1 USB1 TBL2 RGR ERGIC1 FSCN2 NDUFB9 IER3IP1 INS DMPK PTPN1 NSMCE2 GPR101 HNF4A PPARG IFT140 PPARG PDE4D GCK TRNS1 SPINK1 PPP1R15B ABCC8 STAT1 IGF1R TRNE
    Protein Mutations 12
    A54T C1858T C282T C282Y E158K E23K H63D I191V K1270A K3048A P12A S9C
    SNP 16
    rs10830963 rs13266634 rs2266782 rs2281135 rs2294918 rs35874116 rs35874116rs rs5215 rs5219 rs738409 rs780094 rs780094s rs78408340 rs7903146 rs9701796 rs9939609
    HP:0002094: Dyspnea
    Genes 440
    TBX20 ELN ND4 TERT CHRNA1 DPM2 NABP1 EDA NUMA1 ORC6 HLA-DRB1 FGFR2 RNU4ATAC FBN1 XYLT1 HBB COL2A1 LAMA3 DSP ZIC3 DNAAF3 TRIP11 TRPV6 TRNE SERPING1 MYL3 TTN CITED2 DBH GATA6 ABCG8 TARDBP MUSK AIMP2 SFTPB SCNN1A EIF2AK4 EPHB4 ORC1 TRNL1 VPS33A STAT5B VCP CCR6 LRP4 ORC1 BMPER GATA4 TSC2 LTBP3 SCNN1G CHRNB1 ORC6 KCNJ6 MUC5B ATP6 PET100 TRAK1 LAMB2 LIFR FIP1L1 FIG4 COQ7 FBP1 MYLK SLC35A1 SOX9 PRPH MMAA VPS33A SCO1 DISC1 TET2 ISCU TGFB2 GLA DNAJC21 CHRNE NUP214 COL13A1 ALAS2 POMT1 RPS28 VAMP1 CHRNB1 SDCCAG8 NAGS SFTPC SCN4A EOMES ACADM ND6 PON1 HLA-B FGFR2 PYGM TRNE TWNK DMPK ATRX FOXP3 COX14 PSAP SLC2A10 SERPINA1 DNAJB6 ENG OPTN CYB5R3 GATA4 DPM1 NKX2-5 TK2 SURF1 HLA-DRB1 TACO1 ND1 TBX4 CDT1 UBE3B MYH11 NEB GBA HBB MYBPC3 USP9X ABCA3 STT3B CYB5A GATA6 CSPP1 TSC1 KRT6B KIF20A GNAS COX6B1 PLCB4 ETFDH TAF15 GNAS PLEC CITED2 LMNA ETFA ATP11A SCN4A IFT81 TRNV NPPA GNAI3 NEFH ALMS1 NKX2-5 CSF2RB PUF60 TRNK SMAD4 TBL1XR1 ACTC1 STT3B SCNN1B ADAMTS13 ABCA3 DPP9 MYL2 SFTPA1 TRPM4 IRAK1 TLL1 APOB FAM20C UNC13A TRIP11 ATXN2 GATA6 CSF2RB CHRND PRRX1 GMNN GTPBP3 CHRNA1 NDUFAF3 ABCA3 BTNL2 PCSK9 TRMU CCNF TET2 TERT ZMPSTE24 MARS1 NKX2-1 ANXA11 DAO SOD1 ACADVL IRF5 MEGF10 MAPT COL1A2 DSC2 EDN1 SLC25A1 EPHA4 MYH6 LDLRAP1 DCTN1 SLC25A4 CNTNAP1 SCN5A SFTPC COL13A1 FGFR1 DPM2 SH2B3 LOX ND3 FAM13A CASR TRMT5 MFAP5 ZBTB16 BTNL2 TRNN CHAT ARX FLNC AIFM1 MRPL3 SFTPC TNNT2 MYH11 NEK1 SLC18A3 TSC1 USP9X SFTPA2 PRRX1 COA3 TGFB3 MUC5B HNRNPA1 NR2F2 CFTR TBK1 SCN4A CHRNE ADNP STAT4 SCO2 SCN5A PON3 SLC52A3 FLNC CRELD1 SFTPC COX7B MAPT LAMC2 COX20 SIK1 JAK2 MMUT ALDH7A1 JPH2 CYB5R3 SLC25A1 FUS ETFB RRM2B SFTPB PMM2 LDLR DNASE1L3 SPP1 TRNS1 ZFPM2 RUNX2 PFN1 VCL SFTPA2 NAGS ASXL1 SCO2 TBC1D24 BMPR2 PARN CSF2RA CHRNE CAV1 PRKG1 CRLF1 PNKD GNAS TLL1 GLE1 COL2A1 KAT6A BCOR MGME1 TNNI3 RARA DOK7 MAT2A SCN1B ORC4 CHRND HLCS PON2 PPARGC1A COX8A MMAB GBA POLG2 DNA2 EFTUD2 SLC12A3 SLC25A3 ACTA2 NDUFB8 GAA FGFR2 CHMP2B COA8 TERT ND5 FBP1 ADCY6 IKZF1 VCP SRP54 AGRN TSC2 CLCNKB CDC6 HCCS COLQ NDUFB11 SNAP25 SMPD1 COX10 MGME1 DHX16 PRKAR1A STAT3 SRSF2 RUNX1 LYRM4 WIPF1 GALC PRRT2 DYNC2LI1 NDUFS2 AGRN SSR4 EPOR PRKCSH CHCHD10 ASAH1 SBDS MPC1 ACVRL1 TET2 LAMB3 SLC5A7 FOXE3 DNA2 CBL TGFBR2 CHAT RAPSN MATR3 CDC45 TBX20 IL1RN CFAP410 IFT52 NOD2 FOXF1 GBA STAT5B C9ORF72 RTEL1 NGLY1 STN1 SQSTM1 PIGT KCNA1 CAV1 KRT16 BMPER KRT17 RPS26 OTX2 TRNW LGI4 CCN2 COPA SMAD3 PRKAR1A MYPN EP300 TGFBR1 TRNK AK9 NPM1 ERF KRT6A GLT8D1 MYO9A IRF2BP2 VAPB STX16 TNNC1 PML ND2 POLG CREBBP KLHL7 ERBB4 UBQLN2 SETBP1 WAS MMUT TREM2 NKX2-1 GATA6 FGFR2 TUBB4A SYT2 TERC ANG CPT2 ABCG5 COA8 PGM1 ITGA3 RNF13 HLA-DRB1 GYG1
    Protein Mutations 0
    SNP 0
    HP:0100584: Endocarditis
    Genes 20
    HLA-B TLR4 IL12A C4A UBAC2 IL23R MEFV KLRC4 NR2F2 IL10 IL12A-AS1 GATA6 PRKAR1A CCR1 ERAP1 GATA4 STAT4 CRELD1 PRKAR1A FAS
    Protein Mutations 0
    SNP 0
    HP:0030127: Endometriosis
    Genes 2
    THOC6 THOC6
    Protein Mutations 0
    SNP 4
    rs10859871 rs11031006 rs2273773 rs7521902
    HP:0100633: Esophagitis
    Genes 27
    ADAMTS2 SLC2A10 SLC6A5 CARMIL2 GLRB ATAD1 IARS1 STXBP1 TGFBR1 RPL11 PGM3 MEN1 LMX1B PHGDH ATP7A FERMT1 GPHN TCF4 TGFB3 TCF4 TRAPPC11 TGFBR2 CDKN1B SMAD3 PSPH TGFB2 GLRA1
    Protein Mutations 1
    D961H
    SNP 0
    HP:0012378: Fatigue
    Genes 394
    TBX20 COL5A1 NABP1 NUMA1 DDB2 SDHC MMADHC RET NLRP3 CCND1 TNFSF15 HLA-DPB1 CITED2 DBH KRAS SCNN1A TARDBP SOX2 CDC73 CDH23 BIRC3 MDM4 GPR35 JAK2 HBA1 ARMC5 STAT5B VCP SERPINA6 TSHR TXNRD2 PSTPIP1 NKX2-5 TICAM1 MLH3 GATA4 TSC2 FAN1 CTLA4 SLC26A4 MSH2 TG TCF4 CD244 RET IGHM IL12RB1 AIP CD79A SDHB LHX3 OTX2 FIP1L1 FIG4 SYNJ1 PTPN22 DNMT3A CALR MRAP PRPH SLC5A5 ERCC3 COL5A2 TET2 CDH23 HLA-DRB1 IGH GLA ALAS2 LHX4 POMGNT1 ACADM POU1F1 PON1 BCR HLA-B NKX2-1 AIP KIT CPT1A COL1A1 PYGM HNF4A ABCC2 VHL ARNT2 TWNK ATRX SLC18A3 PDE11A TGFBR2 SLC2A10 PIEZO1 STAT6 POU1F1 ALB COQ2 OPTN PRKACA HBA2 TK2 ERCC2 STAR BRCA2 OPA1 MET DNAJC6 MDH2 SLC25A26 BRCA1 PAX8 ATP7A KCNQ1 TAF15 SLC18A2 UBAC2 CITED2 CAV3 TRHR NF1 LBR PTPN3 MST1 PIK3CA INSR KIT HLA-B MORC2 NEFH NKX2-5 CHRND FOXP1 TLR3 TRNK PROP1 PLEC IGH BCL2 TBL1XR1 ACTC1 NFKB2 MPL HELLPAR KRAS PROKR2 GCK SDHD PRKAR1A TLL1 MMEL1 BCL6 UNC13A TAZ IRF5 SLC26A4 ERAP1 ATXN2 NAB2 HMGCL PRTN3 BTK HESX1 BTNL2 DUOXA2 SDHD SPIB KIF23 CCNF PTPN22 TET2 FGF23 DNM1L TNXB PIGA TCF3 IL12A ANXA11 DAO SOD1 KCNN4 TSHR NNT SLC3A1 TBX19 COL1A2 HAVCR2 IVNS1ABP EPHA4 ERCC4 TSHB IL23R MYH6 HLA-DPA1 NFKBIL1 SMAD3 DCTN1 SLC25A4 C1QBP SLC12A3 XPC SDHA SH2B3 MLH1 ZBTB16 PADI4 MC2R GNAS CFH CTNNB1 KLRC4 CCND1 IL12A-AS1 SOX3 NEK1 HFE FOXA2 TSC1 NR3C1 SDHAF2 AP2S1 HNRNPA1 USP8 TBK1 HLA-B PDE8B GBA PROP1 MEN1 BMPR1A MLX GCH1 PMS1 XPA PON3 PDGFRA VHL JAK2 FH JAK2 LHX4 PYGL AGK FUS GATA2 RRM2B TET2 SMAD4 CCDC78 CDKN2A HESX1 IL18BP PFN1 LRRC8A NAGS NLRP3 ASXL1 IGLL1 KCNE1 CD79B PNPLA8 TMEM127 BLNK HNF1A CD46 TLL1 HESX1 IGH GLE1 GLI2 EPCAM FOXE1 IL10 BCOR SLC25A11 RARA NLRC4 BCL10 ATP13A2 STEAP3 PON2 PPARGC1A MYD88 TP53 ATM POLG2 KL SOX3 SLC22A4 CHMP2B ARMC5 IKZF1 TNPO3 MEN1 CDH23 MEFV SCNN1B TWNK RPS20 SDHC ABL1 STAT3 PALLD SRSF2 RUNX1 WIPF1 ERCC5 DMD PROP1 SDHA EPOR NLRP3 CHCHD10 CDC73 SCNN1G PALB2 DYSF MPL PAX8 TET2 FAS IYD MAX CBL PHKA2 MATR3 POU2AF1 TBX20 SLC40A1 CFAP410 STAT4 DLST MYH7 SMAD3 MALT1 PHKG2 PODXL SEMA4A MMACHC C9ORF72 FGFR1 SQSTM1 PIGT SLC11A1 IL12A TLR4 UNC93B1 SLC4A1 PREPL TPO PRKAR1A ELANE NPM1 MSH6 TRAF3 GLT8D1 IRF2BP2 VAPB SDHB C4A PML POLG IL12B ERBB4 NR3C1 UBQLN2 TET2 WAS EPAS1 TREM2 DUOX2 GATA6 CFI RUNX1 COMP IL10 CCR1 FTL ATP13A2 PIK3R1 KIF1B TFR2 ANG VHL DMPK ALB OTX2 GPR101 PMS2 PGM1 SDHB TBK1 CIITA HLA-DRB1 PTPN22
    Protein Mutations 3
    T25W V158M V18M
    SNP 0
    HP:0001945: Fever
    Genes 365
    VANGL2 DCLRE1C ZBTB16 AVP PADI4 AK2 ND4 TRNL1 KLRC4 LPIN2 IL12A-AS1 NLRP3 CACNA1A NABP1 IL2RG EDA NUMA1 TSC1 ACAT1 HLA-DRB1 PRNP SPTB CFTR DDB2 CD247 WT1 NTRK1 NLRP3 HBB HMBS LAMA3 CFTR EIF2B5 NLRP12 AVPR2 CALR CHD7 HLA-B MVK STAT4 NLRP3 CCND1 RYR1 RYR1 STING1 TNFRSF1A CTRC MLX HLA-DPB1 XPA PRSS1 UNC13D NCF4 IRF8 GCH1 TRIP13 MPL NCF2 BIRC3 NLRC4 SCNN1A RB1 DIS3L2 CFH LAMC2 GPR35 JAK2 SLC29A3 CYP21A2 ADAR P4HTM TRNL1 PRF1 KIF1B JAK2 STAT5B GATA2 NLRP3 IL6 TRNQ RAG1 NCF1 CD3D COX2 BRCA2 TP53 PSTPIP1 PMM2 TICAM1 TET2 CACNA1S TSC2 HAVCR2 CYBA CTLA4 SCNN1G SPP1 SPTB POU6F2 RAB27A TCF4 STAT3 VANGL2 ATP6 LRRC8A CD244 IGHM NLRP3 TRIM28 CD79A IGLL1 CD79B LIFR FIP1L1 KCNJ1 TRNH BLNK PTPN22 CALR SPTA1 CHEK2 HLA-DRB1 LYST CYP11B2 ERCC3 XIAP CYBB CRLF1 NLRP3 IGH CD3E HLA-DRB1 IGH IL10 COX3 PRSS2 BCOR GLA RARA NLRC4 SLC4A1 MEFV PSMB8 BCL10 ATP13A2 CPT2 RNF168 ND1 PMP22 ND6 BCR MYD88 HLA-B G6PD ATM COL1A1 SLC19A3 EIF2B2 IRF8 ABCC2 CASK SLC22A4 CFHR3 TNFAIP3 GAA MEFV PSAP H19 ND5 FBP1 AQP2 SH3KBP1 IKZF1 SCYL1 CYTB TRNS2 IL2RG MEFV TRNS1 STAT6 COG6 RYR1 RAG2 CYBC1 WDR1 AVPR2 TREX1 IFIH1 ERCC2 GPC3 PRKAR1A ABL1 GYPC ND1 STAT3 BACH2 NOD2 EIF2B4 WIPF1 GALC ERCC5 HBB NGF RNASEH2A CD27 COL1A1 NLRP3 HTR1A ND4 ASAH1 LACC1 ELANE LIFR ND5 PSMB9 MEFV F5 TET2 FAS RIPK1 LPIN1 LAMB3 MTHFR IL7R STXBP2 ORAI1 SPINK1 UBAC2 TCIRG1 COX1 EIF2B1 MYD88 LBR PTPN3 DST GALC MST1 NOD2 STAT4 SLC29A3 ELANE ADA2 POMP TRNV QDPR EIF2B3 MALT1 LACC1 TMEM165 HLA-B TP53 RAG1 RNASEH2C AQP2 SLC12A1 FOXP1 NGLY1 TLR3 MTHFR IGH BCL2 SPTA1 RANBP2 TBL1XR1 MPL NLRP1 SCNN1B SLC11A1 ADAMTS13 ALPL MIF CYBC1 STAT2 KRT18 PSMB4 TLR4 STX11 IRAK1 TRNW UNC93B1 TRNW TH PEX6 BCL6 POLR3A KRT8 PRKAR1A ERAP1 REST TREX1 IBA57 NTRK1 TRNK IFNG EPB41 ELANE NPM1 RAG2 NAB2 TNFRSF1A TRAF3 ND6 HMGCL IRF2BP2 ZFHX2 C4A PML PRTN3 BTK ND2 IL12B RNASEH2B TRNF CFHR1 ANK1 KLHL7 BTNL2 JAK2 RMRP WAS PTPN22 MVK NKX2-1 TCF3 IL12A RUNX1 ELP1 TRIM28 CACNA1S GFI1 SAMHD1 BCAP31 MEFV IL10 CCR1 PIK3R1 ADA WT1 CYP11B2 HAVCR2 LIG4 ATP1A3 IL7R ERCC4 LPIN2 IL36RN EPB42 HMGCL SH2B3 IL23R HLA-DPA1 NFKBIL1 LIPA IFNGR1 SRP54 STIM1 TBK1 ATP1A2 PTS SLC12A3 CIITA HLA-DRB1 XPC PTPN22 ND3
    Protein Mutations 7
    D312N E148Q K751Q P46L Q12H R92Q V600E
    SNP 2
    rs222797 rs2297201
    HP:0007359: Focal-onset seizure
    Genes 278
    LMAN2L GRIK2 POGZ CAMTA1 KCNQ3 TRNL1 SLC25A22 PIGP AIMP1 SCN1B POLR3A DMXL2 MICAL1 PRRT2 LINS1 CDH2 SMO GABRA1 STXBP1 CRADD KCNQ2 MTOR SLC25A10 FA2H ADRA2B GNB1 KCNQ2 PTPN23 SETD2 CHD2 RELN CNTN2 MED25 PDGFB NDST1 SRPX2 CRBN GALNT2 PIGC CNTNAP2 ERMARD SCN1A SCN1A BRAT1 SCN1B FBXO31 SDHD RSRC1 PRSS12 TSC2 MAN1B1 STX1B TRNQ SMARCE1 BAP1 COX2 TUSC3 SDHA SEC31A TICAM1 TUBB3 KCNJ11 SCN2A NHLRC1 C12ORF4 NSD1 TBC1D24 OPHN1 SMS FOXG1 KCNQ3 SLC13A5 KCNA1 SYN1 ACSF3 DMXL2 GABRD FLNA ADGRG1 MED23 EPM2A COQ2 TRIM8 SCN1A TBC1D24 MAP1B PNPLA8 TRNH HNMT TMTC3 GRIA2 CACNA1D SCN1B MBOAT7 PI4KA SLC22A5 FIG4 EPM2A CUX2 COX3 VAMP2 GRIN2A SCN2A CYP26C1 ND1 POLG SCN8A ARF1 SCN2A WASHC4 MTOR FMN2 SLC12A3 AP4S1 GABRG2 SZT2 KDM5B TBC1D24 GABRD SRPX2 GABRB3 CARS2 MAP1B ARFGEF2 SDHAF1 DCX TSC2 GRIN2A CLCNKB TRNS2 TRNS1 HCN1 CHRNA4 PRRT2 PCDH19 SCN1A MARCHF6 TERT CTNND2 TUBB2B PIK3CA CLCN4 SCN2A SCN9A KCNA1 KCTD7 ZEB2 GAL NF2 DNM1 SRPX2 ATXN10 ND4 CDKL5 DYNC1H1 ND5 SUFU NEUROD2 CASK GAMT ARHGEF9 TSC1 TBCK ATP1A2 IQSEC1 NEDD4L BAP1 GABRG2 EXTL3 FIG4 COX1 CLN8 GABRA5 SLC45A1 SCN1A NGLY1 PAFAH1B1 NSUN2 B3GALNT2 SMARCB1 YEATS2 PUS3 EZR LAMA2 KCNMA1 PHGDH MAPK10 PRRT2 SIK1 SIK1 CDKL5 SCN2A SLC12A5 LGI1 CDKL5 STXBP1 RELN KCNQ2 TLR3 DCPS APC2 TBC1D24 PLCB1 AP2M1 CLIP1 ST3GAL3 PIGQ TSC1 SLC25A22 TNIK TRNW UNC93B1 SRPX2 SCN9A METTL23 STRADA KCNQ3 AKT1 PCDH19 SCN1B WARS2 ADGRV1 CLN8 SCN8A CC2D1A PCDH19 TRAF3 ND6 GRIN2A PGAP1 TRAPPC9 CEP85L TMEM231 TRAF7 ARX TRNF SARS1 GABRG2 EDC3 PDSS2 TECR CACNA1A DNM1L HACE1 NHLRC1 TANGO2 PIGQ PNKP MARCHF6 RARS1 SCN1A SAMD12 FRRS1L PYCR2 FMN2 VPS11 ZC3H14 PCYT2 CNTN2 MTHFR STX1B PRRT2 GABRA1 PACS1 RPL10 SCN9A CPA6 TBK1 KCNT1 MBOAT7 ZEB2 PRRT2 DOCK7 PRRT2 GLI3 CRIPT GNAO1 SDHB
    Protein Mutations 0
    SNP 0
    HP:0002578: Gastroparesis
    Genes 28
    POLG UCHL1 SON TMEM70 POLG PODXL PRKN EIF2AK2 VPS13C POLG ATP7A SNCA TWNK LRRK2 SYNJ1 PINK1 DNAJC6 POLG POLG2 PARK7 SLC25A4 POLG TWNK TWNK HTRA2 POLG2 RRM2B TYMP
    Protein Mutations 0
    SNP 0
    HP:0002197: Generalized-onset seizure
    Genes 373
    LMAN2L AP2M1 TBC1D24 GLB1 KCTD7 TRNS1 GRIK2 ND4 KCNMA1 PRDM8 ARX SLC25A22 PIGP AIMP1 SCN1B GPHN DPM2 MID2 PRRT2 LINS1 ZNF41 TRIT1 RAB39B CNKSR2 GRN USP27X RNU4ATAC GABRA1 STXBP1 CRADD PAK3 MTOR CAMK2A CILK1 GABRA1 TARS1 ADRA2B KCNQ2 CDKL5 SETD2 CHD2 GABRB3 GBA MED25 PIGA COG2 NDST1 CILK1 DMD NUS1 DHFR CRBN FTL IQSEC2 CPLX1 PIGC RELN PIGT ADGRG1 CNTNAP2 FTSJ1 HCFC1 EHMT1 SCN1A APC2 EFHC1 KCNMA1 SCN1A BRAT1 PTRH2 BTD SCN1B FBXO31 SDHD RSRC1 TBC1D24 PRSS12 SIK1 GTF2E2 EFHC1 TRNL1 ALDH7A1 ELOVL4 MAN1B1 UPF3B SLC9A6 STX1B GABRD TUSC3 SDHA SEC31A PCDH12 SCN2A NHLRC1 C12ORF4 SLC6A1 NSD1 TBC1D24 OPHN1 FGFR3 SMS DPM3 CXORF56 LNPK PRRT2 KCNQ3 ATP6 SLC2A1 ACSF3 DMXL2 SLC2A1 GABRD ZNF711 GATAD2B TRNQ ERCC3 MED12 DLG3 MED23 EPM2A TRIM8 USP9X EFHC1 RPS6KA3 TRNK TRNP INS SMARCA2 JRK HNMT KCNMA1 SCN1B GNAO1 MBOAT7 SYNGAP1 MPLKIP EPM2A SPATA5 CACNA1H CUX2 PIK3CD SMPD1 GABRG2 CLCN4 SCN2A PIGM TRNI ND6 CACNB4 SCN8A WASHC4 TRAPPC9 FMN2 GDI1 GABRG2 SZT2 WAC KDM5B GABRD GCK SRPX2 GABRB3 ARHGEF6 CARS2 PSAP KCNQ2 ND5 SCN1B GDI1 SDHAF1 HACE1 DCX GRIN2A TRNL1 STXBP1 CSTB HCN1 PCDH19 SCN1A MARCHF6 SCARB2 CTNND2 TK2 CLCN4 SAMD12 SYP PLAGL1 ND1 PRICKLE1 SCN2A SCN9A GABRG2 KCNA1 KCTD7 ZEB2 SLC9A6 GALC NEXMIF CLCN2 GBA TRNF DNM1 HYMAI ATXN10 CDKL5 GLUD1 RNR1 NEUROD2 CASK GAMT ARHGEF9 SLC6A1 AFG3L2 TSPAN7 SLC25A15 IQSEC1 MFSD8 SLC25A15 ERCC2 GABRG2 EXTL3 TRNF PDX1 NDUFA1 GABRA5 SLC45A1 SCN1A NGLY1 SLC35A3 PAFAH1B1 SLC12A5 PSAP NSUN2 BUB1B B3GALNT2 YEATS2 EZR LAMA2 PHGDH TRNV MAPK10 SIK1 SIK1 CDKL5 DHDDS SCN2A TRNH KCNQ3 PLAA ALMS1 CDKL5 STXBP1 MED13 AGTR2 ATP1A1 KCNQ2 JRK DCPS APC2 PLCB1 TRNK AP2M1 ALDH5A1 NFKB2 CLIP1 EFHC1 CUX2 CHD2 ALG13 ST3GAL3 CACNB4 STAT3 SON SLC25A22 TNIK AP3D1 TRNW SCN9A METTL23 KCNQ3 GOSR2 PCDH19 SCN1B TRNP ADGRV1 TRNK ASAH1 ASAH1 TBCD CC2D1A PCDH19 CPLX1 NDE1 ANO10 GRIN2A PGAP1 HCN1 TRAPPC9 IL1RAPL1 CLCN2 CEP85L ACSF3 ALDH5A1 ARX ND2 SLC25A22 SARS1 GABRG2 KCNMA1 EDC3 NEU1 SLC9A7 TECR DNM1L DYRK1A WDR26 TMX2 HACE1 MECP2 KNSTRN NHLRC1 TANGO2 PTCHD1 PIGQ XK OSTM1 NTNG1 PNKP NUBPL KCNJ11 ASPA RNF113A MECP2 SCN1A RORB SAMD12 FRRS1L ATAD3A GABBR2 ZC3H14 KCNT2 PCYT2 IER3IP1 CNTN2 MTHFR STX1B ZNF81 PRRT2 GABRA1 GABRB3 GTF2H5 RPL10 SCN9A FRMPD4 GABRA1 ND5 STXBP1 CHD2 ADGRV1 MBOAT7 ARX ZEB2 PRRT2 DOCK7 TRNS2 GBA TRNL1 ACSL4 GNAO1 ABCC8 ND3 AFG3L2 SDHB
    Protein Mutations 0
    SNP 0
    HP:0012174: Glioblastoma multiforme
    Genes 27
    TGFBR2 MLH1 MLH3 BMPR1A EPCAM PMS1 FAN1 MSH2 TP53 PIK3CA MSH2 MLH1 MSH6 RPS20 SEMA4A TP53 PMS2 MDM2 APC PMS2 BRCA2 CHEK2 IDH1 KRAS MSH6 CDKN2A ERBB2
    Protein Mutations 31
    C797S G12D G13D G20210A G719A K27M K650E K656E L858R L861Q P13K P140K R132C R132G R132H R132L R132S R132V R140L R140Q R140W R172G R172K R172M R172S R172W T790M V600D V600E V600K V600R
    SNP 1
    rs17782313
    HP:0012538: Gluten intolerance
    Genes 2
    NRXN1 CNTNAP2
    Protein Mutations 0
    SNP 0
    HP:0001997: Gout
    Genes 24
    PRPS1 HNF1B PFKM EPB42 APOE SLC37A4 CLCNKB LRP6 SLC12A3 ANK1 MUC1 SPTA1 G6PC SLC4A1 SPTB SLC37A4 DNAJB11 UMOD SEC61A1 HPRT1 HPRT1 HPRT1 HPRT1 UMOD
    Protein Mutations 0
    SNP 0
    HP:0001395: Hepatic fibrosis
    Genes 150
    NPHP1 AP1S1 WDR35 PEX1 TNPO3 IARS1 GLIS3 SCYL1 CTNNB1 TMEM107 SDCCAG8 DYNC2H1 CC2D2A CC2D2A PNPLA6 DLL4 INSR IFT122 LIPA SCYL1 HBB ABCD3 MET HBB MKS1 DYNC2I1 BBIP1 MKS1 ASAH1 BBS2 BBS1 BBS12 HAMP BBS1 IFT27 ARHGAP31 NPHP3 NPHP1 IFT140 FADD TNFSF15 GPD1 NPHP3 DLL4 PHKA2 RINT1 WDR35 POU2AF1 DYNC2I2 C8ORF37 CCDC28B CEP164 TRAF3IP1 MST1 GPC1 RPGRIP1L CC2D2A BBS7 NPHP4 PHKG2 ALMS1 GPR35 TMEM67 CC2D2A RPGRIP1L TRAF3IP1 NPHP3 CEP290 PYGL TTC37 PMM2 FADD DCDC2 PKHD1 NHP2 TRIM32 CEP290 OFD1 IL12A SKIV2L DZIP1L BBS5 PMM2 TMEM231 IFT172 TMEM67 MMEL1 ALG9 KIF3B PTRH2 IRF5 AGL RPGRIP1L MKKS WDPCP TCF4 TMEM67 INPP5E TALDO1 CYP7B1 IFT172 WDR19 ABCB4 BBS4 SLC25A13 IL12RB1 B9D2 TCTN2 NEK1 TMEM67 INPP5E PKHD1 TMEM67 LZTFL1 ARL6 BBS10 NOP10 HJV SPIB CSPP1 MPI ANKS6 SLC40A1 SDCCAG8 NEK8 BBS9 TMEM67 TTC37 CEP290 ASL DOLK DOCK6 SLC40A1 DGUOK IFT80 TTC8 EOGT WDPCP CEP55 ARL6 INVS MTTP B9D1 MPI TMEM216 PLIN1 RPGRIP1 IQCB1 NOTCH1 RBPJ
    Protein Mutations 7
    C282Y C677T G20210A H63D Q80K R506Q V617F
    SNP 0
    HP:0001397: Hepatic steatosis
    Genes 141
    TRMU AGPAT2 IARS1 HADH FOS ACADM CAV1 HFE LMNA CBS CPT2 CAV1 MRPL44 LMNA LIPA SLC25A13 SKI PPARG AKT2 LYRM4 TARS2 CYP7A1 HADHA HNF4A MRPS7 TYMP ACAD9 CAVIN1 TMEM199 ADK POLG BSCL2 ACOX1 BSCL2 PNPLA2 CYP19A1 LMNA PCK2 ETFDH GPD1 APOE PHKA2 RINT1 ETFA NGLY1 ABCG8 AGPAT2 PLIN1 DDOST HADH CIDEC TRAPPC11 LARS1 PHKG2 VCP ALMS1 HNRNPA1 CIDEC BCS1L TRAPPC11 LRPPRC PMM2 RMND1 IARS1 VPS33A COX15 ETFB EARS2 LMNA ABHD5 LDLR MCCC1 APOB TFAM HNRNPA2B1 LMNA RRM2B POLR3A PTRH2 CAVIN1 LIPE PNPLA2 CPT2 TKFC SLC25A13 SAR1B ATP6AP1 XRCC4 MPV17 ATP7B SLC25A13 CEP19 HNF1B BCS1L POLD1 NDUFAF1 PCSK9 FBP1 CPT2 ABHD5 SLC40A1 MARS1 BSCL2 POLG LIPE SLC40A1 DGUOK HADHB LMNB2 ACADM CPT2 FARSB ACADL NSMCE2 ABCG5 ALMS1 COA8 GABRD ALDOB PCK1 DNAJC19 DNAJC19 MTTP ACADVL PGM1 PPARG ACAD9 RERE PLIN1 LDLRAP1 PRDM16 PPARG CPT1A NSMCE2 KCNAB2 CLPB MPV17 ATP6AP2 SLC22A5 HSD17B4 CARS2
    Protein Mutations 4
    C282Y E167K H63D I148M
    SNP 10
    rs1260326 rs2281135 rs2293152 rs2294918 rs2854116 rs2854117 rs58542926 rs641738 rs73049 rs738409
    HP:0000752: Hyperactivity
    Genes 587
    LMAN2L ZIC2 KCNA2 SLC1A4 TRIO POGZ SLC25A22 PIGP TTI2 SETBP1 DYNC1I2 MID2 NODAL SPR LINS1 ZNF41 RAB39B LIMK1 CIC CNKSR2 SCN8A LHCGR UBTF USP27X EEF1A2 IGF1 NR2F1 NTRK1 CSGALNACT1 SIX3 STXBP1 ACTL6B CRADD SLITRK1 GP1BB GATA4 MTOR MLXIPL C12ORF4 PRKAR1A SEC24C PAH CHD2 SYNJ1 NSDHL DMD CRBN RLIM UBE3A FRMPD4 WWOX PIEZO2 TSHR DLL1 DISP1 FTSJ1 HCFC1 GAS1 ARF1 FOXH1 MANBA ELN IKBKG SETBP1 CXORF56 OCRL NF1 AFF2 TCF20 JMJD1C MAN1B1 UFD1 ZMIZ1 CREBBP FBXW11 CHRNA7 TSC1 DLL1 SIX3 GTF2I MBD5 MLH3 NECAP1 GNB5 C12ORF4 NSD1 GABRB2 FBXO11 PLA2G6 SATB2 FAN1 STS CXORF56 LNPK MSH2 FOXH1 SETD5 GABRA2 NAGLU SHROOM4 SLC2A1 CDON PTCH1 PPP2R1A TBX1 HERC2 MED12 NLGN1 TRAK1 GRIA4 USP9X TLK2 GAS1 SCN3A KIF11 TIMM8A PWAR1 HGSNAT TKT MBOAT7 AMT CACNA1H CUX2 CYFIP2 NODAL NBN CACNA1B CUL4B SLC1A4 KMT2A SHH DISP1 EBP RAD21 ABCD1 DDX6 CSNK2A1 PANK2 TRIO PPP1R12A GLI2 HIVEP2 PTCHD1 DYM NPAP1 TANC2 DISP1 KDM5B FGD1 SLC13A5 SLC6A8 SNORD116-1 SRPX2 FGF8 ARHGEF6 MAP1B GABRA5 TDGF1 TGFBR2 BCR GDI1 WDFY3 GLI2 FGF8 YY1 DDX3X HTT TUBB2B IFNG FGFR1 SYP CREBBP HERC2 GABRB3 BCORL1 NIPBL MKRN3 SNORD115-1 NDP CASK GAMT TSC1 TNIK AASS TSPAN7 FMR1 CDON WAC GRIN2D STAG2 PSMD12 DNM1 FLI1 ADSL SIX3 RAI1 GNE TMCO1 PRODH NSUN2 B3GALNT2 PIK3CA ZDHHC9 NKAP CAMTA1 RAI1 EZR MED12 RERE ZIC2 HDAC8 KMT2E ATRX RIC1 DCPS ASH1L PUF60 AUTS2 PAH SHOC2 RUSC2 GABRG2 KRAS ST3GAL3 DRD5 DOCK3 FGF8 PNKP CCBE1 SHH ARV1 STXBP1 GALC CNTNAP2 FMR1 STAG2 PCGF2 NODAL SLC1A2 TRMT1 PCDH19 PTCH1 ZIC2 NTRK1 SMC1A CLTC CC2D1A CPLX1 GAS1 PGAP1 TRAPPC9 GLDC SLC25A13 ARX NTRK2 PCNT KCNB1 PIGY TECR NDN MECP2 FLCN CDON DPF2 PTCHD1 PIGQ HCN1 KIF14 TRAPPC4 GRIN2A DNAJC21 PTCH1 FRRS1L DNAJC12 GLI2 MKRN3-AS1 NSUN2 YME1L1 AARS1 ANK3 GABRB3 FRMPD4 GABRA1 CHD7 CRKL DHCR7 ZMIZ1 TRAPPC14 ACSL4 CLTC SNRPN PHF21A DPH1 KDM6B SMC1A PRNP MLH1 LIG4 NTNG1 GRIK2 AIMP1 GNAQ DYRK1A UQCC2 HDC SH2B1 CDH2 ANK3 SMC1A PAK3 TCF20 IQSEC1 ADNP NRXN1 CDK19 TKT DHTKD1 SETD2 RREB1 MED25 BMPR1A ARVCF YWHAG NDST1 PANK2 PMS1 IQSEC2 PIGC CLIP2 SIM1 TBX1 SETD5 SYNGAP1 PPP3CA CNTNAP2 CC2D1A ODC1 SPG7 FBXO31 BAZ1B ZSWIM6 RSRC1 ACTL6A TBC1D24 PRSS12 METTL5 RAI1 STAG2 SHANK3 UPF3B NSDHL MED13 EBP RFC2 SIX3 KIF15 TUSC3 AP3B2 TDGF1 THRB ATR CACNA1A SGSH PRKCG PDE4D SCN2A HAL OPHN1 AFF2 USP7 FGF12 EP300 ARG1 SEMA3E ACTL6B SHANK3 DMXL2 ZNF711 GATAD2B CDON OPHN1 DLG3 MED23 TRIM8 KMT2A RPS6KA3 CDK8 PARS2 PPM1D DRD4 TAF6 JRK HNMT MED12 MED12L MYT1L RAI1 ZIC2 MYT1L ARID2 EPCAM CRBN SLC6A8 SMPD1 GABRG2 FOXH1 WDR62 CLCN4 UBA5 HUWE1 STS MCTP2 TRIP12 FGF8 WASHC4 MAGEL2 CORO1A SHROOM4 EP300 PHIP FMN2 TGIF1 WAC PSMD12 NTNG2 RAB39B GABRB3 UBE3A HDAC4 KRAS DHCR7 PTCH1 SH3KBP1 ADNP TDGF1 TSC2 SHH SMARCC2 CARS1 GLI2 CLCN4 RPS20 PNP DHDDS GAS1 TRAPPC9 KCNA1 NEXMIF BPTF RERE DNM1 GNE COMT TBX1 TGIF1 PAK3 SPRED1 GLUD1 BSCL2 WAC ACY1 GTF2IRD1 NEUROD2 STAG2 SCN8A ATRX NUS1 KCNA2 IQSEC1 NFIX DEAF1 MED13L PAH GABRG2 PTCH1 FGD1 DALRD3 SLC45A1 SATB2 SCN1A ADAT3 YWHAG SMC3 FOXH1 APC2 KCNK9 CUL4B TAF1 MAPK10 FLII BSCL2 SIK1 TSHR CNKSR2 HOXA2 TGIF1 SEMA4A CDKL5 MED13 AGTR2 ATP1A1 IPW VPS13A MECP2 APC2 ALDH5A1 ASPM SZT2 CLIP1 ALG13 IL1RAPL1 TDGF1 UPF3B TNIK DLL1 METTL23 BCORL1 DYRK1A TET3 SHH NOP56 TGIF1 MED12 SCN1B EP300 GATAD2B HSPG2 MSH6 INPP5E PWRN1 IGF1 ADAT3 FOXP1 GRIN2A FGFR1 TBX1 SIN3A IL1RAPL1 KANSL1 CREBBP SARS1 ELN EDC3 ALKBH8 TSC2 GCSH SLC9A7 POLA1 PUS7 MAPK1 NKX2-1 SOX5 ATP6V1A PNKP FOXP1 DDX3X KDM3B NODAL DPP6 BCAP31 KAT8 TSHR TBL2 DLL1 MID2 MED12 HIRA ZC3H14 IQSEC2 SVBP ZNF81 RSRC1 PMS2 DLL1 FGFR3 CNKSR2 ARX PDE4D TANC2 NBN GNS TBL1X TTI2 DPYD GNAO1 DISP1 SH2B1
    Protein Mutations 0
    SNP 0
    HP:0002487: Hyperkinetic movements
    Genes 32
    CACNA1B SYT1 PNKD NEUROD2 GNAO1 CACNA1E PTS SLC6A3 GNE NGLY1 FOXG1 PSAP THOC2 ZNF142 GCH1 SYT1 YME1L1 PRRT2 TRAPPC11 TRAPPC11 VPS13A NGLY1 RTTN ALDH5A1 PDE10A PYCR2 FRRS1L SLC9A6 IQSEC2 THOC2 GRIN1 SUCLA2
    Protein Mutations 1
    T380A
    SNP 0
    HP:0000822: Hypertension
    Genes 421
    ELN FBN1 SDCCAG8 PRKAR1A ALX4 LIMK1 PDE11A NR3C2 FBN1 KCTD1 VHL GP1BB ANGPTL6 ENPP1 MLXIPL NKX2-5 LEMD3 NOTCH2 SLC37A4 RET SEC24C BBS12 NPHP1 MMP14 EGFR HLA-DPB1 KCTD1 ABCG8 SCNN1A SLC25A11 COX3 CYTB TRAF3IP1 HGD MEF2A VHL PKD1 TRIP13 GANAB RPGRIP1L ITGA8 CDH23 BBS7 ELN DIS3L2 SMARCAL1 GATA5 PKD2 NPHP3 KIF1B JMJD1C UFD1 ARMC5 CCR6 SERPINA6 KLHL3 LMX1B BRCA2 GTF2I YY1AP1 TNFRSF11B LMNA CTLA4 G6PC NOTCH1 MDM2 WDR19 MAFB TRPC6 RET LMNA ERCC4 XYLT2 SDHB CACNA1D TMEM67 LZTFL1 ERCC4 COQ7 MYLK KIF1B PTPN22 COL4A5 NPHP1 DNMT3A SCNN1A CACNA1D BBS9 CDH23 WT1 FGFR2 TGFB2 GLA BICC1 TTC8 ND1 ADA2 WDPCP ARHGAP31 ARL6 AIP FGFR2 ALMS1 INVS FBN1 VHL WT1 IDUA SMAD4 CFHR3 PDE11A WNK1 NPHP1 WRN SLC2A10 SMAD6 OSGEP ABCC6 LRIG2 SDHB PRKACA FLT1 INVS HBB POU3F4 NOTCH3 LMNA MC4R PRKACA HLA-DRB1 TRNK MYH7 HSD11B2 MYH11 VANGL1 EDA2R PHF21A MDH2 MKS1 BBS2 DNAJB11 TSC1 CFB MTRR GNAS MTTP PRKAR1A LMNA NF1 MUC1 ND6 HPSE2 CYP11B1 CUL3 EDA NPHP4 ALMS1 VAC14 TRNK SMAD4 THBD OFD1 STAT2 BBS5 SDHD PRKAR1A HMBS APOB ECE1 KCNJ5 REST RET MKKS FMO3 PRTN3 ERCC6 PKHD1 CFHR1 LRP6 CYP11B2 BBS10 SDHD FN1 PCSK9 CBS ZMPSTE24 SDCCAG8 ERCC8 CDKN1A IRF5 C3 TRNL1 PKD1 FUZ COX1 HLA-DPA1 MGP PLIN1 LDLRAP1 CLCN2 SH2B3 LYZ LOX MFAP5 GNAS CYP17A1 CYP11B1 B2M TMEM127 KCNJ5 PAM16 NR3C1 ACAT1 TRNK CDKN1B MEN1 SDHAF2 WT1 STAT1 BNC2 TGFB3 HMBS USP8 BBIP1 LMX1B GANAB HLA-B PDE8B IFT27 LMNA RREB1 MMP2 CYP11B1 TRNL1 ARVCF MLX GCH1 ABCC6 CLIP2 C8ORF37 OFD1 TBX1 CEP164 JAK2 NFU1 FH GJA1 SDHC BAZ1B CFH CYP21A2 JAK2 CEP290 CD2AP TRNQ TRIM32 STOX1 RFC2 AIP RET CYP11B1 LDLR SPRY2 TMEM70 NDUFAF6 GUCY1A1 WT1 CDKN2C TRNF POU6F2 ADA2 IFT172 ADAMTSL4 TRIM28 GNAS BMPR2 TMEM127 PKD2 CORIN CAV1 PRKG1 ABCB6 VHL SLC25A11 EXT2 MAT2A NFIX XPNPEP3 KCNJ5 GBA SCNN1B MAX CACNA1H ENG AIP ACTA2 TRNW ARMC5 H19 SDHD TRNS2 TSC2 COL4A4 BRCC3 FGA PDE3A USP8 SCNN1B FIG4 COX2 ELP1 WDR35 INF2 GPC3 SDHC ACTN4 ABCC6 SCN2B SLC2A10 TRNV SDHA COMT CYP17A1 WNK4 TBX1 SMAD4 BSCL2 ENPP1 SCNN1G BBS1 SUGCT GTF2IRD1 GLA CFI ACVRL1 MPL NOS3 BBS1 APRT APOA1 FOXE3 MAX TGFBR2 XYLT1 TP53 CCDC28B NOD2 ADA2 PLIN1 DLST CC2D2A FN1 COL4A3 BANF1 TGFBR3 SCNN1G LARS2 GDNF SLC37A4 PPOX PKHD1 CEP290 ACP5 KRT18 DZIP1L CCND1 ERCC8 GUCY1A1 TRNC CCN2 SMAD3 KRT8 SDHB FBN1 TGFBR1 SDHD POR COL4A3 BBS4 SDHB IL12B MYMK FMR1 ELN NF1 CEP19 CPOX ARL6 NR3C1 TET2 EPAS1 ND5 DYRK1B PDE3A ELP1 TRIM28 YY1AP1 CD46 TMEM237 TBL2 ERCC6 THSD1 CDKN2B HIRA ACTA2 WT1 KIF1B VHL NSMCE2 GPR101 COL3A1 ABCG5 HSD11B2 PPARG PPARG TNFRSF11A COL3A1 LEMD3 TRNS1 IQCB1 TRNE
    Protein Mutations 18
    A1166C A118G C282Y C344T C677T D565H E298D G1051A G1691A G20210A G308A G3514C G389R H295R M235T S49G T393C V617F
    SNP 9
    rs1017783 rs10177833 rs13333226 rs1801133 rs2398162 rs2540923 rs254093 rs5068 rs7571842
    HP:0000829: Hypoparathyroidism
    Genes 55
    LIG4 DGCR8 FAM111A TRNW TRNL1 TRNS2 TBCE TRNS1 DGCR6 FAM111A ND6 HBB IRX5 HADHA HBB GP1BB TBX1 COMT TRNF TBX1 ND4 TBCE ND5 TRNH SEC24C PTH COL4A5 NKX2-1 RREB1 ARVCF GCM2 COX1 COX3 HADHB TBX1 PIGT HIRA ESS2 TBCE PTH1R ND1 GATA3 NSUN2 GATA3 HBB ATP7B TBX2 JMJD1C UFD1 TBCE AIRE AIRE DGCR2 TRNQ COX2
    Protein Mutations 0
    SNP 0
    HP:0012418: Hypoxemia
    Genes 21
    FGFR3 SFTPB PTRH2 CNOT1 BTNL2 HBB ASCL1 SFTPC CSF2RB ABCA3 PHOX2B EDN3 RET GDNF HBB ZFPM2 GATA6 SLC35A1 FBN1 HLA-DRB1 CSF2RA
    Protein Mutations 2
    P317R R200W
    SNP 0
    HP:0000794: IgA deposition in the glomerulus
    Genes 5
    NUP107 NUP107 SPRY2 COL7A1 MMP1
    Protein Mutations 0
    SNP 0
    HP:0006515: Interstitial pneumonitis
    Genes 9
    SFTPB TERC PLCG2 RAG1 TINF2 SFTPC TERT FOXP3 STAT3
    Protein Mutations 1
    S1009A
    SNP 0
    HP:0006530: Interstitial pulmonary abnormality
    Genes 161
    GAS8 TERT DNAL1 ZCCHC8 NUP107 BTNL2 RAG1 TERT CCDC40 RSPH4A DNAJB13 CCDC39 STAT3 ODAD3 DNAH9 HLA-DRB1 HLA-DRB1 SFTPA2 BACH2 TTC12 GBA MUC5B ABCA3 FAS DSP SCARB2 HLA-DRB1 ASAH1 DNAAF2 CCR6 TERT FAS DNAI2 CFAP221 GBA SPEF2 STING1 PLCG2 PLEC ODAD4 RNF168 HLA-DPB1 OFD1 ATP11A RTEL1 IL1RN HPS4 NME8 ODAD2 DRC1 DNAAF4 SFTPC DNAAF6 DNAH5 SP110 RTEL1 CSF2RB STN1 SPIDR POLR3H PARN IRF5 DNAAF3 FOXJ1 GAS2L2 CCDC103 ODAD1 CCR6 NHP2 ABCA3 STK36 DPP9 CYBC1 HPS1 SFTPA1 SFTPB CCDC65 FAM111B LRRC6 AP3D1 NDUFAF6 CLCA4 STX1A CCN2 ZMYND10 BNC1 CTLA4 COPA DNAI1 TERC TERC MUC5B ERF RAC2 SFTPA2 TERT DNAH11 DNAAF1 CCNO TGFB1 BMP15 AP3B1 CFTR PRTN3 PRKCD RCBTB1 FSHR BTNL2 PARN NOP10 PTPN22 NEK10 RPGR CSF2RA TERT NR5A1 NKX2-1 MARS1 RASGRP1 DNAH1 CAV1 DKC1 LRRC56 NSMCE3 DCTN4 IRF5 CCN2 SMPD1 HYDIN BMPR2 CAV1 SFTPB TINF2 RSPH9 SFTPC MRPS22 RSPH1 RNF168 TERC CFAP298 MCIDAS PSMC3IP TINF2 FARSB MARS1 GBA KIAA0319L HLA-DPA1 SPAG1 CFAP300 RSPH3 DNAAF5 FASLG UNC119 ITGA3 SFTPC HLA-DRB1 FOXP3 THOC2 CASP10 FAM13A
    Protein Mutations 0
    SNP 0
    HP:0100512: Low levels of vitamin D
    Genes 19
    RPS10 DZIP1L EFL1 FARSB SRP54 OCRL GPR35 SBDS MTTP COL7A1 ACOX2 MMP1 DNAJC21 GALNT2 RPL11 MST1 TCF4 PKHD1 COL7A1
    Protein Mutations 0
    SNP 4
    rs10766197 rs1790349 rs2060793 rs4588
    HP:0001888: Lymphopenia
    Genes 151
    MSN NHEJ1 CR2 RAG1 RFXANK LEPR IL2RA ATM CD81 CD3E WDR1 PGM3 IL2RG CD3G FOXN1 AK2 ZAP70 IL2RG PNP FOXN1 CD247 DOCK2 WIPF1 CD3D STAT1 ZBTB24 FAS DCLRE1C EXTL3 ELANE DNMT3B PSMB9 TERT FAS STAT4 PGM3 G6PC3 MS4A1 NFKB2 CD19 STK4 EXTL3 ADAMTS3 TCIRG1 NFKB1 TCF3 SAMD9 IKZF1 RFXAP CHD7 TNFRSF13B HELLS FAT4 MDM4 IL7 ATM SMARCAL1 SP110 XRCC4 TTC37 NFKB2 TRNT1 CD247 CTPS1 MYC PNP MYD88 ADA RAG1 ICOS RAG1 CDCA7 RFX5 GFI1 BCL11B CYBC1 RMRP CD3D PRKCD GATA2 PSMB4 SKIV2L IRAK1 WAS JAK3 RAG1 RAG2 SGPL1 SPP1 TERC PTEN ELANE RAG2 CXCR4 RAC2 CTLA4 DNMT3B MAGT1 CIITA MYSM1 LEP RAG1 PRKCD CCBE1 ACP5 MTHFD1 WAS KNSTRN LCK PTPRC SEMA3E RASGRP1 RAG2 ICOS IL7R CD3E GFI1 EPG5 NSMCE3 TCN2 PIK3CD TINF2 TNFSF12 RAG2 TPP2 RAC2 TFR2 IVNS1ABP IL7R TNFRSF13C RRAS2 CORO1A PIK3R1 PIK3CD WIPF1 SRP54 PTEN TNFSF12 IGHM ADA FASLG UNC119 SMARCAL1 DOCK8 TNFAIP3 NBN TTI2 FOXN1 CD8A STAT1 CASP10
    Protein Mutations 0
    SNP 0
    HP:0001268: Mental deterioration
    Genes 494
    PRDM8 KCNA2 VCP TRNL1 TBP SNCB DNAJC13 PNPLA6 MAPT RBM28 COMT PDE11A SCN8A PSEN2 ERCC8 PRNP ERCC6 GRN TREM2 EEF1A2 FTL HFE SNCA GBA2 ACTL6B TYMP SNCA HTT MAPT TTR CHD2 SYNJ1 TRNE C19ORF12 SYNJ1 NPC1 ABCC8 ATXN2 WFS1 C9ORF72 CSTB WWOX COX3 CYTB MFN2 ZFYVE26 PRKN NDP CHI3L1 ADH1C ACTB LRRK2 AUH TLR3 MAPT DNAJC6 GDAP2 SLC44A1 CHCHD10 TINF2 CREBBP C9ORF72 COX2 SDHA PMPCA CUBN NECAP1 PDGFB NHLRC1 GABRB2 PLA2G6 PINK1 GABRA2 WDR45 NAGLU CHMP2B NOTCH2NLC TOMM40 GALC TRAK1 CSF1R CHMP2B COL18A1 VCP SCN3A JAM2 ARSA TIMM8A HIBCH TREX1 TRNH MATR3 CHMP2B HGSNAT LYST GRN MPO PRNP APP TREM2 CUX2 PPP2R2B CYFIP2 NBN CACNA1B COASY ND1 ADA2 CLN6 CST3 ATP6V1A SQSTM1 CLN6 MECP2 ABCD1 DNAJC5 PDGFRB TREM2 PSAP SLC13A5 HNF4A ATP6V1E1 ATXN2 MYORG GBA SLC20A2 FMR1 COL4A1 HLA-DQB1 SLC13A5 ATXN7 PLP1 SCARB2 PSAP GABRA5 GRN PSEN1 TYROBP PSEN1 ATN1 RNF216 CHMP2B NRAS APOE TRNS2 TRNS1 NOTCH3 HTT XPR1 ROGDI NR4A2 TK2 SURF1 SNCA PSAP CREBBP SPG11 TRNK APP OPA1 MAPT RRM2B TBK1 DGUOK GBA2 ITM2B WFS1 TARDBP ND4 PDE10A POLG APP APOL2 GBA TUBA4A ND5 LRRK2 SLC6A1 SPG21 PANK2 UBAP1 PSEN2 GRIN2D MFSD8 PRKAR1A DNM1 CP COX1 PRNP SORL1 CLN8 UBQLN2 CYP27A1 ND6 RAB27A GALC HEXA PRDX1 MAPT A2M QDPR ATP6 APP MMACHC VCP CERS1 SNORD118 ALDH18A1 HNRNPA2B1 TRNK TBK1 TYROBP GABRG2 SQSTM1 HTRA1 AARS2 SUMF1 ARV1 STXBP1 GALC FA2H DCTN1 HTT SLC1A2 RRM2B TIMM8A CLN8 CLTC ASAH1 ASAH1 CPLX1 SLC2A3 HSD17B10 NDUFAF3 NTRK2 PPT1 TRNF GBE1 KCNB1 MAPT FTL VCP C9ORF72 PLA2G6 NHLRC1 DNM1L HEXB ERCC8 UCHL1 PSEN1 POLG MAPT HCN1 PSEN1 PLAU FBXO7 APOE MAPT CHCHD10 UCP2 MTHFR SNCAIP AARS1 TRNL1 ATP7B COX1 NDUFA6 DISC2 PARK7 PTS CTC1 AP2M1 GLB1 PRNP GIGYF2 PSAP GRN IRF6 C9ORF72 TREX1 APP PDGFRB KCNC1 ATP13A2 SMC1A PINK1 PPP2R2B HMBS PRNP MAPT FA2H PRNP CDK19 GLUD2 PSEN1 TRPM7 SCO2 GBA SYN2 ATP6V0A2 IDUA PSEN1 PANK2 MCOLN1 RNASEH1 SYNGAP1 ROGDI PPP3CA CNTNAP2 DNMT1 KCNJ11 FUS GCH1 SNCA ATP1A2 DAOA SPG11 SYNJ1 TBK1 MAPT SCN1A SNCA SERPINI1 HNRNPA1 SDHD TBC1D24 VPS13C GCDH GBA APP ATP6 CSF1R PDGFRB DRD3 TRNQ TRNQ SYNJ1 DCTN1 SPG21 AP3B2 CACNA1A AP5Z1 TIMMDC1 PRKCG RTN4R TBP PODXL FGF12 TRNF ATP13A2 ADA2 VCP PLEKHG4 CTSD ATXN7 PDGFB C9ORF72 JPH3 EPM2A TTPA GNAS KMT2A CLN5 NPC2 PARS2 DARS2 JPH3 HNF1A ERCC2 DCAF17 HTR2A LRRK2 EPM2A VCP TMEM106B COX3 ALDH18A1 PRNP MATR3 ATP13A2 VPS13C TMEM106B SNCA ND1 VPS35 UBA5 EIF4G1 EP300 PRNP XPA GRN SQSTM1 MTHFR DNMT1 NDUFB8 GABRB3 TRNW PRDM8 TRNS2 TREM2 SDHAF1 CSTB ERCC6 COX2 TWNK GM2A ERCC4 RNF216 GBA ATXN10 DHDDS PRKAR1B KCTD7 GALC PRICKLE1 NDUFS2 DNM1 APP TRNV RBM28 BSCL2 TARDBP ATP1A3 NUS1 KCNA2 MAPT PAH DALRD3 SCN1A YWHAG TREM2 PLA2G6 SQSTM1 MAPK10 GBA MBTPS2 BSCL2 FA2H CNKSR2 SPAST RAB39B VPS13A ATN1 VPS13A CTNS ARSA SZT2 ATXN3 CLN3 MAPT CTSF ATXN2 MAPT APOL4 TRNW CHMP2B TRNC HNRNPA2B1 SGPL1 TBP NOTCH3 DNMT1 ND6 WDR45 ATXN8OS SUMF1 CFAP43 ITM2B FMR1 APTX LMNB1 UBTF ND5 ATP6V1A TUBB4A TREM2 CISD2 RRM2B ARSA HTRA1 ATP13A2 NOTCH2NLC ABCA7 PSEN1 NOS3 DMPK C19ORF12 HEPACAM TMEM106B CHD2 HTRA2 TRNS1 GBA SDHB
    Protein Mutations 3
    K56M V158M V66M
    SNP 10
    rs10524523 rs11126727 rs11126731 rs12467815 rs12472215 rs429358 rs6739405 rs6971 rs7412 rs993607
    HP:0003560: Muscular dystrophy
    Genes 154
    FKTN FKTN LMNA DNAJB6 DAG1 POMT1 SGCB ANO5 DMD ITGA7 DPM1 POMT1 POMT2 POMK LARGE1 COL4A1 PSAT1 LMNA FKTN ANO5 RXYLT1 POMK CAVIN1 CHKB DPM3 DYSF RXYLT1 SELENON INPP5K FKRP POMGNT2 BVES CEP57 FKTN LMNA LIMS2 SYNE2 POMGNT1 COL6A1 CAV3 TMEM43 COL6A3 LMNA POMT1 HNRNPDL PIEZO2 FKRP TMEM43 POMGNT2 POMK SIL1 FKRP LAMA2 TRIP13 PLEC GMPPB ACTA1 GK POMT2 LARGE1 TRAPPC11 HNRNPA1 MYH7 EMD POMT2 GMPPB TTN TRAPPC11 TRAPPC11 POMT2 COL6A1 SMCHD1 FKRP HNRNPA2B1 CAPN3 GMPPB SGCD RYR1 TRIM32 FHL1 LMNA FRG1 COL12A1 FKRP TTN B4GAT1 PLEC B3GALNT2 DYSF FKTN BUB1B CRPPA SYNE1 POMGNT1 LAMA2 SGCG TTN DMD DAG1 RYR1 BUB1 TCAP FKRP TRIP4 HNRNPA1 DAG1 POMT1 PNKP FKTN NR0B1 B4GAT1 POMT2 POMT1 CRPPA B3GALNT2 POMGNT1 SGCA POMGNT1 CRPPA COL6A3 FKRP SYNE1 GMPPB CRPPA AHCY LMNA LARGE1 POMT1 LIPE FKRP ANO5 CAPN3 POMT1 DAG1 COL6A2 POMGNT1 POMT2 PHGDH CRYAB TNPO3 TOR1AIP1 LARGE1 SYNE2 SGCA SELENON POMT2 POMK BAG3 COL6A2 CRYAB FKTN COL12A1 DPM3 BUB3
    Protein Mutations 0
    SNP 4
    rs10835211 rs165599 rs17601696 rs6265
    HP:0001658: Myocardial infarction
    Genes 76
    PTPN11 WRN SLC2A10 TLR4 IKZF1 LDLR GTF2I APOB MEFV KLRC4 IL12A-AS1 LPL SCNN1G ERAP1 CYP27A1 CBS LIMK1 CTNNB1 CALR LMNA C4A MYH9 ABCC6 TET2 IL12B CFTR LRP6 ENPP1 CEP19 PCSK9 GTF2IRD1 GLA MEFV HLA-B FAS ZMPSTE24 TP53 BRAF DYRK1B PIGA SH2B3 IL12A UBAC2 MLX IL10 LMNA CYP27A1 TBL2 ABCG8 CLIP2 HGD CCR1 STAT4 MEF2A VHL HLA-B HLA-B ELN SCNN1A MYH9 BAZ1B ABCG5 BRAF MPL IL23R JAK2 LDLRAP1 SCNN1B RAF1 RFC2 THOC2 SH2B3 ABCA1 JAK2 ABCA1 BCHE
    Protein Mutations 20
    A1166C C282Y C344T C807T G1051A G20210A G3514C G681A G98T H63D I843S L28P L33P M235T Q192R Q222R R389G S49G T174M V34L
    SNP 11
    rs10153820 rs16969968 rs1761667 rs4244285 rs4986893 rs6434222 rs6971 rs7586970 rs7903146 rs8069645 rs8176528
    HP:0100582: Nasal polyposis
    Genes 63
    GAS8 ODAD4 DNAL1 STK11 CCDC40 CCDC65 LRRC6 RSPH4A PTGER2 DNAJB13 CCDC39 ODAD3 ZMYND10 DNAH9 DNAI1 ECM1 ZMYND10 TAPBP TTC12 DNAH11 DNAAF1 CCNO LRRC6 TAP1 MCIDAS DNAAF2 DNAAF3 NEK10 RPGR DNAI1 TBX21 DNAI2 DNAH1 CFAP221 SPEF2 ODAD4 LRRC56 OFD1 HYDIN HYDIN STK11 NME8 ODAD2 RSPH9 RSPH1 DRC1 CFAP298 MCIDAS ODAD3 DNAAF4 DNAAF6 DNAH5 SPAG1 CFAP300 RSPH3 DNAAF5 DNAAF3 FOXJ1 GAS2L2 CCDC103 ODAD1 TAP2 STK36
    Protein Mutations 0
    SNP 0
    HP:0003811: Neonatal death
    Genes 28
    FGFR3 FLNB ETFDH GLE1 SUCLG1 ATAD3A FOXF1 ETFA HSPG2 GBA FLNB QRSL1 NDUFB11 GLE1 CEP55 INTU GLI3 GATC MBTPS2 PIP5K1C PKHD1 GALT FGFR3 ETFB GLUL DSP LBR FAM20C
    Protein Mutations 0
    SNP 0
    HP:0040187: Neonatal sepsis
    Genes 3
    COG4 IL7R SERAC1
    Protein Mutations 0
    SNP 0
    HP:0000112: Nephropathy
    Genes 111
    VPS33B NPHP1 WT1 B2M TRNL1 TRNS2 FAM20A TRNS1 CCND1 FGA CC2D2A SCNN1B SCARB2 TREX1 IFT80 HIC1 WIPF1 DYNC2LI1 TMEM237 WFS1 KCNJ11 ND4 OSGEP TMEM138 SCNN1G ND5 SEC61A1 MEFV DYNC2H1 LAGE3 DYNC2I1 IFT172 IFT140 TMEM216 APOA1 ZNF423 COX1 HNF4A BLK TP53RK SCNN1A NOD2 PRDX1 ABCC8 DYNC2I2 UMOD TTC21B CEL TMEM237 MMACHC MYH9 PRODH PAX6 SLC26A4 APPL1 CLDN19 TRNQ LMX1B RPGRIP1L ALG1 TMEM231 TPRKB WDR19 COX2 EIF2AK3 NEUROD1 TRNW WAS WT1 IFT140 WDR4 RPGRIP1L WDR73 MAFB ND6 NUP133 TMEM67 PDX1 INPP5E TRNF CEP290 VIPAS39 TRNH WAS CC2D2A CEP120 TTR NLRP3 CISD2 INS MAFB COX3 GLA WDR19 HNF1A ADA2 COL4A1 PAFAH1B1 PAX4 ND1 HPRT1 YWHAE KLF11 FOXI1 CPOX NUP107 WT1 GCK SAA1 LYZ KCNJ10
    Protein Mutations 0
    SNP 0
    HP:0001513: Obesity
    Genes 490
    NR2E3 WT1 LMNA TBX3 POGZ PROK2 DCC MID2 SDCCAG8 ZNF41 RAB39B LIMK1 CNKSR2 PRPF4 PDE11A RP2 USP27X BBS10 CTNNB1 KIDINS220 FGFR3 XYLT1 PDE6B TOPORS GP1BB BBS7 GATA4 ARL2BP KCNJ11 MLXIPL HS6ST1 CEP290 GHRL EGF TAF1 PRKAR1A SEC24C PROM1 BBS12 POMC NPHP1 CARTPT C8ORF37 APOE DMD ZBTB20 BBS2 SYNE2 BLK UBE3A CCDC141 TMEM43 FTSJ1 HCFC1 FEZF1 SOX2 CACNA1S CDH23 BBS7 EMD ELN IFT172 CEL MAGEL2 TMEM67 JMJD1C UFD1 NIN ARMC5 CREBBP MKKS PDE6A BAP1 FHL1 GTF2I NEUROD1 USH2A SIN3A KIF7 RBMX PCARE CXORF56 EXOC6B MCM3AP LEP TBX1 HERC2 MED12 PDX1 OTX2 USP9X ARL6 LZTFL1 PWAR1 ADRB3 BBS9 RPE65 REEP6 RLBP1 HNF1A ERMARD TTC8 POMGNT1 INPP5E WDPCP CUL4B SAG SDCCAG8 SDC3 HESX1 KMT2A BLK RAD21 SEMA4A MOG ATP6AP2 CEP164 ARL6 BBS12 POMC MAN1B1 CTSH ALMS1 HSD11B1 NPAP1 CDHR1 RERE BLM HCRT ARNT2 FLRT3 BBS4 ROM1 SNORD116-1 ARHGEF6 ZNF711 ZNF513 GDI1 GNAS VPS13B RP1 FTO DDX6 PCNT POU3F4 TULP1 DUSP6 MC4R PNPLA6 SYP CREBBP SPATA7 LMNA GABRA3 H6PD CA4 NIPBL GNAS MKRN3 FMR1 SNORD115-1 RP9 MC3R MKS1 BBS2 PHF6 SUFU GNAS-AS1 WDR11 TSPAN7 MERTK GNAS MTTP PRPF6 NR0B2 GNAS BAP1 PRKAR1A MYT1L HNF4A RAI1 DYNC2I2 RPGR BBS9 SMARCB1 NKAP RAB23 GUCA1B LAS1L ZNF365 ALMS1 PAX6 HDAC8 ATRX TRAF3IP1 HDAC8 KIAA1549 CNNM2 PROKR2 MOG SEMA3A BBS5 PAX6 LEPR LZTFL1 SYNE1 SNRNP200 MKKS SMC1A PRMT7 CNGB1 MEGF8 CLRN1 TTC8 MAPK8IP3 TRAF7 AKT2 SETD2 IQSEC2 PCNT PPARG P2RY11 HESX1 BBS10 NDN POMC RAB23 MECP2 SOX10 PRPH2 PTCHD1 KCNJ18 BBS2 INS ACADVL LIPE KMT2D DHDDS WNT4 HLA-DQB1 MKRN3-AS1 KLF11 IDH3B TUB BBIP1 CCDC141 FRMPD4 CNGA1 ARL13B ADCY3 ACSL4 SNRPN PHF21A GNAS GNAS TBX3 STX16 ARL3 SH2B1 TUB SMO HUWE1 SHOX CYP7A1 NEK2 PRPF3 PAK3 RDH12 TCF20 USP8 IFT172 BBIP1 FGF8 ADNP IFT27 CYP19A1 ARHGEF18 RREB1 ABCA4 SLC10A7 PDGFB LRAT ARVCF PKDCC IQSEC2 MTFMT CLIP2 C8ORF37 SIM1 TBX1 BEST1 PIGT SETD5 PDSS1 EHMT1 SPG11 SCAPER ZNF408 RPS6KA3 SIM1 SH2B1 BAZ1B BRAF SLC25A4 P4HTM CEP290 C8ORF37 APPL1 UPF3B ENPP1 TRIM32 AFF4 SMARCE1 RFC2 AIP RNPC3 PRCD DHX38 UCP3 IFT172 BBS5 SLC7A14 PDE4D ATRX WT1 FAM161A ANOS1 SHANK3 IFT172 FGFR1 ZNF711 MC4R LEP DLG3 NSMF PNKP GNAS MAGEL2 RPS6KA3 KIZ SLC7A7 ADRB2 RAI1 MEGF8 AFF4 HDAC8 FXR1 GNAS CLCN4 PSMD12 PHF6 OFD1 PAX4 TRIP12 MAGEL2 GABRD EP300 TRAPPC9 SOX3 PHIP PTEN KCNAB2 WAC NDNF FGF17 ARMC5 HDAC4 SH3KBP1 IMPG2 LARS2 HACE1 ADNP AGRP LEPR PROK2 IL17RD AGBL5 USP8 TERT BPTF THOC2 PIK3CA SKI AHR TRAPPC9 CRX CRB1 PRMT7 KISS1R NF2 COMT TBX1 IMPDH1 SMAD4 BBS1 GTF2IRD1 EIF2S3 BBS1 PRPF31 PCSK1 KLHL7 DEAF1 COL10A1 AKT2 SMC3 CCDC28B CUL4B ABCC8 FLII DPYD PDE4D NRL PDE6G RBP3 MRAP2 AGTR2 VPS13B KDM6A IPW IGFALS PROKR2 MECP2 XRCC4 TRIM32 FGFR1 SPRY4 MKS1 ALG13 HGSNAT CERKL AKT1 RHO IDH3A RP1L1 EHMT1 EP300 PWRN1 IGF1 TACR3 SIN3A EYS EIF2S3 BBS4 IL1RAPL1 LAS1L IFT88 ARL6 CREBBP AHI1 CHD7 ELN CEP19 ARL6 PRPF8 SLC9A7 PCSK1 MAK SRY DNMT3A HACE1 HLA-DRB1 TTC8 TNFSF4 DYRK1B FOXP1 KIDINS220 OFD1 TBL2 BDNF RGR FSCN2 HIRA GHR NTRK2 IQSEC2 IFT74 ZNF81 XYLT1 ALB PRDM16 IFT140 IFT27 MAN1B1 ARX PDE4D SIM1 GCK IGF1R CANT1 SH2B1
    Protein Mutations 3
    G20210A P12A W64R
    SNP 17
    rs10163409 rs11548193 rs1544410 rs1558902 rs1761667 rs2075252 rs2228171 rs3755166 rs4343 rs45500792 rs571312 rs573112 rs58542926 rs731236 rs738409 rs7975232 rs9939609
    HP:0002758: Osteoarthritis
    Genes 84
    EXT2 COL2A1 TNFRSF11B MATN3 F8 AEBP1 KIF7 MMP13 CLCN7 CCN6 COL5A1 TRPS1 ZNF687 PHEX CLCN7 COL9A2 COMP KIF22 TRAPPC2 TGFB3 ACAN MATN3 COL2A1 GBA TRPV4 UFSP2 MATN3 ASPN HPGD COMP SCARB2 COL1A1 MIR140 MEFV TRAPPC2 COL11A2 ZMPSTE24 FGFR3 COL2A1 COL9A1 HLA-B COL2A1 COL5A2 FBN1 COL11A2 GNAS EXT1 COMP LMNA COL9A1 ANKH FRZB COL2A1 COL9A3 SLC40A1 HGD F9 SLC26A2 ACAN TRPV4 GHR COL9A2 COL11A1 SMAD3 ACAN GDF5 COMP PHEX AIP COL9A3 COL2A1 COL11A2 GPR101 COL3A1 COL1A1 CCN6 ATP7B COL5A1 UFSP2 SMAD3 MMP13 ANKH LMX1B CANT1
    Protein Mutations 1
    Q28D
    SNP 0
    HP:0100847: Palmoplantar pustulosis
    Protein Mutations 0
    SNP 0
    HP:0004950: Peripheral arterial stenosis
    Genes 31
    MFAP5 LMNA ELN LDLR PRKG1 FOXE3 APOB APOE TGFBR2 TGFB2 MYH11 JAK2 SMAD3 ABCG8 MAT2A TGFBR1 FBN1 MYH11 MPL ELN AGXT TGFB3 ABCG5 LDLRAP1 ABCC6 SMAD4 ACTA2 PCSK9 MYLK LOX THPO
    Protein Mutations 1
    G20210A
    SNP 0
    HP:0002090: Pneumonia
    Genes 272
    TBX20 DCLRE1C ZIC2 HLA-DQA1 GAS8 GRHL3 DNAI2 SFTPC CARD11 DNAJC21 CD81 NODAL PGM3 IL2RG GNPTAB ORC6 SFTPA2 CD247 NTRK1 TNFRSF13C SIX3 ACTA1 MUC5B LAMA3 IL2RG DNMT3B MED25 CHD7 TNFRSF13C EGFR ZBTB24 CACNA1C CYBB RNF125 NFKB1 CITED2 SMARCD2 SLC25A24 BLNK LRBA IRF8 DISP1 GAS1 KIAA0586 FOXH1 SFTPB CFTR KMT2D MAN2B1 LAMC2 P4HTM MASP2 CR2 CREBBP COL11A2 AFF4 ADA ICOS RAG1 FCGR2A CD3D SIX3 PRKCD DLL1 RANBP2 SIX3 TDGF1 PMM2 IL21R GATA4 WAS LTBP3 CFB KCNJ6 FOXH1 SGCG RNU4ATAC CDON TAF1 SLC35C1 LEP CDON EPM2A KDM6A UBB GAS1 FBLN5 ACP5 MCIDAS TBC1D24 CD79B MAN2B1 MTHFD1 TIMM8A SLC35A1 DNAI1 RAG2 ZIC2 BTK IL7R CD3E AFF4 PIK3CD NODAL NBN FOXH1 EFEMP2 NCF1 NFIX OFD1 RNF168 RAG2 SHH RAC1 DISP1 CD19 PANK2 TNFRSF13C FGF8 FANCF GLI2 IGLL1 ALMS1 SBDS EP300 CASP8 BLM ICOS DISP1 TGIF1 CRLF1 ADA UNC119 PIGN FOXP3 FGF8 TDGF1 PTCH1 NCF2 CR2 TDGF1 IL2RG GLI2 FGF8 NIPBL RAG2 WDR1 SHH BTK ZAP70 GLI2 TK2 FGFR1 CREBBP IL2RG GAS1 STAT3 DDR2 TGIF1 DCLRE1C GBA CFAP410 ELANE LAMB3 CDON IL7R MS4A1 NFKB2 STAG2 CD19 EXTL3 PTCH1 SIX3 TCIRG1 TBX20 PAFAH1B1 FOXH1 SAMD9 TNFRSF13B TGIF1 RAG1 ALMS1 NKX2-5 ZIC2 SP110 CD55 CYBA ACTC1 NFKB2 PEPD PNP PKHD1 FGF8 CYBC1 ACP5 TNFRSF11A CSPP1 WDR19 SHH DZIP1L TDGF1 DCLRE1C TLL1 JAK3 DLL1 STAG2 SHH NODAL POLA1 NOS1 TGIF1 PTCH1 ZIC2 ASAH1 TBCD CXCR4 RAC2 FGFR1 GAS1 EFL1 FMO3 HLA-DQB1 RYR1 SRP54 RAG1 BTK ABCA3 ZAP70 CARD11 SETBP1 USB1 SELENON RMRP KNSTRN NADK2 TERT CDON NHLRC1 NKX2-1 PTPRC GATA6 ICOS OSTM1 NODAL GFI1 ACADVL DLL1 PTCH1 TGFB1 TNFRSF13B KPTN TNFSF12 GLI2 ADA JAK3 LIG4 COL11A2 ODAD1 PLOD1 MYH6 DLL1 IFNGR1 SRP54 TNFSF12 IGHM RNU4ATAC SFTPC DOCK8 NBN FOXN1 DISP1 SMC1A
    Protein Mutations 6
    A2063G G551D K55R L460D R287Q S1009A
    SNP 0
    HP:0005764: Polyarticular arthritis
    Genes 21
    ANKRD55 ENPP1 PADI4 IL36RN PTPN22 NFKBIL1 SLC22A4 IL2RA IL10 MEFV STAT4 NOD2 NLRP1 TNFAIP3 IL2RB CIITA PTPN22 CD247 PTPN2 CD244 DMP1
    Protein Mutations 0
    SNP 0
    HP:0003765: Psoriasiform dermatitis
    Genes 26
    HLA-B HLA-DQB1 PIK3CD LIG4 HLA-C TTC7A FLI1 SLC29A3 NFKB2 HLA-DRB1 TP63 TTC7A ADAM17 CTLA4 IRF2BP2 GATA3 DSG1 AP1S3 IL36RN CARD14 CACNA1G EGFR NFKB2 MSMO1 KNSTRN FOXP3
    Protein Mutations 2
    V600E V66M
    SNP 1
    rs6265
    HP:0000709: Psychosis
    Genes 120
    WFS1 SPART PRDM8 TRNL1 TRNS2 DNASE1 TRNS1 MECP2 CACNA1A USP8 SH2B1 PDE11A FCGR2B TBC1D7 USP8 MKRN3 SNORD115-1 PANK2 C9ORF72 HFE PAK3 ND4 NDP ACADS ND5 STAT4 NPC1 PSEN1 PRKAR1A COX1 CLN8 WFS1 ZDHHC9 ZFYVE26 DNMT1 PUS3 NDP MED12 CDH23 RPS6KA3 SIM1 VPS13A DCAF17 ALDH18A1 PPOX IPW TWNK PAH ALDH5A1 PDGFRB C9ORF72 TTC19 TRNQ CLN3 AIP COX2 UPF3B HMBS IRAK1 TRNW PDGFB NHLRC1 SLC6A19 SPP1 PCDH19 SOBP ATP13A2 LMBRD1 PWRN1 PCDH19 ND6 ATXN7 PDGFB NAGS SLC25A13 TREX1 HERC2 ITM2B CHMP2B TRNF GNAS MAGEL2 ALAD VCP NDN NPC2 TRNH SLC7A7 PWAR1 CBS MED12 DCAF17 PARK7 GCLC MAPT PRNP FIG4 EPM2A COX3 GSS FCGR2A SQSTM1 ND1 MKRN3-AS1 ABCD1 TREM2 MTHFR MAGEL2 MYORG NPAP1 CPOX SLC12A6 SLC20A2 GRN TMEM106B CTLA4 KCNT1 PTPN22 SNORD116-1 SNRPN
    Protein Mutations 6
    D61804R N40D S311C S9G V158M V66M
    SNP 4
    rs1006737 rs1799732 rs3813929 rs6971
    HP:0002206: Pulmonary fibrosis
    Genes 86
    SFTPA1 TERT ZCCHC8 NUP107 BTNL2 TERT FAM111B NDUFAF6 CLCA4 STX1A CCN2 BNC1 CTLA4 TERC TERC MUC5B HLA-DRB1 HLA-DRB1 RAC2 SFTPA2 SFTPA2 TERT BACH2 TGFB1 BMP15 AP3B1 CFTR PRTN3 MUC5B FAS PRKCD DSP RCBTB1 HLA-DRB1 FSHR BTNL2 PARN NOP10 CCR6 PTPN22 TERT TERT NR5A1 FAS NKX2-1 RASGRP1 CAV1 DKC1 PLEC RNF168 HLA-DPB1 DCTN4 IRF5 CCN2 ATP11A RTEL1 CAV1 HPS4 TINF2 MRPS22 RNF168 TERC SFTPC PSMC3IP TINF2 SP110 KIAA0319L RTEL1 HLA-DPA1 STN1 SPIDR POLR3H PARN IRF5 FASLG SFTPC CCR6 HLA-DRB1 NHP2 ABCA3 DPP9 CYBC1 THOC2 CASP10 HPS1 FAM13A
    Protein Mutations 1
    V600E
    SNP 4
    rs35705950 rs3570920 rs3750920 rs6971
    HP:0006536: Pulmonary obstruction
    Genes 101
    TBX20 GAS8 DNAL1 SERPINA1 CCDC40 RSPH4A DNAJB13 CCDC39 ODAD3 DNAH9 CYBC1 MMP1 MYH7 TTC12 WIPF1 GP1BB COMT CFTR TBX1 DNAAF2 GLA SEC24C DNAI2 CFAP221 SPEF2 RREB1 ODAD4 ARVCF CITED2 HLA-DPB1 CITED2 OFD1 TBX20 TBX1 NME8 ODAD2 NCF4 DRC1 DNAAF4 DNAAF6 NCF2 DNAH5 SCNN1A ALMS1 NKX2-5 HMOX1 ACTC1 DNAAF3 JMJD1C FOXJ1 UFD1 GAS2L2 CCDC103 ODAD1 SCNN1B DNAAF4 STK36 NCF1 APC DNASE1L3 TLL1 CCDC65 GATA4 LRRC6 CYBA ZMYND10 CTLA4 SCNN1G DNAI1 NFKB1 RAC2 DNAH11 DNAAF1 CCNO PRTN3 MCIDAS PTPN22 WAS NEK10 RPGR VPS33A DNAH1 GATA6 CYBB TLL1 LRRC56 GLA HYDIN RSPH9 HIRA RSPH1 CFAP298 MCIDAS MYH6 HLA-DPA1 MGP BLM SPAG1 CFAP300 RSPH3 DNAAF5
    Protein Mutations 2
    A118G G551D
    SNP 6
    rs1051730 rs1800470 rs1828591 rs25331 rs4129267 rs7103572
    HP:0002098: Respiratory distress
    Genes 194
    ND4 TRNN CHAT AIFM1 SFTPC DPM2 EDA SLC18A3 USP9X FGFR2 PRRX1 COA3 XYLT1 COL2A1 LAMA3 ADNP ZIC3 DNAAF3 TRIP11 TRPV6 TRNE SCO2 SERPING1 SLC52A3 COX7B AIMP2 SFTPB MAPT LAMC2 COX20 EPHB4 ORC1 SIK1 MMUT TRNL1 ALDH7A1 VPS33A ETFB SFTPB ORC1 PMM2 BMPER TRNS1 ORC6 ZFPM2 RUNX2 ATP6 PET100 TRAK1 NAGS LAMB2 SCO2 LIFR TBC1D24 COQ7 FBP1 SLC35A1 SOX9 CSF2RA MMAA VPS33A CHRNE SCO1 DISC1 COL2A1 KAT6A DNAJC21 NUP214 POMT1 RPS28 VAMP1 SDCCAG8 NAGS SFTPC ORC4 HLCS EOMES ND6 COX8A FGFR2 MMAB TRNE EFTUD2 SLC12A3 SLC25A3 DMPK NDUFB8 FGFR2 FOXP3 COX14 PSAP COA8 ND5 SLC2A10 ADCY6 SRP54 AGRN TSC2 CLCNKB CDC6 HCCS COLQ NDUFB11 SNAP25 COX10 DPM1 DHX16 TK2 SURF1 TACO1 ND1 CDT1 UBE3B LYRM4 GALC GBA USP9X DYNC2LI1 NDUFS2 ABCA3 STT3B SSR4 GATA6 ASAH1 SBDS MPC1 TSC1 KRT6B LAMB3 COX6B1 SLC5A7 PLCB4 ETFDH CHAT ETFA CDC45 IL1RN IFT52 IFT81 TRNV FOXF1 GBA STAT5B GNAI3 ALMS1 CSF2RB NGLY1 PUF60 STT3B KCNA1 ADAMTS13 KRT16 BMPER KRT17 RPS26 OTX2 TRNW FAM20C LGI4 TRIP11 GATA6 EP300 TRNK PRRX1 ERF KRT6A GMNN MYO9A ND2 NDUFAF3 ABCA3 CREBBP KLHL7 SETBP1 TRMU MMUT NKX2-1 FGFR2 NKX2-1 TUBB4A SYT2 ACADVL MEGF10 MAPT EDN1 CPT2 SLC25A1 CNTNAP1 ITGA3 COL13A1 FGFR1 DPM2 RNF13 ND3
    Protein Mutations 1
    A118G
    SNP 1
    rs7103572
    HP:0011947: Respiratory tract infection
    Genes 785
    SMARCA4 TBC1D24 SNX10 SLC1A4 GRHL3 CFAP298 RSPH4A CARD11 CD3E COG4 PGM3 ECM1 GNPTAB LIMK1 CD247 NTRK1 ZBTB24 MANBA CLEC7A IL2RG TARS1 DNAAF2 NSD2 DNAJB13 DNAAF3 EXOSC9 NELFA EDARADD STING1 MAP3K20 HLA-DPB1 OFD1 SMARCD2 ABCA12 SCNN1G SLC25A24 BLNK GAS2L2 TYK2 HELLS FOXH1 DNAAF6 INPPL1 OCRL GTF2E2 MASP2 COL11A2 MYO5A FCGR2A PRKCD RANBP2 IL21R GATA4 TSC2 LTBP3 CYBA SPINK5 CTLA4 KCNJ6 FOXH1 NAGLU GUSB SHROOM4 LIPN RNU4ATAC TPM3 HERC2 EPG5 GAS1 FBLN5 NRAS ACP5 MCIDAS MAN2B1 TIMM8A COL13A1 PTPN22 SLC35A1 SLC46A1 HGSNAT LYST ZNF341 XIAP LRRC56 IGH NODAL LETM1 TRIP4 EFEMP2 NCF1 MCM4 SFTPC RSPH4A IL2RB RAG2 RAC1 DISP1 WRAP53 PANK2 TNFRSF13C ARID2 SBDS NPAP1 ACTA1 BLM CD40LG ICOS CCDC103 SNORD116-1 FOXP3 TDGF1 IL6R CIITA GLI2 FGF8 DNAJB13 CCDC39 IDUA GATA4 NOP10 GNPTAB TBX6 MKRN3 SNORD115-1 ELANE SMN1 KIF20A PGM3 PEX13 CDON IL7R SCNN1A STAG2 PLEC FLI1 SIX3 TCIRG1 ZNHIT3 LAMA2 CYP4F22 DNAAF4 FAT4 ZIC2 CSF2RB CD55 NFKB2 PEPD TNFRSF13B FGF8 STK36 RFX5 RYR1 SHH DCLRE1C SLC25A22 TLL1 AP3D1 NODAL ZMYND10 NOS1 TPM2 TRIP11 ZIC2 CTCF RAC2 CTLA4 PLP1 GAS1 EFL1 FMO3 RYR1 CIITA DLL3 PRTN3 ABCA3 AGA PCNT RSPH1 ZAP70 NDN NHLRC1 DNAH1 SCNN1G ACADVL DCTN4 PTCH1 DKC1 GMNN TNFRSF13B GLI2 MCIDAS SCN11A ROR2 IVNS1ABP ODAD1 MESP2 SLC12A6 MGP CFAP300 RSPH9 UMPS KRAS SFTPC COL13A1 SNRPN GAS8 CACNA1B AK2 INPPL1 CHAT CCDC40 IL2RG CD3G TASP1 SLC18A3 SCNN1G KAT6B STAT1 ACTA1 MUC5B SMN1 TAP1 MED25 CHD7 COG4 SULT2B1 GBA SPEF2 SDR9C7 CFI IDUA FUCA1 SAMD9L FLNC NCF4 LRBA DRC1 RFXAP KIAA0586 DNAH5 DOCK8 MAN2B1 ATM LAMC2 TRAF3IP2 CR2 GALNS TAP2 AFF4 UNG DNAAF4 RFC2 NCF1 CD3D RELB ODAD4 TDGF1 PMM2 RUNX2 SGSH WAS IL17F IL6ST IRAK4 LRRC8A TAPBP CCNO PLCG2 HK1 MYL2 LEP ERCC3 IGLL1 EPM2A CCDC65 CD79B FLNA XIAP CYBB CD3E AFF4 MESP2 POLE FOXH1 HYDIN TNNI3 NFIX BCL10 RNF168 NEU1 NPM1 IGLL1 TGIF1 WAC ADA UNC119 PIGN GAA CD8A IKZF1 TSC2 LEPR ARSB COG6 VPS51 COLQ WDR1 BTK GAS1 TTC12 WASHC5 CD3D STAT3 CCDC40 ASAH1 DNAI2 LAMB3 NFKB2 PTCH1 COL6A3 PAFAH1B1 FOXH1 MBTPS2 RYR1 TNFRSF13B TGIF1 CLCN7 SP110 COL6A1 TCTN3 SMARCC2 PNP GLUL PKHD1 ALPL ACP5 WDR19 TDGF1 TFRC MGP DLL1 SHH TGIF1 EHMT1 EP300 ITGA7 ERF DNMT3B FGFR1 HLA-DQB1 SPAG1 SRP54 UBE2A TINF2 CARD11 ARID1B SELENON RMRP WAS NEK10 MAPK1 GATA6 SCNN1B SYT2 USB1 DLL1 POLR3A PRPS1 RSPH1 TNFSF12 PIK3R1 IER3IP1 GSN NME8 LIG4 IL7R ALB COL11A2 TGFB1 DLL1 IFNGR1 LAMTOR2 DNAAF5 NXN PTPN22 TBX20 RAB3GAP2 ALOXE3 ZIC2 LRRC56 HLA-DQA1 KIF1A GAS8 PSAP DNAI2 NOTCH2 DPM2 CD81 NODAL DNAH9 TBC1D23 NFKB2 ORC6 SMARCB1 SIX3 LAMA3 DNAH5 ATP6V0A2 EGFR ZBTB24 LYST ODAD4 CACNA1C CYBB RNF125 DPF2 CITED2 GATA6 IRF8 DISP1 GAS1 ABCA12 ODAD3 DNAAF2 MECP2 BIRC3 SFTPB ELN CFTR SCNN1A KMT2D MDM4 IL17RA CCDC39 IL17RA FCGR3A VPS33A ODAD1 IKBKB RSPH3 CREBBP TNFSF11 SCNN1B AGA SCNN1A ADA RAG1 RAG1 TGM1 DLL1 SIX3 CARMIL2 GTF2I CCDC65 ARID1A CFB RAG2 SCNN1G SOX4 NECTIN1 ZMYND10 SGCG DNAAF6 CDON TAF1 IGHM LAMB2 LEP CD79A CFTR HPS6 CCBE1 PWAR1 RPGR VPS33A BTK SCNN1A IL7R EPG5 PIK3CD NBN HYDIN PSMB8 VAMP1 SDCCAG8 SHH RAC2 CD19 HLA-B GLI2 FLNA ALMS1 SCNN1B ITCH SPAG1 DISP1 DNAAF5 IDUA FGF8 MSN SMARCE1 BCR SERPINA1 PRPS1 NIPBL RAG2 ZAP70 TK2 FGFR1 CREBBP ALOX12B RFXANK IFIH1 GBA USP9X IKBKB MYOD1 CCNO TBCE GBA TSC1 PLCG2 G6PC3 MS4A1 CD19 EXTL3 GUSB DYNC2I2 NGLY1 SAMD9 NME8 TRAIP PYROXD1 SIK1 SLC26A2 RAG1 ALMS1 NKX2-5 IL21 FOXP1 LAMTOR2 ACTC1 FOXJ1 ARID1B SCNN1B CYBC1 CSPP1 SMARCD1 JAK3 STAG2 PCGF2 CXCR4 LEPR POLA1 PTCH1 RPGR ASAH1 ASAH1 RAG2 MYSM1 BTK DCLRE1C CFTR KNSTRN FOXJ1 PEPD TERT CDON TCF3 NKX2-1 ICOS DNAH11 OSTM1 ALG12 KATNIP TGFB1 KPTN ADA TPP2 MKRN3-AS1 SLC25A1 MYH6 HLA-DPA1 FBLN5 SRP54 TNFSF12 IGHM NEK10 RSPH3 TTC12 CRKL RASGRP1 SELENON DOCK8 GLI3 SMC1A DCLRE1C DNAL1 RIPK1 SFTPC CD79A TNNT2 DNAJC21 TSC1 CTSC USP9X SFTPA2 PIK3R1 TNFRSF13C NR2F2 CFTR ADNP DNMT3B TCIRG1 CFAP221 TNFRSF13C NFKBIA NFKB1 NEPRO SLC52A3 CLIP2 CRELD1 FCN3 NCF2 SIM1 BAZ1B P4HTM DNAAF3 GAS2L2 CCDC103 UGP2 GATA2 ICOS CDCA7 SIX3 JAGN1 CLCA4 STX1A MYH3 STAT3 DNAH11 LRRC6 SLC35C1 CDON IL17RC CD79B KDM6A UBB NHP2 NCF4 CCDC22 MAGEL2 TBC1D24 MTHFD1 MIR140 BLNK LCK NFE2L2 CSF2RA MYSM1 DNAI1 RAG2 ZIC2 HACD1 MPLKIP TLL1 COL6A2 OFD1 PARN SCN9A FGF8 MAGEL2 FANCF CORO1A PIK3R1 PRKDC CR2 EP300 PIK3CD CASP8 CRLF1 PTCH1 NCF2 SH3KBP1 CR2 DNAAF1 AGRN RFXANK TDGF1 IL2RA SOX11 IL2RG ATM ODAD3 CYBC1 SNAP25 SMPD1 TRPS1 SHH ELP1 GLI2 CHRM3 IL2RG PNP BACH2 CREBBP SH2D1A WIPF1 DDR2 CTC1 TGIF1 RFX5 DCLRE1C CFAP410 GTF2IRD1 SLC5A7 ERCC2 TERC ADAMTS3 TBX20 ODAD2 SLC29A3 MALT1 DSG1 TECPR2 IPW NGLY1 CYBA EP300 TNFRSF11A DZIP1L CD81 LRRC6 RTEL1 RAG1 DNAI1 MYPN NFKB1 ODAD2 TBCD ELANE CXCR4 PWRN1 TNFRSF1A FOXP1 MYO9A DNAAF1 TGFB1 RFXAP RAG1 SMPD1 CREBBP SETBP1 USB1 NADK2 MS4A1 CHAMP1 TERT NKX2-1 PTPRC SCN10A ELP1 POLR2A NODAL GFI1 PLG RNF113A TBL2 RSPH9 CFAP298 CD19 JAK3 AICDA GLB1 GTF2H5 NIPAL4 PLOD1 RNU4ATAC ITGA3 NBN GNS FOXN1 STAT1 DISP1 B2M
    Protein Mutations 1
    H275Y
    SNP 0
    HP:0001370: Rheumatoid arthritis
    Genes 29
    HLA-DRB1 ANKRD55 PADI4 STAT4 GCH1 IL2RA IL10 STAT4 IL2RB IL2RA PTPN2 PTPN22 CD244 CD247 ANKRD55 PTPN2 PTPN22 NFKBIL1 DCLRE1C SLC22A4 ACP5 LACC1 IL2RB CIITA IL6 PTPN22 MIF CD247 ACP5
    Protein Mutations 4
    A147T N363S R620W V600E
    SNP 10
    rs2246704 rs2853884 rs35705950 rs3747158 rs3790515 rs3828057 rs4820059 rs7291050 rs933226 rs9826
    HP:0001708: Right ventricular failure
    Genes 16
    TBX20 MYH7 GATA6 TTN NKX2-5 TLL1 GATA4 MYH6 SDHD CITED2 TBX20 ACTC1 BMPR2 SELENON ATRX DAXX
    Protein Mutations 0
    SNP 0
    HP:0100753: Schizophrenia
    Genes 72
    CIB2 APOL4 WFS1 UPF3B ADGRV1 MYO7A ARSG GIGYF2 RTN4R RBM12 DNAJC13 USH1C KRT83 COMT CAT PSAP MSTO1 PDZD7 TBX1 GP1BB HARS1 SNCA ESPN COMT TBX1 APOL2 ARSA DNMT3A SEC24C KRT81 WHRN TRNS2 MED12 NKX2-1 TRNE RREB1 CDH23 CLRN1 HTR2A CEP78 SYN2 LRRK2 ARVCF FLI1 KRT86 GJA5 TBX1 PRODH ATP2A2 ZDHHC9 HIRA USH1G CHI3L1 VPS35 DAOA EIF4G1 DSG4 PCDH15 USH2A MYO7A PRODH DISC2 GBA PRODH MTHFR JMJD1C SHANK3 GJA8 UFD1 DRD3 CHRNA7 MSTO1
    Protein Mutations 7
    D61804R N40D P50I S311C S9G V158M V66M
    SNP 14
    rs1006737 rs1256049 rs1799732 rs1801132 rs2023239 rs2069514 rs2234693 rs2494732 rs3813929 rs4244285 rs4680 rs6971 rs762551 rs9340799
    HP:0001250: Seizure
    Genes 2887
    SMARCA4 TBC1D24 ND4 PRDM8 SLC1A4 ZBTB18 GYS2 TMEM94 SCN1B SETBP1 GAD1 GPHN TXN2 COG4 LSS PGM3 FXYD2 TRIT1 POMT1 FOXG1 GRN BCL10 CTNNB1 EEF1A2 NR2F1 CRADD GP1BB ANGPTL6 ASS1 HS6ST1 GABRA1 ADRA2B EXTL3 GDNF NDUFS1 SLC25A19 SEC24C CALM1 SUCLA2 ANK2 PAH NELFA GABRB3 NOVA2 NCAPD3 KCNQ1 CHN1 COG2 AP4E1 PEX11B PEX11B RYR2 FKRP TDP1 FRMPD4 CCDC141 WWOX NSD2 CYTB FBXL4 PCYT1A KRAS ATP5F1D TSEN54 TRIP13 FTSJ1 ERCC1 FEZF1 KCNH1 ARF1 RNU4ATAC FOXH1 PERP IKBKG SETBP1 BTD MAGEL2 GTF2E2 PEX10 CDK19 NF1 HEPACAM PRF1 NDUFS6 HNRNPH2 ASXL1 AHDC1 KCNJ6 SEC31A IRF3 MLH3 NECAP1 FTSJ1 GCDH PIGG C12ORF4 NSD1 TSC2 PLA2G6 SPINK5 PRPS1 LAMA2 WDR45 NAGLU KMT2A DLD SHROOM4 EMC1 C12ORF57 PPP2R1A KIF2A COQ2 GRIA4 PGAP2 TMEM67 ARX ATP6V0A2 CSNK2B EFHC1 KIF11 JAM2 ARSA SYNJ1 TRNP CDH15 KIF5C SUCLA2 RASGRP1 LYST FKRP UFC1 TWNK GDF6 NEUROD2 TSFM TMEM67 SPOP CACNA1H CUX2 DPYS GPT2 LETM1 ACTL6B SCN2A ATP6V1A SQSTM1 FAM149B1 PEX19 ABCA2 TRNI ACADM APP PEX3 PANK2 TRIO GLI3 PEX13 MAN1B1 HNF4A SCN2A NPAP1 RERE TANC2 KLLN ARNT2 KDM5B SLC13A5 KIF7 SNORD116-1 SRPX2 PEX19 SEMA6B TGFBR2 OSGEP IARS1 SVBP VPS13B ENG FTO GLI2 TRAPPC12 HLCS ATIC NOTCH3 HIBCH RARS2 HIC1 ANKRD11 IFNG SURF1 ARL13B TACO1 HERC2 TRNK ZFP57 GFM2 COL4A1 SLC9A6 TBK1 STT3B MKRN3 KCNJ10 ATN1 MYO1H POLG VDR OCLN ND5 CASK PIGO FAR1 TSEN54 F8 NDUFS7 ARHGAP31 PIGH RFT1 CDON KCNQ1 SCN8A FGFR1 NEDD4L BAP1 SIX3 SERAC1 CYP27A1 GALC SMARCB1 LMNB2 PRDX1 INSR WDR11 LAMA2 KCNMA1 PHGDH TRNV QDPR ADAMTSL2 PEX14 TMEM165 FAT4 SCN2A PRODH SNORD118 ZIC2 KMT2E DHX37 TRNK TUBB3 GABRG2 NFKB2 CAV3 ALDH3A2 CNNM2 PEPD ST3GAL3 PIGQ FGF8 STAT2 SHH COL18A1 STXBP1 SON SLC25A22 GALC HMBS RET COG2 TPP1 NODAL JAK2 PCDH19 BUB1B EIF3F ERAP1 GRIA3 SMC1A CLN8 EIF2AK2 CC2D1A ADD3 MTFMT GAS1 SLC25A13 MAPK8IP3 TMEM231 ARX PRTN3 FLNA PIGN AKT2 NTRK2 RAB11B TRNF TDGF1 HTRA2 B4GAT1 VCP DYRK1A HCFC1 DNM1 BCOR FLCN NHLRC1 NAXE CTH PIGQ XK IL12A IDH2 PLK4 PLA2G6 CDKN1A HCN1 TUBB2A RORB ARL3 TBX19 CASQ2 TBCE NDUFV2 LMAN2L MTHFR GABRA1 TRNL1 GABRB3 ZEB2 RPL10 COX1 FRMPD4 ARCN1 TUBB2B NUP107 CENPJ COL13A1 ACSL4 MDH1 HSD17B4 EGF BUB3 GJA1 CACNA1B LIG4 LARP7 NTNG1 GRIK2 ANKRD11 ZBTB18 ALG11 TREX1 APP NF2 CCDC88C HUWE1 COA3 CD96 SEPSECS PSAT1 DLG4 COL4A1 TMEM237 EIF2B5 MSX2 SLC2A1 NRXN1 KCNQ2 CDKL5 TULP1 CTSA GBA SLC35A2 PIGK PQBP1 CPS1 PTS CIT ERLIN2 XPA ANKH RELN OFD1 CDK13 VARS1 SETD5 SYNGAP1 DPAGT1 PPP3CA CNTNAP2 COX7B APC2 GDF2 TRMT10A FBXO31 ALDH18A1 LAMC2 ACTL6A TBC1D24 D2HGDH PEX26 MMUT LRPPRC TRAF3IP2 GP9 KATNIP APP ALDH7A1 HCCS PIK3R2 SMARCB1 CTNNA2 PPM1B UPF3B PIGV NSDHL SLC33A1 STX1B GMPPB TRNQ RRM2B SYNJ1 GLI3 BCL11B ALG1 KIF15 TDGF1 ATR PMM2 SGSH KCNJ11 TANGO2 USP7 ARX TRNS1 MLYCD CTSA NLGN4X IL17F SCN10A SLC13A5 SHANK3 ACSF3 SLC35A2 ZNF711 PHOX2B HK1 NAGS ADPRS FLI1 ETHE1 CLCN4 TBR1 PEX19 PEX12 SETD1A CDK8 INS CC2D2A HNF1A MED12 MAP2K1 GJC2 PEX14 SYNGAP1 NFIA PAFAH1B1 PGK1 MOGS FIG4 EPM2A TBL1XR1 SMG9 SNRPN HSPD1 SLC6A8 VAMP2 FOXH1 NDUFAF5 EOGT PAFAH1B1 PHF6 FARS2 ACTA2 ND1 GPHN GPR161 NAXD NDUFS4 TRIP12 ARF1 PTEN PHOX2B SLC20A2 GUF1 SMAD4 EIF2B2 ACY1 PRNP SOX3 FMN2 WAC ADAM22 CHRNA2 PHACTR1 NTNG2 NDUFB8 SDHA FGFR2 FGF17 TRNW CARS2 WFS1 IFIH1 KRAS COA8 PSAP DHCR7 PEX1 PEX12 FBP1 AARS1 TREM2 PTCH1 MEN1 CLCNKB SLC35A1 PROK2 CKAP2L TRAPPC2L CC2D2A RAC3 AVPR2 BPTF COX10 PIK3CA UBA1 CLCN4 SAMD12 MED17 PLAGL1 ARMC9 GABRG2 ATXN10 GAS1 SMARCE1 LAMC3 GALC ERCC5 RERE LHX4 ERLIN2 TRNV HYMAI CACNA1C MKS1 ARHGEF9 SHH MEFV ACVRL1 ATP1A3 STAG2 CDON DOLK AKT1 FAM149B1 NNT CCDC88A RPE65 NFIX DEAF1 PEX2 HADHA PAH TRNF PIGL DALRD3 SATB2 PHGDH SLC12A5 PSAP PEX12 TAF1 NALCN PDE4D TRAPPC11 FA2H SDHAF1 ALDH7A1 PIGW TGFBR3 PODXL TGIF1 RAB39B COQ6 LARS2 ATN1 SMC3 RPS6KA3 LIPT2 PROKR2 MECP2 APC2 ARHGDIA GCK SMARCC2 FGFR1 ATAD3A PQBP1 PPOX EARS2 GLUL PET100 IL1RAPL1 TUBA8 TPRKB RAB3GAP1 ISCA1 GLRB TDGF1 MEIS2 GUCY1A1 KCNJ11 ASNS FARS2 PEX6 TSEN15 TRNW GLYCTK SCN9A METTL23 STRADA CERT1 ARX TGIF1 NOTCH3 WDR4 EHMT1 NOS1AP RPGRIP1L TRNK CEP120 WDR81 CNOT1 ANO10 CLCN2 MEF2C UBE2A ATP6AP1 RPGRIP1 TUBGCP6 CEP290 INTS8 CACNA1A WDR26 TMX2 DNMT3A UBTF TANGO2 CEP290 SDHB ADSL NUBPL SET MARCHF6 RARS1 CISD2 ATP5F1A DHCR24 GCM2 MFSD2A HTRA1 MID2 THSD1 SMC1A GOT2 KCNT2 HPRT1 TUBGCP4 NTRK2 SVBP ALDOB NSD1 DLL1 AP4M1 CPA6 GNB5 PUM1 CHD2 CNKSR2 PDE10A ENG TBCE TRNS2 KDM6A UNC80 CASP10 PPP3CA TUBG1 KCTD7 KIF1A TRNT POGZ FOXH1 PROK2 TRNL1 PIGP PEX11B DYNC1I2 KCNA1 NODAL HESX1 SPR MECP2 ANKRD11 CACNA1A ALX4 TBC1D23 RAB39B CIC COX10 SCN8A POMT2 LAMA2 RNU4ATAC SMARCB1 GRIN1 NDUFA2 STXBP1 BCOR HADHA ALG13 GRIN2B DNMT3A HTT KIF11 ADK MCCC2 CPS1 PCLO RAB18 PEX5 CHD2 CYP27B1 AVPR2 CPLX1 ATP6V0A2 CACNA1C NSDHL DMD GNB1 SRPX2 DPF2 STAG1 RLIM UBE3A ZFYVE26 CDK10 FKTN SCYL2 MSX2 DISP1 PEX13 GAS1 RPGRIP1L JAM3 AIMP2 TLR3 SCN11A TCTN3 CLCF1 CRADD ANKLE2 ISG15 TP53RK TCF20 IL17RA MAN1B1 UFD1 C9ORF72 GABRD FRA16E CPLANE1 TSC1 DLL1 TRMT10A TUBB4A TXNRD2 EIF2AK3 L1CAM AKT1 POLE ARID1A NACC1 NHLRC1 B3GALNT2 GABRB2 ABCC9 FBXO11 FAN1 FOXG1 PMPCB LNPK RORA RAB27A MSH2 DEGS1 HERC1 KCNA1 SYN1 SDHC CDON PTCH1 PDCD10 TBX1 PREPL MED12 TMEM67 INPP5E MYORG CHMP2B CCBE1 USP9X LRP2 PWAR1 SMARCA2 MECP2 TMTC3 SCO1 KIF5A DCC GFM1 PIK3CD ACTB PHOX2B BRAF CACNA1B ERMARD LHX4 PSMB8 VAMP1 NTRK2 DHDDS TCTN1 FCGR2A CLN6 MAPRE2 AKT3 EBP RAD21 LMNB2 GPC4 DNAJC5 ARHGAP31 CEP164 TREM2 YEATS2 CSNK2A1 TRPM6 GLI2 CPT1A SLC13A5 HIVEP2 TBCD PEX26 SCN9A WDR26 DISP1 SZT2 SIX3 FLRT3 TDP2 KATNB1 FGF8 AP4M1 PSAP GABRA5 SMARCE1 BCR POLG WDFY3 ATAD1 PRPS1 DCX GP1BA TRNS2 TK2 PIGB DNASE1 NIPBL KIF1A POU1F1 CEP41 TSEN54 PRRT2 AP4B1 ARMC9 CHD1 DDX3X SCN1A HTT SDHA DPM1 TUBB2B XPR1 IFIH1 ROGDI TK2 SYP SPG11 ND1 APP BCORL1 GPAA1 ZEB2 NODAL TUBGCP6 CLCN2 LETM1 RRM2B DNAJC6 USP9X CLDN16 MAFB BMP4 L1CAM GAMT PEX3 TBCK SLC13A5 FMR1 COX6B1 PLAA MFSD8 OCRL UBAC2 COX1 SORL1 CEP104 RAI1 NDE1 GNE NGLY1 SLC35A3 SAMD9 BUB1B HEXA EZR DDOST PIGW CRB2 PEX1 SIK1 GMPPB LAS1L DHDDS MMACHC MORC2 RERE LGI1 KCNQ3 ALMS1 AQP2 HDAC8 TRAPPC11 ALDH18A1 KCNQ2 ERCC6 JRK FKRP ASH1L TWNK PUF60 TBC1D24 TRNK RANBP2 SNTA1 CASR STT3B TYROBP ARID1B SPR FLVCR1 OCLN KRAS DOCK3 USP7 SUMF1 PROKR2 CCBE1 GCK PIK3CA STX11 DCX IRAK1 CPLANE1 ARX STAG2 PEX6 SLC6A19 SOX10 ECE1 KCNQ3 LRAT HTT POLA1 POLR3A GOSR2 MTOR PPP2CA SEC23B GJC2 TRNP SLC39A8 CLTC AMPD2 ASAH1 PIGP EML1 HYMAI ALG13 PIBF1 HMGCL HNRNPU KCNT1 NDUFA11 SLC25A12 PLA2G6 HSD17B10 SETD2 RPS6KA3 KCNB1 PPP2R1A L2HGDH CLPB TECR NDUFA12 ABCC8 CPT2 KNSTRN CBS TMEM216 CDON NDUFA4 SPTAN1 PACS1 PSEN1 NNT MAPT GUCY2D KMT2D GRIN2A NDUFB11 FRRS1L ATAD3A HAX1 NUS1 CTNNB1 MEGF10 GABBR2 AUH CKAP2L MKRN3-AS1 TCF4 SLC25A1 USP45 NOTCH1 ERCC4 AARS1 ANK3 AIFM1 LARGE1 SMPD4 HLA-DPA1 ABAT SURF1 GNAQ PTS PEX16 PTPN22 OTX2 CLPB NDUFA2 EPRS1 DPM2 COX7B THOC2 PIGN ND3 SMC1A SCN3A PEX1 AP2M1 GLB1 TRNN SUFU AIMP1 PSAP KLRC4 RHOBTB2 COG7 PCCA TSC1 USP9X KCNC1 PDCD10 PIGU SMC1A MEN1 ASCL1 NDUFAF6 HMBS CAMK2A GBA PPP1R15B FGF8 HLA-B CTU2 STAT4 SETD2 RELN ATP6V1B2 AMER1 TMEM216 MEN1 NDUFS1 BMPR1A PDGFB KIAA0753 ATP6V0A2 ZNF423 ARVCF ERCC5 AKT3 PMS1 IQSEC2 PEX16 MTFMT ALDOB PGAP2 CRB1 TMLHE GRM1 POGZ ROGDI NDUFS2 KCNJ11 EHMT1 ATP1A2 KLHL7 SCN1A ZIC2 RECQL4 RPS6KA3 KCNMA1 NDUFS8 SIM1 DLG3 LARS1 BRAT1 FUCA1 SERPINI1 CFH SLC25A20 SDHD KRIT1 COL3A1 ADAR WHCR SLC9A6 PEX26 DOCK7 TRNQ SMARCE1 LIAS ESCO2 TUSC3 SARS1 AP3B2 ATAD1 GLS CACNA1A TIMMDC1 POMT1 UBE2A MBTPS2 PSPH TBC1D24 FGFR3 OFD1 ARG1 ANOS1 SLC2A1 POMGNT1 NPRL3 MRPS22 KRIT1 FGFR1 CTSD DMXL2 EEF1A2 IL17RC FLNA DLG3 NSMF KDM6A TRIM8 ALG2 RPS6KA3 ALAD GABRA2 MTHFD1 FDFT1 DARS2 PHACTR1 CNPY3 PIK3R2 GLRA1 KCNMA1 GNAO1 GPSM2 GLI2 GLI2 VLDLR GTPBP2 IL10 COX3 SMPD1 GRIN2A POMT2 ECHS1 TRIP13 WWOX EZH2 PEX13 GABBR2 MCTP2 SCN8A FGF8 COX8A WASHC4 MAGEL2 SLC19A3 RAB18 NSUN2 DNAJC19 EP300 GLRA1 EFTUD2 NDUFB11 ENG NDUFAF6 TRAPPC4 CLP1 TUBA8 PRDM8 NDUFV1 PDE6D ZSWIM6 AP1S2 SDHAF1 GRM7 SLC19A3 HACE1 L1CAM CDH23 TDGF1 LGI4 SOX11 RUBCN HCN1 ERCC6 IL17RD CHRNA4 SMARCC2 TERT COX2 ARID1A MVK PURA CREBBP DHDDS NKX6-2 TRAPPC9 POMK EIF2B4 PEX3 CHRNA7 NEXMIF MTR SLC16A1 NANS NF2 ATP6V1B2 NADK2 DNM1 SLC19A3 GNE FAS RNASEH2A MPDZ TGIF1 OSGEP GLUD1 SMAD4 BSCL2 RNR1 HNRNPU L2HGDH NEUROD2 ARHGEF9 NLGN3 LAGE3 NEDD4L SLC25A15 FADD SLC5A7 NUS1 KCNA2 IQSEC1 AKT2 PGAP3 FIG4 PDX1 TDP2 HS6ST2 METTL23 CASQ2 TP53RK ADAT3 SMC3 POMT1 RAC1 STAG1 CUL4B STAT4 IREB2 POMGNT2 GBA PROKR2 GATA3 KLF13 GABRB2 GMPPB MEF2C KMT2C PEX1 VPS13A ALG11 AGTR2 ATP1A1 KDM6A ALDH5A1 SPRY4 SZT2 EFHC1 CUX2 TACO1 ALG13 CLN3 BCKDHA RPGRIP1L CTSF SLC6A5 KRAS TLR4 ERCC8 ETHE1 UPF3B ARV1 PEX19 XPR1 PEX3 MRM2 TRNC CACNA1E EDN3 ERCC6 MED12 SCN1B AIMP1 CTBP1 ADGRV1 IBA57 TBC1D20 TBCD CXCR4 PWRN1 ADAT3 TBX1 CENPE LAS1L MC1R MPL STX16 C4A ACSF3 TREX1 CAMKMT SLC25A22 TBX19 KANSL1 CHD8 CHD7 EDC3 PCCB TSC2 SLC9A7 SETBP1 STAMBP PEX10 VLDLR MVK IMPDH1 SLC17A5 TRAPPC11 FGFR2 TRIM71 PNKP DDX3X POLR2A RNF113A MECP2 SLC46A1 CLIC2 MAF SCN1A ALG9 KAT8 ARSA EMG1 NOTCH2NLC MED12 CDKN2B VPS11 ZC3H14 PGAP1 PEX10 STX1B ZNF81 ZC4H2 PEX5 DLD NAGA OTX2 RSRC1 GTF2H5 SCN9A PCK1 PRDM16 IDS ATP1A2 COL3A1 IKBKG GBA ITPA TRNS1 GBA CRIPT CAMK2A DPYD DOCK6 DISP1 LMAN2L IVD RNASEH2A KCNA2 TRIO NDUFA10 SLC25A22 PEX5 DCC ARX HERC1 NRAS SHANK3 MTHFR TRAF7 ECM1 CHRNB2 CNKSR2 NRAS EXT2 USP27X KCNH2 EEF1A2 CEP290 COX15 PIGO MMADHC FGFR3 MANBA SLC2A1 RALGAPA1 CLEC7A EGF WDR37 TARS1 SCN2A NSD2 FOXRED1 PTH STXBP1 FDXR POMC EXOSC9 SYNJ1 CNTN2 CAMK2B ATP1A3 NPC1 MYO5A PIGA DPAGT1 DHFR HLA-DPB1 UPB1 FTL POMK GPC1 SOX2 AUH SCN1B NFASC OCRL TMTC3 SPAST PTF1A TRAPPC6B GLS PSPH INPP5K LRP2 FBXW11 NAT8L CHRNA7 FCSK MYO5A KRAS ASXL3 RANBP2 SPATA5 LYST KIAA1109 ASPA TICAM1 MBD5 TUBB3 BTD SELENOI MED25 SNX14 SMS ATP5F1A CTLA4 ECM1 STS CXORF56 VPS11 NDUFAF4 KCNJ6 FOXH1 MECP2 GABRA2 LMBRD1 GLUD1 SYN1 STT3A NAGA PET100 ACTG1 SLC2A1 TRAK1 TRNQ TOE1 NOTCH2NLC AIP HERC2 TRAK1 CACNA1D WDR73 COL18A1 PTCH1 SCN1A EPG5 TLK2 ALG3 GAS1 BCS1L PLPBP STAG2 HIBCH TREX1 BCOR KCNJ1 TRNH FBP1 PTPN22 MRAP POMGNT1 SLC46A1 HGSNAT SLC2A1 ERCC3 FLVCR2 GM2A UFM1 CRPPA CDH23 TWIST1 GNAO1 AMT HMGCS2 FGFR1 TREM2 MIPEP NODAL NUP214 GBA ADA2 SCN3A ATP2A2 CLN6 NAGS HESX1 KMT2A GUF1 CPT2 RAC1 DISP1 ADGRG1 POU3F3 ATP6AP2 AHSG PIGM HCN1 TMEM70 NTRK2 RBM10 NDUFV1 PLCB1 PEX1 PIGG CYP2R1 NIPA1 ARID2 NRROS ST3GAL5 GDI1 PDGFRB ACADSB FASLG GABRD CFHR3 SLC6A8 PTEN PLP1 CARS2 MAP1B COX14 THPO TDGF1 AMACR PSEN1 KIF7 AQP2 MPDU1 NPHP1 GDI1 NDUFA13 NRAS CYTB PEX5 ATAD3A FGF8 PIGC STXBP1 BRAF NEU1 COQ2 POU3F4 CYB5R3 PCDH19 SCARB2 PDHA1 PRUNE1 MTHFS PSAP ERCC2 GABRB3 LARGE1 WDR73 ARX PHF21A NIPBL GABBR2 CYB5A SNORD115-1 POMK SRPX2 ACO2 PHF6 ACADS ACOX1 MBD5 SLC6A1 ATP1A3 RPL10 ZBTB20 DBT KCNB1 WDR11 MTRR PEX2 WAC STAG2 STXBP1 ARL6IP6 GNAS PSMD12 DNM1 FLI1 ADSL MYRF NDUFA1 ITGB6 HPD SLC12A6 RAB27A SON NSUN2 ABCC8 B3GALNT2 PIK3CA YEATS2 SLC17A5 ZNHIT3 CDK5 CAMTA1 DSTYK GRIK2 ATP6 ABCA5 HLA-B NARS2 CA8 MC2R RNASEH2C PLAA STXBP1 RBM8A ST3GAL3 FAM50A UGDH ATIC BCS1L TRMT1 HDAC8 TLR3 DCPS PAH GRIA3 LONP1 HADH RNU12 SC5D RPIA PNKP OFD1 TMEM231 RAPGEF2 TSC1 SURF1 ARV1 FMR1 HNF1B AP3D1 BCKDHB DHPS FA2H PEX6 ZIC2 WARS2 SC5D COQ8A PTEN SCN8A PRMT7 SLC2A3 FGFR2 ZIC2 GTPBP3 PGAP1 KCNC3 GLDC KCNJ10 CEP85L GPC3 NDUFAF3 AP3B2 PEX16 AGA PPT1 IQSEC2 PCNT CFHR1 B3GALNT2 PDSS2 PIK3R2 MFF NDN FOXP3 POMC COG5 BCKDK SOX10 DNM1L OSTM1 AKT1 DISP1 GSS TRAPPC4 RNF213 PTCH1 CRLF1 SCN2A ALDH3A2 NF1 COL1A2 GLI2 COL4A2 YWHAE NSUN2 TRRAP IL23R ALG6 BOLA3 SLC12A6 MGP SLC25A4 PRRT2 DOCK7 CTC1 DHCR7 ZMIZ1 PRRT2 XPC CLTC SNRPN DPH1 KDM6B GNAS FKTN SCN10A PRNP STT3A KCNMA1 CHAT ARX KCNQ3 TBCE GNAQ CNPY3 ALG2 SH2B1 CDC42 TASP1 FOXA2 CDH2 CYP27A1 SLC18A3 CBS LCA5 ANK3 ACAT1 KAT6B NDUFB8 RUBCN KCNA2 PROP1 PRKAG2 DHX30 RTTN CHKB CDK19 MED25 PEX10 CCND2 MVK COG4 PTPN23 ACTL6B SMS RREB1 KPTN MED25 RTTN PROP1 CEP57 B9D2 PSEN1 NEK9 YWHAG CILK1 FBLN1 TBCE MLX KMT5B ZNF592 FUCA1 CPLX1 CEP41 PIGC ZNHIT3 TBX1 PIGT ALG1 GEMIN4 CASK TUBA1A GCH1 ERMARD NIN PIK3CA GK CC2D2A CDH11 COLGALT1 EFHC1 NIPA1 PTEN PTRH2 ATM COX20 KDM5C FLNA RELA GCDH RAI1 RMND1 MED13 HRAS KAT6B POLA1 PNPO SCN2A TBP FAM111A SCN4B WDR4 PTRH2 PIGL SPP1 FKTN PEX7 TP53 ADA2 ACTL6B FAM111A CPT2 FGFR1 SLC45A1 GYS1 GATAD2B LBR ASPA KCNE1 NUP133 ERCC3 TRPV3 MED23 EPM2A PRKCD POMT1 TXN2 OTUD6B PNPLA8 ROBO3 MACF1 RAI1 SCN1B INSR CRLF1 PI4KA GNAS MYT1L HDAC8 EPCAM CRBN TP53 ATP6V1A SPATA5 KAT6A DGUOK GABRG2 IQCB1 WDR62 PSMD12 MAST1 ATP6AP2 SIN3A HLCS NEU1 UBA5 CACNB4 NAA10 SHROOM4 ATRX POLG2 MTOR PSAP SLC12A3 PIGA CLTCL1 CPT1A GABRG2 TGIF1 ARID1B PSMD12 POLG2 PIGN RAB39B UBE3A ERLIN2 GRIN1 CSPP1 ARFGEF2 FAM111A TSC2 CAD VPS51 HCCS BDNF CARS1 THOC2 PRRT2 CPT2 DHX16 GM2A SKI RPS20 NRAS SCN9A KCNA1 KCTD7 INPP5E BPTF TRNF AP4S1 FKTN NDUFS2 TFAP2A LAMB1 SSR4 COMT IFT140 INPP5E PAK3 ASAH1 DYNC1H1 FITM2 ACY1 GLA CACNA1A NOS3 BRAF PIGV ATRX KCNJ5 ATP1A2 LAMB3 PCSK1 DEPDC5 ANK1 PIEZO2 SLC25A15 NDUFS8 GABRG2 ACTB PTCH1 FGF12 CCM2 NPRL2 POMT2 UBA5 PHKA2 GABRA5 TBC1D20 GRIN2B DENND5A SNAP29 PAFAH1B1 FOXH1 TREM2 PEX6 PAX2 HADH MAPK10 MBTPS2 FLII PRRT2 ATP6V1A PHKG2 MDH2 SLC12A5 CDKL5 MED13 SMARCA4 SP110 VPS13B TCTN2 KCNK4 AP2M1 ARSA PMM2 BRAT1 CLIP1 ALPL ELMO2 ACP5 KCNQ2 POLG STAT3 PEX26 MGP TNIK SRD5A3 UNC93B1 DLL1 DYRK1A SHH SGPL1 NDUFAF3 EP300 TREX1 CLIC2 MSH6 FAR1 LSS TBCK GLI3 GRIN2A FGFR1 SIN3A SMARCA2 CCNQ BUB1 ALDH5A1 ABCC8 GLRX5 SARS1 GABRG2 ALKBH8 PC NF1 OTC POMT2 DHCR24 DNM1L ARID1B NDST1 NUP133 PEX6 POMGNT1 IQSEC2 MAPK1 MICOS13 GRIN2B SOX5 ATP6V1A COQ8A KCNJ11 ASPA SYT2 DOCK6 PIK3CA DLL1 CCR1 TRDN HIRA IER3IP1 JAM2 SARDH GMPPA HEPACAM NHLRC2 NECAP1 TGFB1 TBC1D24 MOCS2 TELO2 SSR4 FGFR3 COQ4 ADGRV1 TBK1 CTLA4 MAN1B1 KCNT1 ARX PYCR2 ERCC2 KDM5C MKS1 SH2B1 ZIC2 CDC42 TRNS1 CAMTA1 PTEN PSAP NONO DPM2 MID2 DMXL2 MICAL1 PRRT2 ACADM LINS1 ZNF41 POLG DLL4 PSAT1 UBTF ERCC8 LAGE3 SPTAN1 USP18 DDB2 BMP2 FCGR2B SIX3 CALM3 ACTL6B CYP27B1 DIAPH1 GATA4 LAMA3 KMT2E TIMM50 GMPPB MTOR CDON TMEM106B CILK1 KAT6A ALG3 TAF1 AVPR2 SLC1A3 STRADA GNAQ TTR PAK1 ABCC8 FOLR1 NUS1 RNF125 CRBN MTRR EXOSC3 COX3 MTO1 DLL1 DEAF1 FGF8 HCFC1 NDP LARGE1 MANBA MECP2 KMT2D PPP2R5D WARS2 CASK SLC44A1 NMNAT1 EFHC1 TRNL1 KCNE2 ELOVL4 JMJD1C IARS1 TRNT1 NIN FRRS1L FADD ZMIZ1 CREBBP GMPPB HECW2 DIS3L2 AGA HRAS HYLS1 BAP1 WDR45 COX2 SLC25A20 KIAA0586 SIX3 SDHA PLPBP TUBB2B MCCC1 SYNGAP1 PCDH12 EFTUD2 IRF2BPL MN1 ACTG1 SOX4 ALX4 MFF SETD5 ZNF142 ATP6 NECTIN1 SLC2A1 TWNK MGAT2 GABRD ERCC4 MOGS TOMM40 GTPBP3 TCF4 VPS53 OTX2 PEX2 SCN3A TRNK OTUD6B CCM2 MMAA GRIA2 CACNA1D PEX2 MBOAT7 AIFM1 SETBP1 ASL EPG5 SIX3 CYFIP2 FKRP GLA NDUFAF5 PEX13 SIK1 ND1 CUL4B SLC1A4 SHH SDHD CYP26C1 MECP2 ANTXR1 ABCD1 ND6 DDX6 PSAP SCN2A DEAF1 B3GLCT ATP6V1E1 ADGRG1 CPOX TRDN TWNK AKAP9 TBC1D24 DLL1 GABRB1 ARHGEF6 KCNQ2 NBAS DBH SCN1B FGFR3 TYROBP ATN1 LIPT1 FH SLC19A2 GRIN2A TRNS1 RAB39B MARCHF6 LINGO1 DUSP6 AHI1 ERMARD SPATA7 MECP2 FGFR1 PLAGL1 STAR CREBBP NDUFAF2 PDSS2 OPA1 GAL GBA MBTPS2 DALRD3 GNAS GAMT RXYLT1 GATA6 WFS1 CASK ATXN10 ND4 ALPL CDKL5 TBCE NDP GBA SUFU NF2 NAA10 ATP7A TSC1 FAS AASS TSPAN7 GJA1 GNAS MAF PSEN2 GRIN2D TBL1XR1 PROC WASF1 TCIRG1 EXTL3 CLN8 EIF2B1 ND6 PRODH BCAP31 ZDHHC9 MYO5A PUS3 ADARB1 MED12 NEU1 CDKL5 TRNH SLC3A1 CERS1 PDGFB RELN ATRX TRAPPC11 PLCB1 AUTS2 NFIX PEX12 NDUFS7 NEK1 TWNK RPL10 CHD2 RNASET2 SLC25A42 SMARCB1 SEMA3A SMARCD1 ALDH4A1 CNTNAP2 MOCS1 SLC5A6 SRPX2 ABCC8 SLC2A1 SLC1A2 TRMT1 PTCH1 ATP8A2 LMX1B ASAH1 CPLX1 NDE1 GAS1 NDUFS3 CNTNAP1 TRAPPC9 TRAF7 ROBO1 GJC2 TCF4 ERCC6 RNASEH2B FKTN PIGY NEU1 HESX1 GPT2 NEXMIF PGAP3 NDUFA9 SLC1A3 MECP2 TGIF1 CDKL5 PLA2G6 SCN1A KCNJ11 PTCHD1 TECPR2 ERCC8 OSTM1 ACVRL1 SLC1A2 POLG SAMHD1 MSL3 GP1BB PYCR2 PLK4 KPTN PCYT2 PIGY ATP7A FARSB UCP2 SALL4 CHD1 PACS1 GLI2 AHI1 CCDC141 GABRA1 PEX14 ND5 CRKL COX15 SLC12A3 LHX1 NDUFAF8 GLI3 ATP6AP2 TRNL1 PHF21A RBPJ AFG3L2 MLH1 MLC1 NALCN MC2R PNPO POLR3A DYRK1A IL12A-AS1 UQCC2 CNNM2 SIK3 SMO CDKN1B GABRA1 KIFBP SDHA DNM1L KCNH1 PAK3 KCNQ2 TCF20 SCN8A SLC25A10 FA2H TDP1 TMEM138 PARS2 IQSEC1 ADNP GNB1 NACC1 KCNN3 RDH12 SCO2 C11ORF95 CD96 NDST1 GPHN GALNT2 AP4B1 PROKR2 ADGRG1 PIGT PIGS FGFR3 KIF4A CLP1 TGDS ODC1 POMT2 SCN1A MYH14 CLPP CEP120 RSRC1 GYS2 BRAF PRSS12 AP4E1 METTL5 SIK1 TP53 TSC2 P4HTM ATP6 CSF1R TBCE ARX SLC25A1 UGP2 EBP CALM2 SIX3 ARSA EBF3 DNASE1L3 B4GAT1 SASS6 KLHL15 TMEM70 PLEKHG2 MTM1 FASTKD2 SLC6A1 CDKN2C OPHN1 DPM3 ATRX FGF12 GRIN2D DIP2B TRNF PRRT2 MYH3 KCNQ3 SLC39A8 ATP13A2 GLE1 SLC35C1 B9D1 CDON ADGRG1 RD3 OPHN1 KCNE1 TSEN2 KMT2A AMACR PDHA1 MAGEL2 TBC1D24 MAP1B SYP CLN5 NPC2 PARS2 JRK HNMT MED12L PDP1 MYT1L ZIC2 TBC1D24 MPLKIP HESX1 SLC22A5 ACOX1 GRM1 ST3GAL3 NONO DAG1 ASXL3 EXT2 HADHB EXT2 CLCN4 SPTBN4 FGFR3 GPAA1 XPNPEP3 NDUFS4 HUWE1 POLG COQ9 NAGA PRKDC GABRD TRAPPC9 ZSWIM6 GRN AIPL1 AP4S1 KCNAB2 ARX SNX14 USF3 POMGNT1 GCK NDNF ACOX1 GABRB3 NOTCH1 HDAC4 ND5 PTCH1 SCN5A FOXRED1 TRNS2 GFAP ADNP AGRN PDHX PEX16 SDHD MEFV TRNL1 CSTB ATM HADH NDUFB11 SNAP25 RAB3GAP2 SHH CTNND2 TREX1 ELP1 TWNK ASXL1 GLI2 IQSEC2 PRICKLE1 SCN2A FOXG1 ARX GATA6 SUOX PRMT7 CCDC115 KISS1R KCNJ13 FUT8 UNC80 TBX1 WAC WWOX MPC1 EIF2S3 PEX14 PPA2 PACS2 FAS AFG3L2 SLC6A19 LAMB1 ERCC2 COG6 ASXL2 ADAMTS3 PIGL CYFIP2 MMADHC SLC45A1 QARS1 DNAJC6 SCN1A YWHAG COG8 MRPL12 EIF2B3 CC2D2A BSCL2 PEX5 SIK1 SOX10 CNKSR2 TMEM237 SEMA4A SNIP1 MMACHC STARD7 SLC12A1 TECPR2 OAT KCNH1 IPW VPS13A NGLY1 PPP2R5D ASPM STUB1 SLC2A1 CACNB4 COG8 TNFRSF11A INTS1 FRG1 TNFRSF11B MCPH1 TRNW BCORL1 PEX5 SLC35A3 TET3 AKT1 ACVR1 ALG9 NSD1 WDR73 PCDH19 TRAF3 FOXP1 GNB5 ND6 WDR45 MYO9A HCN1 TACR3 EIF2S3 KCNQ5 TMEM237 FGFRL1 IL1RAPL1 ND2 POLG IVD IL12B FGFR2 CREBBP CPA6 HTT KCNMA1 NDUFAF2 VARS2 GCSH NDE1 HACE1 NADK2 ND5 AAAS CRX NTNG1 FAM126A KDM3B NODAL SAMD12 ERCC6 ARNT2 FMN2 RFT1 TAT ABCA7 TSEN54 KCNH1 CPT2 ARG1 CNTN2 IQSEC2 UGT1A1 PRRT2 TRAPPC12 HMGCL PMS2 COA8 TOE1 CLN8 STXBP1 TMEM106B MBOAT7 ZEB2 TANC2 MPDU1 GNS RNF13 ARFGEF2 GNAO1 PPP1R15B ABCC8 MSX2 TPK1 SDHB DPM1
    Protein Mutations 1
    A147T
    SNP 5
    rs1024611 rs1360780 rs222797 rs2297201 rs2298771
    HP:0100806: Sepsis
    Genes 92
    TGM1 DCLRE1C ALOXE3 IKZF1 SEMA3C TFRC AK2 LMOD1 RAG1 IL2RG SFTPC DNAJC21 CYBA RAG2 COG4 CYBC1 PGM3 IL2RG AK2 ELANE CTCF CXCR4 RAC2 LRRC8A CTLA4 ALOX12B LIPN EFL1 WIPF1 ECE1 IGHM SRP54 CD79A BTK ACTG2 GDNF IGLL1 LAMA3 CD79B ABCA3 HYOU1 APC GALT PLEC RMRP BLNK CHD7 WAS ATP7A EDN3 MMUT VPS33A SULT2B1 TCF3 LAMB3 SDR9C7 IL7R CYBB G6PC3 SERAC1 MYLK EDNRB MRTFA SAMD9 RET CTNNB1 NCF4 PIK3R1 ITGB4 ADA MNX1 ABCA12 CYP4F22 NCF2 SFTPB HLA-B LIG4 MYH11 IL7R RAG1 LAMC2 SBDS NIPAL4 CD40LG NFKB2 NRTN SEMA3D RNF13 FERMT3 MYD88 FOXP3 NCF1
    Protein Mutations 2
    G20210A N682S
    SNP 8
    rs150018775 rs2234237 rs2234237r25r rs2234246 rs3210140 rs4883263 rs4883264 rs61729512
    HP:0001257: Spasticity
    Genes 1210
    LMAN2L PMPCA RNASEH2A ND4 PRDM8 KCNA2 SLC1A4 NDUFA10 SLC25A22 PEX5 SCN1B GAD1 ARX GPHN ISCA2 RNASEH2C TXN2 CAPN1 TRIT1 LIMK1 ARL6IP1 BICD2 ERCC6 KIDINS220 EEF1A2 NR2F1 PSAT1 COX15 GAN GBA2 CRADD SLC30A10 SLC2A1 MARS2 RALGAPA1 TARS1 FDXR VPS13D EXOSC9 SYNJ1 SPG7 C19ORF12 NOVA2 NPC1 PIGA COG2 AP4E1 TDP1 FRMPD4 WWOX MFN2 SYNE1 AP5Z1 PRKN TARDBP ARF1 ATP6AP2 AUH FOXH1 IKBKG SOX4 DNAJC6 GDAP2 TMTC3 SPAST GTF2E2 HEPACAM INPP5K VCP MYO5A KRAS HPRT1 COASY KCNJ6 RANBP2 PMPCA SPATA5 SEC31A ASPA TUBB3 ATP6 SELENOI NECAP1 NUP62 MAG GCDH EZH2 MED25 C12ORF4 SNX14 ATXN8 PLA2G6 ERCC6 PRPS1 VPS11 NDUFAF4 KCNJ6 FOXH1 GABRA2 WDR45 DLD MCCC1 NAGA SLC2A1 TRAK1 TOE1 SIL1 UCHL1 KIF2A TRAK1 CACNA1D GRIA4 CSF1R WDR73 RARS1 TMEM67 GAS1 ARX ACP5 BCS1L ARSA BCOR KIF1A TRNP KIF5C SUCLA2 SLC2A1 LYST ERCC3 UFC1 HSD17B4 GM2A UFM1 NDUFV2 GNAO1 PRNP ALDH18A1 GPT2 NODAL NUP214 ACTL6B ATP6V1A ERCC4 DISP1 PHGDH POU3F3 TRNI PON1 NTRK2 OPA1 PANK2 NDUFV1 NIPA1 KDM5B SLC13A5 USP8 SLC6A8 PLP1 TDGF1 AMACR OSGEP NDUFA13 IARS1 SELENOI SVBP ATAD3A C12ORF65 GLI2 FGF8 STXBP1 TRAPPC12 OPTN CYB5R3 NOTCH3 REEP2 PRUNE1 ATXN8OS MTHFS RARS2 PAX3 HSPD1 SPG7 SURF1 PSAP ERCC2 SIX6 EDNRB GFM2 COL4A1 WDR73 VAMP1 RAB3GAP1 ARX CYB5A TARDBP SRPX2 OCLN CASK FAR1 CTNNB1 SPG21 RFT1 CDON ZFYVE27 STAG2 SLC18A2 STXBP1 FGFR1 DNM1 ADSL SIX3 SERAC1 CYP27A1 RAB27A NSUN2 GALC B3GALNT2 SLC17A5 SIL1 DSTYK PHGDH TRNV PEX14 NARS2 NEFH RNASEH2C SNORD118 ZIC2 UGDH BCS1L DCPS TRNK GRIA3 TUBB3 GABRG2 ALDH3A2 HTRA1 AARS2 RPIA ST3GAL3 FGF8 SHH CACNA1G LYRM7 SURF1 ARV1 STXBP1 SON GALC TRNW COG2 DHPS FA2H NODAL BSCL2 VWA3B TIMM8A ATXN2 ZIC2 WARS2 EIF2AK2 CC2D1A ANG ADD3 MTFMT PLP1 GAS1 TAF2 PGAP1 BEAN1 MAPK8IP3 TMEM231 ARX NDUFAF3 PEX16 NTRK2 PPT1 RAB11B PAX3 B4GAT1 MFF BCOR NHLRC1 DNM1L NSD1 PIGQ OSTM1 UCHL1 ANXA11 DAO HCN1 GSS CYP2U1 C19ORF12 PTCH1 SCN2A ALDH3A2 GSX2 STUB1 GLI2 COL4A2 CYP7B1 NDUFV2 MTHFR EPHA4 BOLA3 NDUFA6 PARK7 ENTPD1 SETX REEP1 CTC1 XPC CLTC HLA-DQB1 GJA1 SOD1 POLR3A GRIK2 ARX MAN2B1 CNPY3 ALG11 NEK1 ERLIN1 CYP27A1 ANK3 ACAT1 DSTYK SACS SEPSECS PSAT1 MRPS34 POLR3B EIF2B5 RAD50 RTTN SLC2A1 CDK19 HPRT1 MED25 CDKL5 PTPN23 TUBGCP2 SPTBN2 MED25 RTTN PQBP1 FBLN1 TBCE PTS CIT ERLIN2 ZNF592 FARS2 FUCA1 XPA PON3 PIGC KLC2 SYNGAP1 PPP3CA CNTNAP2 CASK TUBA1A TPI1 SNCA SUZ12 SPG11 SYNJ1 APC2 COLGALT1 CYP2U1 NIPA1 SPG7 MAN2B1 IBA57 FXN TRMT10A FBXO31 ATM TIMM50 KDM5C PEX3 FLNA CTNNA2 CYB5R3 OPA1 PDCD1 TTC19 AP1S2 SYNJ1 RFC2 BCL11B ERCC2 SPG21 TDGF1 POLA1 RAB3GAP2 SCN2A TANGO2 WDR4 ARX SOD1 PEX7 REPS1 SIGMAR1 PNPLA6 SLC13A5 PFN1 MARS2 EED SLC35A2 KANK1 GATAD2B CLCN4 SOX2 ERCC3 MED23 EPM2A NT5C2 PEX19 OTUD6B ABHD12 PNPLA8 MACF1 HIKESHI GJC2 CRLF1 PI4KA PAFAH1B1 FIG4 SPATA5 HSPD1 REEP1 ALDH18A1 FOXH1 NDUFAF5 WDR62 SACS ATP6AP2 SPTBN2 VPS13C GPHN NEU1 UBA5 PPARGC1A NDUFS4 GUF1 EIF2B2 ATRX PRNP PSAP XPA FMN2 DDHD1 TGIF1 ADAM22 NTNG2 NDUFB8 SDHA TFG ERLIN2 GRIN1 CARS2 IFIH1 PEX1 PEX12 NEFL AARS1 THOC2 GM2A CLCN4 MED17 HSPD1 HLA-DRB1 GAS1 TFG KCNA1 ALS2 GALC ERCC5 POLR3B ELP2 AP4S1 NDUFS2 LAMB1 CHCHD10 ASAH1 DYNC1H1 SPG11 AGTPBP1 POLR1C ATRX ZFR WDR48 MED13L SLC25A15 TRNF PTCH1 ATP2B3 UBA5 DALRD3 GABRA5 MATR3 TBC1D20 PHGDH DENND5A PAFAH1B1 FOXH1 CFAP410 TREM2 KIF1A TAF1 NALCN FA2H SDHAF1 ATP6V1A SLC33A1 CPT1C RNASEH2B TGIF1 SPAST CDKL5 C9ORF72 LIPT2 MECP2 ARSA NEFH ATAD3A PQBP1 CLIP1 PNP ATXN3 EARS2 PET100 ACP5 KCNQ2 RAB3GAP1 RAB3GAP2 ISCA1 GLRB TDGF1 PEX26 ASNS KIF1C TNIK FARS2 PEX6 TSEN15 TRNW DLL1 GLYCTK METTL23 OPA3 DDHD1 SHH PNPLA6 ARX TGIF1 TREX1 ACER3 TRNK CLIC2 ALS2 FAR1 CNOT1 FGFR1 GLT8D1 VAPB PNPLA6 ITM2B ABCC8 CACNA1G GLRX5 SARS1 ALS2 LMNB1 ERBB4 INTS8 ERCC3 UBQLN2 IDUA DHCR24 TMX2 LIPT1 POMGNT1 UBTF TREM2 MICOS13 GRIN2B ATP6V1A PQBP1 NUBPL RARS1 DHCR24 ASPA MFSD2A ATP13A2 DLL1 CAPN1 TPRKB GOT2 ANG GAN TCTN2 HEPACAM SLC39A14 SLC52A2 DLL1 MOCS2 TELO2 AP4M1 RTN2 PUM1 PRPH KIF5A PYCR2 KDM5C HTRA2 UNC80 KCNA4 PPP3CA TUBG1 ZIC2 TBP PIGP PEX11B DYNC1I2 PNPLA6 KCNA1 NODAL SPR MECP2 LINS1 TBC1D23 COX10 SCN8A UBTF LAGE3 GBA2 SPTAN1 NUP62 DDB2 FTL RNU4ATAC MECR GRIN1 SIX3 STXBP1 ACTL6B GRIN2B TIMM50 ALS2 KIF11 CHMP1A MCCC2 TAF1 KLC2 PCLO RAB18 TTR DARS1 CRBN ERCC8 EXOSC3 MTO1 ZFYVE26 TUFM KY SCYL2 DISP1 GAS1 RPGRIP1L JAM3 LRRK2 WASHC5 MECP2 NKX6-2 ELN WARS2 VCP ANKLE2 C12ORF65 TRNL1 TP53RK ELOVL4 IARS1 MAN1B1 FRRS1L AGA DLL1 TUBB4A SIX3 SDHA APC GTF2I L1CAM MCCC1 PCDH12 NACC1 GABRB2 DCTN1 IRF2BPL FOXG1 PMPCB ATXN8 MFF DEGS1 ATP6 CDON ERCC4 ADAR VPS53 GALC MAG PEX2 SCN3A TELO2 OTUD6B FIG4 PRPH FUS GRIA2 CACNA1D MBOAT7 SETBP1 GLRX5 RLIM GFM1 CYFIP2 PLP1 NDUFAF5 CACNA1B COASY SLC1A4 DHDDS SHH SDHD MECP2 ABCD1 ECHS1 ND6 PSAP GLI2 MARS1 SLC13A5 TBCD ATP6V1E1 SLC2A1 ATXN2 MICOS13 SLC33A1 WDR26 DISP1 LMNB1 REEP2 IDUA ATXN7 KATNB1 FGF8 AP4M1 PSAP GABRA5 BSCL2 TYROBP ATAD1 LIPT1 KIF1A OPA1 TSEN54 AP4B1 DDX3X LINGO1 SDHA IFIH1 KIF1C ROGDI FGFR1 SPG11 SCYL1 ND1 GPAA1 OPA1 ZEB2 MAPT GBA CACNA1G GBA2 ITM2B CASK ATXN10 SPG11 GBA ATXN3 L1CAM NAA10 ATP7A MTPAP FBXO7 GJA1 INPP5K PANK2 UBAP1 GRIN2D PLAA RETREG1 TAF15 EXTL3 EIF2B1 IBA57 OPA3 EZR CCT5 ADARB1 RERE ALDH18A1 CHP1 PLCB1 AUTS2 RANBP2 RUSC2 NDUFS7 TYROBP OCLN RNASET2 MRE11 DCX MOCS1 SLC5A6 ARX STAG2 ZC4H2 SOX10 SLC2A1 PEX6 SLC1A2 UNC13A POLR3A C19ORF12 PTCH1 GJC2 LMX1B CLTC AMPD2 ZNF335 EML1 NDE1 NDUFS3 CNTNAP1 HMGCL TRAPPC9 KCNT1 ELOVL4 SLC25A12 PLA2G6 HSD17B10 GJC2 RNASEH2B GBE1 RPS6KA3 KCNB1 L2HGDH NEU1 GPT2 SPART FTL CLPB TECR L1CAM NDUFA12 NDUFA9 CCNF PLA2G6 CDON TECPR2 NDUFA4 SOD1 PSEN1 PGAP1 FLRT1 TAF2 SLC1A2 SAMHD1 MSL3 FBXO7 FRRS1L ATAD3A PYCR2 NUS1 GFM2 STN1 CTNNB1 GABBR2 AUH CKAP2L PCYT2 ERCC5 ERCC4 AARS1 ANK3 DCTN1 SURF1 COX15 CLPB NDUFA2 EPRS1 KCNA1 THOC2 PIGN ND3 SMC1A AFG3L2 AFG3L2 SCN3A TRMT5 MLC1 B4GALNT1 NALCN GLB1 SPART DDHD2 AIMP1 PSAP POLR3A VPS37A SAMHD1 L1CAM ATP13A2 PIGU NDUFAF6 SDHA PINK1 PFN1 DDHD2 ARSI TCF20 HNRNPA1 ACP2 TBK1 SLC25A10 CAMK2A FA2H CCDC88C PPP1R15B PARS2 CCDC88C B4GALNT1 NACC1 SCO2 VAMP1 NDUFS1 ATP6V0A2 AMPD2 NDST1 PANK2 MCOLN1 AP4B1 CLIP2 ROGDI DNMT1 NDUFS2 GRM1 CLP1 ODC1 NDUFS8 BAZ1B FUCA1 SDHD RSRC1 PRSS12 AP4E1 METTL5 ADAR VPS13C ALS2 GJB1 CSF1R TBCE UGP2 FUS LIAS SIX3 ARSA TUSC3 BCL11B AP3B2 ERCC5 WASHC4 CACNA1A AP5Z1 PODXL ATL1 ATRX FGF12 COPB2 ARG1 PRRT2 SLC2A1 ATP13A2 MRPS22 CTSD DMXL2 CDON ADGRG1 ATXN3 OPHN1 TRIM8 TSEN2 ALDH18A1 PDHA1 GABRA2 NPC2 PARS2 DARS2 PHACTR1 WDR45B HNMT KMT2B GLRA1 ERCC2 ZIC2 ALDH18A1 MPLKIP GLE1 GTPBP2 ALS2 AMPD2 SNCA GPAA1 ECHS1 WWOX EZH2 PEX13 NDUFS4 PON2 HUWE1 POLG FGF8 WASHC4 RAB18 NSUN2 DNAJC19 MTPAP AP4S1 TRAPPC4 DNMT1 SNX14 CLP1 ENTPD1 CHMP2B PRDM8 ND5 PTCH1 FOXRED1 KIF5A AP1S2 ATXN3 SDHAF1 SLC19A3 HACE1 GFAP L1CAM SCYL1 PDHX TDGF1 TRNL1 WASHC5 RAB3GAP2 SHH SLC30A10 TREX1 RTN2 GLI2 PNP SLC39A14 DHDDS NKX6-2 FOXG1 EIF2B4 ARX PEX3 NEXMIF NADK2 SLC19A3 RNASEH2A UNC80 AFG3L2 PANK2 UBA5 TGIF1 BSCL2 WWOX GTF2IRD1 L2HGDH NEUROD2 AFG3L2 SLC25A15 NUS1 KCNA2 IQSEC1 ERCC2 EXOSC8 CYFIP2 SLC45A1 ATL1 DNAJC6 ADAT3 YWHAG IREB2 ATXN8OS ZFYVE26 PLA2G6 GBA EIF2B3 CC2D2A BSCL2 SIK1 SOX10 CNKSR2 GABRB2 CYP7B1 ALG11 NT5C2 STUB1 SQSTM1 SZT2 TACO1 FDX2 SLC6A5 ERCC8 GBE1 MRM2 CACNA1E CPT1C SCN1B AIMP1 PEX16 IBA57 TBC1D20 TBCD SLC16A2 C12ORF65 ADAT3 FOXP1 WDR45 ATXN1 EIF2S3 SUMF1 ERCC1 ERLIN1 DARS2 SYNE1 CCT5 SMPD1 ND2 SLC25A22 NDUFA13 HTT EDC3 NDUFAF2 SETBP1 NDE1 MTFMT STAMBP HACE1 NADK2 NTNG1 PNKP DDX3X ERLIN2 KIDINS220 NODAL RNF113A MECP2 CLIC2 ATP6 ARSA TBL2 ERCC6 ARNT2 VPS11 AIFM1 ZC3H14 SIGMAR1 TSEN54 PGAP1 ARG1 PEX10 C19ORF12 ZC4H2 L1CAM NAGA TRAPPC12 HMGCL GTF2H5 COA8 MCCC2 TOE1 STXBP1 ARL6IP1 ZEB2 IKBKG RNF13 GBA GNAO1 PPP1R15B DISP1 TPK1 SDHB
    Protein Mutations 0
    SNP 18
    rs1049522 rs1049524 rs137852620 rs2032892 rs2269272 rs2269273 rs2562582 rs2731886 rs377637047 rs4869675 rs4869676 rs529802001 rs544684689 rs547987105 rs549927573 rs550842646 rs562696473 rs573562920
    HP:0100651: Type I diabetes mellitus
    Genes 56
    PSTPIP1 INS TRNW KCNJ11 TRNL1 CLCNKB TRNS2 TRNS1 KCNJ11 FLT1 IL18BP CAT TTC7A TCF4 ITCH CNOT1 ND6 ABCC8 STAT1 KCTD1 EDA2R TRNF NEUROG3 ND4 FOXP3 ND5 TRNH CORIN TRNE TKT MMP2 MMP14 INS SLC16A2 ABCC8 COX1 COX3 MST1 GCK ND1 INS EDA GPR35 SLC29A3 DNAJC3 ITCH EIF2AK3 SLC12A3 HNF1A STUB1 AIRE PDX1 TRNQ FOXP3 STOX1 COX2
    Protein Mutations 7
    C1858T C282T I191V K1270A K3048A R620W S9C
    SNP 4
    rs35874116 rs35874116rs rs9701796 rs9939609
    HP:0005978: Type II diabetes mellitus
    Genes 186
    WRN NR2E3 IMPG2 ZNF513 RP1 TRNL1 CLCNKB TRNS2 PPARG TRNS1 PCNT AGBL5 ARL3 FBN1 TULP1 TUB CARS1 MC4R PNPLA6 LIMK1 PRPF4 RP2 TRNK MEN1 AHR KLF11 CTNNB1 CRX SPATA7 CRB1 DMXL2 PPP1R3A GLRX5 NEK2 ENPP1 PRPF3 LIG4 PDE6B CA4 TOPORS RDH12 MKRN3 IFT172 ARL2BP SNORD115-1 ABCC8 RP9 SLC30A8 IMPDH1 ND4 ND5 GTF2IRD1 HMGA1 PROM1 ABCC8 CYP19A1 NEUROD1 MERTK LMNA KCNJ11 ARHGEF18 SLC2A2 PRPF31 RETN ABCA4 KLHL7 PRPF6 LRAT C8ORF37 TRNL1 BBS2 COX1 WFS1 RPGR CLIP2 BEST1 XRCC4 GUCA1B SCAPER NRL PDE6G ZNF408 ELN RBP3 SIM1 ALMS1 PDX1 BAZ1B ATM BRAF IPW TCF7L2 KIAA1549 STUB1 IRS1 HNF1A TRNQ RFC2 BLM PDE6A PDX1 PRCD COX2 DHX38 GCK HGSNAT GTF2I IRS2 CERKL USH2A TRNW SLC7A14 POLR3A RHO PCARE IDH3A RP1L1 FAM161A SNRNP200 CAT PWRN1 CNGB1 AIP CLRN1 ND6 EYS GCK TTC8 PLCD1 HNF1A HERC2 IFT88 ARL6 AHI1 TRNF AMACR CEP19 MAGEL2 PRPF8 POLA1 NDN MAPK8IP1 MAK KIZ TRNH PWAR1 PRPH2 PAX4 LIPC RPE65 REEP6 HNF4A AR RLBP1 OFD1 COX3 IGF2BP2 MTNR1B TBL2 DHDDS POMGNT1 PEX10 RGR SAG FSCN2 GPD2 AKT2 ND1 SEMA4A MKRN3-AS1 INSR MOG IDH3B PTPN1 MAGEL2 NPAP1 CDHR1 SLC12A3 IFT140 HNF1B CNGA1 ROM1 SNORD116-1 SPINK1 SNRPN TRNE
    Protein Mutations 12
    A54T E158K E23K G174S G212A G401S G465R I349V K121Q P12A R230C R61C
    SNP 9
    rs10401969 rs13266634 rs2266782 rs2854275 rs35652124 rs780094 rs780094s rs78408340 rs7903146
    HP:0002635: Type IV atherosclerotic lesion
    Genes 1
    APOE
    Protein Mutations 0
    SNP 0
    HP:0100279: Ulcerative colitis
    Genes 11
    BACH2 MASP2 NOD2 MAP3K7 INAVA IL6 PLCG2 MST1 GPR35 TCF4 CYBC1
    Protein Mutations 2
    H180Q V600E
    SNP 1
    rs2097432

    HPO

    Alphabetical listing of all HPO terms. Navigate: Correlations   Clinical Trials


    Related HPO nodes (Using clinical trials)

    HP:0005162: Abnormal left ventricular function
    Genes 88
    TBX20 MFAP5 SDHA ELN TRNS2 LDLR SDHAF1 TLL1 APOB GATA4 TRNC TNNT2 MYH11 SMAD3 MYPN TRNF TGFBR1 COX2 TOP3A TRNK MYH7 GTPBP3 PRDM16 FBN1 MYH11 TGFB3 POLG PPCS TRNV MYH11 PCSK9 MYLK LDB3 ZMPSTE24 KIF20A ND5 EYA4 GATA6 PRKG1 FOXE3 GDF1 SGCG POMT1 TGFBR2 TGFB2 RYR2 CITED2 LMNA LMNA TNNI3 ND6 TBX20 ABCG8 ND1 MAT2A COX3 CYTB FKRP DYSF TRDN FLNC VHL CASQ2 LAMA2 POMT2 DMPK TTN TAB2 NKX2-5 TRNL1 ABCG5 SDHD POLG2 COX1 MYH6 POMT2 LDLRAP1 SLC25A4 SMAD4 ACTC1 TWNK ACTA2 TRNS1 TRNQ RRM2B TRNW LOX SDHB
    Protein Mutations 0
    SNP 0
    HP:0002088: Abnormal lung morphology
    Genes 1393
    CDC45 SMARCA4 TBC1D24 ELN SNX10 SLC1A4 GRHL3 CFAP298 RSPH4A EDNRB TMEM94 CARD11 LPIN2 CD3E COG4 PGM3 ECM1 GNPTAB LIMK1 HLA-DRB1 CFTR CD247 PDGFRA LMNA FBN1 NTRK1 SOS2 PSAT1 ZBTB24 GP1BB MANBA CLEC7A IL2RG TARS1 DNAAF2 NSD2 SEC24C DNAJB13 DNAAF3 EXOSC9 DYNC2LI1 NELFA EDARADD NPHP3 STING1 GDF1 COL2A1 MAP3K20 CTRC HLA-DPB1 OFD1 SMARCD2 ABCA12 ERCC6 FGF20 LZTR1 SCNN1G SLC25A24 BLNK NKX2-5 TRIP13 SOX10 GAS2L2 TYK2 HELLS TTC21B FOXH1 DNAAF6 INPPL1 ITGA8 PERP EIF2AK4 OCRL GPR35 GTF2E2 NEB FOXC2 MASP2 STAT5B COL11A2 FBXW11 MYO5A CTLA4 LBR FCGR2A PRKCD RANBP2 HYLS1 IL21R DGCR8 BMPER GATA4 NSD1 TSC2 FLCN LTBP3 CYBA SPINK5 ATP5F1A CTLA4 FLT4 TERC KCNJ6 FOXH1 TCF4 NAGLU GUSB SHROOM4 EVC LIPN RNU4ATAC TPM3 PTPN11 CDT1 MUSK HERC2 NEK1 FLNB EPG5 GAS1 FBLN5 NRAS ACP5 MCIDAS MAN2B1 TIMM8A COL13A1 BCOR MYLK PTPN22 SLC35A1 SLC46A1 HGSNAT RASGRP1 LYST ZNF341 XIAP LRRC56 FGFR1 IGH NODAL WDR19 LETM1 TRIP4 EFEMP2 NCF1 MCM4 SFTPC SOS1 STRA6 RSPH4A IL2RB RAG2 RAC1 DISP1 PHGDH WRAP53 PSMC3IP RBM10 PANK2 PEX1 TNFRSF13C GLI3 WNT3 ARID2 SBDS NPAP1 ACTA1 BLM CD40LG BRAF ICOS FASLG PRKN CCDC103 SNORD116-1 FOXP3 MEFV PTEN TDGF1 IL6R CIITA SLC2A10 CYTB ENG GLI2 FGF8 DNAJB13 CCDC39 STAT6 INVS IDUA GATA4 RPS15A NOP10 IFNG HLA-DRB1 FLNA JAG1 HABP2 VANGL1 GNPTAB MYBPC3 TBX6 MKRN3 SNORD115-1 LACC1 ELANE SMN1 DYNC2H1 KIF20A RPL10 ARHGAP31 PGM3 PEX13 CDON IL7R RAF1 SCNN1A STAG2 PLEC FLI1 CITED2 SIX3 TCIRG1 ETFA MITF MST1 ZNHIT3 LAMA2 IFT81 PDGFRB CYP4F22 DNAAF4 HLA-B FAT4 ZIC2 CALCRL KMT2E HFE CSF2RB CD55 IGH TTC37 DICER1 NFKB2 PEPD GPC6 TNFRSF13B FGF8 RAF1 ABCA3 STK36 RFX5 DPP9 RYR1 SFTPA1 SHH SKIV2L IRF1 LAT DCLRE1C SON SLC25A22 TLL1 AP3D1 TGFBR1 NODAL AGT ZMYND10 SOX18 NOS1 TPM2 BUB1B TRIP11 ERAP1 TNFRSF1B REST ZIC2 CTCF RAC2 CTLA4 PLP1 GAS1 EFL1 FMO3 TRIP4 RYR1 CIITA DLL3 AP3B1 PRTN3 PIGN TBX1 ABCA3 EFEMP2 AGA CHRND PCNT PKHD1 RSPH1 ZAP70 PAX3 NDN CHRNG NHLRC1 ACE DNAH1 KRAS IL12A KEAP1 ALDH18A1 SCNN1G ACADVL DCTN4 IRF5 TRAPPC4 CCN2 PTCH1 DKC1 GMNN TNFRSF13B GLI2 MCIDAS SCN11A ROR2 IVNS1ABP TRPV4 TSC1 FANCB ZEB2 RPL10 ODAD1 MESP2 CHST14 IL23R SLC12A6 MGP CFAP300 SMAD3 RSPH9 UMPS DHCR7 KRAS SFTPC COL13A1 SNRPN BUB3 FAM13A GAS8 WDR35 MFAP5 CACNA1B ZCCHC8 NTNG1 FLCN AK2 INPPL1 CHAT CCDC40 IL2RG CDC42 DYNC2H1 CD3G TASP1 SLC18A3 DGCR6 HOXD13 SCNN1G WT1 KAT6B WT1 MAP3K8 STAT1 ACTA1 TGFB3 MUC5B PRKAG2 SMN1 TAP1 SMAD4 ABL1 MED25 CHD7 TERT COG4 LMNA SULT2B1 GBA SPEF2 RREB1 SDR9C7 CEP57 CFI IDUA FUCA1 FLCN TBX1 HPS4 PIGT SAMD9L FLNC ESS2 NCF4 LRBA DRC1 DYNC2I2 RFXAP KIAA0586 DNAH5 DOCK8 PTEN MAN2B1 ZMPSTE24 TP53 ATM LAMC2 ACTL6A TRAF3IP2 POLR3H RELA TBX5 PARN CR2 IRF5 MED13 NUP88 GALNS TAP2 AFF4 UNG DNAAF4 RFC2 BCL11B NCF1 HPS1 CD3D RELB PTPN11 ODAD4 TDGF1 KAT6B PMM2 CYP2A6 RUNX2 POLA1 SGSH RIPPLY2 SERPINA1 WAS NDUFAF6 MMP21 SPP1 GLDN NSDHL ZFPM2 IL17F IL6ST IRAK4 KAT6B ACTL6B LRRC8A TAPBP CCNO GLI3 PLCG2 HK1 BMP15 TMEM260 MYL2 LEP ERCC3 TRPV3 IGLL1 EPM2A CCDC65 PRKCD SLC18A3 TAPT1 BMPR2 CD79B SLC7A7 FLNA FAM20C HLA-DRB1 SLCO2A1 CD46 XIAP DKC1 CYBB MYT1L CD3E AFF4 MESP2 VHL POLE BCOR FOXH1 BMP2 HYDIN TNNI3 RARA MAT2A EOGT NFIX MEFV DVL3 PTH1R BCL10 RNF168 CBL ITGA8 NEU1 KRAS CEP55 MYD88 NPM1 IGLL1 TP53 RSPO2 RRAS TRIP11 TGIF1 WAC ADA PKD1L1 UNC119 ACTA2 PSMD12 ACTA1 STRA6 PIGN GAA CD8A BCOR NEK9 TERT DHCR7 IKZF1 TSC2 LEPR SLC35A1 MUSK ARSB COG6 VPS51 COLQ WDR1 RASA2 TTC7A LTBP4 BTK GPC3 STAT3 GAS1 RUNX1 TTC12 WASHC5 INTU CD3D WT1 STAT3 BPTF CRTAP SLC2A10 COL2A1 COMT CCDC40 ASAH1 LIFR MEFV ACVRL1 MYH3 FAT4 DNAI2 LAMB3 PIEZO2 FOXE3 GRIP1 NFKB2 PIGL PTCH1 TGFBR2 ATP6V1E1 COL6A3 IL1RN PAFAH1B1 FOXH1 TP53 CRELD1 MBTPS2 RYR1 TNFRSF13B GRIP1 TGIF1 CLCN7 SP110 CC2D2A COL6A1 STN1 APC2 ITPR1 TCTN3 SMARCC2 PNP SLC11A1 GLUL PKHD1 ALPL BLM ACP5 WDR19 ASCC1 TDGF1 TFRC MGP DLL1 WNT4 IFT140 CCN2 SHH SMAD3 TGIF1 PRKAR1A EHMT1 EP300 CASP8 TGFBR1 ITGA7 AARS2 ERF DNMT3B FGFR1 IRF2BP2 CHRNG HLA-DQB1 SPAG1 SRP54 UBE2A CCNQ TINF2 BUB1 LFNG CARD11 DHCR24 ARID1B SELENON RMRP WAS NEK10 MAPK1 GATA6 SCNN1B TRIM28 DHCR24 SYT2 DOCK6 USB1 B3GLCT DLL1 CCR1 POLR3A PRPS1 HIRA RSPH1 SLC26A2 TNFSF12 PIK3R1 IER3IP1 GSN TINF2 NME8 SVBP LIG4 IL7R ALB COL11A2 COL3A1 NHLRC2 KIAA0319L TGFB1 DLL1 IFNGR1 LAMTOR2 DNAAF5 NXN CTLA4 CEP57 HLA-DRB1 MINPP1 CASP10 PTPN22 TBX20 RAB3GAP2 ALOXE3 ZIC2 NUP107 HES7 LRRC56 HLA-DQA1 KIF1A GAS8 TERT PSAP DNAI2 NOTCH2 DPM2 CD81 NODAL DNAH9 NABP1 PRKAR1A NUMA1 TBC1D23 NFKB2 DLL4 ORC6 FANCB SMARCB1 FCGR2B SIX3 GBA GATA4 MDM2 LAMA3 DSP KIF11 MLXIPL HLA-DRB1 NOTCH2 ADGRG6 DNAH5 SLC26A2 DYNC2I1 ATP6V0A2 EGFR ZBTB24 LYST ODAD4 CACNA1C CYBB RNF125 DPF2 RIT1 CITED2 RLIM WDR35 DYNC2I2 GATA6 RTEL1 IRF8 DISP1 GAS1 ABCA12 TRIP13 GPC3 ODAD3 DNAAF2 MECP2 BIRC3 SFTPB ELN CFTR NOTCH3 SCNN1A KMT2D DIS3L2 MDM4 IL17RA EPHB4 CCDC39 FBLN5 SPIDR TCF20 KLHL41 WNT3 IL17RA FCGR3A JMJD1C VPS33A UFD1 ODAD1 IKBKB CHEK2 FADD RSPH3 ZMIZ1 CREBBP TNFSF11 SCNN1B FREM2 CCR6 AGA SCNN1A ADA RAG1 RAG1 LMNA BRCA2 TGM1 TSC1 DLL1 SIX3 CARMIL2 GTF2I AKT1 CCDC65 ARID1A FGF20 RIPK4 ALG9 CFB RAG2 SCNN1G APOE SOX4 RAB27A MUC5B EWSR1 NECTIN1 ZMYND10 SGCG DNAAF6 CDON TAF1 IGHM LMNA LAMB2 LEP CSF2RA CD79A CFTR HPS6 DOK7 RCBTB1 CCBE1 FIP1L1 COQ7 SERPINF2 PWAR1 RPGR VPS33A ELN SPECC1L TET2 BTK SCNN1A RLIM IL7R EPG5 HLA-DRB1 TGFB2 PIK3CD GLA NBN HYDIN PSMB8 VAMP1 SDCCAG8 TINF2 FCGR2A SHH ARHGAP31 RAC2 CD19 DSE DDX6 HLA-B SERPINH1 GLI2 FLNA MARS1 ALMS1 SCNN1B ITCH SPAG1 DISP1 DNAAF5 IDUA TGFB2 FGF8 MSN SMARCE1 CHST14 WRN BCR FGFR3 SERPINA1 WDFY3 RAG1 PRPS1 FASLG DNASE1 NIPBL KLHL40 RAG2 MRAS RHOH ZAP70 TK2 FGFR1 CREBBP MYRF ALOX12B NOD2 RFXANK MYH11 EVC2 DYNC2LI1 ZEB2 IFIH1 RARB GBA USP9X IKBKB ABCA3 MYOD1 GATA6 CCNO CSPP1 TBCE GBA RARB NAA10 TSC1 FAS WNT4 PLCG2 ETFDH G6PC3 MS4A1 SPINK1 CD19 UBAC2 FLCN EXTL3 GUSB DYNC2I2 ATP11A NGLY1 SAMD9 NME8 TRAIP RRAS2 PYROXD1 SIK1 SLC26A2 RAG1 MYOD1 ALMS1 NKX2-5 IL21 FOXP1 PUF60 LAMTOR2 BCL2 SMAD4 TBL1XR1 ACTC1 FOXJ1 ARID1B HELLPAR SCNN1B DGCR2 DOCK3 FSHR MIF CYBC1 SNAI2 CSPP1 CCBE1 SMARCD1 IRAK1 JAK3 STAG2 PCGF2 CXCR4 LEPR DDR2 BCL6 POLA1 TRMT1 PTCH1 RPGR GATA6 CSF2RB CHRNA1 ASAH1 ASAH1 RAG2 NAB2 TERT MYSM1 BTK FRAS1 DCLRE1C BTNL2 CFTR NOP10 KNSTRN FOXJ1 PEPD TERT NR5A1 CDON MARS1 BRAF TCF3 NKX2-1 ICOS ZMPSTE24 DNAH11 OSTM1 ALG12 KATNIP AGTR1 PPP1CB BMPR2 CAV1 TGFB1 KPTN ADA TPP2 MKRN3-AS1 SLC25A1 FARSB GPC4 FUZ MYH6 HLA-DPA1 FBLN5 SRP54 TNFSF12 IGHM NEK10 RSPH3 TTC12 CRKL RASGRP1 SELENON PTPN22 DLL3 CLPB DOCK8 GLI3 HPGD THOC2 LOX RBPJ PIGN SMC1A DCLRE1C DNAL1 RIPK1 ZBTB16 CFH BTNL2 GLE1 SFTPC FOXF1 KLRC4 CCND1 CD79A EGFR TNNT2 DNAJC21 IL12A-AS1 IFT80 TSC1 CTSC USP9X MKKS SFTPA2 PIK3R1 CHRNG CITED2 TNFRSF13C ELN ADAMTS2 NR2F2 RSPO2 CFTR SCARB2 NKX2-5 SOX18 ADNP DNMT3B CCR6 TCIRG1 PAX6 STAT4 SETD2 DRC1 CFAP221 C11ORF95 TSC2 IFT172 TNFRSF13C FBN1 ARVCF RNF168 NFKBIA NFKB1 BAP1 NEPRO SLC52A3 PRSS1 SLC26A2 CLIP2 MKS1 GLI1 CRELD1 FGFR3 SFTPC FCN3 NCF2 SIM1 CD28 BAZ1B P4HTM DNAAF3 GAS2L2 CCDC103 UGP2 CEP120 GATA2 ETFB DICER1 IL6 ICOS CDCA7 CDKN2A SIX3 JAGN1 SFTPB DNASE1L3 PPP2R1B MBTPS2 CLCA4 STX1A KIAA0586 AGGF1 BNC1 POU6F2 MYH3 PHGDH STAT3 HRAS SFTPA2 DNAH11 LRRC6 SLC35C1 CDON IL17RC ASXL1 TRIM28 COL3A1 CD79B KDM6A UBB NHP2 NAA10 NCF4 CCDC22 MAGEL2 TBC1D24 PARN NRAS MTHFD1 MYH7 MIR140 BLNK LCK NFE2L2 CSF2RA MYSM1 DNAI1 MYT1L RAG2 CAV1 ZIC2 PRKG1 HACD1 MPLKIP TLL1 PIK3CA NSMCE3 IL10 PRSS2 SMPD1 IFT80 NLRC4 COL6A2 FLNB OFD1 PARN RB1 SCN9A MCTP2 FGF8 MAGEL2 FANCF CORO1A PIK3R1 PRKDC CR2 GBA EP300 TGFBR2 PIK3CD CASP8 CRLF1 PLVAP RAPSN NOTCH1 H19 PTCH1 NCF2 SH3KBP1 CR2 ERBB2 DNAAF1 AGRN RFXANK TDGF1 LGI4 GLE1 IL2RA SOX11 IL2RG MEFV ATM STAT3 ODAD3 SERPINF2 CYBC1 SNAP25 SMPD1 TRPS1 REN SHH ELP1 GLI2 CHRM3 IL2RG PNP GREB1L BACH2 SRSF2 NPHP3 CREBBP RIT1 BGN SH2D1A WIPF1 GATA6 DDR2 CTC1 FAS DYNC2I1 KITLG TBX1 TGIF1 RFX5 DCLRE1C CFAP410 GTF2IRD1 GPKOW FAS DONSON CCNQ ELN FADD SLC5A7 GDF1 ERCC2 TERC CBL ADAMTS3 TBX20 ODAD2 STAT4 SLC29A3 FOXE1 CBL FBN1 DVL3 MALT1 IFT43 DSG1 TECPR2 RTEL1 IPW NGLY1 CYBA PIEZO1 NHP2 EP300 TNFRSF11A DZIP1L CCND1 TLR4 CD81 FAM111B LRRC6 RTEL1 BCORL1 PORCN RAG1 SLC34A2 COPA DICER1 FRAS1 DNAI1 TERC MYPN NFKB1 ODAD2 ITCH TBCD ELANE NPM1 CXCR4 PWRN1 TNFRSF1A FOXP1 MYO9A DNAAF1 TGFB1 RFXAP C4A PML RAG1 TREX1 SMPD1 CREBBP SLC22A18 ELN TSC2 A2ML1 FSHR SETBP1 USB1 NADK2 MS4A1 CHAMP1 TERT NKX2-1 PTPRC SCN10A NEK8 CEP120 SMO CFI LMOD3 ELP1 NAA10 POLR2A NODAL GFI1 PLG RNF113A HSPG2 TBL2 EMG1 SFTPB STK11 SLC7A7 RSPH9 MRPS22 TERC CFAP298 WT1 CD19 RET JAK3 AICDA GLB1 GTF2H5 NIPAL4 PLOD1 MESP2 DYNC2I1 RNU4ATAC ZEB2 TANC2 ITGA3 NBN GNS FOXN1 STAT1 DISP1 B2M
    Protein Mutations 11
    A105G A118G D299G G551D G719A L858R L861Q R753Q S1009A T399I T790M
    SNP 6
    rs1051730 rs1800470 rs1828591 rs25331 rs4129267 rs7103572
    HP:0001626: Abnormality of the cardiovascular system
    Genes 4365
    NR2E3 ND4 MMUT EDNRB NDUFS6 TMEM94 LPIN2 COG4 VEGFC PGM3 GATA1 PDE11A KIAA1549 SLMAP LBR CD247 RHBDF2 AGK ABCD3 SEMA5A GP1BB HS6ST1 FANCC SEC61A1 SEC24C PROM1 CALM1 TRNL1 ANK2 NELFA HPS3 STING1 GDF1 MMP14 APOE PEX11B POLR1A OFD1 ABCA12 FGF20 ABCG8 CCDC141 NSD2 CYTB HGD KRAS NKX2-5 JUP KCNH2 TRIP13 FEZF1 PERP IKBKG BTD LDB3 GDF1 RAD51 ERCC4 FGB NDP SLC25A4 ASXL1 CTLA4 ABCC9 LBR FLT4 KCNJ2 SEC31A ATP6 USH2A FLNC GATA4 MYH6 PLEC NSD1 FHL1 GLB1 TSC2 LMNA CAVIN1 TNFRSF4 FLT4 GUSB AIP EVC C12ORF57 RET RNU4ATAC PPP2R1A TPM3 XYLT2 COQ2 FBLN5 HBA1 LZTFL1 ACP5 NUP188 IL7 MAP2K1 ROBO4 MYLK PUF60 FKRP TPM2 TTR TSFM TMEM67 FGFR2 SPOP IGH KDSR DNAJC21 LETM1 ACTN2 POMGNT1 PTDSS1 MYF6 CD70 SOS1 ATP6V1A GJB6 NPPA ACADM GATB TERF2IP GLI3 G6PD HNF4A MGMT COA6 RERE KLLN IFNG ARNT2 FANCM WT1 PDE11A FOXP3 USP45 MYCN UBR1 MYOT IARS1 ENG PLEKHM1 GJA1 GLI2 DNAJB13 PRKAG2 FLT1 INVS IDUA CCDC174 NOTCH3 HPGD HIBCH CAV1 IFNG HLA-DRB1 JAG1 ARL13B GFM2 HOXA13 COL4A1 GBE1 SALL4 CFHR1 TBXAS1 DDX58 TGIF1 MKS1 LACC1 DNAJB11 ND5 RPS19 H19-ICR BLOC1S3 CDON PRPF6 PLCB4 GPD1 SLC18A2 FGFR1 EVC2 NEDD4L BAP1 RPGR THPO MST1 LAMA2 HPS5 ADAMTSL2 PEX14 RAB23 NDUFA6 MYH7 ESR1 EDA VCP KCNE3 ZIC2 KMT2E HFE SDHD C2 ITGA2B TET2 CAV3 ALDH3A2 PEPD FGF8 RAF1 SHH XYLT2 PSMB4 SON HMBS TLL1 DTNBP1 ABCD4 FHL2 MMEL1 NODAL JAK2 HEPHL1 TAZ HAAO BUB1B ERAP1 ADAMTSL1 CSTA SMC1A ZNF148 LZTR1 MIB1 CLRN1 FMO3 TMEM231 PRTN3 PIGN CHRND TRNF LRP6 TDGF1 NDUFB11 COL1A1 SCARF2 PTPN22 UBE3B DPF2 ANKS6 DNM2 XK KRAS HEXB IDH2 MYH6 IRF5 HLA-DQB1 ERBB3 DUX4 TBX19 SIX3 IDH3B MTHFR FANCB TERT EPB42 TRNL1 ZEB2 ODAD1 NECTIN1 COX1 ARCN1 COL1A2 LDLRAP1 TP63 SMAD3 F13A1 CAV1 GJA1 VPS33B CASR WDR35 LIG4 LARP7 CCDC40 CUL7 DDRGK1 IL2RG PLOD1 HAND2 PRRX1 SACS SCN5A WT1 CD96 WT1 TGFB3 PRPF3 ACTA2 BBIP1 SLC4A1 HAMP LMNA GBA CYP11B1 SGCG IDUA TRNL1 CTSK KLF1 ABCC6 SIM1 SETD5 SAMD9L SF3B1 ESS2 NCF4 DRC1 FERMT1 TPI1 NFU1 NDUFS2 COX7B SCAPER DNAH5 SAMHD1 MAN2B1 KCNJ18 FXN AGXT ZMPSTE24 ALDH18A1 ACTL6A GFI1B D2HGDH EOGT GP9 CEP290 HCCS SMARCB1 PIGV GMPPB TRIM32 DNAAF4 HPS1 KIF15 ODAD4 SPECC1L TDGF1 PMM2 SGSH WAS SOX9 DCAF8 HAVCR2 ND5 CDKN2A ARX GNPTAB SEMA3E IL17F SCN10A LRRC8A SLC35A2 CCNO LMNA MYL2 SOX2 NKX2-5 NOS3 SETD1A NEXN BMPR2 CDK8 POMT1 ERGIC1 TMEM127 NCKAP1L CC2D2A JAK2 HNF1A BAP1 DKC1 CYBB COL1A1 PAFAH1B1 VHL SCN5A TTC7A FOXH1 NDUFAF5 TNNI3 SLC25A11 PAFAH1B1 ND1 ITGA8 GLMN MYD88 EIF4G1 ARF1 KCNJ5 SLC20A2 PRNP RRAS XPA GATA4 AKAP9 STRA6 SDHA FGF17 FANCC TRNW ARMC5 COA8 PSAP DHCR7 PTCH1 CALM3 MEN1 CLCNKB MAB21L1 PROK2 CKAP2L CC2D2A F7 BPTF COX10 MGME1 TKFC ADAM17 CRYAB PLAGL1 ABL1 NDUFS1 WASHC5 SMARCE1 INTU ERCC5 ACTN4 STAT3 DYNC2LI1 TRNV HGD HYMAI WNK4 LIFR SHH AEBP1 MEFV DNAI2 AKT1 ND4L NFIX NFKB2 DCDC2 PIGL TGFBR2 ATP6V1E1 XYLT1 CRELD1 PTPN11 DLST MYH7 FOXF1 SDHAF1 TGFBR3 GDF2 LARS2 GDNF RPS6KA3 PROKR2 APC2 TNFRSF1B CTNS SMARCC2 FGFR1 PQBP1 COX15 PPOX F10 PNP GLUL PKHD1 NKX2-5 HYLS1 CAV1 BLM ASCC1 MYH6 MEIS2 KCNJ11 TFRC IDH1 PEX6 RPS26 COL6A3 CIB1 SOS2 RPL18 DVL1 RHO TGFBR1 RPGRIP1L TRNK CEP120 EPB41 CYP7B1 FECH SF3B4 UBE2A CRYAB MNS1 FGFR2 MEOX1 VAMP7 LMNB1 GP1BA ARL6 JAK2 NDUFAF1 SRY CFC1 DNMT3A EPAS1 KCNQ1OT1 WNT10A TANGO2 GATA6 TNFSF4 DYRK1B GATA6 BSCL2 RUNX1 ATP5F1A AKR1D1 DHCR24 OFD1 ABCC9 USB1 TSHR HTRA1 THSD1 SMC1A SVBP GYG1 ALB F8 COL2A1 TFAP2B COL3A1 ABCG5 ALDOB DLL1 IFNGR1 SDHB TNFRSF11A CEP57 CASP10 PTPN22 RAB3GAP2 ABCA4 TERT POGZ F8 CA2 PIGP PEX11B NOTCH2 COL5A1 NRXN1 CD81 NODAL MYBPC3 ANKRD11 SDCCAG8 F13B PPARG NDUFA2 CSGALNACT1 SF3B4 STXBP1 BCOR HADHA SNCA DNMT3A ARL2BP DSP KIF11 WRN SLC37A4 GNAQ SCN9A AGXT EDNRA AVPR2 CCND1 RYR1 ATP6V0A2 XYLT2 MYL3 NBEAL2 ODAD4 CACNA1C FGF8 RIT1 RLIM GATA1 TFAP2B TMEM43 F9 MEF2A DISP1 CNGA3 GPC3 TCTN3 PRF1 ETV6 SLC29A3 CLCF1 NPHP3 TCF20 IL17RA CANT1 LMNA FREM2 RAG1 FRA16E LMNA LMNA CPLANE1 DLL1 EIF2AK3 AKT1 HSPG2 FAN1 G6PC NFIX MUC5B EWSR1 ZMYND10 ACTG2 SDHC DHODH SGCG PTCH1 CD79A ARL6 COL5A2 FIP1L1 PBX1 LRP5 SMARCA2 SOX9 RPGR SCO1 SPECC1L GINS1 GLRX5 TGFB2 PIK3CD PHOX2B BRAF ALAS2 TCTN1 SLURP1 EBP ECHS1 NF1 ARHGAP31 GATA4 IDH3B CDH2 CSNK2A1 GLI2 PROS1 ALMS1 PEX26 SIX3 FGFR2 ATRX TGFB2 FGF8 PSAP ACAD8 BCHE NPHP1 AP1S1 CHST14 POLG WDFY3 LRIG2 DCX NDP DNASE1 NIPBL POU1F1 CEP41 OPA1 ARMC9 TULP1 SDHA IFIH1 TWIST1 RNF135 GATAD1 ND3 MYRF ND1 BRCA2 APP IFIH1 ND5 FXN FOXE3 APP BRCA1 FIBP NXN PEX3 ATPAF2 CIZ1 EYA4 ALDOA ORAI1 MTAP CD19 COX1 CEP104 LMNA RAI1 GUSB LRP5 GNE NGLY1 TMCO1 SAMD9 SDHA F13A1 POMP GMPPB GUCA1B PKP2 NPHP4 HDAC8 TRAPPC11 ALDH18A1 PUF60 PTCH2 SMAD4 RANBP2 KIAA1549 MPL SCN5A OCLN THBD DOCK3 SUMF1 SNAI2 MYL2 PIK3CA CYTB FAH STAG2 POLR3A KRT83 SEC23B GATA6 FOXC1 MYSM1 SERPINC1 SARS2 GJA1 CDKN2A ABCC8 CPT2 CBS TET2 PRPH2 ZMPSTE24 SDCCAG8 NR3C2 TCF3 RPL11 NKX2-1 NDUFA4 ZMPSTE24 TCAP PACS1 ALG12 KMT2D RPL15 TGFB1 IGF2 CKAP2L CASR CCDC47 GGCX NOTCH1 RRAS2 PDE6H ADCY5 MYOZ2 HLA-DPA1 CHD7 RPGRIP1 RSPH3 GNAQ SELENON RYR1 CLPB PIGN ND3 SMC1A TGFBR1 IDH1 PADI4 CFH HSD3B2 TRNN SUFU MRPL3 FOXF1 KLRC4 COG7 B3GALT6 SMAD6 WWOX USP9X ATP2C1 PDCD10 PIGU KRT5 KCNJ2 NDUFAF6 CITED2 NLRP3 ESCO2 RPL5 ZFPM2 ELN JAK1 ZFPM2 NR2F2 FGF8 TKT WASHC5 HLA-B CTU2 SETD2 PNPLA2 ATP6V1B2 ARHGEF18 FBN1 JAG1 MEN1 BMPR1A KIAA0753 ATP6V0A2 ZNF423 STK4 GCH1 AKT3 PMS1 C8ORF37 CPN1 RHAG POGZ DSP NDUFS2 F12 JAK2 ATRX TTN BRAT1 FUCA1 CFH ADAR KCNE2 JAK2 NLRP3 CCDC103 CEP120 HBA1 AGK SMARCE1 ERCC5 CLCC1 GPD1L GUCY1A1 PRCD AGGF1 DOLK DCHS1 TRDN CALM1 FSCN2 FAM161A TNNI3K MRPS22 KRIT1 FGFR1 DMXL2 DNAH11 IL17RC FLNA FCGR2C NSMF NAA10 GNAS KDSR KIZ MKKS LDB3 DNAI1 AGTR1 ERCC2 BRF1 IGH LRRK2 GLI2 FGG SNRPB IL10 FZD2 QRSL1 SLC4A1 STEAP3 SLC26A2 OFD1 GJB3 PEX13 SCN9A MCTP2 ANK2 FGF8 PIK3R1 EP300 SCNN1B CASP8 KCNE5 EFTUD2 RP1L1 SCN1B PLVAP FOXH1 IMPG2 SDHAF1 DNAAF1 CDH23 TDGF1 IL2RA MAP3K7 COL4A4 FGA PDE3A USP8 REN AMER1 CC2D2A TERT GJB3 ZIC2 ARID1A WDR35 PRKAR1A PRDM16 RIT1 BGN WIPF1 GNA11 SF3B4 F2 NF2 SLC29A3 SLC19A3 FAS RNASEH2A DYNC2I1 TGIF1 FLNA DCLRE1C SMAD4 BBS1 PALB2 GTF2IRD1 CFI TET2 KDR FADD APOA1 COX7B AKT2 TAB2 PDX1 SLC39A4 MYLK SMC3 FKRP SLC29A3 PLIN1 FLNA FOXE1 SPARC GBA GATA3 COL6A2 PCARE KLF13 BANF1 ESCO2 MYH11 SCN4A FBN2 DCAF17 RTEL1 RPGRIP1L LIPC SBDS KRT9 HMCN1 CACNA1D FANCE KRAS TLR4 ETHE1 GPD1L PEX19 XPR1 TRNC FANCA ODAD2 NEK9 FBN1 IFNG SDHD ANTXR1 ELANE CXCR4 COL4A3 CENPE BBS4 DMD C4A IFT88 UROS KANSL1 MMP1 FMR1 KRT16 F13A1 PCCB TSC2 NR3C1 PRPF8 SETBP1 USB1 LAMP2 TET2 BPGM MVK NKX2-1 SLC17A5 CTCF PNKP DDX3X RRM2B GFI1 RNF113A CLIC2 MAF DDC ALG9 KAT8 TMEM237 NEBL STK11 IL10 SLC7A7 MED12 CDKN2B LONP1 ERBB3 RET JAK3 PEX10 OTX2 SYNE2 AICDA GLB1 GTF2H5 ZFPM2 PLOD1 RPS28 PRDM16 COL3A1 IKBKG ITGA3 ITPA CIITA GBA DOCK6 ACTC1 JAK2 KIT CDC45 CARD11 GALE CFAP298 PEX5 DCC COL7A1 TRPM4 WNT5A SHANK3 MTHFR TRAF7 MAP2K2 LIMK1 NRAS HLA-DRB1 EXT2 LMNA FBN1 SOS2 HBB PSAT1 FANCI MITF TNNI3 SALL1 PAX8 TARS1 NSD2 DNAAF3 DAXX DYNC2LI1 NLRP3 NPHP3 NPC1 HJV TNFRSF1A HLA-DPB1 SYNE2 DSG4 RINT1 LZTR1 SLC25A11 COL1A2 TRAF3IP1 TRPM4 MPIG6B VHL POMK GANAB TCAP NLRC4 EIF2AK4 RPSA GPR35 POMT2 CLRN1 LRP2 STAT5B FBXW11 NLRP3 CHRNA7 KRAS FCGR2A KIAA1109 CNGB3 SELENOI MYOC ATP8B1 CYBA ERCC6 SF3B1 PLN GNA14 FOXH1 MDM2 CAT TCF4 THOC6 PET100 ACTG1 ITGB3 NOTCH2NLC IL12RB1 CYP11B2 ATP6V0A2 CACNA1D PITX2 PKLR TCOF1 GAS1 ERCC4 PLN STAG2 TRNH KIF1B PTPN22 SPTA1 POMGNT1 HGSNAT F10 SLC2A1 ERCC3 IDUA HLA-B COL5A2 GM2A NDUFV2 TWIST1 MIPEP EFEMP2 NCF1 ADA2 RPS15A HESX1 KMT2A F2 IL2RB ERCC4 DISP1 CSRP3 ATP6AP2 BCR RBM10 PEX1 FGFR2 WNT3 COL1A1 AP1B1 GATA1 NR5A1 ACTA1 HCRT PDGFRB FASLG SMAD4 DMPK CYSLTR2 ROM1 CCDC103 CACNA2D1 HBA2 PEX5 ATAD3A FGF8 CCDC39 NEU1 COQ2 POU3F4 LMNA RPS15A NKX2-5 HBA2 PSAP HSD11B2 GJB4 ITGB3 MDH2 CA4 RP9 BBS2 PITX2 KCNE3 PALB2 RAF1 KCNN4 LMBR1 CFB WDR11 PEX2 WAC ARL6IP6 GNAS PLEC FLNA TCIRG1 TP63 NF1 SON PIK3CA NKX2-5 LMNA CHD7 CUL3 NMNAT1 KCND3 SLC4A1 BCS1L CAPN5 CD55 TTC37 LONP1 SHOC2 GJA8 HTRA1 GPC6 ABCA3 STK36 LMNA OFD1 PALB2 TECRL HLA-A SURF1 FGFR2 FMR1 APOB TFAP2A AP3D1 ACTA2 DHPS PEX6 AGT ZMYND10 SOX18 TGM5 TPM2 REST ZIC2 SNRNP200 SC5D PTEN TBX22 CTCF PRRX1 RAC2 CTLA4 PLP1 MEGF8 FGFR2 ZIC2 TAF2 EFL1 TTC8 DDB2 B9D2 PEX16 EFEMP2 PTEN PCNT NEUROG3 CFHR1 PDSS2 PIK3R2 FGFR2 SPIB TGFB3 FANCB USH2A TNXB MYH7 PRPH2 SCNN1G UMPS ACVR2B TRAPPC4 XPNPEP2 PTCH1 LEMD3 CRLF1 TNFRSF13B MYH8 COL1A2 MYPN MCIDAS F2 GNAT2 YWHAE CYP11B2 IVNS1ABP NSUN2 CHRM3 COL1A2 SLC25A4 STIM1 DHCR7 KRAS TMC8 RBM10 DPH1 LYZ KDM6B FAM13A MFAP5 CWC27 TBX3 MRAS MAN2B1 KRAS KRAS SH2B1 ANO5 TUB CDH2 CYP27A1 CBS NODAL IFT122 ACAT1 RBM20 NDUFB3 ROR2 COL4A1 MUC5B USP8 LIPN RTTN CRPPA SMAD4 HBG1 MED25 CCND2 SELENON COG4 RREB1 JUP PROP1 CEP57 DLL4 SH3PXD2B DES CEP41 TBX1 CEP164 RNASEH1 ADCY5 ERMARD NRAS GJA1 GPIHBP1 ZNF408 COLGALT1 PTEN AMMECR1 SDHC ATM DPH1 SLC25A4 AKT1 CYP21A2 FLNA NR2F2 TBX5 GCDH ATP2C1 STAG2 MED13 GATA6 GALNS ACTC1 IDH2 UNG MRPS16 CTLA4 KAT6B SMAD4 CLCN7 POLA1 SCN2A HBG2 RPS7 TNNI3 MMP21 GLB1 SCN4B NDUFS3 PIGL AKAP9 WDPCP ADA2 COL4A1 KAT6B VANGL2 SCN3B ACTL6B EED GLI3 PLCG2 ADAMTSL4 FGFR1 BRIP1 ZNF513 KCNE1 ERCC3 PTPN11 TRPV3 PRKCD FBN1 RIN2 CD79B ALOX5AP TECRL ABHD5 CD46 RAI1 MYT1L GP6 COL3A1 MAP3K7 ARID2 HDAC8 SPATA5 KAT6A BCOR DGUOK CACNA1C DVL3 BCL10 ABCB4 TP63 HLCS TRPS1 NEU1 ACADL BMPR1A RSPO2 NADSYN1 POLG2 GDF6 MAX SOX2 TRIP11 ARID1B SLFN14 POLG2 GAA UBE3A FKTN SNTA1 FGG CSPP1 TERT GDF6 ARFGEF2 DES UBE2T GALNT3 CSRP3 KYNU HCCS KCNMB1 HMGA2 LMNA CPT2 TMPO TTC7A SLC25A24 SKI STAT3 NRAS TTC12 RPS24 INPP5E BPTF FLNA TFAP2A RPL35 SLC2A10 RPS17 SDHA CYP17A1 INPP5E NLRP3 CCDC40 ASAH1 POLR1A CTNND2 MYH3 MVK NOS3 BRAF ATRX KCNJ5 APRT PRPF31 PIEZO2 MED13L KCNQ1OT1 NDUFS8 DTNA CCM2 PHKA2 NKX2-5 GJA5 POU2AF1 SNAP29 PAFAH1B1 FOXH1 SLC40A1 SULT2B1 HADH MBTPS2 FLII FN1 NRL PDE6G RBP3 PHKG2 ARPC1B CDKL5 SMARCA4 SP110 HCN4 TCTN2 ITPR1 FANCA PMM2 RASA1 ROR2 COX3 CEP290 ALPL POLG STAT3 DNMT3B PEX26 MGP ABCC9 OTX2 DLL1 KCNE1 SHH COQ2 ABCA1 EP300 DDRGK1 CLIC2 ITGA7 SCN9A IRF2BP2 CCNQ TNNC1 RIN2 ADGRE2 ALKBH8 NF1 CPOX OTC DHCR24 ARID1B MAK RMRP LIPT1 NEK10 SGCA FGFR2 MICOS13 SOX5 NEXN SYNE1 BIN1 TGM1 PSTPIP1 COL7A1 FOXE3 EDN3 IGF2 H19-ICR B3GLCT TUBB MYCN TNFSF12 PIK3R1 RASA1 F5 SARDH GSN SH2B3 DSP KIAA0319L SLC52A2 CDKN1B LIPA TELO2 SSR4 GJC2 DACT1 TRPM4 GYG1 FIBP RBM8A ZIC2 CDC42 LRRC56 LMNA TNNT2 DNAI2 NONO FAT4 PPCS ERCC8 USP18 VWF SALL4 PQBP1 GBA GJB2 GATA4 PDE6B GATA4 MYH11 HFE EED CDON PROC STRADA TTR SLC26A2 BMP2 WWOX BVES C8ORF37 CALM3 TPM2 CITED2 PTEN DYNC2I2 COX3 SNRPB MTO1 DHX37 SLX4 LOX ACTA1 IRF8 XRCC4 TRIP13 CDC73 ODAD3 DNAAF2 MANBA CFTR SCNN1A PPP2R5D WARS2 CCDC39 PKD2 TNNT2 PRKCH SMAD9 RYR1 ELOVL4 JMJD1C TRNT1 VPS33A ODAD1 ZMIZ1 CREBBP DIS3L2 AGA SETX SGCD BAP1 COX2 SLC25A20 KIAA0586 GTF2I POT1 EFTUD2 ALG9 KIF3B TRDN LMNA ACTG1 ALX4 COX1 ACAD8 ATP6 TRPC6 LMNA LAMB2 ERCC4 GTPBP3 PDE6A HPS6 GATA1 OTUD6B COQ7 LRP5 BEST1 MPI CALR CCM2 HBB VPS33A GDF3 CYP11B2 OTC SEC23B RPE65 ANKRD26 TET2 SCNN1A RLBP1 EPG5 DSP POLR1C SIX3 KRT5 GLA MTHFR HBB RPL35A ND1 FGG SDHD MARS2 CYP26C1 ANTXR1 APOB HLA-B TRMT10C ATP6V1E1 TRNE UVSSA CPOX CDHR1 SLC20A2 RBCK1 TWNK AKAP9 APOC2 NDUFAF3 SAA1 HBA2 KCNQ2 TAF1A NBAS DBH SMAD6 TEK EXT2 ABCC6 FZD4 NKX2-6 RAG1 LIPT1 F8 BAP1 NCAPG2 YY1 LPL TMEM107 DUSP6 SLC25A3 AHI1 PRKACA PNPLA6 RHOH FGFR1 PLAGL1 SNCA CREBBP SCN5A MYH11 EVC2 LDB3 GBA PRDM5 GATA6 WFS1 ND4 NDP SLC25A26 GBA SLC19A2 ND1 NEXN RARB NDUFAF1 ATP7A F5 DCHS1 GJA1 APOE ELN GNAS MAF PLCG2 HLA-DQB1 HBB TCIRG1 RAF1 EXTL3 ATP11A ND6 PCCA TPI1 SOX10 KIT NPPA APP GNAI3 NKX2-5 VAC14 PDGFB BIN1 LIPA TGFBR2 SPTA1 NDUFS7 FOXJ1 NEK1 RPL10 SCNN1B ECE1 KIT ATP7A FSHR CYBC1 SEMA3A SMARCD1 PRKAR1A JAK3 CD109 SPTB PCGF2 LIG4 FERMT1 MYH7 LZTFL1 SGCD IRF5 PTCH1 CA2 SYNE1 NTRK1 CHRNA1 FGA RSPRY1 KCNJ8 FRAS1 ERCC6 RNASEH2B P2RY11 NEU1 GP1BA MYH7 BTNL2 NDUFA9 KIF23 ND2 HSPA9 PIGA MEIS2 CACNA1S DNAH11 GCLC ACVRL1 POMT1 AGTR1 DMD POLG MSL3 PLCB3 GP1BB CAV1 KCNH2 TPP2 FARSB UCP2 IRF6 SALL4 PACS1 GLI2 AHI1 SHOC2 FUZ MAP3K1 MYH6 SRP54 IGHM CRKL C1QBP IL10RA COX15 SLC12A3 DLL3 RPS26 FERMT3 LOX RBPJ RB1 ZBTB16 LCAT CYP11B1 GIGYF2 SFTPC HSD3B7 IL12A-AS1 RECQL4 SIK3 MKKS SFTPA2 ABCA1 BNC2 IFT172 LMX1B SDHB SCARB2 RNF6 PARS2 XYLT1 CALR GP1BA GLI1 CRELD1 FGFR3 FANCF RAF1 SFTPC MPL PRKCSH ODC1 ALG10B IARS2 GPC6 GJA1 BAZ1B BRAF METTL5 JAK2 ATP6 DNAAF3 WDR19 CALM2 EBP STOX1 ICOS CALM2 DCTN1 SIX3 FKRP TMEM231 DNASE1L3 TTN SPRY2 TMEM70 FASTKD2 KIAA0586 ATF6 TRNF PLEKHM1 POU6F2 MYPN NBEAL2 SRD5A3 LRRC6 MIR17HG FGA KCNE1 B2M COG4 NHP2 CCDC22 TBC1D24 IGF2 KCNA5 CORIN TNXB MYT1L RAG2 MYL4 NDUFS8 DCAF17 PRKG1 NLRP3 FGA FOXRED1 MPLKIP TLL1 HESX1 NSMCE3 CCDC22 HADHB RPL35A EXT2 SCN1B NDUFB10 VPS35 NDUFS4 C8ORF37 ACTA1 HBB GABRD TGFBR2 APC BRCA1 AIP SNX14 SGO1 NDNF SCN5A NOTCH1 SDHD NCF2 FOXRED1 KIF5A HRAS TRNS2 ADNP PEX16 SDHD IL2RG MEFV TULP1 ATM ODAD3 RYR1 NDUFB11 CYBC1 SMPD1 CDON FIG4 DMD TREX1 ELP1 C2CD3 TWNK PNP BACH2 CRX TXNL4A CCDC115 KISS1R FUT8 ROM1 SUGCT PPA2 FAS CCNQ ERCC2 COG6 CBL PIGL GPC4 COG8 DSP NOD2 ODAD2 RAI1 CBL TGFBR2 CC2D2A MALT1 COL4A3 KDM1A SIK1 TAB2 TMEM237 SEMA4A PPARG SLC12A1 SLC37A4 VPS13A MYH7 TERT FAS TNFRSF11A COL1A2 ATOH7 DSG2 DZIP1L BCORL1 COPA AKT1 FRAS1 NSD1 LTBP4 YARS2 NPM1 DLEC1 ND6 TACR3 TMEM237 PML ND2 POLG IL12B MYMK NDE1 DISP1 ND5 TTC8 RPS10 KDM3B NODAL KIT PLG INTU CD46 HSPG2 AIPL1 RGR RSPH9 TERC CD19 CEP55 NOS3 RDH5 KCNH1 VHL GPR101 PMS2 HSD11B2 MCCC2 ANAPC1 B9D1 PGM1 TTN SLC26A3 IFT140 RNU4ATAC LMAN1 CRYAB GNS GNAO1 ABCC8 PLEC SDHB SMARCA4 RPS19 GPR101 RSPH4A AEBP1 RNASEH2C OBSL1 PEX1 LAMA4 PRPH2 FANCB ND2 POMT1 LIPA SPTB TERC CTNNB1 NR3C2 PDGFRA NTRK1 KCTD1 ANGPTL6 ASS1 ENPP1 SH3PXD2B IL2RG KRT14 RET PTGIS MED13L TRIP11 PAH PRKAR1A CNBP KCNQ1 COL2A1 CHN1 ELAC2 COG2 TMEM43 FLT4 RYR2 DBH FBXL4 ATP5F1D UNC13D SOX10 CACNA1S KCNH1 RNU4ATAC FOXH1 CDH23 PIEZO1 SOX4 JAK2 COL1A1 GTF2E2 FOXC2 NF1 PRF1 GPI GFI1B POLG AKAP10 DVL3 IGSF3 PSTPIP1 CRYAB RHO DGCR8 SMCHD1 MLH3 SIN3A SCN5A ERCC2 GATA4 SPINK5 FANCL NDUFA1 NOTCH1 NAGLU DLD STX3 MCCC1 ND2 GNPTG SDHB NEK1 POLH TMEM67 BRAF DSG2 MAN2B1 ARSA CALR HJV BRAF MYLK COL4A5 HADHB PAX3 SEMA3E RASGRP1 KIF7 LYST TKT H19 XIAP APP LRRC56 CITED2 COL4A1 FKBP14 WDPCP MCM4 RAG2 FAM149B1 PEX19 PHGDH PRKAG2 TNFRSF13C RPL26 SBDS POMT2 COL6A1 KIF7 MEFV PTEN TGFBR2 SLC2A10 OSGEP ELOVL4 SVBP VPS13B FTO RNASEH1 ALB COL1A1 GAS1 GATA4 NT5E PLN KRT14 HIC1 ANKRD11 SURF1 SIX6 RRM2B TACO1 TRNK ZFP57 VANGL1 LMNA GNPTAB FANCG TBX6 RAD51C ATN1 ELANE CASK PIGO SHH MYPN F8 KIF20A ARHGAP31 IDH2 MERTK KCNQ1 RAF1 SCNN1A PRKAR1A SIX3 CYP27A1 MUC1 DST MITF SMARCB1 RPL27 NKAP TOR1A RAI1 TRNV RBP4 RB1 DNAAF4 HPSE2 TCIRG1 FAT4 CYP3A5 CALCRL CSF2RB ALDH18A1 BMPR1A SAMD9 LPL CLDN1 NFKB2 MYD88 SELENON POLR1D STAT2 SFTPA1 TPM1 SKIV2L COL18A1 LAT TPM1 SKI KCNJ5 SEC23A LORICRIN XPC MTFMT SGCD GAS1 ATP6 STAC3 TRIP4 KCNJ2 ARX FLNA TBX1 ABCA3 GATA1 PKHD1 ZAP70 HTRA2 PAX3 VIPAS39 DYRK1A BCOR RAB23 FLCN CYP24A1 FGF23 CHRNG ACE NSD1 PIGQ TSR2 IL12A SGCB ALDH18A1 CDKN1A CCN2 ARL3 DKC1 FBN2 CASQ2 BAP1 ALX1 DSE SCN11A ROR2 HAVCR2 NDUFV2 DGUOK RIPK4 COQ2 TAB2 RPL10 PRKCD F2 CLCN2 C1S PEX7 SLC22A5 SH2B3 BUB3 GAS8 NTNG1 GNAS CYP17A1 RPGRIP1 LDLRAP1 TMEM127 ARL3 KRT1 DYNC2H1 TREX1 HOXA1 NR3C1 FGB LCAT KCNE5 PLOD3 COA3 SCNN1G TGFB3 SDHAF2 SDHD SLC39A13 STAT1 RDH12 PHOX2B TMEM237 FBN1 NRXN1 ABL1 CHD7 GP9 CTSA ERCC6 MMP2 CDAN1 CERKL PQBP1 NDUFS7 CYP11A1 LIMS2 XPA PDGFRA OFD1 VHL CDK13 FLNC LRBA TTC8 GDF2 TNNC1 PRG4 LAMC2 MMUT TRAF3IP2 KCNQ1 KATNIP FANCD2 GBA PYGL APP CR2 PIK3R2 IRF5 VPS45 PDGFRB CYP11A1 TRNQ RRM2B DSP CTSB RFC2 BCL11B NCF1 ALG1 CD3D PRCD STEAP3 MEOX1 SLC7A14 WT1 TANGO2 TLL1 TRNS1 SPTB MLYCD CASQ2 CTSA CST3 DDX59 NAGS TMEM260 ETHE1 NLRP3 PEX19 RAD21 TAPT1 MYH6 SLC7A7 INS MED12 CENPF HLA-DRB1 MAP2K1 NDUFAF4 NFIA PPA2 AFF4 POLE SMG9 MGME1 BMP2 RARA EOGT DYSF PTH1R PTH1R CACNA2D1 CBL ACTA2 GJB4 NAXD NDUFS4 NPM1 PTEN SMAD4 MTTP SOX3 TMEM216 CASK CEP290 FGA SP7 NOTCH1 PKD1L1 ACTA2 AIRE PHKG2 NDUFB8 WFS1 IFIH1 KRAS PEX1 PEX12 FBP1 CYLD VCL ZNF423 BRCC3 SLC35A1 ARSB MMP1 COLQ AGBL5 RPL27 WDR1 RHAG APOE SCNN1B AVPR2 OTULIN PIK3CA LMNA MID1 GPC3 PALLD GAS1 SOS1 AQP5 GALC MYH9 ABCC6 CRTAP RERE MKS1 PRKCSH CACNA1C KBTBD13 MKS1 ACVRL1 MPL FAT4 DOLK RIPK1 TGM5 FOXE3 DEAF1 NDUFAF8 HADHA CALM1 MRPS14 PSAP PEX12 ITGA2B PRDM6 ABCA4 LRP5 TNFRSF13B POMT2 PDE4D GRIP1 PIGW TGIF1 CLCN7 LAMP2 SMC3 MECP2 TCTN3 ATAD3A JAG1 PET100 MAPT RANGRF IL12A KRT18 TDGF1 GUCY1A1 CERKL TRNW STRADA PROS1 CDSN TGIF1 PRKAR1A ZNF687 NOTCH3 EHMT1 NOS1AP TGDS POR ANO10 TCIRG1 SDHB SPAG1 ATP6AP1 LFNG INSR CEP290 LRP1 IDUA WDR26 KRAS PHYH SDHB WNT5A SCNN1B CISD2 TRIM28 CFAP53 KRT5 POLR3A RSPH1 AKR1D1 FGFR1 TFR2 LIG4 IL7R TPM3 RMRP GNB5 DNAAF5 NXN GP1BB DNAH1 ENG KDM6A IQCB1 MINPP1 TBX20 HES7 LMOD1 TRNT GLIS3 FOXH1 TRNL1 DNAH9 DNAJC13 ALX4 ANTXR2 PRPF4 PLD1 GSN SMCHD1 RP2 ENPP1 SMARCB1 VHL TOPORS MLXIPL NKX2-5 HLA-DRB1 ADK MYH7 DNAH5 CPS1 TF CACNB2 EYA4 ND1 CPLX1 ITGB3 RYR1 CHST3 CYBB DPF2 BBS2 TP63 ERCC8 KRAS CDK10 SUFU MSX2 PEX13 GAS1 RPGRIP1L SFTPB DSP FBN1 ASCL1 GATA5 FBLN5 ISG15 GJA5 UFD1 TNFSF11 SCNN1B SERPINA6 NKX2-5 FHL1 TSC1 TXNRD2 APC PIK3CA YY1AP1 MMP2 CCDC65 GNB5 GATA6 ARID1A CACNA1S WAS SCNN1G NDUFA11 RAD21 KRT1 RAB27A MSH2 HLA-DRB1 CYP7B1 MAFB CDON PDCD10 ALX3 TBX1 TMEM67 INPP5E MYORG CCBE1 ITK LRP2 NPHP1 SCNN1A NPHP3 SCN4B PIK3C2A TMTC3 REEP6 GATA6 ELN TTC37 BTK RS1 RLIM IL7R ISCU HLA-DRB1 ACTB POMT1 LHX4 PSMB8 SAG CALM2 FANCE FCGR2A ADAMTS10 AKT3 CFHR3 RAD21 GPC4 COL11A1 UROS RAC2 CD19 NAGA CP ARL6 AIP CPT1A INVS NFIX FANCI FBN1 BAG3 DISP1 PRDM16 DNAAF5 FLRT3 NF1 FGD1 AIRE TNNC1 WNK1 PIK3CA SMARCE1 WRN BCR KCNQ1 SRCAP GP1BA TRNS2 SDHB GJA1 PCNT MRAS SGCB CASR DPM1 IDUA TOP3A ZAP70 MEN1 CYTB MYH7 NOD2 GNE ZEB2 ATP5F1E NODAL F13B LETM1 USP9X KRAS MAFB RORC PSMB9 PLAU FLT4 WNT4 TBCK ZNF469 FMR1 COX6B1 UBAC2 NKX2-5 LBR NME8 TRAC HEXA CRB2 PEX1 SLC26A2 HABP2 RERE ALMS1 AQP2 SERPING1 FOXP1 EYS RUNX1 TRNK FLT4 ASAH1 SNTA1 ACTC1 ARID1B HELLPAR KRAS DGCR2 MIF PROKR2 ABCA1 CCBE1 TSPYL1 MOG BBS5 TRPM4 STX11 IRAK1 CPLANE1 AAAS EVC PEX6 DDR2 ECE1 TMC6 FGFR2 PPP2CA RET MKKS B3GAT3 RAG2 C1R HYMAI PIBF1 TERT HMGCL ANTXR1 NDUFA11 IRX5 BTK HSD17B10 CAV3 GNAI2 RPS6KA3 CYP11B2 FTL CITED2 NDUFA12 SDHD TTN CSPP1 KCNJ2 KNSTRN TMEM216 CDON BRAF FLAD1 FZD4 ICOS TMEM126A KCNN4 FHL1 NNT PPP1CB DHDDS BMPR2 NDUFB11 ATAD3A STN1 DSC2 MYH7 NOTCH3 ERCC4 GPC4 IL36RN CNGA1 PEX16 PTPN22 NDUFA2 GATA4 GREM1 HPGD COX7B PSEN2 COL1A1 THOC2 DCLRE1C CHCHD2 GLB1 BTNL2 FLNC CCND1 TNNT2 DNAJC21 CAV1 PCCA TSC1 TRNK MEN1 DMD TNFRSF13C EPHB2 ADAMTS2 HMBS ADA2 SLC4A1 CFTR CAVIN1 C4A GANAB GBA NKX2-5 WT1 FKBP14 CLCNKB PPP1R15B SOX18 CCR6 IFNGR1 BSCL2 TCIRG1 DDX11 STAT4 PDE8B CHST3 AMER1 TMEM216 TJP2 NDUFS1 PDGFB ARVCF PROC NFKB1 MTFMT PGAP2 SLC26A2 DNM2 RECQL4 MKS1 KCNJ11 EHMT1 POLG XRCC2 KLHL7 FH RECQL4 NCF2 RPS6KA3 GGCX NDUFS8 CD28 MYH9 NT5E SLC25A20 SDHD NDUFS2 KRIT1 COL3A1 WHCR ND4L CD2AP MAP3K7 JPH2 GATA2 TRNQ LIAS RET ESCO2 SFTPB EXT1 SPEG CYP11B1 TET2 BEST1 MBTPS2 COL2A1 NF1 OFD1 ANOS1 PHGDH HRAS TKFC TALDO1 TRIM28 TCTN2 GATA4 CD79B KDM6A TRIM8 FBN1 SLC25A13 FDFT1 POLD1 MAP2K2 NFE2L2 PIK3R2 MCFD2 CAV1 DOLK COX3 SMPD1 NLRC4 ECHS1 PIK3C2A COX8A GBA DNAJC19 PIK3CD NDUFB11 ENG ATP6 ALOXE3 ND6 DPM3 PDE6D ITGB3 SRP54 SCYL1 SOX11 EBP ERCC6 F11 IL17RD SLC30A10 EPHB4 COX2 CHRM3 MVK SDHC GREB1L DNAL1 CRB1 SH2D1A PEX3 CHRNA7 GLRX5 MAP2K2 GNE ACAD9 CD27 FN1 BSCL2 LTBP2 HNRNPU NEUROD2 GATA5 SOX9 ELN KLHL7 GDF1 MAX TDP2 LTBP3 CASQ2 ADAT3 TBX20 STAG1 STAT4 ADA2 FBN1 SMAD3 FGFR2 TCOF1 GMPPB NDUFS2 FBLN5 KDM6A RYR2 MAD2L2 SPRY4 TACO1 CLN3 MPLKIP RPGRIP1L SCNN1A RPGR RFWD3 HGSNAT CCND1 PROS1 ERCC8 UPF3B CD81 CARD9 LRRC6 PORCN MED12 DNAI1 IDH3A PKP2 SCN1B CTBP1 TNFRSF1A BRCA2 TBX1 CHRNA3 MPL STX16 ERCC1 RAG1 TREX1 SMPD1 ALG8 TBXA2R CHD7 ELN HADHA A2ML1 ENG STAMBP SDHC NEK8 PDE3A CFI ELP1 SALL4 APOA5 ESPN TBL2 EMG1 WT1 SRCAP JUP DMPK PEX5 DLD PPARG DYNC2I1 CASP10 IDS LTBP2 KDM5B IRF8 GBA TRNS1 DISP1 TRNE IVD ELN SNX10 RNASEH2A LAMA4 TRIO NDUFA10 SLC25A22 ARX LDB3 GNPTAB ERCC6 CACNA1C ALOXE3 KCNH2 SRY PIGO P2RY12 FGFR3 ABCC6 LEMD3 CLEC7A WDR37 DNAAF2 NOTCH2 CAV3 FOXRED1 ZIC3 EXT1 TNFSF15 PIGA MAP3K20 FBN1 KCTD1 DMRT3 CFAP300 PIEZO2 SLC25A24 CTNNB1 SCN10A TNNT2 GPC1 RYR2 SOX2 PSEN1 DNAAF6 FOXC2 INPPL1 ITGA8 EMD NID1 SERPIND1 IFT172 GJB6 PTF1A HBA1 MYC COL11A2 PDE6A PRKCD HYLS1 TNNI3 LYST BTD KCNQ1 EZH2 MED25 SDHC CTLA4 ADD1 RYR1 MNX1 AGL NDUFAF4 RLBP1 CD244 NAGA TUBB GATA4 PTPN11 AIP SLC25A4 FKRP FHL1 EPG5 NRAS PRKAR1A HIBCH TREX1 BCOR KCNJ1 FBP1 NEB SLC35A1 DNMT3A PDGFB MRAP PTPN14 RFWD3 CDH23 RPL15 FGFR1 RNF113A NODAL BICC1 GATA1 TTC8 GBA CST3 STRA6 RAC1 WRAP53 NR0B1 PIGM TMEM70 UQCRFS1 NDUFV1 CTSH PYGM ARID2 SEC23A IRF8 VHL BLM ACTA1 CD40LG ICOS CAV3 RPS27 CFHR3 PTEN ABCC9 COX14 THPO TDGF1 GGCX MED13L KIF7 NPHP1 NDUFA13 SELENOI PIEZO1 CYTB RP1 DDX6 BRAF WDPCP HBB ZIC3 MRPL44 NOP10 WNT10A FLNA ERCC2 CALR FHL1 ACD NEB HABP2 DPP6 PHF21A MYBPC3 NIPBL ITGA2 HYOU1 EGFR ACADS DES TPM3 RPL10 MTRR PGM3 KCNQ1 MTTP IL7R STAG2 STXBP1 PSMD12 FLI1 CITED2 TMEM43 SMAD4 PRKACG IFT81 HLA-B SPINK5 KCNQ1 RNASEH2C SP110 RBM8A TIMMDC1 ATIC BAG3 SLC39A13 IGH TOP3A DPP9 TMEM231 DCLRE1C SDHD GJA5 TGFBR1 TNFRSF1B WARS2 TNNI3 GTPBP3 ITGA2B TXNL4A AP3B1 TCTN3 GPC3 DVL1 FLNB KCNQ1 TTN NDUFAF3 AGA BBS10 FOXP3 KYNU COG5 FN1 PCSK9 TRMU SOX10 DNAH1 KCNJ18 OSTM1 HADHA AKT1 FKTN BBS2 ACADVL RPL26 DISP1 RNF213 CDKN1C SH2B3 GLI2 GLI2 COL4A2 EDN1 CYP1B1 TSC1 JUP TRRAP GATAD1 CHST14 IL23R BOLA3 MGP PLIN1 CFAP300 STIM1 SCN5A UMPS CTC1 ZMIZ1 SFTPC XPC CHD4 ND6 FRG1 ANK1 FKTN STK11 SPEG AK2 MASP1 GNAQ MYCN MYH11 LRP5 SOX3 PHYH HFE CDC42 TASP1 FOXA2 DGCR6 TEK HOXD13 B3GALT6 RPL5 SLC39A4 KAT6B NEK2 ACTA1 PRKAG2 SMN1 NLRP12 GDNF CHKB ABCG8 PEX10 MVK COG1 TP63 IFT27 SPEF2 COL2A1 ABCA4 ND4 CFI LRAT ATP5MD RAD51C MLX SEC23B FUCA1 PKDCC FGB HPS4 PIGT JAK2 ALG1 AHCY FOXC1 SUZ12 PIK3CA VCL DOCK8 DNAH9 LOXL1 COX20 HCN4 KLHL41 RAI1 RMND1 PIK3CA HRAS AFF4 ERCC2 DHX38 PTPN11 KCNE2 IFT172 ND1 RIPPLY2 NDUFAF6 MYBPC3 GGCX FAM111A SPP1 NSDHL ZFPM2 NDUFAF2 TBX20 VCL SPECC1L CPT2 GYS1 CLCN7 PTCH1 LEP LBR IGLL1 NOTCH3 PPCS SCO2 PTCH1 OTUD6B PIK3CA NKX2-6 PORCN FLNA TK2 FLNC SLCO2A1 FAH XIAP HES7 GNAS MEGF8 CD3E ABCB6 KCNJ8 EPCAM ATP6V1A TDGF1 VWF PEX6 MAT2A NFIX PSMD12 SCN3B ZNF462 RNF168 TBX5 FYB1 CYB561 ATM NAA10 COL5A1 ATRX MPL SERPING1 ATP8 ACAD9 PTEN SLC12A3 SLC25A3 PKP1 CPT1A TGIF1 ADA PSMD12 UBR1 PIGN BCOR NEK9 IKZF1 AGT TSC2 LEPR WIPI2 RASA2 CARS1 EPB42 LTBP4 BTK STIM1 INF2 APOA1 RPS20 RUNX1 KCNA1 TNNT2 WT1 NDUFS2 COMT CDC73 SBDS SCNN1G ARL2BP POLH GLA CTSB CLCN7 BBS1 PIGV LAMB3 MTHFR TPM2 ANK1 STXBP2 CSRP3 ACTB PTCH1 CPOX C12ORF57 IL1RN TP53 CCDC28B SNX10 TGFB1 GP1BB ALPK3 SALL1 VPS13B NDUFAF5 STN1 HAMP XRCC4 PIGT NLRP1 ABCC9 SOX18 ELMO2 ACP5 TWIST1 FLNA TRIM37 RPL31 FLNB SRD5A3 EPB41 SLC4A1 DMD WNT4 SERPINC1 CCN2 HNRNPA2B1 RET SMAD3 RP1L1 SDHB TREX1 CNGA1 HSPG2 AARS2 ATP7A MSH6 F5 TALDO1 RPE65 C2CD3 GLI3 FGFR1 SIN3A EYS SRP54 TINF2 BUB1 ARL6 KCNE1 AHI1 SMAD4 SHPK ATP7B ERCC3 TXNRD2 SCN5A SELENON GATA6 WAS ACSL4 MAPK1 F7 KCNJ11 DOCK6 YY1AP1 PDE6C PIK3CA MEFV DLL1 FLI1 CCR1 TRDN COQ2 COX4I2 FSCN2 HIRA JAM2 KRT2 TBX1 GATC NHLRC2 ACADVL COQ4 PPARG CTLA4 GJA5 MKS1 LEMD3 HLA-DRB1 PYCR1 ADAMTS10 IGF1R CHST3 KRT10 SNRNP200 CACNB2 TBX3 PSAP RAF1 COL5A1 NABP1 FBN1 PRKAR1A NUMA1 FECH MYO18B DLL4 COL7A1 DDB2 TBX1 BMP2 FCGR2B SIX3 CALM3 SDHC LIG4 COA5 LAMA3 GMPPB MTOR NOTCH2 KAT6A BBS12 GNAQ NUP155 TP53 SCN1B SERPING1 SYT1 NPHP1 BMPR1A EGFR ABCC8 LYST LRP5 RNF125 GATA6 SCNN1A FGF8 PKD1 BBS7 BIRC3 ELN KMT2D DIS3L2 SMARCAL1 NR2F2 EPHB4 KLF1 IL6 TRNL1 KIF1B GNA11 KCNE2 ARMC5 FADD CCR6 KLHL3 HRAS HYLS1 LMX1B ADA RAG1 ACTN2 BRCA2 RPS17 SIX3 SDHA ABCB11 TNFRSF11B VWF APOE PCARE KYNU SOX4 SETD5 WDR19 TWNK POR TNFSF11 MGAT2 HK1 DNAAF6 IGHM DLX5 THOC6 TFAP2B OTX2 PEX2 SERPINF2 ZNF469 B4GALT7 CACNA1D BBS9 FGG PEX2 SETBP1 HOXA11 LMNA CTNNA3 WT1 KRT14 HYDIN CD40 CD28 SHH MNX1 SEMA4A MECP2 KCNK3 DSE ND6 DDX6 KIT FLNA B3GLCT KRAS ITCH SPAG1 TRDN GJB2 LMNB1 TSPYL1 IDUA DLL1 NDUFS4 ZNF513 FGFR3 KCNQ1 SLC19A2 PPP1CB MYOT RBBP8 TRNS1 CDON PRKACA RAG2 RPL11 KCND3 MAP2K1 MC4R STAR SCYL1 GYPC TBX4 SPATA7 NODAL GABRA3 RARB EDA2R HBB COX3 FGB MBTPS2 TMEM126B SUFU MYOCD NAA10 TSC1 PCCB FAS G6PC3 MS4A1 PROC LMNA KRT5 ZDHHC9 TRAIP RRAS2 MYH7 MED12 NEU1 CYP11B1 ZNF365 RAG1 NDUFA10 IGF2 PROP1 AUTS2 FANCD2 BCL2 TBL1XR1 PEX12 ACTC1 TWNK GATA5 LMNA DCDC2 MRE11 LMNA SEMA3A ABCA1 CNTNAP2 TMEM67 SLC2A1 BCL6 TRMT1 PSEN2 DLL1 LMX1B FOXC1 CNGB1 EMD GAS1 NDUFS3 TRAF7 HCN4 FKTN ANK1 PIGY HESX1 ACTN2 PGAP3 SMOC1 RPS29 TGIF1 PEPD TERT BAG3 ERCC8 FIG4 CDK4 TAF2 NUBPL SAMHD1 RBM20 ACTC1 MAPRE2 MAP3K7 SDHA KPTN KCNH2 ADA PIGY ATP7A IGFBP7 NUP107 C3 PKD1 CCDC141 FBLN5 NFKBIL1 PEX14 DSG2 TNFSF12 RASGRP1 GLI3 SDHA DNAL1 MLH1 MC2R AGPAT2 KCNN3 GMPPA KIT B2M FOS DYRK1A PEX7 KCNJ5 PAM16 EXOC6B ABCC9 SMO TBX1 CDKN1B CHRNG CYP7A1 ACTG2 CALM1 AMMECR1 DPM3 TMEM138 TNNI3 ADNP CYLD PAX6 KCNN3 NDUFV1 SCO2 CFAP221 RGR PKLR TSC2 MSX1 KDSR CD96 SCN2B SCN5A MFAP5 CLIP2 BEST1 PIGT PIGS SCN1B PDSS1 TGDS POR POMT2 CEP120 HNRNPA1 PPOX ATR GAS2L2 FASLG ALOX12B TPM3 IL6 AIP LDLR XRCC2 MTM1 CDKN2C PSEN1 MYH6 STAT3 IFT172 ANKRD1 SFTPA2 ITGA2B ATXN7 PDGFB B9D1 CDON ASXL1 CDKN2B COL3A1 TTPA PDHA1 MAGEL2 INSR PARN MAP1B NRAS NPC2 TP63 PRKG1 MYH7 PKD2 BLNK DIS3L2 DES CSF2RA SMOC1 MYPN ZIC2 SH2B3 HACD1 TBC1D24 AHCY CEP290 PCNA SUFU GPX4 PRPF3 NONO IFT80 EXT2 MYMK PARN FGFR3 SCN5A XPNPEP3 COQ9 TP53 NAGA NAGA TAZ CACNA1H SLC22A4 KCNAB2 USF3 GCK H19 HDAC4 ND5 PTCH1 SCN5A CR2 MYPN TNPO3 F5 F5 MPL HADH SERPINF2 DSP SHH HSD3B7 NDUFB11 AK2 ND4 ASXL1 GLI2 MYOC AHR TNFRSF11A SRSF2 SDHB NUP107 GATA6 TET2 SCN2B CCDC8 CTC1 KITLG NDUFV2 TBX1 IMPDH1 IGBP1 ENPP1 CFAP410 SOX6 PACS2 GPX4 BMPR1A SKI ASXL2 TERC ADAMTS3 TOPORS COG7 PUF60 CAP2 AGPAT2 MRPL12 TTN DVL3 IFT43 DSG1 SOX10 SNIP1 SCNN1G TBX2 GNB3 NGLY1 TF CYBA PIEZO1 SEC63 TMEM126B INTS1 CDIN1 FRG1 GBE1 TRNW RTEL1 PEX5 TET3 PCNA KRT8 MYPN ITCH PNPLA2 FOXP1 GNB5 MYO5B DNAAF1 PEX7 FGFRL1 AMMECR1 SUMF1 MTMR14 TPM1 FGFR2 CREBBP PDE6G NDUFAF2 CEP19 APC NDP HLA-DRB1 TERT PTPRC MC1R SCN10A GDAP1 SMO NAA10 ERCC6 SFTPB CACNA1S EPHB4 KAT6B NDUFB9 RFT1 CFAP298 ACTA2 KIF1B CPT2 IQSEC2 NSMCE2 COA8 DNAJC19 MYLK2 MESP2 ERF WDPCP ZEB2 SIM1 TANC2 LIPC TAZ FBXW11 TPK1
    Protein Mutations 20
    C807T D36Y E138K G20210A G98T H295R I349V I843S K55R L33P M235T N155H Q148H R399G R4E R506Q S49G T1405N V34L Y113H
    SNP 14
    rs1024611 rs11569562 rs11687951 rs13333226 rs2250656 rs28459296 rs3808607 rs4149056 rs4244285 rs6318 rs6841581 rs738409 rs7579240 rs867186
    HP:0000077: Abnormality of the kidney
    Genes 1793
    SMARCA4 H19 RPS19 WT1 ND4 MMUT EDNRB NDUFS6 LPIN2 PGM3 FXYD2 FANCB PGAM2 NTRK1 KCTD1 GP1BB HS6ST1 FANCC RET SEC61A1 SLC6A20 SEC24C PAH NELFA CHN1 APOE PEX11B BLK FGF20 ABCG8 CCDC141 HGD FBXL4 TRIP13 PTH1R SOX10 FEZF1 KCNH1 RNU4ATAC TTC21B CDH23 MCC FOXC2 NF1 EIF2AK3 C1QB RAD51 ERCC4 NPHP1 NSD1 TSC2 SPINK5 FANCL NDUFA1 STX3 EVC RET CFTR PPP2R1A PLCD1 APRT XYLT2 SDHB NEK1 FLNB COQ2 TMEM67 BRAF FBLN5 LZTFL1 ACP5 PAX7 MAP2K1 PUF60 COL4A5 TP63 SEMA3E RASGRP1 TKT SIX1 TTR H19 SPOP DNAJC21 LETM1 COL4A1 WDPCP SFTPC ACTG2 FAM149B1 PEX19 ADCY10 BBS12 GLI3 RPL26 HNF4A RERE NEK8 EYA1 KLLN FANCM WT1 FOXP3 MEFV MYCN UBR1 OSGEP IARS1 PDGFRL FAM20A FLT1 INVS TMEM231 SLC3A1 CPLANE1 HIC1 IFNG SURF1 HLA-DRB1 JAG1 TACO1 ZFP57 VANGL1 GBE1 SALL4 FANCG RAD51C KCNJ10 ATN1 MKS1 DNAJB11 ND5 RPS19 CASK DYNC2H1 H19-ICR F8 C1QC ATP6V0A4 ETFA MUC1 MITF ALG8 INSL3 MST1 PRDX1 TOR1A ADGRG2 TRNV PDGFRB RAB23 HPSE2 FAT4 NDUFA6 CIT PRODH WT1 ALDH18A1 PIGQ RAF1 NPHP4 STAT2 SKIV2L SON KCNJ5 HAAO BUB1B TRIP11 ERAP1 ADAMTSL1 SMC1A ZNF148 NPHS2 TMEM231 ARX PRTN3 PIGN TRNF PKHD1 TDGF1 NDUFB11 B4GAT1 VIPAS39 DYRK1A FLCN CYP24A1 ANKS6 TMEM231 ACE CTH PIGQ TSR2 IL12A CDKN1A IRF5 ERBB3 ROR2 RIPK4 FANCB ZEB2 BBIP1 NUP107 LDLRAP1 PRKCD NCAPD3 PEX7 HSD17B4 BUB3 VPS33B CASR WDR35 LIG4 GNAS PAX2 SDCCAG8 GNA11 FAN1 TMEM127 HPSE2 DYNC2H1 TREX1 LCAT MET COA3 WT1 CD96 SDHAF2 WT1 STAT1 TNXB TMEM237 BBIP1 GATM PTPRJ HPRT1 CHD7 LMNA GBA SDR9C7 PQBP1 NDUFS7 TRNL1 CIT SLC5A2 ABCC6 SLC9A3R1 OFD1 IQCB1 SETD5 GDF2 PLG AGXT TP53 LAMC2 MAGI2 BICC1 MMUT TRAF3IP2 GP9 CEP290 FANCD2 PYGL PIK3R2 APPL1 HOXA13 PPM1B PIGV TRNQ TRIM32 RFC2 ALG1 HPS1 SPECC1L PMM2 SERPINA1 WAS SOX9 WT1 TRNS1 APOL1 SEMA3E IL17F HOGA1 SHANK3 SLC35A2 DDX59 TMEM260 NUP160 PYCR2 TAPT1 DSTYK TMEM127 APC SLC7A7 INS CC2D2A FREM2 FAM20C CENPF BUB1 CEP83 DKC1 NDUFAF4 NFIA PGK1 RAD54B AFF4 VHL CLDN10 SRC SLC25A11 RARA PAFAH1B1 MEFV ND1 ITGA8 GLMN MYD88 PTEN FGF10 TP53 SMAD4 WDR19 TMEM216 CEP290 GATA4 WAC AIRE ITGA6 STRA6 NDUFB8 PLCE1 FGFR2 FGF17 FANCC WFS1 IFIH1 COA8 DHCR7 PTCH1 CDC73 LAMB2 CLCNKB ZNF423 RNF139 H19-ICR PROK2 CLCNKB RPL27 CC2D2A SCNN1B AVPR2 COX10 MGME1 GPC3 NDUFS1 WASHC5 MDM2 ACTN4 ABCC6 CRTAP DYNC2LI1 MKS1 PRKCSH SHH MEFV REN DEAF1 NDUFAF8 PIGL XYLT1 PEX12 PTPN11 SLC4A4 ITGA2B DLST FOXF1 GRIP1 PIGW PHEX CRB2 COQ6 GDNF EYA1 LIPT2 PROKR2 APC2 ARHGDIA CTNS TCTN3 SMARCC2 PPOX F10 PKHD1 ODC1 TPRKB WDR19 RAB3GAP1 KCNJ11 RPS26 TRNW STRADA RPL18 CDK5RAP2 PRKAR1A ZNF687 WDR4 EHMT1 RPGRIP1L TRNK SLC30A9 INPP5E UMOD SDHB TMEM67 SF3B4 INSR MEOX1 VAMP7 CEP290 FAT4 PTPN22 ARL6 SLC34A1 BCS1L SRY EPAS1 KCNQ1OT1 PHYH SDHB CISD2 TRIM28 PAX2 HPRT1 GCM2 LIG4 COL3A1 ABCG5 ALDOB NXN GP1BB ENG CENPJ IQCB1 MINPP1 CASP10 PTPN22 LMOD1 TRNT GLIS3 POGZ F8 CA2 FOXH1 TRNL1 PIGP NOTCH2 SDCCAG8 ALX4 PLD1 GSN ENPP1 RNU4ATAC SMARCB1 SF3B4 STXBP1 BCOR VHL GREB1L KCNJ11 MLXIPL SLC37A4 RAB18 AGXT MAPKBP1 RYR1 NPHP3 GNB1 DPF2 TP63 CEP135 HNF1B HPRT1 PEX13 GPC3 RPGRIP1L WDR19 JAM3 PRPS1 CEL TCTN3 SIX5 NPHP3 TP53RK IL17RA UFD1 CHEK2 FREM2 AAGAB MKKS TGM1 TSC1 EIF2AK3 APC AKT1 YY1AP1 ARID1A CACNA1S ITPR3 NDUFA11 RAD21 G6PC RORA MAFB SDHC PTCH1 ALG8 HNF4A TBX1 PREPL TMEM67 INPP5E CCBE1 ARL6 FIP1L1 DNA2 PBX1 NPHP1 SOX9 NPHP3 PIK3C2A SCO1 SPECC1L TTC37 TMEM216 APC PIK3CD BRAF SDCCAG8 DHDDS KIF14 FANCE FCGR2A TAF13 RAD21 LMNB2 GPC4 CEP164 ARL6 SERPINH1 CPT1A MARS1 ALMS1 INVS FANCI PEX26 FLRT3 SMARCAL1 NPHP1 SMARCE1 CHST14 WRN SRCAP LRIG2 GP1BA TRNS2 FGFR3 DNASE1 SDHB NIPBL RPGRIP1L SLC22A12 TMEM107 TMEM138 ZAP70 ND3 GNAS ALOX12B ND1 CILK1 NOD2 ZEB2 B9D1 NODAL RRM2B USP9X CLDN16 MYOD1 CSPP1 MAFB FIBP PEX3 WNT4 COX6B1 ETFDH OCRL UBAC2 COX1 HNF4A RAI1 TMCO1 BUB1B MAGED2 CRB2 PEX1 NPHP4 MMACHC RERE ALMS1 AQP2 HDAC8 TRAF3IP1 TBC1D8B PUF60 CASR ARID1B OCLN HELLPAR THBD SNAI2 CSPP1 CCBE1 MCM5 PIK3CA BBS5 IRAK1 CPLANE1 ARX POU6F2 POLR3A FGFR2 SEC23B RET TFE3 MKKS HYMAI SHH SARS2 CD151 SDHD ABCC8 CSPP1 KNSTRN TMEM216 SDCCAG8 BRAF SLC7A9 RPL11 KIF14 KMT2D SLC3A1 IGF2 NUP85 CASR PLA2G2A MLH3 GPC4 HLA-DPA1 CHD7 RPGRIP1 PEX16 PTPN22 CLPB PIGN ND3 DCLRE1C PEX1 CFH TRNN SUFU NPHS1 FOXF1 KLRC4 CCND1 COG7 IFT80 TSC1 BSND USP9X TRNK SMC1A MEN1 ADCY10 ESCO2 ZFPM2 AP2S1 JAK1 PRCC HMBS ADA2 SLC4A1 RSPO2 C4A GANAB WT1 CLCNKB PPP1R15B FGF8 CTNS WASHC5 CTU2 BSCL2 STAT4 SETD2 XDH AMER1 IFT172 TMEM216 KIAA0753 ZNF423 ARVCF AKT3 ATRX BAP1 ALDOB PGAP2 C8ORF37 RECQL4 MSH2 MKS1 EHMT1 KLHL7 FH RECQL4 MYH9 CFH NDUFS2 CD2AP FGFR2 CEP120 CDKN2A OFD1 AGGF1 FLNB ANOS1 PHGDH HRAS MRPS22 FGFR1 DMXL2 MOCOS TALDO1 IL17RC TRIM28 TCTN2 NSMF KDM6A TRIM8 CEP63 BAX WDR62 MAP2K2 MKKS CPT2 MCFD2 CAV1 BRF1 SNRPB IL10 COX3 OFD1 PAX4 TRIP13 MCTP2 CLCNKA PIK3C2A COX8A SLC34A3 EP300 DGKE SCNN1B PIK3CA KCNE5 PLVAP PDE6D CEP152 ITGB3 SRP54 SOX11 MAP3K7 COL4A4 ERCC6 IL17RD SLITRK6 FGA USP8 REN CC2D2A WT1 WDR35 CHRM3 POLE SDHC GREB1L NPHP3 WIPF1 GNA11 SF3B4 F2 HNF4A FAS DYNC2I1 LRP4 PDE6D OSGEP BBS1 HNRNPU GTF2IRD1 NEUROD2 CFI GPC4 LAGE3 LAMB2 LPIN1 SOX9 APOA1 MAX PDX1 MYLK EP300 TP53RK ADAT3 SMC3 STAG1 STAT4 SLC29A3 FOXE1 ITGB4 FGFR2 CLCN5 GATA3 ESCO2 MYH11 SLC34A1 ATP1A1 KDM6A RPGRIP1L MAD2L2 SPRY4 RPGRIP1L RFWD3 FANCE KRAS CCND1 TLR4 ERCC8 CD81 PEX19 PORCN PREPL DICER1 FANCA SCN1B ANTXR1 BRCA2 COL4A3 TBX1 BBS4 CHRNA3 C4A TREX1 KIAA0753 CAMKMT DCHS1 ANLN KANSL1 MMP1 CHD7 ELN TSC2 SETBP1 WT1 PEX10 MMUT FLNA SLC17A5 NEK8 LMX1B PNKP CFI ELP1 ALG9 TMEM237 TBL2 STK11 SLC7A7 CDKN2B WT1 RET NUP133 PEX5 PCK1 NIPAL4 RPS28 CASP10 AKT1 PRDM16 ASPM IFT27 ITGA3 NBN GCK CDKN1C TRNE SLC25A22 DCC COL7A1 WNT5A SHANK3 CFHR5 LIMK1 BBS10 FAM20A SASS6 SRY SLC34A1 PIGO FANCI LEMD3 CLEC7A SALL1 NOTCH2 NSD2 ZIC3 DYNC2LI1 BMP4 YAP1 NLRP3 NPHP3 CLDN19 OGG1 PIGA HLA-DPB1 ATP6V1B1 KCTD1 DMRT3 TRAF3IP1 PIEZO2 CTNNB1 VHL GANAB KLLN ITGA8 OCRL GPR35 TMEM67 LRP2 STAT5B NLRP3 ROBO2 HPRT1 MSH3 HYLS1 NEUROD1 BMPER MED25 FLCN SMS CTLA4 STS MDM2 TCF4 LIPN THOC6 PET100 PDX1 CACNA1D WDR73 EPG5 ERCC4 TREX1 BCOR KCNJ1 TRNH KIF1B IL6 PTPN22 DNMT3A CDC73 RFWD3 KANK2 RPL15 FGFR1 WDR19 BICC1 HNF1A EFEMP2 TTC8 ADA2 RPS15A HESX1 KMT2A STRA6 NR0B1 TMEM70 RBM10 PEX1 GATA3 WNT3 PYGM ARID2 TBX15 NR5A1 VHL BLM RPS27 FASLG CFHR3 COX14 PPP2R3C KIF7 AQP2 NPHP1 CYTB DDX6 COQ2 HBB ZIC3 POU3F4 MSH6 SCARB2 FLNA PPP3CA SLX4 LARGE1 HABP2 CLCN5 WDR73 PHF21A ITGB3 MDH2 NIPBL ITGA2 BBS2 PALB2 CFB KRT17 WDR11 MTRR PEX2 PGM3 IL7R STXBP1 ARL6IP6 FLI1 NF1 SON DSTYK CYP4F22 CHD7 HLA-B NARS2 BRCA2 APOE PAX6 RBM8A TIMMDC1 BCS1L GRIA3 TTC37 DICER1 SC5D OFD1 TMEM231 PALB2 NRAS SDHD SIX5 APOB TFAP2A HNF1B FREM1 PEX6 AGT SOX18 REST ANKLE2 SC5D TBX22 PRMT7 ZIC2 KCNJ10 TCTN3 GPC3 DVL1 B9D2 KCNQ1 NDUFAF3 HMGA2 CFHR1 SLC4A1 PDSS2 PIK3R2 BBS10 FOXP3 KYNU HNF1B FN1 PCSK9 FGFR2 SOX10 FANCB DMP1 KIF14 ENPP1 OSTM1 AKT1 KEAP1 PHC1 INS UMPS OCRL RPL26 DISP1 CDKN1C LEMD3 YWHAE CYP11B2 LRP4 NSUN2 TRRAP COLEC10 ATP7B CHST14 IL23R PTPN12 CHRM3 DHODH DHCR7 ZMIZ1 CHD4 RBM10 DPH1 LYZ KCNJ10 CWC27 OPLAH MASP1 MYCN KRAS PHYH CDC42 TMEM216 DNASE1L3 TASP1 CYP27A1 DACT1 IFT122 NDUFB3 HOXD13 RPL5 ROR2 COL4A1 USP8 RTTN MED25 PEX10 CCND2 MVK IFT27 SULT2B1 RREB1 CEP57 B9D2 CFI RAD51C COQ8B DLL4 ZNF592 PKDCC TBX1 CEP164 PIGT GEMIN4 DYNC2I2 PIK3CA KIAA0586 PTEN AMMECR1 COX20 DPH1 PEX3 FLNA GCDH RAI1 RMND1 PIK3CA MCPH1 HRAS AFF4 PTPN11 IGF2 KAT6B HNF1B IFT172 ND1 NDUFAF6 SCN2A RPS7 NDUFS3 PIGL SPP1 PLCD1 NSDHL NDUFAF2 WDPCP KAT6B TMEM67 CPT2 GLI3 FGFR1 BRIP1 CDKN1B NUP133 PRKCD POMT1 PIK3CA AHI1 PORCN FLNA CD46 FAH RAI1 TMEM67 BCOR NEU1 CYB561 CEP55 NADSYN1 NAA10 ATRX GDF6 MAX SLC12A3 CPT1A ADA C1QA UBR1 PIGN GDF6 IKZF1 UBE2T GALNT3 TSC2 CAD KYNU HMGA2 TTC21B DHX16 LTBP4 COL4A3 INF2 SKI STAT3 NRAS KCNA1 DCC RPS24 FKTN FLNA NDUFS2 TFAP2A RPL35 RPS17 SDHA COMT CDC73 SBDS SCNN1G GLA LRP5 BBS1 PIGV APRT LAMB3 PIEZO2 KCNQ1OT1 SLC36A2 ACTB NUP93 TBC1D20 SNAP29 CCDC28B ABCC8 PAX2 MBTPS2 FLII FN1 SALL1 CDKL5 SLC26A4 CC2D2A EBP NDUFAF5 XRCC4 FANCA NUP205 YAP1 PMM2 CLDN19 CEP290 ALPL ACP5 FLNA CPT2 STAT3 TRIM37 RPL31 WNT4 IFT140 CCN2 DLC1 SGPL1 NDUFAF3 SDHB EP300 HSPG2 TBCK IRF2BP2 CCNQ BUB1 MYO1E SHPK C3 PC NF1 CEP41 POMT2 DHCR24 ARID1B RMRP NUP133 PEX6 WAS ACSL4 MICOS13 KCNJ11 IGF2 H19-ICR B3GLCT CCR1 TPRKB FH HIRA LRIG2 TTC21B GSN PGK1 FOXI1 TLR2 MOCS2 CDKN1B TELO2 SSR4 CTLA4 DACT1 HLA-DRB1 FIBP SH2B1 RBM8A ALOXE3 CDC42 HNF1A TCTN2 VHL TBX3 FAT4 NABP1 FBN1 NUMA1 LMNB2 PTPRO ERCC8 LAGE3 FANCB FCGR2B SALL4 GBA DZIP1L MDM2 LAMA3 CDON NOTCH2 KAT6A AVPR2 STRADA BBS12 CLCN5 NRIP1 DYNC2I1 ARL3 NPHP1 WWOX PCK2 SI LRP5 WDR35 DYNC2I2 CTNNB1 SCNN1A SNRPB DHX37 SLX4 FGF8 ABCA12 PKD1 TRIP13 CDC73 BBS7 NPHP4 ELN NOTCH3 KMT2D DIS3L2 SMARCAL1 PKD2 TRNL1 WNT3 JMJD1C IARS1 TRNT1 VPS33A ARMC5 CREBBP CCR6 DIS3L2 LMX1B COX2 BRCA2 SLC25A20 GTF2I KNL1 AURKA ALG9 ACTG1 KYNU SOX4 GPC3 ATP6 WDR19 TRPC6 POR VDR LMNA ERCC4 THOC6 MBTPS2 GATA1 SLC1A1 COQ7 VPS33A GDF3 FH CACNA1D BBS9 PEX2 SETBP1 WT1 SIX3 FKRP GLA PEX13 RPL35A MNX1 ANTXR1 DSE ND6 HLA-B FLNA B3GLCT CPOX LEMD3 FREM1 DLL1 BBS4 NDUFAF3 SLC2A2 NDUFS4 SAA1 FGFR3 ABCC6 RBBP8 TRNS1 NCAPG2 COL14A1 YY1 RAG2 RPL11 TMEM107 DUSP6 PNPLA6 PLAGL1 MFSD2A CREBBP PDSS2 EVC2 DYNC2LI1 RARB MBTPS2 WFS1 ND4 TMEM126B NDUFAF1 MYOCD NAA10 TSC1 FAS DCHS1 SLC6A17 G6PC3 FLCN EXTL3 DYNC2I2 PAX1 PUS3 CTNS CDK6 SLC3A1 RAG1 VAC14 BUB1B ATRX IGF2 FANCD2 TBL1XR1 PEX12 ADAMTS13 DCDC2 ATP7A LMNA CYBC1 NPHP1 SEMA3A SMARCD1 MOCS1 CD109 TMEM67 LZTFL1 CA2 LMX1B GAS1 DYNC2H1 FRAS1 ERCC6 PIGY NEU1 GP1BA FANCL BTNL2 PGAP3 SMOC1 PLEC REST RPS29 ND2 TGIF1 HSPA9 PIGA ERCC8 ACVRL1 AGTR1 TCN2 MAFB NUBPL DDX59 GP1BB WNT4 WNT4 MAP3K7 ADA PIGY KLF11 NUP107 SALL4 C3 PACS1 GLI2 PKD1 LDHA CCDC141 FUZ MAP3K1 PEX14 C1QBP SLC12A3 LHX1 RPS26 GLI3 AR ZBTB16 SPART B2M AXIN2 CEP290 DYRK1A IL12A-AS1 UQCC2 MME MKKS CDKN1B STIL TP53 WDR4 BNC2 ACTG2 LMX1B ITGB4 SCARB2 ZAP70 AMMECR1 TMEM138 GNB1 NDUFV1 SCO2 HMOX1 IFT140 GRHPR CD96 CLIP2 PROKR2 PIGT GLI1 FGFR3 FANCF UMOD POR PRKCSH BAZ1B C8ORF37 WDR19 FLCN ETFB STOX1 AIP DICER1 GCM2 TMEM231 LDLR XRCC2 DNASE1L3 FGF23 SPRY2 GLIS2 HNF1A CDKN2C COLEC11 SIX1 MEN1 ATRX POU6F2 IFT172 ITGA2B SOX17 KMT2A CCDC22 TBC1D24 CEP290 INSR PKD2 INF2 DIS3L2 CORIN TNXB NDUFS8 TBC1D24 NLRP3 FOXRED1 CEP290 IFT80 EXT2 EXT2 NDUFB10 SLC2A9 COG1 XPNPEP3 CDK4 HBB CFH GABRD BRCA1 KCNAB2 USF3 GCK NDNF H19 EMP2 HDAC4 SDHD ND5 F5 SDHD IL2RG MEFV SERPINF2 RAB3GAP2 FIG4 ELP1 ASXL1 FGFR3 TXNL4A ARX NUP107 CASR KISS1R METTL5 FUT8 KITLG NDUFV2 TBX1 CLCN5 EYA1 ENPP1 IFT43 GPKOW COL4A4 FAS CCNQ NPHS1 COG6 ADAMTS3 PIGL PUF60 TRAPPC14 AGPAT2 NOD2 RAI1 HOGA1 CC2D2A IFT43 COL4A3 SIK1 TMEM237 SLC12A1 COPB2 SLC37A4 TRIM32 SEC63 TMEM126B INTS1 BMPER DZIP1L TRNW PEX5 CCND1 COPA FRAS1 NSD1 MLH1 NPM1 WDR73 FLCN FOXP1 ND6 GRHPR MYO5B TACR3 PEX7 AVIL AMMECR1 TBX18 PML ND2 CREBBP MYMK APC NADK2 TTC8 RPS10 CEP120 SMO PLG INTU CD46 ERCC6 ARNT2 SLC26A1 NDUFB9 SLC6A19 KIF1B CEP55 VHL CPT2 IQSEC2 ANOS1 HSD11B2 COA8 B9D1 LMAN1 ZEB2 UMOD GNAO1 ABCC8 FBXW11
    Protein Mutations 4
    C282T C677T K55R Y93H
    SNP 5
    rs2281135 rs2294918 rs35652124 rs738409 rs7903146
    HP:0001919: Acute kidney injury
    Genes 32
    CD46 RYR1 DZIP1L APRT LPIN1 CFH CFI CACNA1S CCND1 TCN2 CD46 FLT1 SLC22A12 SLC26A1 HPRT1 C3 CFH PYGM HNF4A DGKE CFHR1 HNF1B CFHR3 HELLPAR CFI PKHD1 THBD SAA1 STOX1 STAT2 CFB CORIN
    Protein Mutations 0
    SNP 0
    HP:0012393: Allergy
    Genes 29
    CARMIL2 PGM3 PSTPIP1 CNTNAP2 MS4A2 IL4R PGM3 TGM5 CHD1 CCDC28B COX4I2 CSTA IL6ST SIK3 CTLA4 FOXP1 SPINK5 PLCG2 ARL6 PLA2G7 JAK1 RBM8A MTOR FOXP3 NRXN1 BBS1 SOX6 FOXP3 ADA
    Protein Mutations 5
    A118G C677T G20201A L858R P12A
    SNP 2
    rs11648486 rs1761667
    HP:0002511: Alzheimer disease
    Genes 13
    HFE APOE PSEN1 MPO APP CACNA1G PLAU GATA1 APOE A2M PSEN2 ABCA7 NOS3
    Protein Mutations 5
    E280A K56M P200T R199W R38H
    SNP 10
    rs10524523 rs11870474 rs2227902 rs3742376 rs3745274 rs3796529 rs4900442 rs6971 rs7157609 rs754203
    HP:0001681: Angina pectoris
    Genes 39
    ABCC6 PIGA PMM2 LDLR LCAT APOB APOE HLA-DPB1 GLA LMNA CYP27A1 CTLA4 GATA6 ABCC6 XYLT1 ABCG8 GATA4 CYP27A1 JAK2 CRELD1 LMNA ABCG5 XYLT2 PRTN3 HLA-DPA1 NR2F2 LIPC LDLRAP1 ABCC6 ENPP1 IDUA PCSK9 TET2 GLA PTEN PTPN22 MPL LIPC ZMPSTE24
    Protein Mutations 0
    SNP 2
    rs10455872 rs3798220
    HP:0000458: Anosmia
    Genes 69
    SEMA3A SMCHD1 SHH PROK2 DCC SOX10 CHD7 PROK2 SMCHD1 IL17RD PHYH PEX7 DUSP6 SEMA3E KISS1R ANOS1 ATP13A2 SOX10 WDR11 FGFR1 TACR3 PEX7 KISS1R KISS1 NSMF NSMF OTX2 CHD7 HS6ST1 NDNF HESX1 FGF8 SOX10 DNAI1 SEMA3A SEMA3E PHYH WDR11 FEZF1 ANK1 IL17RD CCDC141 PROKR2 ARSL HESX1 GNRH1 MFN2 FEZF1 SOX10 SOX2 CHD7 FGFR1 ANOS1 FGF8 CCDC141 SOX3 CHD7 PROKR2 FGFR1 ARNT2 SPRY4 FLRT3 ADCY3 TAC3 PEX7 SCN9A NDNF FGF17 PROKR2
    Protein Mutations 0
    SNP 0
    HP:0001369: Arthritis
    Genes 269
    PADI4 AEBP1 KLRC4 IL12A-AS1 NLRP3 COL5A1 HLA-DRB1 TGFB3 NTRK1 NLRP3 FCGR2B GBA GJB2 GP1BB TRPV4 PTPN22 NLRP12 SCARB2 LEMD3 SLC37A4 ABCG8 SEC61A1 IL2RB HPRT1 SEC24C TRAPPC2 HLA-B MVK TF STAT4 FGFR3 NLRP3 RREB1 MMP2 COL2A1 FBN1 MMP14 EXT1 CFI APOE HJV ARVCF MLX STAT4 GCH1 ANKH HLA-C COL2A1 TBX1 HGD F9 ACAN HPRT1 LRBA IL2RA UMOD COMP PRPS1 MYH14 GJB6 PRG4 OCRL ADAR UFSP2 MMP13 JMJD1C UFD1 CCR6 ANKH IL6 LMX1B RAG1 HPRT1 PSTPIP1 HNF1B DNASE1L3 MATN3 KIF7 SPP1 G6PC PHEX SPTB PTPN2 LRRC8A COL9A2 PTPN22 CD244 IGHM NLRP3 CD79A IGLL1 MATN3 CD79B PRKCD HOXD10 COMP ACP5 MTHFD1 MIR140 BLNK HLA-DRB1 SLCO2A1 RASGRP1 ANKRD55 CAV1 HLA-B COL5A2 PFKM NLRP3 BTK IL10 PIK3CD GLA COL9A1 SLC4A1 MEFV FCGR2A RNF168 RAG2 COL11A1 PTPN2 GDF5 AIP COL1A1 COL5A1 SLC12A3 SLC22A4 FASLG MEFV CD247 SH3KBP1 EXT2 COL2A1 F8 CLCNKB DNASE1 MEFV STAT3 IL2RA TRPS1 HPGD CLCN7 IFIH1 BTK HLA-DRB1 KIF22 ANKRD55 NOD2 TRAPPC2 WIPF1 ACAN MATN3 HNF4A FAS HGD ASPN RNASEH2A COMT TBX1 HPGD ASAH1 LACC1 DNAJB11 PSMB9 MEFV FAS FAS COL2A1 UBAC2 LMNA LBR FRZB MUC1 SLC40A1 STAT4 STAT4 ADA2 TRPV4 SMAD3 CD247 HLA-B ACAN PHEX RNASEH2C SLC37A4 VPS13A SPTA1 ASAH1 MYD88 MIF ACP5 PSMB4 TLR4 TNFRSF11B IRAK1 CCN2 MMP13 CLCN7 CCN6 COPA ZNF687 ERAP1 TREX1 IL2RB TNFRSF1A COMP CTLA4 C4A COL2A1 TREX1 BTK UFSP2 IL12B AGA RNASEH2B DCLRE1C ATP7B LRP6 ANK1 FOXP3 HNF1B COL1A1 WAS KNSTRN PTPN22 COL11A2 ZMPSTE24 MVK COL9A1 TCF3 IL12A COL11A2 PSTPIP1 GNAS NOD2 COMP SAMHD1 IRF5 COL9A3 IL10 CCR1 SLC26A2 HIRA GHR PIK3R1 COL9A2 HPRT1 EPCAM TFR2 COL9A3 IL36RN COL2A1 EPB42 COL11A2 GPR101 COL3A1 CCN6 ATP7B IL23R NFKBIL1 SMAD3 CTLA4 PTPN22 UMOD CIITA HPGD CASP10 PTPN22 CANT1
    Protein Mutations 4
    A147T N363S R620W V600E
    SNP 10
    rs2246704 rs2853884 rs35705950 rs3747158 rs3790515 rs3828057 rs4820059 rs7291050 rs933226 rs9826
    HP:0002099: Asthma
    Genes 108
    LIG4 PTCH1 ALOX5 HNMT SUFU FOXH1 GP1BA PEX5 CARD11 VPS51 TNF PGM3 NFKB2 SIK3 CREBBP SRSF2 NOD2 RUNX1 GRHL2 NODAL JAK1 GP1BB ADRB2 COMT MTOR TBX1 CDON BBS1 PLA2G7 SHH SEC24C TBCK IL13 FLG PGM3 RREB1 STXBP1 ARVCF CBL SCN4A CCDC28B TBX1 TRAIP LRBA FGF8 ODAD3 SPINK5 ODC1 CFTR DOCK8 GTF2H5 SCGB3A2 SDHD RIC1 GP9 ELOVL4 JMJD1C UFD1 PEPD CREBBP HLA-G AFF4 FCGR2A BCL11B CARMIL2 PTGER2 ERCC2 IL4R SPINK5 USP7 CDSN NEK9 LMX1B TALDO1 FGFR1 ZIC2 GAS1 PLCG2 PLA2G7 ASXL1 LIFR TDGF1 TGIF1 TBX21 NKX2-1 NKX2-1 TET2 MS4A2 SIX3 DISP1 GP1BB TGFB1 COX4I2 CCL11 HIRA ARL6 MUC7 NSUN2 DDX41 GLI2 ALMS1 EP300 CASP8 IDS WAC ADA DLL1 DOCK8
    Protein Mutations 4
    D299G G16R Q27E T399I
    SNP 18
    rs1042711 rs1042713 rs1042714 rs1042718 rs11958940 rs11959427 rs12654778 rs12936231 rs1504982 rs17778257 rs1800888 rs1801275 rs1805010 rs2053044 rs2895795 rs324011 rs324015 rs4950928
    HP:0002621: Atherosclerosis
    Genes 86
    MFAP5 WRN ABCC6 ELN LDLR LCAT APOB LDLRAP1 ACTA2 BRCC3 GLB1 MYH11 ERCC6 LMNA GGCX SMAD3 SMPD1 ZNF687 KCNJ5 ABCA1 LMNA CYP27A1 TGFBR1 SC5D LCAT ANTXR1 ERCC8 LMNA FBN1 MYH11 CYP7A1 LMNA LMNA TGFB3 XYLT2 SMPD1 ANGPTL6 MYH11 CEP19 ASAH1 ENPP1 NPC2 ABCG8 PCSK9 MYLK AGXT CSF2RA ZMPSTE24 LMNA TNXB PRKG1 NPC1 FOXE3 APOE APOA5 TGFBR2 TGFB2 LMNA SMPD1 ABCC6 XYLT1 ABCG8 MAT2A THSD1 HGD LOX APOB GGCX ESR1 BANF1 SERPIND1 TGFBR3 ABCG5 ALMS1 CSF2RB LDLRAP1 PPARG SMAD4 ENG COL3A1 ACTA2 LIPC LMNA LOX ABCA1 ABCA1
    Protein Mutations 3
    G21210A V167F V617F
    SNP 7
    rs1024611 rs1051931 rs10757274 rs10757278 rs16874954 rs1799724 rs2383206
    HP:0007018: Attention deficit hyperactivity disorder
    Genes 377
    PRNP ZIC2 MLH1 LIG4 NTNG1 KCNA2 TRIO SETBP1 DYNC1I2 GNAQ MID2 NODAL DYRK1A HDC SH2B1 ZNF41 CDH2 RAB39B LIMK1 CIC CNKSR2 SCN8A LHCGR USP27X EEF1A2 NR2F1 CSGALNACT1 SIX3 ACTL6B PAK3 SLITRK1 GP1BB GATA4 MLXIPL IQSEC1 ADNP C12ORF4 CDK19 TKT SEC24C DHTKD1 SETD2 SYNJ1 RREB1 BMPR1A ARVCF YWHAG DMD PMS1 RLIM IQSEC2 CLIP2 SIM1 TBX1 WWOX PIEZO2 SETD5 SYNGAP1 PPP3CA DLL1 DISP1 FTSJ1 HCFC1 GAS1 ARF1 FOXH1 ODC1 ELN IKBKG SPG7 BAZ1B OCRL ACTL6A TBC1D24 METTL5 NF1 TCF20 JMJD1C STAG2 UPF3B UFD1 MED13 ZMIZ1 FBXW11 CHRNA7 RFC2 SIX3 TSC1 DLL1 AP3B2 SIX3 TDGF1 THRB GTF2I CACNA1A MLH3 NECAP1 GNB5 PRKCG NSD1 GABRB2 OPHN1 SATB2 USP7 FAN1 FGF12 STS CXORF56 SEMA3E MSH2 FOXH1 SETD5 GABRA2 ACTL6B SLC2A1 ZNF711 CDON CDON TBX1 HERC2 MED12 DLG3 NLGN1 TRAK1 GRIA4 USP9X TLK2 GAS1 RPS6KA3 SCN3A CDK8 KIF11 TIMM8A PARS2 PPM1D DRD4 PWAR1 JRK MED12 MED12L MYT1L RAI1 TKT ZIC2 MYT1L ARID2 EPCAM CRBN CACNA1H CYFIP2 NODAL NBN SMPD1 GABRG2 CACNA1B FOXH1 CLCN4 KMT2A SHH DISP1 RAD21 ABCD1 UBA5 STS DDX6 MCTP2 CSNK2A1 PANK2 TRIO PPP1R12A FGF8 MAGEL2 GLI2 PTCHD1 DYM NPAP1 PHIP TANC2 DISP1 TGIF1 WAC PSMD12 FGD1 SLC13A5 SLC6A8 SNORD116-1 SRPX2 FGF8 ARHGEF6 UBE3A MAP1B GABRA5 TDGF1 HDAC4 TGFBR2 PTCH1 BCR SH3KBP1 GDI1 WDFY3 TDGF1 TSC2 GLI2 FGF8 YY1 SHH CARS1 TUBB2B IFNG GLI2 FGFR1 SYP RPS20 DHDDS GAS1 BCORL1 BPTF RERE NIPBL MKRN3 GNE COMT SNORD115-1 TBX1 TGIF1 SPRED1 GLUD1 NDP WAC GTF2IRD1 SCN8A TSC1 TSPAN7 FMR1 CDON WAC GRIN2D NUS1 KCNA2 STAG2 DEAF1 PAH DNM1 FLI1 GABRG2 PTCH1 FGD1 SIX3 DALRD3 RAI1 GNE TMCO1 YWHAG SMC3 FOXH1 PIK3CA ZDHHC9 NKAP TAF1 RAI1 FLII CNKSR2 HOXA2 TGIF1 RERE SEMA4A ZIC2 MED13 HDAC8 KMT2E AGTR2 IPW RIC1 APC2 AUTS2 PAH ASPM GABRG2 SZT2 KRAS ALG13 DRD5 DOCK3 FGF8 SHH ARV1 TDGF1 STXBP1 UPF3B GALC DLL1 STAG2 BCORL1 PCGF2 TET3 SHH NODAL SLC1A2 TRMT1 NOP56 TGIF1 MED12 PTCH1 ZIC2 SMC1A CLTC HSPG2 MSH6 PWRN1 IGF1 CPLX1 FOXP1 GRIN2A FGFR1 GAS1 TBX1 SIN3A IL1RAPL1 NTRK2 PCNT KCNB1 ELN ALKBH8 TSC2 SLC9A7 POLA1 NDN MECP2 MAPK1 CDON PTCHD1 SOX5 ATP6V1A KDM3B NODAL HCN1 KIF14 TRAPPC4 GRIN2A KAT8 TBL2 DLL1 PTCH1 MED12 DNAJC12 HIRA GLI2 MKRN3-AS1 IQSEC2 SVBP ZNF81 NSUN2 AARS1 GABRB3 RSRC1 PMS2 DLL1 FRMPD4 GABRA1 CHD7 FGFR3 CNKSR2 CRKL ARX TANC2 DHCR7 ZMIZ1 TRAPPC14 TBL1X ACSL4 CLTC SNRPN PHF21A DISP1 DPH1 SH2B1 SMC1A
    Protein Mutations 2
    D203E G143E
    SNP 2
    rs2307227 rs71647871
    HP:0000717: Autism
    Genes 197
    WFS1 KCNA2 NFIB SHANK3 SH2B1 LIMK1 SCN8A EEF1A2 ACTL6B GP1BB NRXN1 PRKAR1A CDK19 SEC24C SYNJ1 RREB1 TBR1 ARVCF CACNA1C ZBTB20 CLIP2 TBX1 WWOX TMLHE SETD5 SYNGAP1 PPP3CA DEAF1 SOX2 EHMT1 ELN BAZ1B PLXND1 JMJD1C UFD1 CHRNA7 RFC2 TSC1 AHDC1 AP3B2 GTF2I CACNA1A NECAP1 FTSJ1 PDE4D GABRB2 SATB2 ATRX FGF12 STS NLGN4X SEMA3E GABRA2 SDHC NAGA SLC35C1 HERC2 TRAK1 OTX2 AUTS2 SCN3A PARS2 PWAR1 MECP2 GATM SNRPN CYFIP2 NONO CACNA1B EXT2 KMT2A NHS RAD21 UBA5 STS PTEN MAGEL2 NAGA GABRD PTCHD1 DYM NPAP1 SOX3 PTEN RERE REV3L KLLN KCNAB2 ARNT2 SLC13A5 USF3 SNORD116-1 UBE3A GABRA5 HDAC4 DHCR7 MED13L TSC2 SDHD YY1 ANKRD11 IFNG SKI DHDDS SLC9A6 MAOA NIPBL MKRN3 COMT SNORD115-1 TCF12 TBX1 SMAD4 NDP GTF2IRD1 GAMT TSC1 NLGN3 TBCK FMR1 NLGN3 GRIN2D NUS1 KCNA2 SCN8A MED13L PAH DNM1 ADSL PIGL DALRD3 GABRA5 GJA5 YWHAG SMC3 RAI1 MED12 CNKSR2 HDAC8 IPW ALDH5A1 FGFR1 GABRG2 GJA8 SZT2 PROKR2 IL1RAPL1 PIK3CA ARV1 MEIS2 STXBP1 CNTNAP2 FMR1 HNF1B DYRK1A SLC1A2 SEC23B GRIA3 EHMT1 EP300 SMC1A CLTC PWRN1 ALG13 TBX1 SIN3A CREBBP NTRK2 IQSEC2 CHD8 KCNB1 TSC2 HESX1 NDN BCKDK FLCN ATP6V1A SDHB AKT1 HCN1 TBL2 HIRA MKRN3-AS1 DMPK AARS1 RPL10 CHD7 PRDM16 MAN1B1 PDE4D SIM1 LHX1 DHCR7 KDM5C DPYD NLGN4X SNRPN
    Protein Mutations 1
    S1009A
    SNP 1
    rs6971
    HP:0000729: Autistic behavior
    Genes 638
    LMAN2L WFS1 KCNA2 TRIO POGZ CAMTA1 SLC25A22 PIGP NDUFS6 GPHN MID2 LSS SHANK3 LINS1 ZNF41 TBC1D23 RAB39B LIMK1 CNKSR2 SCN8A UBTF EXT2 USP27X EEF1A2 GRIN1 NR2F1 STXBP1 ACTL6B CRADD PIGO GP1BB ALG13 MTOR EGF C12ORF4 TAF1 PRKAR1A SEC24C CHD2 SYNJ1 SYT1 NOVA2 ATP1A3 CACNA1C DMD NUS1 ZBTB20 CRBN WFS1 RLIM FRMPD4 WWOX DLL1 PRKN DEAF1 FTSJ1 HCFC1 SOX2 RPS23 TM4SF20 LRRK2 MECP2 ELN PPP2R5D SCN1B DNAJC6 CXORF56 AFF2 TCF20 JMJD1C MAN1B1 UFD1 ZMIZ1 CREBBP FBXW11 C9ORF72 HECW2 ZFPM2 HNRNPH2 CHRNA7 TSC1 AHDC1 GTF2I TUBB3 NECAP1 FTSJ1 SYNGAP1 C12ORF4 NSD1 SNX14 GABRB2 SATB2 NDUFA1 NDUFA11 FOXG1 STS CXORF56 RORA NDUFAF4 SETD5 GABRA2 HERC1 MSTO1 SYN1 SDHC NAGA GABRD TCF4 HERC2 MED12 NLGN1 TRAK1 CHMP2B OTX2 USP9X TLK2 AUTS2 SCN3A JAM2 OTUD6B BCOR CDH15 PWAR1 PUF60 MECP2 GRIA2 MBOAT7 NEUROD2 GATM GFM1 CUX2 CYFIP2 CACNA1B POMT1 KMT2A SCN2A NAA15 SQSTM1 RAD21 MECP2 POU3F3 DDX6 TREM2 ZIC1 PIGG RIMS2 HIVEP2 SBDS PTCHD1 DYM NPAP1 RERE TANC2 KLLN ARNT2 KDM5B SLC13A5 NDUFAF3 SLC6A8 SNORD116-1 NDUFS4 ARHGEF6 CARS2 MAP1B GABRA5 MED13L GDI1 WDFY3 IARS1 SVBP DCX STXBP1 YY1 CHD1 PCDH19 DDX3X SCN1A ANKRD11 IFNG RNF135 SYP CREBBP ND3 HERC2 GFM2 BCORL1 SLC9A6 NIPBL MKRN3 SNORD115-1 TCF12 CDKL5 TMEM126B NDP ACOX1 CASK GAMT NDUFAF1 NAA10 TSC1 DEAF1 SLC6A1 TBCK TSPAN7 FMR1 NLGN3 WAC GRIN2D SCN8A PSMD12 DNM1 EXTL3 ADSL SLC35A3 PRODH NSUN2 B3GALNT2 RAI1 EZR MED12 NDUFA6 CDKL5 RERE ALMS1 STXBP1 HDAC8 KMT2E TIMMDC1 ALDH18A1 DCPS ASH1L TWNK PUF60 AUTS2 GRIA3 GABRG2 GJA8 CNNM2 CHD2 ST3GAL3 DOCK3 USP7 PROKR2 TMEM231 PIK3CA ARV1 STXBP1 SON CNTNAP2 FMR1 HNF1B PCGF2 SLC1A2 TRMT1 PCDH19 PPP2CA SEC23B GRIA3 SMC1A CLTC PIGP CC2D1A CTCF ALG13 PGAP1 EFL1 TRAPPC9 KCNT1 CEP85L SLC25A12 RSPRY1 MAPK8IP3 ARX AP3B2 SETD2 NTRK2 IQSEC2 RAB11B KCNB1 NDUFB11 HESX1 CNOT3 NEXMIF TECR VCP MFF PGAP3 NDN COG5 DYRK1A BCKDK MECP2 ND2 FLCN PTCHD1 PIGQ AKT1 UCHL1 MEIS2 MAPT HCN1 NUBPL TRAPPC4 FRRS1L CTNNB1 GABBR2 KPTN MKRN3-AS1 PIGY TCF4 AARS1 TRRAP PACS1 RPL10 FRMPD4 PARK7 CHD7 LHX1 DOCK7 DHCR7 ZMIZ1 ACSL4 SNRPN PHF21A THOC2 KDM6B AP2M1 NTNG1 GRIK2 NFIB AIMP1 GNAQ DNAJC21 DYRK1A ALG11 SH2B1 CDH2 ANK3 NDUFB3 GABRA1 DLG4 PINK1 PAK3 TCF20 TMEM138 ADNP NRXN1 CDK19 CDKL5 SETD2 NDUFV1 RREB1 MED25 TMEM216 TBR1 NDUFS7 ZNF423 PSEN1 ARVCF NDST1 GALNT2 KMT5B IQSEC2 PGAP2 PIGC CLIP2 SIM1 TBX1 TMLHE SETD5 SYNGAP1 PPP3CA CNTNAP2 EHMT1 SYNJ1 SIM1 SH2B1 FBXO31 BAZ1B RSRC1 ACTL6A NDUFS2 PRSS12 METTL5 PLXND1 UPF3B PIGV SLC25A1 MED13 UGP2 AP1S2 RFC2 TUSC3 AP3B2 CACNA1A POLA1 ND1 PDE4D SCN2A PODXL OPHN1 USP7 ATRX FGF12 EP300 NDUFS3 PIGL NLGN4X NDUFAF2 RSPRY1 SEMA3E ACTL6B SHANK3 SPECC1L DMXL2 ZNF711 SLC35C1 GATAD2B CLCN4 DLG3 MED23 TBR1 TRIM8 OTUD6B MAGEL2 TBC1D24 RPS6KA3 CDK8 GABRA2 PARS2 PPM1D CC2D2A HNMT MED12L MYT1L NDUFS8 SCN1B NDUFAF4 SYNGAP1 MYT1L FOXRED1 SPATA5 KAT6A SMG9 SNRPN SLC6A8 VAMP2 ST3GAL3 NONO ASXL3 EXT2 FOXP2 CLCN4 ZNF462 NHS VPS13C SIN3A NDUFB10 SNCA NDUFS4 UBA5 STS SRP54 MCTP2 PTEN ACADL WASHC4 MAGEL2 NAGA GABRD EP300 SOX3 PTEN FMN2 GRN REV3L GABRG2 KCNAB2 WAC SNX14 PSMD12 CLP1 USF3 NTNG2 GABRB3 UBE3A HDAC4 DHCR7 ADNP TSC2 SDHD HCN1 SKI CLCN4 SCN2A SCN9A CREBBP DHDDS NDUFS1 FOXG1 KCNA1 NEXMIF BPTF RERE MAOA DNM1 COMT NDUFV2 TBX1 SMAD4 AGTPBP1 GTF2IRD1 NEUROD2 STAG2 PACS2 NLGN3 DEPDC5 NUS1 KCNA2 IQSEC1 MED13L NDUFAF8 PAH PIGL UBA5 DALRD3 GABRA5 SLC45A1 GJA5 SCN1A YWHAG SMC3 STAG1 IREB2 TAF1 MAPK10 DPYD NALCN PDE4D SIK1 CNKSR2 PIGW TMEM237 MEF2C KMT2C CDKL5 MED13 AGTR2 TBX2 IPW NDUFAF5 APC2 AP2M1 ALDH5A1 FGFR1 SZT2 CLIP1 CUX2 ALG13 EP300 INTS1 CACNA2D2 IL1RAPL1 MEIS2 TNIK SCN9A METTL23 BCORL1 DYRK1A SLC35A3 TET3 NDUFAF3 EHMT1 SCN1B EP300 ADGRV1 PWRN1 FOXP1 TBX1 HCN1 SIN3A IL1RAPL1 SRP54 MEF2C NDUFA13 CREBBP CHD8 SARS1 GABRG2 EDC3 TSC2 CEP290 SLC9A7 POLA1 ARID1B WDR26 SRY IQSEC2 MICOS13 ATP6V1A SDHB CTCF NTNG1 PNKP NAA10 RARS1 KDM3B POLR2A MECP2 SCN1A KAT8 TBL2 HIRA ZC3H14 NDUFB9 NTRK2 SVBP DMPK STX1B ZNF81 GNB5 PRDM16 TMEM106B CHD2 MAN1B1 MBOAT7 ARX PDE4D SIM1 TANC2 KDM5C HTRA2 ARFGEF2 DPYD GNAO1 NLGN4X FBXW11 SH2B1
    Protein Mutations 1
    S1009A
    SNP 1
    rs6971
    HP:0002069: Bilateral tonic-clonic seizure
    Genes 298
    AP2M1 ND4 KCNMA1 SLC1A4 KCNQ3 TRNL1 PSAP SLC25A22 PIGP GPHN MID2 MICAL1 ZNF41 RAB39B CNKSR2 USP27X GABRA1 STXBP1 PAK3 KCNQ2 PIGO SCN8A FA2H GABRA1 SLC2A1 GNB1 SLC25A19 KCNQ2 SETD2 CHD2 RELN CNTN2 PSEN1 CILK1 DMD IQSEC2 PGAP2 COX3 CYTB PIGT ADGRG1 FTSJ1 HCFC1 ATP1A2 SCN1A EFHC1 SCN1B TBC1D24 SIK1 EFHC1 TRNL1 ALDH7A1 PSPH UPF3B PIGV SLC9A6 C9ORF72 STX1B TRNQ TRNQ GABRD COX2 ASPA KCNJ11 SCN2A NHLRC1 NSD1 TBC1D24 PRPS1 FOXG1 PIGL TRNF CXORF56 KCNQ3 HERC1 ZNF142 ATP6 SLC2A1 DMXL2 GABRD ZNF711 GYS1 LBR MED12 DLG3 EPM2A CACNA1D COQ2 CHMP2B TRIM8 TXN2 USP9X SETD1A EFHC1 TBC1D24 RPS6KA3 TRNH INS JRK GRIA2 KCNMA1 CACNA1D SCN1B SLC22A5 FIG4 EPM2A SPATA5 CACNA1H CUX2 COX3 GPT2 VAMP2 GABRG2 ND1 GRIN2A CLCN4 SCN2A SQSTM1 ND1 GPAA1 ATP6AP2 POLG ACADM ND6 CACNB4 TREM2 YEATS2 SCN8A SCN2A PIGG NIPA1 SCN2A ST3GAL5 GRN CLTCL1 GABRG2 WAC GABRD GCK SRPX2 GABRB3 ARHGEF6 TRNW ND5 SCN1B TRNS2 GDI1 GRIN2A TRNS2 TRNS1 CSTB HCN1 PCDH19 SCN1A COX2 DHX16 CLCN4 SAMD12 SYP ND1 TRNK SCN2A SCN9A GABRG2 KCNA1 KCTD7 LAMC3 CLCN2 DNM1 TRNV ND4 HNRNPU ND5 NEUROD2 CASK GAMT SLC6A1 AFG3L2 TSPAN7 GABRG2 PDX1 COX1 CLN8 GABRA5 SCN1A ND6 SLC12A5 BUB1B PUS3 KCNMA1 PHGDH TRNV MAPK10 TRAPPC11 SIK1 DHDDS SCN2A PIGW SLC12A5 LGI1 KCNQ3 CERS1 CDKL5 STARD7 STXBP1 SP110 AGTR2 VPS13A JRK APC2 AP2M1 GRIA3 ALDH5A1 NEK1 EFHC1 SLC2A1 ALG13 CACNB4 TUBA8 STAT3 TRNW SRPX2 AP3D1 TRNW TRNC SCN9A CERT1 PCDH19 SCN1B ADGRV1 TRNK CLN8 ASAH1 TBCD PCDH19 CPLX1 ND6 GRIN2A IL1RAPL1 CLCN2 CEP85L ALDH5A1 ARX ND2 TRNF GABRG2 PDSS2 SLC9A7 VCP PGAP3 DNM1L DYRK1A WDR26 TMX2 HACE1 MECP2 ND5 NHLRC1 TANGO2 PTCHD1 PIGQ PNKP MARCHF6 MAPT KCNJ11 SCN1A RORB PYCR2 SCN2A PCYT2 SARDH PIGY MTHFR STX1B ZNF81 TRNL1 GABRB3 RPL10 SCN9A COX1 FRMPD4 GABRA1 CPA6 STXBP1 TMEM106B CHD2 ADGRV1 ARX PRRT2 TRNS1 RNF13 ATP6AP2 ACSL4 GNAO1 ABCC8 THOC2 ND3 AFG3L2
    Protein Mutations 0
    SNP 0
    HP:0002110: Bronchiectasis
    Genes 175
    GAS8 DNAL1 RIPK1 CR2 LRRC56 GAS8 BTNL2 DNAAF1 TERT CFAP298 CCDC40 RSPH4A DNAI2 DNAJB13 CCDC39 ATM ODAD3 CD81 DNAH9 WDR1 PGM3 HLA-DRB1 DNAL1 BACH2 TTC12 TNFRSF13C STAT1 DSP CFTR TAP1 CCNO CCDC40 DNAH5 DNMT3B DNAAF2 DNAJB13 DNAAF3 DRC1 DNAI2 CFAP221 SPEF2 PGM3 MS4A1 NFKB2 CD19 ODAD4 NFKB1 OFD1 ATP11A CFAP300 NME8 ODAD2 SCNN1G SLC29A3 LRBA IRF8 DRC1 GAS2L2 ODAD3 DNAAF4 SFTPC TNFRSF13B DNAAF6 DNAH5 CFTR SCNN1A RTEL1 CCDC39 STN1 CR2 DNAAF3 NFKB2 FOXJ1 GAS2L2 CCDC103 ODAD1 RSPH3 SCNN1B TAP2 SCNN1A DNAAF4 ABCA3 ICOS STK36 BLM DPP9 FCGR2A PRKCD SFTPA1 ODAD4 CARMIL2 IL21R CCDC65 LRRC6 CXCR4 ZMYND10 SCNN1G DNAI1 ODAD2 IL6ST MUC5B CXCR4 RAC2 LRRC8A ZMYND10 CTLA4 SFTPA2 TAPBP DNAAF6 DNAH11 DNAAF1 CCNO LRRC6 IGHM SPAG1 CD79A IGLL1 CD79B CCDC65 RSPH1 MCIDAS RIN2 BTNL2 CFTR PARN BLNK NCKAP1L FOXJ1 NEK10 RPGR DNAI1 DNAH1 TCF3 ICOS ZNF341 DNAH11 LRRC56 HYDIN HYDIN TGFB1 TNFRSF13B RSPH9 RSPH1 TERC TNFSF12 RSPH4A PIK3R1 CFAP298 MCIDAS CD19 TNFRSF13C ARHGEF1 PIK3R1 ODAD1 PIK3CD SCNN1B TNFSF12 IGHM SPAG1 CFAP300 NEK10 ICOS RSPH3 TTC12 DNAAF5 DNAH1 RASGRP1 RSPH9 NBN CCDC103 HLA-DRB1 IRF9 CD8A B2M FAM13A
    Protein Mutations 1
    C19P
    SNP 0
    HP:0012387: Bronchitis
    Genes 62
    CARMIL2 CR2 SERPINA1 HLA-DQA1 GAS8 DNAAF1 CFAP298 CD79A ATM CD81 NOS1 GNPTAB RPGR ODAD2 RAC2 ZMYND10 IL2RG TAPBP LRRC6 TNFRSF13C HLA-DQB1 SPAG1 CCDC65 TAP1 CFTR CD79B DNMT3B DNAJB13 EGFR ICOS ZBTB24 MS4A1 NFKB2 CD19 CACNA1C NFKB1 HYDIN SCNN1G TNFRSF13B RNF168 TNFSF12 RSPH4A ODAD3 TNFRSF13B CD19 TNFRSF13C ALMS1 IL17RA SCNN1B MGP BLM TNFSF12 DNAAF5 ICOS CR2 CRLF1 NFKB2 NBN TAP2 SCNN1A ICOS PRKCD
    Protein Mutations 1
    G551D
    SNP 0
    HP:0002608: Celiac disease
    Genes 19
    IL12A IVNS1ABP ODC1 WAC TNPO3 IL12RB1 TNFSF15 SRCAP GPR35 STAT3 MMEL1 STAT5B ELN POU2AF1 MLXIPL IRF5 MST1 SPIB TCF4
    Protein Mutations 1
    Q65E
    SNP 0
    HP:0004469: Chronic bronchitis
    Genes 19
    CARMIL2 LRRC6 SPAG1 SERPINA1 ALMS1 ZBTB24 CFAP298 SCNN1B CCDC65 DNAAF5 CFTR ODAD2 DNMT3B SCNN1G SCNN1A RSPH4A RAC2 ODAD3 ZMYND10
    Protein Mutations 1
    G551D
    SNP 0
    HP:0012622: Chronic kidney disease
    Genes 144
    NPHP1 OSGEP LAMB2 TSC2 MMUT COL4A4 FAN1 COL7A1 CEP290 FLT1 INVS CFHR5 TTC21B IFT122 LAGE3 INF2 JAG1 NTRK1 NUP107 CLCN5 ACTN4 BNC2 CLDN16 DZIP1L RAD51C GANAB CLCN5 DNAJB11 SEC61A1 CTNS MYOCD AGXT TSC1 CLCN5 LAMB2 MAPKBP1 APRT IFT140 CLDN19 REN COQ8B NUP93 PKDCC ALDOB MUC1 CEP164 TRAF3IP1 IQCB1 NOD2 PUS3 PAX2 WDR19 IFT43 COL4A3 NPHP4 NPHP4 ALMS1 MAGI2 TRAF3IP1 PKD2 NPHP3 TBC1D8B ARHGDIA GCDH TP53RK CTNS NUP205 PPOX DCDC2 PKHD1 STOX1 CEP290 TMEM126B NPHP4 ACP5 NPHP1 CPT2 WDR19 DZIP1L HNF1B IFT172 SPRY2 GLIS2 NDUFAF6 SOX18 SGPL1 LZTFL1 KYNU APOL1 TMEM67 NPHS2 COL4A3 WDR19 TRPC6 AVIL CHRNA3 TMEM67 SARS2 TMEM231 NUP160 MYO1E CD151 ANLN MMP1 CEP290 DSTYK FN1 WT1 PKD2 INF2 SLC7A7 AHI1 COL4A5 NPHP1 NPHP3 CORIN SDCCAG8 CEP83 TMEM67 OCRL BICC1 TPRKB NUP85 PAX2 TTC21B GSN XPNPEP3 NUP133 NUP107 GATA3 PKD1 INVS CFH PYGM DGKE WDR19 NEK8 WT1 UMOD PLCE1 SAA1 IQCB1 MEFV SH2B1
    Protein Mutations 1
    C677T
    SNP 4
    rs2281135 rs2294918 rs35652124 rs738409
    HP:0012532: Chronic pain
    Genes 5
    FLVCR1 TGFB2 ATXN3 COL7A1 MMP1
    Protein Mutations 1
    K15210D
    SNP 2
    rs1042713 rs12654788
    HP:0006510: Chronic pulmonary obstruction
    Genes 34
    RREB1 CYBB SERPINA1 ARVCF HLA-DPB1 GLA CYBA CTLA4 CYBC1 MMP1 TBX1 NFKB1 HIRA NCF4 RAC2 MYH7 NCF2 WIPF1 ALMS1 PRTN3 GP1BB HLA-DPA1 COMT BLM HMOX1 TBX1 MCIDAS JMJD1C UFD1 SEC24C PTPN22 WAS DNAAF4 NCF1
    Protein Mutations 2
    A118G G551D
    SNP 6
    rs1051730 rs1800470 rs1828591 rs25331 rs4129267 rs7103572
    HP:0001394: Cirrhosis
    Genes 177
    AP1S1 UROD TERT PEX1 TRMT5 AGPAT2 SERPINA1 TNPO3 NR1H4 ENG FOS AXIN1 HSD3B7 COG4 APOE HFE HSD3B7 CC2D2A SLC30A10 TREX1 FECH DLL4 CAV1 NOP10 LIPA SFTPA2 JAG1 PPARG SRSF2 RUNX1 GBE1 HBB GLRX5 GBA PIK3CA HBB CCDC115 MUC5B TYMP CTC1 ASS1 APC SLC30A10 SCARB2 TP53 POLG BSCL2 ACVRL1 TERT BSCL2 F5 COG4 NHP2 ARHGAP31 NPHP3 TNFSF15 PIGA HJV DCDC2 COG6 TERC CBL KRT18 PHKA2 LBR POU2AF1 NGLY1 AGPAT2 MST1 GPC1 JAK2 RPGRIP1L CC2D2A IFT43 GDF2 CASP8 PHKG2 ALMS1 HFE GPR35 LIPA MET HAMP PYGL TTC37 JAK2 KRT8 IL12A KRT18 SKIV2L IL21R ABCB11 RTEL1 TFAM HFE MMEL1 IGF2R ATP8B1 KIF3B RRM2B KRT8 CAVIN1 IRF5 TERC ARG1 TERC RPGRIP1L CYP7B1 TCF4 ITCH TALDO1 TALDO1 TINF2 IL12RB1 ATP6AP1 ASXL1 TMEM67 INPP5E NHP2 AMACR ATP7B TMEM67 BCS1L TREX1 SPIB MPI ABHD5 TERT SLC40A1 TERT MARS1 FAH DKC1 TTC37 BSCL2 TET2 POLG ACVRL1 DOCK6 SLC40A1 USB1 SMPD1 DGUOK BMP2 EOGT DKC1 SLC7A7 TINF2 ABCB4 PARN AKR1D1 F5 WRAP53 SKIV2L PDGFRL TFR2 FARSB NPM1 HBB AP1B1 SMAD4 CTNNB1 ATP7B SLC25A13 ALDOB MTTP GALT PPARG CD40LG PPARG ENG PHKG2 SFTPC MPV17 ATP6AP2 NOTCH1 RBPJ
    Protein Mutations 0
    SNP 0
    HP:0100543: Cognitive impairment
    Genes 877
    SPG11 PRKRA PRDM8 KCNA2 VCP RBM12 SNCB MAPT ITGA7 RBM28 COMT PDE11A PRNP ERCC6 GRN BBS10 EEF1A2 HFE GBA2 PNKP MAPT GDNF SEC61A1 SYNJ1 TRNE SPG7 C19ORF12 SYNJ1 ATP1A3 NPC1 ATXN2 PEX11B FKRP WFS1 WWOX CYTB MFN2 AP5Z1 PRKN CHI3L1 ADH1C ACTB AUH IKBKG SCN1B DNAJC6 GDAP2 SPAST CHCHD10 POLG COASY PMPCA NPHP1 CUBN MLH3 NECAP1 PDGFB TSC2 PLA2G6 PINK1 ECM1 GABRA2 WDR45 NAGLU LIPN TRNQ NOTCH2NLC TRAK1 CSF1R COL18A1 VCP JAM2 ARSA TIMM8A HIBCH TREX1 TRNH B3GALNT2 UQCRC2 HGSNAT LYST ERCC3 ALG12 HSD17B4 GM2A MPO TSFM PRNP APP TREM2 CUX2 ADA2 CLN6 NAGS SCN2A CST3 ATP6V1A SQSTM1 PEX19 PANK2 BBS12 CTSH HNF4A GBA HCRT KLLN PCNT COL4A1 SLC13A5 CFHR3 PLP1 SLC2A1 TGFBR2 PSEN1 NRAS C12ORF65 RNASEH1 PCDH19 NOTCH3 REEP2 NR4A2 SURF1 PSAP ERCC2 TRNK CEP120 VAMP1 GNPTAB ERCC3 TBK1 DGUOK TARDBP MYO1H POLG TUBA4A ND5 LRRK2 SLC6A1 TMEM240 SPG21 SLC18A2 ARL6IP6 BAP1 PRKAR1A DNM1 CYP27A1 RAB27A GALC SMARCB1 PIK3CA PRDX1 A2M LAMA2 QDPR CYP4F22 ATP6 ABCA5 HLA-B VCP PLAA SNORD118 STXBP1 HNRNPA2B1 GABRG2 SQSTM1 HTRA1 AARS2 ABCA7 TSC1 ARV1 STXBP1 GALC FA2H DCTN1 PEX6 RRM2B ERAP1 TIMM8A CLN8 ADD3 SLC2A3 GTPBP3 SLC25A13 NDUFAF3 NTRK2 PPT1 TRNF CFHR1 MAPT B3GALNT2 VCP CHRNG NHLRC1 DNM1L HEXB IL12A AKT1 UCHL1 POLG HCN1 OCRL CYP2U1 CRLF1 HLA-DQB1 APOE STUB1 CHCHD10 MTHFR TRNL1 BBIP1 ATP7B IL23R COX1 NDUFA6 RBBP8 PARK7 NUP107 SLC25A4 CTC1 XPC GNAS PRNP LAMA1 PRNP GRN IRF6 ALG2 TMEM240 SPTBN2 TREX1 APP PDGFRB DSTYK NF2 PRNP AIFM1 EIF2B5 PRNP CDK19 GLUD2 PEX10 GJB6 SPTBN2 SULT2B1 GBA SDR9C7 IDUA PSEN1 CTSK XPA SIM1 ERF RNASEH1 SYNGAP1 PPP3CA CNTNAP2 GCH1 SNCA DAOA SPG11 SYNJ1 CYP2U1 TBK1 MAPT SPG7 SNCA ATM TBC1D24 SLC25A4 GCDH GBA APP PDGFRB DRD3 TTC19 TRNQ RRM2B SYNJ1 SPG21 BBS5 PRKCG TBP CCDC78 SPP1 KRT83 ADA2 MARS2 VCP ACSF3 PTPN22 ADAMTSL4 PHOX2B NAGS NUP133 JPH3 EPM2A CEP152 KRT81 HNF1A TK2 ROBO3 SCN1B GJC2 NFIA EPCAM TP53 EPM2A TMEM106B ALDH18A1 PRNP MATR3 VPS13C ND1 UBA5 MYD88 EIF4G1 PTEN EIF2B2 POLG2 GDF6 PRNP MTOR XPA SQSTM1 GABRG2 NDUFB8 TRNW TREM2 MEN1 BDNF GM2A PIK3CA UBA1 RNF216 RPS20 SCN9A ATXN10 KCTD7 MAOA GALC ERCC5 PRICKLE1 TRNF NDUFS2 APP TRNV TARDBP ATP1A3 MYH3 BRAF MAPT PAH CCM2 POMT2 DALRD3 PEX12 TREM2 SQSTM1 MAPK10 MBTPS2 POMT2 FA2H SDHAF1 SPAST RAB39B ATN1 SMC3 XRCC4 CTNS ARSA ATXN3 PKHD1 MAPT TPRKB POLG SCN9A HNRNPA2B1 SGPL1 COQ2 TBP NOTCH3 WDR4 SLC30A9 DNMT1 MSH6 RIN2 ITM2B MEOX1 GABRG2 APTX LMNB1 UBTF TNFSF4 ATP6V1A SDHB TREM2 CISD2 CENPJ HTRA1 ATP13A2 CCR1 ATP13A2 SMC1A PSEN1 NOS3 GSN DSG4 HEPACAM COL3A1 RMRP CHD2 KCNT1 HTRA2 TRNS2 ALOXE3 TRNS1 CAMTA1 TRNL1 TBP DNAJC13 PNPLA6 SCN8A PSEN2 ERCC8 TREM2 DDB2 FTL SNCA ACTL6B TYMP SNCA HTT GMPPB TTR CHD2 ABCC8 ITPR1 C9ORF72 CSTB COX3 MTO1 ZFYVE26 FKTN PEX13 NDP ABCA12 ATG5 LRRK2 TLR3 NKX6-2 MAPT SLC44A1 CLCF1 C12ORF65 TINF2 CREBBP C9ORF72 GMPPB BAP1 COX2 TGM1 SDHA GRID2 NHLRC1 GABRB2 FAN1 FOXG1 MSH2 SDHC TWNK GABRD CHMP2B TOMM40 GALC MAG ATRIP CHMP2B GDF5 SCN3A TRNK MATR3 CHMP2B GDF3 PEX2 TTC37 GRN DCC PPP2R2B CYFIP2 GLA NBN CACNA1B COASY ND1 SDCCAG8 CLN6 SDHD MECP2 ABCD1 DNAJC5 PDGFRB TREM2 CP PSAP SLC13A5 ATP6V1E1 SLC2A1 ATXN2 MYORG FBN1 PEX26 SLC20A2 FMR1 HLA-DQB1 TWNK FGD1 ATXN7 KATNB1 PRKCG SCARB2 PSAP GABRA5 CENPJ GRN FGFR3 TYROBP GNAS PSEN1 ATN1 POLG RNF216 SRCAP CHMP2B APOE DCX TRNS2 TRNS1 CLMP SCN1A HTT SDHA TUBB2B XPR1 ROGDI TK2 SNCA ATXN1 CREBBP SPG11 ALOX12B APP OPA1 MAPT RRM2B CACNA1G GJB2 GNAS GBA2 ITM2B C9ORF72 WFS1 ND4 PDE10A APP APOL2 GBA ATXN3 SUFU CTDP1 PEX3 AASS TBCK PANK2 UBAP1 PSEN2 GRIN2D MFSD8 UBAC2 CP COX1 PRNP SORL1 CLN8 EIF2B1 UBQLN2 GNE ND6 OPA3 HEXA MAPT PEX1 CTNS APP ZNF365 TRNH DGUOK MMACHC CENPE CERS1 ALMS1 ALDH18A1 DNAJC3 TRNK TBK1 TYROBP SOST SPR TWNK KRAS SUMF1 MOG PIK3CA IRAK1 HTT SLC1A2 LZTFL1 SEC23B TRNP CLTC ASAH1 ASAH1 CPLX1 ALG13 TRAF7 HSD17B10 GJC2 GBE1 KCNB1 P2RY11 FTL C9ORF72 PLA2G6 ERCC8 PSEN1 MAPT DMD POLG PSEN1 PLAU FBXO7 FGF14 MAPT UCP2 ERCC4 SNCAIP AARS1 LARGE1 PEX14 DISC2 ND5 PTS PEX16 EPRS1 TRNL1 FLNA AP2M1 MLH1 GLB1 SPART GIGYF2 PSAP KLRC4 VPS37A IL12A-AS1 C9ORF72 TSC1 KCNC1 ATP13A2 SMO PDCD10 SMC1A GABRA1 PINK1 PPP2R2B HMBS MAPT FA2H GRID2 PSEN1 STAT4 TRPM7 SLC5A7 SCO2 IFT140 VAMP1 BMPR1A PDGFB SYN2 ATP6V0A2 PANK2 KCND3 PMS1 MCOLN1 MTFMT ROGDI DNMT1 KCNJ11 FUS ATP1A2 SCN1A TRAIP SERPINI1 CFH HNRNPA1 SDHD VPS13C TSC2 ATP6 CSF1R PLK4 TRNQ SMARCE1 DCTN1 AP3B2 CACNA1A AP5Z1 TIMMDC1 POMT1 RTN4R PODXL FGF12 TRNF ATP13A2 KRIT1 PLEKHG4 CTSD ATXN7 PDGFB C9ORF72 ATXN3 TTPA PNKP GNAS KMT2A MAGEL2 CLN5 NPC2 PARS2 DARS2 JPH3 KMT2B ERCC2 DCAF17 HTR2A LRRK2 DOLK VCP IL10 COX3 ITPR1 ATP13A2 FAS TMEM106B SNCA VPS35 NAGA EP300 POMK GRN MTHFR DNMT1 SLC18A2 USF3 POMGNT1 GABRB3 PRDM8 KIF5A TRNS2 ATXN3 SDHAF1 LARS2 SDHD MEFV CSTB HCN1 ERCC6 TERT COX2 TWNK ERCC4 CHRM3 GBA SCN2A DHDDS EIF2B4 PRKAR1B NF2 DNM1 AFG3L2 PANK2 RBM28 OSGEP BSCL2 RNR1 SCN8A FAS AFG3L2 LAGE3 SLC25A15 NUS1 KCNA2 ATR METTL23 DNAJC6 KRT86 TP53RK SCN1A GPC4 YWHAG STAT4 PLA2G6 GBA EIF2B3 BSCL2 CNKSR2 SEMA4A CYP7B1 VPS13A STARD7 VPS13A STUB1 SZT2 CLN3 CTSF ATXN2 DZIP1L TLR4 MAPT APOL4 GBE1 FGF14 TRNW CHMP2B TRNC PORCN PEX5 EDN3 AKT1 ALG9 PEX16 ADGRV1 IBA57 LTBP4 WDR73 C12ORF65 ND6 WDR45 ATXN1 ATXN8OS SUMF1 CFAP43 C4A DARS2 POLG FMR1 LAMP2 HLA-DRB1 ND5 TTC8 TUBB4A RRM2B SCN1A ARSA NOTCH2NLC SLC7A7 ABCA7 DMPK STX1B UGT1A1 C19ORF12 PMS2 NIPAL4 TMEM106B MPDU1 TRNS1 GBA SDHB
    Protein Mutations 0
    SNP 0
    HP:0002583: Colitis
    Genes 47
    RASGRP1 CIITA CARMIL2 SKIV2L XIAP OPLAH RTEL1 PLCG2 PSTPIP1 POLA1 NLRC4 MST1 TCF4 LRBA ZAP70 ELANE FERMT1 SKIV2L BACH2 GPIHBP1 RFXANK IVNS1ABP NOD2 IL6 RFXAP STAT1 GPR35 TGFB1 FAS PRKCD MASP2 TTC37 NCF4 RFX5 MAP3K7 ZAP70 IL10RA INAVA FASLG RET TNFAIP3 IL10RB FOXP3 CYBC1 CASP10 FAS HPS1
    Protein Mutations 2
    H180Q V600E
    SNP 0
    HP:0012423: Colonic inertia
    Protein Mutations 0
    SNP 0
    HP:0001635: Congestive heart failure
    Genes 261
    TBX20 RAB3GAP2 AGPAT2 FLNC LDB3 TMEM127 FOS COG7 PHYH HFE PRKAR1A GNPTAB KCNJ5 LIMK1 TRNK RBM20 PPARG SDHAF2 HBB STAT1 HADHA VHL FGFR3 PRKAG2 ENPP1 RET CAV3 SELENON EYA4 PNPLA2 PRKAR1A SCO2 LMNA RYR1 FBN1 MYL3 HJV ELAC2 TMEM43 TRNL1 CITED2 DES ABCC6 CLIP2 COX3 CYTB JUP TPI1 ADCY5 PSEN1 FH GDF2 DSP ELN TTN IKBKG GJA1 BAZ1B HNRNPA1 GPR35 COL1A1 CCR6 TRNQ AFF4 RFC2 GTF2I TTN GATA4 CACNA1S GLB1 TNNI3 AGGF1 SF3B1 CAVIN1 PLN TRNF TNNI3K TCF4 VCL TUBB RET ATXN7 LMNA LMNA GTPBP3 XYLT2 SDHB FBLN5 HBA1 MYH7 TMEM127 KIF1B DES HADHB DNMT3A VPS33A CAV1 CDH23 TLL1 EPG5 ATP6V1A GLA BMP2 EFEMP2 SLC25A11 HADHB ACTN2 ND1 PSMB8 SCN1B CP TMEM70 MYD88 HBB SMAD4 ALMS1 MTTP MAX ACAD9 VHL SLC25A3 FGD1 NDUFB8 TRNW HBA2 SDHD BCHE WRN SLC2A10 TRNS2 CYTB ENG SDHB NDUFB11 LMNA DMD COX2 CAV1 NKX2-5 LMNA SURF1 HLA-DRB1 GATAD1 SDHC PRKAR1A TRNK PRDM16 TNNT2 GNA11 IFIH1 ABCC6 HBB MDH2 NDUFS2 TRNV SDHA ACAD9 FXN SLC25A26 SLC19A2 GTF2IRD1 RPS19 GLA PPA2 MYPN EYA4 CITED2 DTNA MAX NF1 LMNA XYLT1 ND6 SNAP29 TBX20 DSP MST1 FLNA DLST MYH7 MYH7 ADAMTSL2 MYH7 VCP SCN4A ALMS1 NKX2-5 GDNF HFE TF MECP2 BAG3 HAMP TRNK TET2 ACTC1 RASA1 LMNA LMNA MYH6 TRPM4 TRIM37 SDHD TLL1 TRNC STRADA CCN2 HNRNPA2B1 MYH7 TAZ RET CLIC2 SGCD GTPBP3 PEX7 SDHB TRIP4 MYSM1 TPM1 NDUFAF3 PTEN CEP19 SDHD NDUFAF1 FGF23 EPAS1 ND5 SLC17A5 HADHA GATA6 BSCL2 ATP5F1A ACVRL1 CLIC2 IRF5 ACTC1 TBL2 MAPRE2 JUP CASR KIF1B VHL NSMCE2 TRNL1 ADCY5 DNAJC19 DSP MYLK2 PLOD1 COX1 MYH6 COL1A2 IDS PPARG ENG SCN5A GBA TRNS1 PSEN2 SLC22A5 TRNE
    Protein Mutations 14
    C1236T C3435T C825T E161K E28A E28C E28D G2677T G308A M235T Q12H S2808A V30M V66M
    SNP 0
    HP:0002019: Constipation
    Genes 478
    ZIC2 TRIO POGZ CAMTA1 TRNL1 NRXN1 NODAL COL5A1 DNAJC13 POLG LIMK1 PRNP EXT2 COL7A1 VANGL1 SIX3 SDHC TSHR GP1BB SNCA LAMA3 HFE MAPT MLXIPL SALL1 PAX8 AVPR2 SEC24C TTR CAMK2B HNRNPK ATXN2 THRA UBE3A SCNN1A NKX2-5 PRKN DEAF1 DISP1 GAS1 SOX2 ADH1C CDC73 CACNA1S LRRK2 FOXH1 MECP2 BIRC3 ELN SCN11A MAGEL2 DNAJC6 OCRL ASCL1 JMJD1C UFD1 CREBBP HNRNPH2 TSHR COX2 DLL1 TXNRD2 SIX3 NKX2-5 GTF2I MBD5 MLH3 NSD1 FAN1 FOXG1 VPS11 RORA SLC26A4 MSH2 TG FOXH1 SETD5 DDOST KMT2A EDN3 CDON EDNRB TCF4 LHX3 OTX2 TLK2 GAS1 SMO OTUD6B KCNJ1 TRNH MRAP SLC5A5 KRT14 UFC1 RET COL5A2 TTR SPOP IGH NODAL BRAF RET LHX4 PSMB8 ACTG2 SHH DISP1 MNX1 MECP2 DSE POU1F1 NKX2-1 CSNK2A1 KIT GLI2 COL1A1 HIVEP2 TBCD RERE SCN9A TANC2 WDR26 DISP1 LMNB1 SIX3 ARNT2 POLG TWNK SLC6A8 FGF8 MEFV TDGF1 TGFBR2 CHST14 AQP2 LRIG2 TRNS2 GLI2 FGF8 TRNS1 STAT6 POU1F1 NR4A2 FGFR1 STAR CREBBP ZEB2 GABRA3 WFS1 ATN1 ND4 CDKL5 PAX8 ND5 PCCB CDON WAC STAG2 OCRL STXBP1 WASF1 FLI1 SIX3 COX1 RAI1 NGLY1 PCCA PIK3CA CAMTA1 DDOST KIT HPSE2 CTNS ZIC2 AQP2 ATRX FOXP1 PROP1 KRAS FGF8 PROKR2 SHH CNTNAP2 HMBS DHPS TH STAG2 PCGF2 NODAL SLC26A4 PTCH1 ZIC2 LMX1B NAB2 TRHR GAS1 ECE1 SLC5A5 TCF4 TRNF HESX1 FTL DUOXA2 DYRK1A UBE3B CDON DPF2 TYMP KCNJ18 UCHL1 TSHR PACS1 NNT CDKN1A MSL3 PTCH1 GLI2 SLC6A3 TCF4 TSHB SNCAIP COQ2 PACS1 ZEB2 CHST14 PARK7 SLC25A4 SLC12A3 NRTN ZMIZ1 SDHA SMC1A SCN10A CASR KRT5 CHCHD2 MLH1 NALCN MC2R KIT SPART GIGYF2 SOX3 PCCA HPSE2 FOXA2 SIK3 TRNK CDKN1B MEN1 PINK1 MRPS34 DDHD2 HMBS TCF20 PHOX2B CAVIN1 GDNF ADNP NRXN1 RET GLUD2 ABL1 MED25 SETD2 RREB1 PROP1 BMPR1A CD96 TRNL1 ARVCF ATRX GALNT2 PMS1 EDNRB ALDOB CLIP2 PDGFRA TBX1 IGHMBP2 POGZ PIGS SYNJ1 BRCA1 ODC1 BAZ1B ZSWIM6 LAMC2 PPOX LHX4 P4HTM GBA RAI1 UGP2 TRNQ RRM2B AFF4 TRH RFC2 SIX3 TDGF1 SEMA3C CDKN2C SLC6A3 PODXL USP7 ATRX HESX1 MLYCD GATAD2B CDON GDNF B2M OTUD6B MAGEL2 ALAD FDFT1 PPM1D EDN3 MED12L RAI1 GJC2 ZIC2 HESX1 LRRK2 GLI2 ARID2 EPCAM FOXE1 SPATA5 COX3 SLC6A8 FOXH1 TRIO EXT2 BCL10 VPS13C SNCA ND1 VPS35 EIF4G1 FGF8 ATRX GABRD POLG2 EP300 APC SOX3 SLC12A3 KCNAB2 TGIF1 WAC POLG2 GRIN1 DHCR7 PTCH1 DES TDGF1 CLCNKB VPS51 MMP1 SHH SCNN1B AVPR2 GLI2 CHRM3 SKI RPS20 GBA SDHB CREBBP GAS1 FOXG1 PROP1 COMT UNC80 TBX1 TGIF1 CDC73 WAC SCNN1G GTF2IRD1 MEFV PAX8 SCN11A PIGV LAMB3 IYD NFIX DEAF1 PTCH1 FGF12 ADAT3 FOXH1 RAI1 TAF1 FLII MALT1 NALCN SOX10 TGIF1 MDH2 SEMA4A SLC12A1 MED13 FLNA KCNH1 KDM1A APC2 FGFR1 PPOX ALPL EP300 TDGF1 TRNW DLL1 SHH RET TPO TGIF1 MED12 TBP PEX16 EP300 SOX10 TBCD MSH6 TNFRSF1A FOXP1 SCN9A ND6 FGFR1 ATXN8OS UBE2A SMPD1 POLG CREBBP CHD8 ELN PCCB CPOX WDR26 SDHC PAX8 DUOX2 ELP1 CISD2 NODAL COL7A1 DDC EDN3 TBL2 DLL1 COQ2 MED12 CDKN2B VPS11 HIRA LRIG2 SRCAP MITF IQSEC2 DMPK OTX2 PMS2 DLL1 PRDM16 SDHB ZEB2 DACT1 SEMA3D HTRA2 TBL1X UNC80 DISP1 SH2B1 TRNE
    Protein Mutations 2
    G1314A G1321A
    SNP 0
    HP:0001677: Coronary artery atherosclerosis
    Genes 52
    MFAP5 ELN LDLR APOB ACTA2 BRCC3 MYH11 ERCC6 LMNA SMAD3 ZNF687 KCNJ5 TGFBR1 ERCC8 LMNA FBN1 MYH11 CYP7A1 LMNA LMNA TGFB3 XYLT2 MYH11 CEP19 ABCG8 PCSK9 MYLK LMNA PRKG1 FOXE3 APOE TGFBR2 TGFB2 SMPD1 ABCC6 XYLT1 ABCG8 MAT2A LOX APOB ESR1 SERPIND1 ABCG5 LDLRAP1 PPARG SMAD4 ACTA2 LIPC LMNA LOX ABCA1 ABCA1
    Protein Mutations 3
    C282Y C825T H63D
    SNP 19
    rs10153820 rs1143623 rs1143633 rs1143634 rs12041331 rs16944 rs16969968 rs17561 rs1761667 rs2043211 rs20432111 rs2305619 rs4612666 rs4848306 rs6434222 rs7586970 rs7903146 rs8069645 rs8176528
    HP:0012735: Cough
    Genes 152
    GAS8 TERT DNAL1 ZBTB16 IKZF1 LRRC56 HLA-DQA1 VCP GAS8 TERT CCDC40 CYTB RSPH4A DNAI2 DNAJB13 CCDC39 LPIN2 ODAD3 DNAH9 NABP1 IL2RG NUMA1 WWOX TSC1 ACAT1 HLA-DRB1 SFTPA2 STAT3 TTC12 GBA MUC5B EPOR DSP CFTR RNF6 CLEC7A DNAAF2 DNAI2 CFAP221 SPEF2 ODAD4 HLA-DPB1 OFD1 ATP11A CFAP300 NME8 ODAD2 DRC1 TGFBR2 ODAD3 DNAAF4 SFTPC DNAAF6 DNAH5 SCNN1A EIF2AK4 DNAH9 SP110 RTEL1 CSF2RB TRAF3IP2 STN1 PARN TBL1XR1 IL17RA DNAAF3 FOXJ1 GAS2L2 CCDC103 ODAD1 STAT5B SCNN1B SLC11A1 ABCA3 STK36 DPP9 SFTPA1 ODAD4 DNASE1L3 CCDC65 LRRC6 TSC2 ZMYND10 CTLA4 COPA SCNN1G NOS1 PRKAR1A DNAI1 IL17F MUC5B STAT3 NPM1 LRRC8A DLEC1 SFTPA2 DNAAF6 DNAH11 DNAAF1 CCNO IRF2BP2 IGHM HLA-DQB1 IL17RC CD79A PML PRTN3 IGLL1 CD79B FIP1L1 BTNL2 PARN BLNK PTPN22 FOXJ1 NEK10 RPGR CSF2RA TERT MARS1 DNAH1 TCF3 SCNN1B SCNN1A SCNN1G LRRC56 BCOR HYDIN POMT1 RARA RSPH9 RSPH1 TERC PIK3R1 CFAP298 MCIDAS FARSB HLA-B PANK2 ODAD1 HLA-DPA1 SPAG1 CFAP300 RSPH3 DNAAF5 CRLF1 SFTPC CCDC103 HLA-DRB1 ERLIN2 PTPN22 FAM13A
    Protein Mutations 0
    SNP 0
    HP:0100280: Crohn's disease
    Genes 10
    BACH2 NOD2 PSTPIP1 IL10RA INAVA IL6 MEFV CYBC1 CTLA4 IGHM
    Protein Mutations 3
    G908R R702W V600E
    SNP 2
    rs2062305 rs2097432
    HP:0000726: Dementia
    Genes 291
    PRNP PRDM8 VCP TRNL1 GIGYF2 GRN IRF6 SNCB C9ORF72 DNAJC13 PNPLA6 MAPT APP PDGFRB PSEN2 ATP13A2 PRNP TREM2 FTL HFE PINK1 SNCA PPP2R2B GBA2 PRNP TYMP SNCA HTT MAPT MAPT PRNP GLUD2 TTR PSEN1 TRPM7 TRNE C19ORF12 GBA NPC1 ATP6V0A2 PSEN1 ATXN2 PANK2 WFS1 C9ORF72 CSTB COX3 CYTB ZFYVE26 ROGDI DNMT1 PRKN NDP FUS SNCA ADH1C LRRK2 AUH SYNJ1 TBK1 MAPT DNAJC6 SNCA SERPINI1 HNRNPA1 SDHD VPS13C GCDH GBA APP CHCHD10 ATP6 C9ORF72 TRNQ TRNQ DCTN1 COX2 SPG21 SDHA CUBN PDGFB TBP NHLRC1 PODXL PINK1 TRNF ATP13A2 WDR45 VCP CHMP2B NOTCH2NLC TOMM40 C9ORF72 JPH3 EPM2A CSF1R CHMP2B VCP ARSA NPC2 TIMM8A TREX1 TRNH MATR3 JPH3 CHMP2B LYST LRRK2 GRN MPO PRNP EPM2A APP VCP TREM2 PPP2R2B TMEM106B COX3 ALDH18A1 ND1 ADA2 PRNP CLN6 MATR3 ATP13A2 CST3 VPS13C ATP6V1A TMEM106B SQSTM1 SNCA ND1 VPS35 MECP2 ABCD1 DNAJC5 TREM2 EIF4G1 SLC13A5 ATP6V1E1 PRNP ATXN2 GBA GRN FMR1 COL4A1 HLA-DQB1 TRNW SCARB2 GRN PSEN1 TRNS2 TYROBP TREM2 PSEN1 SDHAF1 ATN1 RNF216 CHMP2B APOE TRNS2 TRNS1 NOTCH3 HTT COX2 XPR1 TWNK GM2A ROGDI ERCC4 NR4A2 RNF216 SNCA PSAP GBA TRNK ATXN10 APP PRKAR1B OPA1 KCTD7 MAPT PRICKLE1 DGUOK APP TRNV GBA2 ITM2B WFS1 TARDBP ND4 POLG APP TUBA4A TARDBP ND5 LRRK2 SPG21 PANK2 PSEN2 CP COX1 SORL1 UBQLN2 CYP27A1 ND6 TREM2 HEXA PRDX1 MAPT A2M PLA2G6 SQSTM1 MBTPS2 ATP6 APP MMACHC VCP SPAST CERS1 RAB39B VPS13A ATN1 ALDH18A1 HNRNPA2B1 TBK1 TYROBP SQSTM1 HTRA1 AARS2 ATXN3 CLN3 CTSF ATXN2 MAPT TRNW CHMP2B TRNC DCTN1 HNRNPA2B1 RRM2B TBP NOTCH3 ASAH1 DNMT1 ND6 WDR45 ATXN8OS CFAP43 ITM2B TRNF FMR1 GBE1 MAPT APTX FTL VCP C9ORF72 PLA2G6 ND5 NHLRC1 DNM1L ERCC8 UCHL1 TUBB4A TREM2 CISD2 PSEN1 POLG MAPT PSEN1 PLAU FBXO7 HTRA1 ATP13A2 NOTCH2NLC APOE ABCA7 PSEN1 NOS3 CHCHD10 SNCAIP TRNL1 ATP7B COX1 PARK7 TMEM106B HTRA2 TRNS1 GBA SDHB
    Protein Mutations 1
    V158M
    SNP 0
    HP:0000819: Diabetes mellitus
    Genes 547
    VANGL2 NR2E3 WFS1 GLIS3 FOXH1 PROK2 TRNL1 NDUFS6 PPARG PEX1 FBN1 LMNB2 LIMK1 PRPF4 RP2 CFTR PAX4 PPARG CTNNB1 HBB COL2A1 POC1A KCTD1 LIG4 PDE6B TOPORS ARL2BP ABCC8 SLC30A8 KCNJ11 MLXIPL CDON WRN PRKAR1A PROM1 TRNE NEUROD1 CNBP KCNJ11 MMP14 C8ORF37 APOE SLC16A2 CTRC ZBTB20 BBS2 WFS1 BLK WFS1 KRAS COX3 CYTB ZFYVE26 FGF8 SOX2 XRCC4 CDH23 ELN CEL GPR35 SLC29A3 FOXC2 EIF2AK3 PTF1A TCF7L2 HNF1A ARMC5 MKKS PDE6A PDX1 COX2 PSTPIP1 EIF2AK3 GTF2I NEUROD1 CNOT1 ATP6 USH2A ITPR3 LMNA NDUFA1 NDUFA11 CAVIN1 PCARE HLA-DRB1 CAT TCF4 AIP GCK PLCD1 HNF4A HERC2 PDX1 OTX2 HJV TRNH IL6 PWAR1 PAX4 TKT RPE65 REEP6 HNF4A RLBP1 SIX3 CFTR IGF2BP2 HNF1A POMGNT1 ND1 SAG GCK BLK GPD2 RAC1 AKT2 SEMA4A WRAP53 MOG CP ARL6 AIP ALMS1 SBDS NPAP1 CDHR1 ITCH BLM HNF1B NSMCE2 ARNT2 TWNK PDX1 PDX1 DLL1 ROM1 NDUFAF3 SNORD116-1 PDE11A NDUFS4 FOXP3 WRN ZMPSTE24 UBR1 ZNF513 INSR IARS1 SLC19A2 RP1 GJA1 TRNS2 TRNS1 PRKACA PCNT FLT1 NOTCH3 TULP1 LMNA MC4R PRKACA PNPLA6 CAV1 IFIH1 NOP10 NEUROD1 MEN1 PLAGL1 ND3 TRNK ZFP57 BRCA2 SPATA7 OPA1 VANGL1 DMXL2 NODAL GJB4 EDA2R HBB CA4 MKRN3 SNORD115-1 FXN GATA6 WFS1 RP9 ND4 TMEM126B NDP BRCA1 SLC19A2 ND5 HMGA1 NDUFAF1 MERTK RETN PRPF6 HLA-DQB1 SPINK1 CP COX1 HNF4A RPGR ND6 MST1 GUCA1B NDUFA6 EDA HNF1A RNASEH2C ALMS1 TIMMDC1 HFE CIDEC DNAJC3 INS KIAA1549 IRS1 LMNA PROKR2 GCK PRKAR1A HNF1B LEPR POLR3A HYMAI SNRNP200 LIPE HYMAI CNGB1 CLRN1 ZIC2 APOA5 GAS1 EFL1 PIK3R1 TTC8 SARS2 HNF1A GJA1 PTF1A RNASEH2B TRNF NEUROG3 LRP6 TDGF1 NDUFB11 HESX1 NDN FOXP3 HNF1B ABCC8 ND2 TGIF1 PRPH2 DNM1L PRSS2 BBS2 INS NUBPL LIPE SAMHD1 DISP1 DHDDS LEMD3 DKC1 MKRN3-AS1 KLF11 IDH3B TRNL1 GLI2 FUZ SMPD4 COX1 PLIN1 SLC25A4 CNGA1 LHX1 SNRPN INS AGPAT2 GNAS SUFU DNAJC21 FOS SPINK1 CAV1 ARL3 HFE TUB TRNK KLF11 AKT2 NDUFB3 PPP1R3A NEK2 STAT1 PRPF3 RDH12 USP8 IFT172 BSCL2 ABCC8 HAMP PDE8B NDUFV1 PNPLA2 CYP19A1 LMNA ARHGEF18 MMP2 ABCA4 LRAT NDUFS7 INS TRNL1 LMNA ABCC8 PAX4 PRSS1 CLIP2 BEST1 SCAPER PIK3R1 ZNF408 SIM1 KCNJ11 PTRH2 FXN TRMT10A CASR BAZ1B ATM CPA1 NDUFS2 BRAF ADAR ZFP57 APPL1 TRNQ TRNQ RRM2B DNAJC3 STOX1 RFC2 PRCD DHX38 HNF1B IRS2 SMAD4 HNF1A ND1 KCNJ11 SLC7A14 PDE4D CDKN2A IL18BP PTRH2 NDUFS3 TRNF NDUFAF2 FAM161A VANGL2 FGFR1 CISD2 ABCC8 LEP XRCC4 TTPA NHP2 NKX2-5 AMACR MAGEL2 KDSR POLD1 KIZ INS CORIN NDUFS8 DCAF17 NDUFAF4 FOXRED1 PEX6 COX3 PRSS2 MTNR1B BMP2 PEX10 PARN PAX4 NDUFB10 ND1 INSR PRSS1 TP53 NPM1 MAGEL2 HBB POLG2 SOX3 SLC12A3 AIRE UBR1 GCK IL2RA TRNW WFS1 IMPG2 TRNS2 PTCH1 LEPR KCNJ11 IL2RA CLCNKB ATM STAT3 AGBL5 CARS1 HMGA2 COX2 MAFA TTC7A TWNK GJB3 LMNA AHR PLAGL1 PALLD NDUFS1 CRX CRB1 GATA6 GLRX5 ENPP1 CEL HNF4A CTC1 TRNV RNASEH2A HYMAI NDUFV2 IMPDH1 APPL1 BBS1 PALB2 GTF2IRD1 EIF2S3 SHH AEBP1 SLC2A2 PRPF31 MTHFR KLHL7 NDUFAF8 TERC PDX1 GCK TP53 AGPAT2 CCDC28B SLC29A3 ABCC8 PLIN1 GATA3 NRL PDE6G RBP3 PDX1 DCAF17 IPW NDUFAF5 MTHFR XRCC4 CTNS GCK FGFR1 STUB1 HNF1A BLM ELMO2 STAT3 HGSNAT KCNJ11 CERKL TRNW RTEL1 TRNC CTRC KCNJ11 RHO IDH3A RP1L1 TREX1 ITCH PNPLA2 PWRN1 CNOT1 FOXP1 ND6 EYS SRP54 TINF2 INSR IFT88 POLG ARL6 AHI1 ELN PTPN22 CEP19 PRPF8 POLA1 MAPK8IP1 MAK ND5 TERT LIPC BSCL2 AR CISD2 KCNJ11 OFD1 USB1 TBL2 RGR ERGIC1 FSCN2 NDUFB9 IER3IP1 INS DMPK PTPN1 NSMCE2 GPR101 HNF4A PPARG IFT140 PPARG PDE4D GCK TRNS1 SPINK1 PPP1R15B ABCC8 STAT1 IGF1R TRNE
    Protein Mutations 12
    A54T C1858T C282T C282Y E158K E23K H63D I191V K1270A K3048A P12A S9C
    SNP 16
    rs10830963 rs13266634 rs2266782 rs2281135 rs2294918 rs35874116 rs35874116rs rs5215 rs5219 rs738409 rs780094 rs780094s rs78408340 rs7903146 rs9701796 rs9939609
    HP:0002094: Dyspnea
    Genes 440
    TBX20 ELN ND4 TERT CHRNA1 DPM2 NABP1 EDA NUMA1 ORC6 HLA-DRB1 FGFR2 RNU4ATAC FBN1 XYLT1 HBB COL2A1 LAMA3 DSP ZIC3 DNAAF3 TRIP11 TRPV6 TRNE SERPING1 MYL3 TTN CITED2 DBH GATA6 ABCG8 TARDBP MUSK AIMP2 SFTPB SCNN1A EIF2AK4 EPHB4 ORC1 TRNL1 VPS33A STAT5B VCP CCR6 LRP4 ORC1 BMPER GATA4 TSC2 LTBP3 SCNN1G CHRNB1 ORC6 KCNJ6 MUC5B ATP6 PET100 TRAK1 LAMB2 LIFR FIP1L1 FIG4 COQ7 FBP1 MYLK SLC35A1 SOX9 PRPH MMAA VPS33A SCO1 DISC1 TET2 ISCU TGFB2 GLA DNAJC21 CHRNE NUP214 COL13A1 ALAS2 POMT1 RPS28 VAMP1 CHRNB1 SDCCAG8 NAGS SFTPC SCN4A EOMES ACADM ND6 PON1 HLA-B FGFR2 PYGM TRNE TWNK DMPK ATRX FOXP3 COX14 PSAP SLC2A10 SERPINA1 DNAJB6 ENG OPTN CYB5R3 GATA4 DPM1 NKX2-5 TK2 SURF1 HLA-DRB1 TACO1 ND1 TBX4 CDT1 UBE3B MYH11 NEB GBA HBB MYBPC3 USP9X ABCA3 STT3B CYB5A GATA6 CSPP1 TSC1 KRT6B KIF20A GNAS COX6B1 PLCB4 ETFDH TAF15 GNAS PLEC CITED2 LMNA ETFA ATP11A SCN4A IFT81 TRNV NPPA GNAI3 NEFH ALMS1 NKX2-5 CSF2RB PUF60 TRNK SMAD4 TBL1XR1 ACTC1 STT3B SCNN1B ADAMTS13 ABCA3 DPP9 MYL2 SFTPA1 TRPM4 IRAK1 TLL1 APOB FAM20C UNC13A TRIP11 ATXN2 GATA6 CSF2RB CHRND PRRX1 GMNN GTPBP3 CHRNA1 NDUFAF3 ABCA3 BTNL2 PCSK9 TRMU CCNF TET2 TERT ZMPSTE24 MARS1 NKX2-1 ANXA11 DAO SOD1 ACADVL IRF5 MEGF10 MAPT COL1A2 DSC2 EDN1 SLC25A1 EPHA4 MYH6 LDLRAP1 DCTN1 SLC25A4 CNTNAP1 SCN5A SFTPC COL13A1 FGFR1 DPM2 SH2B3 LOX ND3 FAM13A CASR TRMT5 MFAP5 ZBTB16 BTNL2 TRNN CHAT ARX FLNC AIFM1 MRPL3 SFTPC TNNT2 MYH11 NEK1 SLC18A3 TSC1 USP9X SFTPA2 PRRX1 COA3 TGFB3 MUC5B HNRNPA1 NR2F2 CFTR TBK1 SCN4A CHRNE ADNP STAT4 SCO2 SCN5A PON3 SLC52A3 FLNC CRELD1 SFTPC COX7B MAPT LAMC2 COX20 SIK1 JAK2 MMUT ALDH7A1 JPH2 CYB5R3 SLC25A1 FUS ETFB RRM2B SFTPB PMM2 LDLR DNASE1L3 SPP1 TRNS1 ZFPM2 RUNX2 PFN1 VCL SFTPA2 NAGS ASXL1 SCO2 TBC1D24 BMPR2 PARN CSF2RA CHRNE CAV1 PRKG1 CRLF1 PNKD GNAS TLL1 GLE1 COL2A1 KAT6A BCOR MGME1 TNNI3 RARA DOK7 MAT2A SCN1B ORC4 CHRND HLCS PON2 PPARGC1A COX8A MMAB GBA POLG2 DNA2 EFTUD2 SLC12A3 SLC25A3 ACTA2 NDUFB8 GAA FGFR2 CHMP2B COA8 TERT ND5 FBP1 ADCY6 IKZF1 VCP SRP54 AGRN TSC2 CLCNKB CDC6 HCCS COLQ NDUFB11 SNAP25 SMPD1 COX10 MGME1 DHX16 PRKAR1A STAT3 SRSF2 RUNX1 LYRM4 WIPF1 GALC PRRT2 DYNC2LI1 NDUFS2 AGRN SSR4 EPOR PRKCSH CHCHD10 ASAH1 SBDS MPC1 ACVRL1 TET2 LAMB3 SLC5A7 FOXE3 DNA2 CBL TGFBR2 CHAT RAPSN MATR3 CDC45 TBX20 IL1RN CFAP410 IFT52 NOD2 FOXF1 GBA STAT5B C9ORF72 RTEL1 NGLY1 STN1 SQSTM1 PIGT KCNA1 CAV1 KRT16 BMPER KRT17 RPS26 OTX2 TRNW LGI4 CCN2 COPA SMAD3 PRKAR1A MYPN EP300 TGFBR1 TRNK AK9 NPM1 ERF KRT6A GLT8D1 MYO9A IRF2BP2 VAPB STX16 TNNC1 PML ND2 POLG CREBBP KLHL7 ERBB4 UBQLN2 SETBP1 WAS MMUT TREM2 NKX2-1 GATA6 FGFR2 TUBB4A SYT2 TERC ANG CPT2 ABCG5 COA8 PGM1 ITGA3 RNF13 HLA-DRB1 GYG1
    Protein Mutations 0
    SNP 0
    HP:0100584: Endocarditis
    Genes 20
    HLA-B TLR4 IL12A C4A UBAC2 IL23R MEFV KLRC4 NR2F2 IL10 IL12A-AS1 GATA6 PRKAR1A CCR1 ERAP1 GATA4 STAT4 CRELD1 PRKAR1A FAS
    Protein Mutations 0
    SNP 0
    HP:0030127: Endometriosis
    Genes 2
    THOC6 THOC6
    Protein Mutations 0
    SNP 4
    rs10859871 rs11031006 rs2273773 rs7521902
    HP:0100633: Esophagitis
    Genes 27
    ADAMTS2 SLC2A10 SLC6A5 CARMIL2 GLRB ATAD1 IARS1 STXBP1 TGFBR1 RPL11 PGM3 MEN1 LMX1B PHGDH ATP7A FERMT1 GPHN TCF4 TGFB3 TCF4 TRAPPC11 TGFBR2 CDKN1B SMAD3 PSPH TGFB2 GLRA1
    Protein Mutations 1
    D961H
    SNP 0
    HP:0012378: Fatigue
    Genes 394
    TBX20 COL5A1 NABP1 NUMA1 DDB2 SDHC MMADHC RET NLRP3 CCND1 TNFSF15 HLA-DPB1 CITED2 DBH KRAS SCNN1A TARDBP SOX2 CDC73 CDH23 BIRC3 MDM4 GPR35 JAK2 HBA1 ARMC5 STAT5B VCP SERPINA6 TSHR TXNRD2 PSTPIP1 NKX2-5 TICAM1 MLH3 GATA4 TSC2 FAN1 CTLA4 SLC26A4 MSH2 TG TCF4 CD244 RET IGHM IL12RB1 AIP CD79A SDHB LHX3 OTX2 FIP1L1 FIG4 SYNJ1 PTPN22 DNMT3A CALR MRAP PRPH SLC5A5 ERCC3 COL5A2 TET2 CDH23 HLA-DRB1 IGH GLA ALAS2 LHX4 POMGNT1 ACADM POU1F1 PON1 BCR HLA-B NKX2-1 AIP KIT CPT1A COL1A1 PYGM HNF4A ABCC2 VHL ARNT2 TWNK ATRX SLC18A3 PDE11A TGFBR2 SLC2A10 PIEZO1 STAT6 POU1F1 ALB COQ2 OPTN PRKACA HBA2 TK2 ERCC2 STAR BRCA2 OPA1 MET DNAJC6 MDH2 SLC25A26 BRCA1 PAX8 ATP7A KCNQ1 TAF15 SLC18A2 UBAC2 CITED2 CAV3 TRHR NF1 LBR PTPN3 MST1 PIK3CA INSR KIT HLA-B MORC2 NEFH NKX2-5 CHRND FOXP1 TLR3 TRNK PROP1 PLEC IGH BCL2 TBL1XR1 ACTC1 NFKB2 MPL HELLPAR KRAS PROKR2 GCK SDHD PRKAR1A TLL1 MMEL1 BCL6 UNC13A TAZ IRF5 SLC26A4 ERAP1 ATXN2 NAB2 HMGCL PRTN3 BTK HESX1 BTNL2 DUOXA2 SDHD SPIB KIF23 CCNF PTPN22 TET2 FGF23 DNM1L TNXB PIGA TCF3 IL12A ANXA11 DAO SOD1 KCNN4 TSHR NNT SLC3A1 TBX19 COL1A2 HAVCR2 IVNS1ABP EPHA4 ERCC4 TSHB IL23R MYH6 HLA-DPA1 NFKBIL1 SMAD3 DCTN1 SLC25A4 C1QBP SLC12A3 XPC SDHA SH2B3 MLH1 ZBTB16 PADI4 MC2R GNAS CFH CTNNB1 KLRC4 CCND1 IL12A-AS1 SOX3 NEK1 HFE FOXA2 TSC1 NR3C1 SDHAF2 AP2S1 HNRNPA1 USP8 TBK1 HLA-B PDE8B GBA PROP1 MEN1 BMPR1A MLX GCH1 PMS1 XPA PON3 PDGFRA VHL JAK2 FH JAK2 LHX4 PYGL AGK FUS GATA2 RRM2B TET2 SMAD4 CCDC78 CDKN2A HESX1 IL18BP PFN1 LRRC8A NAGS NLRP3 ASXL1 IGLL1 KCNE1 CD79B PNPLA8 TMEM127 BLNK HNF1A CD46 TLL1 HESX1 IGH GLE1 GLI2 EPCAM FOXE1 IL10 BCOR SLC25A11 RARA NLRC4 BCL10 ATP13A2 STEAP3 PON2 PPARGC1A MYD88 TP53 ATM POLG2 KL SOX3 SLC22A4 CHMP2B ARMC5 IKZF1 TNPO3 MEN1 CDH23 MEFV SCNN1B TWNK RPS20 SDHC ABL1 STAT3 PALLD SRSF2 RUNX1 WIPF1 ERCC5 DMD PROP1 SDHA EPOR NLRP3 CHCHD10 CDC73 SCNN1G PALB2 DYSF MPL PAX8 TET2 FAS IYD MAX CBL PHKA2 MATR3 POU2AF1 TBX20 SLC40A1 CFAP410 STAT4 DLST MYH7 SMAD3 MALT1 PHKG2 PODXL SEMA4A MMACHC C9ORF72 FGFR1 SQSTM1 PIGT SLC11A1 IL12A TLR4 UNC93B1 SLC4A1 PREPL TPO PRKAR1A ELANE NPM1 MSH6 TRAF3 GLT8D1 IRF2BP2 VAPB SDHB C4A PML POLG IL12B ERBB4 NR3C1 UBQLN2 TET2 WAS EPAS1 TREM2 DUOX2 GATA6 CFI RUNX1 COMP IL10 CCR1 FTL ATP13A2 PIK3R1 KIF1B TFR2 ANG VHL DMPK ALB OTX2 GPR101 PMS2 PGM1 SDHB TBK1 CIITA HLA-DRB1 PTPN22
    Protein Mutations 3
    T25W V158M V18M
    SNP 0
    HP:0001945: Fever
    Genes 365
    VANGL2 DCLRE1C ZBTB16 AVP PADI4 AK2 ND4 TRNL1 KLRC4 LPIN2 IL12A-AS1 NLRP3 CACNA1A NABP1 IL2RG EDA NUMA1 TSC1 ACAT1 HLA-DRB1 PRNP SPTB CFTR DDB2 CD247 WT1 NTRK1 NLRP3 HBB HMBS LAMA3 CFTR EIF2B5 NLRP12 AVPR2 CALR CHD7 HLA-B MVK STAT4 NLRP3 CCND1 RYR1 RYR1 STING1 TNFRSF1A CTRC MLX HLA-DPB1 XPA PRSS1 UNC13D NCF4 IRF8 GCH1 TRIP13 MPL NCF2 BIRC3 NLRC4 SCNN1A RB1 DIS3L2 CFH LAMC2 GPR35 JAK2 SLC29A3 CYP21A2 ADAR P4HTM TRNL1 PRF1 KIF1B JAK2 STAT5B GATA2 NLRP3 IL6 TRNQ RAG1 NCF1 CD3D COX2 BRCA2 TP53 PSTPIP1 PMM2 TICAM1 TET2 CACNA1S TSC2 HAVCR2 CYBA CTLA4 SCNN1G SPP1 SPTB POU6F2 RAB27A TCF4 STAT3 VANGL2 ATP6 LRRC8A CD244 IGHM NLRP3 TRIM28 CD79A IGLL1 CD79B LIFR FIP1L1 KCNJ1 TRNH BLNK PTPN22 CALR SPTA1 CHEK2 HLA-DRB1 LYST CYP11B2 ERCC3 XIAP CYBB CRLF1 NLRP3 IGH CD3E HLA-DRB1 IGH IL10 COX3 PRSS2 BCOR GLA RARA NLRC4 SLC4A1 MEFV PSMB8 BCL10 ATP13A2 CPT2 RNF168 ND1 PMP22 ND6 BCR MYD88 HLA-B G6PD ATM COL1A1 SLC19A3 EIF2B2 IRF8 ABCC2 CASK SLC22A4 CFHR3 TNFAIP3 GAA MEFV PSAP H19 ND5 FBP1 AQP2 SH3KBP1 IKZF1 SCYL1 CYTB TRNS2 IL2RG MEFV TRNS1 STAT6 COG6 RYR1 RAG2 CYBC1 WDR1 AVPR2 TREX1 IFIH1 ERCC2 GPC3 PRKAR1A ABL1 GYPC ND1 STAT3 BACH2 NOD2 EIF2B4 WIPF1 GALC ERCC5 HBB NGF RNASEH2A CD27 COL1A1 NLRP3 HTR1A ND4 ASAH1 LACC1 ELANE LIFR ND5 PSMB9 MEFV F5 TET2 FAS RIPK1 LPIN1 LAMB3 MTHFR IL7R STXBP2 ORAI1 SPINK1 UBAC2 TCIRG1 COX1 EIF2B1 MYD88 LBR PTPN3 DST GALC MST1 NOD2 STAT4 SLC29A3 ELANE ADA2 POMP TRNV QDPR EIF2B3 MALT1 LACC1 TMEM165 HLA-B TP53 RAG1 RNASEH2C AQP2 SLC12A1 FOXP1 NGLY1 TLR3 MTHFR IGH BCL2 SPTA1 RANBP2 TBL1XR1 MPL NLRP1 SCNN1B SLC11A1 ADAMTS13 ALPL MIF CYBC1 STAT2 KRT18 PSMB4 TLR4 STX11 IRAK1 TRNW UNC93B1 TRNW TH PEX6 BCL6 POLR3A KRT8 PRKAR1A ERAP1 REST TREX1 IBA57 NTRK1 TRNK IFNG EPB41 ELANE NPM1 RAG2 NAB2 TNFRSF1A TRAF3 ND6 HMGCL IRF2BP2 ZFHX2 C4A PML PRTN3 BTK ND2 IL12B RNASEH2B TRNF CFHR1 ANK1 KLHL7 BTNL2 JAK2 RMRP WAS PTPN22 MVK NKX2-1 TCF3 IL12A RUNX1 ELP1 TRIM28 CACNA1S GFI1 SAMHD1 BCAP31 MEFV IL10 CCR1 PIK3R1 ADA WT1 CYP11B2 HAVCR2 LIG4 ATP1A3 IL7R ERCC4 LPIN2 IL36RN EPB42 HMGCL SH2B3 IL23R HLA-DPA1 NFKBIL1 LIPA IFNGR1 SRP54 STIM1 TBK1 ATP1A2 PTS SLC12A3 CIITA HLA-DRB1 XPC PTPN22 ND3
    Protein Mutations 7
    D312N E148Q K751Q P46L Q12H R92Q V600E
    SNP 2
    rs222797 rs2297201
    HP:0007359: Focal-onset seizure
    Genes 278
    LMAN2L GRIK2 POGZ CAMTA1 KCNQ3 TRNL1 SLC25A22 PIGP AIMP1 SCN1B POLR3A DMXL2 MICAL1 PRRT2 LINS1 CDH2 SMO GABRA1 STXBP1 CRADD KCNQ2 MTOR SLC25A10 FA2H ADRA2B GNB1 KCNQ2 PTPN23 SETD2 CHD2 RELN CNTN2 MED25 PDGFB NDST1 SRPX2 CRBN GALNT2 PIGC CNTNAP2 ERMARD SCN1A SCN1A BRAT1 SCN1B FBXO31 SDHD RSRC1 PRSS12 TSC2 MAN1B1 STX1B TRNQ SMARCE1 BAP1 COX2 TUSC3 SDHA SEC31A TICAM1 TUBB3 KCNJ11 SCN2A NHLRC1 C12ORF4 NSD1 TBC1D24 OPHN1 SMS FOXG1 KCNQ3 SLC13A5 KCNA1 SYN1 ACSF3 DMXL2 GABRD FLNA ADGRG1 MED23 EPM2A COQ2 TRIM8 SCN1A TBC1D24 MAP1B PNPLA8 TRNH HNMT TMTC3 GRIA2 CACNA1D SCN1B MBOAT7 PI4KA SLC22A5 FIG4 EPM2A CUX2 COX3 VAMP2 GRIN2A SCN2A CYP26C1 ND1 POLG SCN8A ARF1 SCN2A WASHC4 MTOR FMN2 SLC12A3 AP4S1 GABRG2 SZT2 KDM5B TBC1D24 GABRD SRPX2 GABRB3 CARS2 MAP1B ARFGEF2 SDHAF1 DCX TSC2 GRIN2A CLCNKB TRNS2 TRNS1 HCN1 CHRNA4 PRRT2 PCDH19 SCN1A MARCHF6 TERT CTNND2 TUBB2B PIK3CA CLCN4 SCN2A SCN9A KCNA1 KCTD7 ZEB2 GAL NF2 DNM1 SRPX2 ATXN10 ND4 CDKL5 DYNC1H1 ND5 SUFU NEUROD2 CASK GAMT ARHGEF9 TSC1 TBCK ATP1A2 IQSEC1 NEDD4L BAP1 GABRG2 EXTL3 FIG4 COX1 CLN8 GABRA5 SLC45A1 SCN1A NGLY1 PAFAH1B1 NSUN2 B3GALNT2 SMARCB1 YEATS2 PUS3 EZR LAMA2 KCNMA1 PHGDH MAPK10 PRRT2 SIK1 SIK1 CDKL5 SCN2A SLC12A5 LGI1 CDKL5 STXBP1 RELN KCNQ2 TLR3 DCPS APC2 TBC1D24 PLCB1 AP2M1 CLIP1 ST3GAL3 PIGQ TSC1 SLC25A22 TNIK TRNW UNC93B1 SRPX2 SCN9A METTL23 STRADA KCNQ3 AKT1 PCDH19 SCN1B WARS2 ADGRV1 CLN8 SCN8A CC2D1A PCDH19 TRAF3 ND6 GRIN2A PGAP1 TRAPPC9 CEP85L TMEM231 TRAF7 ARX TRNF SARS1 GABRG2 EDC3 PDSS2 TECR CACNA1A DNM1L HACE1 NHLRC1 TANGO2 PIGQ PNKP MARCHF6 RARS1 SCN1A SAMD12 FRRS1L PYCR2 FMN2 VPS11 ZC3H14 PCYT2 CNTN2 MTHFR STX1B PRRT2 GABRA1 PACS1 RPL10 SCN9A CPA6 TBK1 KCNT1 MBOAT7 ZEB2 PRRT2 DOCK7 PRRT2 GLI3 CRIPT GNAO1 SDHB
    Protein Mutations 0
    SNP 0
    HP:0002578: Gastroparesis
    Genes 28
    POLG UCHL1 SON TMEM70 POLG PODXL PRKN EIF2AK2 VPS13C POLG ATP7A SNCA TWNK LRRK2 SYNJ1 PINK1 DNAJC6 POLG POLG2 PARK7 SLC25A4 POLG TWNK TWNK HTRA2 POLG2 RRM2B TYMP
    Protein Mutations 0
    SNP 0
    HP:0002197: Generalized-onset seizure
    Genes 373
    LMAN2L AP2M1 TBC1D24 GLB1 KCTD7 TRNS1 GRIK2 ND4 KCNMA1 PRDM8 ARX SLC25A22 PIGP AIMP1 SCN1B GPHN DPM2 MID2 PRRT2 LINS1 ZNF41 TRIT1 RAB39B CNKSR2 GRN USP27X RNU4ATAC GABRA1 STXBP1 CRADD PAK3 MTOR CAMK2A CILK1 GABRA1 TARS1 ADRA2B KCNQ2 CDKL5 SETD2 CHD2 GABRB3 GBA MED25 PIGA COG2 NDST1 CILK1 DMD NUS1 DHFR CRBN FTL IQSEC2 CPLX1 PIGC RELN PIGT ADGRG1 CNTNAP2 FTSJ1 HCFC1 EHMT1 SCN1A APC2 EFHC1 KCNMA1 SCN1A BRAT1 PTRH2 BTD SCN1B FBXO31 SDHD RSRC1 TBC1D24 PRSS12 SIK1 GTF2E2 EFHC1 TRNL1 ALDH7A1 ELOVL4 MAN1B1 UPF3B SLC9A6 STX1B GABRD TUSC3 SDHA SEC31A PCDH12 SCN2A NHLRC1 C12ORF4 SLC6A1 NSD1 TBC1D24 OPHN1 FGFR3 SMS DPM3 CXORF56 LNPK PRRT2 KCNQ3 ATP6 SLC2A1 ACSF3 DMXL2 SLC2A1 GABRD ZNF711 GATAD2B TRNQ ERCC3 MED12 DLG3 MED23 EPM2A TRIM8 USP9X EFHC1 RPS6KA3 TRNK TRNP INS SMARCA2 JRK HNMT KCNMA1 SCN1B GNAO1 MBOAT7 SYNGAP1 MPLKIP EPM2A SPATA5 CACNA1H CUX2 PIK3CD SMPD1 GABRG2 CLCN4 SCN2A PIGM TRNI ND6 CACNB4 SCN8A WASHC4 TRAPPC9 FMN2 GDI1 GABRG2 SZT2 WAC KDM5B GABRD GCK SRPX2 GABRB3 ARHGEF6 CARS2 PSAP KCNQ2 ND5 SCN1B GDI1 SDHAF1 HACE1 DCX GRIN2A TRNL1 STXBP1 CSTB HCN1 PCDH19 SCN1A MARCHF6 SCARB2 CTNND2 TK2 CLCN4 SAMD12 SYP PLAGL1 ND1 PRICKLE1 SCN2A SCN9A GABRG2 KCNA1 KCTD7 ZEB2 SLC9A6 GALC NEXMIF CLCN2 GBA TRNF DNM1 HYMAI ATXN10 CDKL5 GLUD1 RNR1 NEUROD2 CASK GAMT ARHGEF9 SLC6A1 AFG3L2 TSPAN7 SLC25A15 IQSEC1 MFSD8 SLC25A15 ERCC2 GABRG2 EXTL3 TRNF PDX1 NDUFA1 GABRA5 SLC45A1 SCN1A NGLY1 SLC35A3 PAFAH1B1 SLC12A5 PSAP NSUN2 BUB1B B3GALNT2 YEATS2 EZR LAMA2 PHGDH TRNV MAPK10 SIK1 SIK1 CDKL5 DHDDS SCN2A TRNH KCNQ3 PLAA ALMS1 CDKL5 STXBP1 MED13 AGTR2 ATP1A1 KCNQ2 JRK DCPS APC2 PLCB1 TRNK AP2M1 ALDH5A1 NFKB2 CLIP1 EFHC1 CUX2 CHD2 ALG13 ST3GAL3 CACNB4 STAT3 SON SLC25A22 TNIK AP3D1 TRNW SCN9A METTL23 KCNQ3 GOSR2 PCDH19 SCN1B TRNP ADGRV1 TRNK ASAH1 ASAH1 TBCD CC2D1A PCDH19 CPLX1 NDE1 ANO10 GRIN2A PGAP1 HCN1 TRAPPC9 IL1RAPL1 CLCN2 CEP85L ACSF3 ALDH5A1 ARX ND2 SLC25A22 SARS1 GABRG2 KCNMA1 EDC3 NEU1 SLC9A7 TECR DNM1L DYRK1A WDR26 TMX2 HACE1 MECP2 KNSTRN NHLRC1 TANGO2 PTCHD1 PIGQ XK OSTM1 NTNG1 PNKP NUBPL KCNJ11 ASPA RNF113A MECP2 SCN1A RORB SAMD12 FRRS1L ATAD3A GABBR2 ZC3H14 KCNT2 PCYT2 IER3IP1 CNTN2 MTHFR STX1B ZNF81 PRRT2 GABRA1 GABRB3 GTF2H5 RPL10 SCN9A FRMPD4 GABRA1 ND5 STXBP1 CHD2 ADGRV1 MBOAT7 ARX ZEB2 PRRT2 DOCK7 TRNS2 GBA TRNL1 ACSL4 GNAO1 ABCC8 ND3 AFG3L2 SDHB
    Protein Mutations 0
    SNP 0
    HP:0012174: Glioblastoma multiforme
    Genes 27
    TGFBR2 MLH1 MLH3 BMPR1A EPCAM PMS1 FAN1 MSH2 TP53 PIK3CA MSH2 MLH1 MSH6 RPS20 SEMA4A TP53 PMS2 MDM2 APC PMS2 BRCA2 CHEK2 IDH1 KRAS MSH6 CDKN2A ERBB2
    Protein Mutations 31
    C797S G12D G13D G20210A G719A K27M K650E K656E L858R L861Q P13K P140K R132C R132G R132H R132L R132S R132V R140L R140Q R140W R172G R172K R172M R172S R172W T790M V600D V600E V600K V600R
    SNP 1
    rs17782313
    HP:0012538: Gluten intolerance
    Genes 2
    NRXN1 CNTNAP2
    Protein Mutations 0
    SNP 0
    HP:0001997: Gout
    Genes 24
    PRPS1 HNF1B PFKM EPB42 APOE SLC37A4 CLCNKB LRP6 SLC12A3 ANK1 MUC1 SPTA1 G6PC SLC4A1 SPTB SLC37A4 DNAJB11 UMOD SEC61A1 HPRT1 HPRT1 HPRT1 HPRT1 UMOD
    Protein Mutations 0
    SNP 0
    HP:0001395: Hepatic fibrosis
    Genes 150
    NPHP1 AP1S1 WDR35 PEX1 TNPO3 IARS1 GLIS3 SCYL1 CTNNB1 TMEM107 SDCCAG8 DYNC2H1 CC2D2A CC2D2A PNPLA6 DLL4 INSR IFT122 LIPA SCYL1 HBB ABCD3 MET HBB MKS1 DYNC2I1 BBIP1 MKS1 ASAH1 BBS2 BBS1 BBS12 HAMP BBS1 IFT27 ARHGAP31 NPHP3 NPHP1 IFT140 FADD TNFSF15 GPD1 NPHP3 DLL4 PHKA2 RINT1 WDR35 POU2AF1 DYNC2I2 C8ORF37 CCDC28B CEP164 TRAF3IP1 MST1 GPC1 RPGRIP1L CC2D2A BBS7 NPHP4 PHKG2 ALMS1 GPR35 TMEM67 CC2D2A RPGRIP1L TRAF3IP1 NPHP3 CEP290 PYGL TTC37 PMM2 FADD DCDC2 PKHD1 NHP2 TRIM32 CEP290 OFD1 IL12A SKIV2L DZIP1L BBS5 PMM2 TMEM231 IFT172 TMEM67 MMEL1 ALG9 KIF3B PTRH2 IRF5 AGL RPGRIP1L MKKS WDPCP TCF4 TMEM67 INPP5E TALDO1 CYP7B1 IFT172 WDR19 ABCB4 BBS4 SLC25A13 IL12RB1 B9D2 TCTN2 NEK1 TMEM67 INPP5E PKHD1 TMEM67 LZTFL1 ARL6 BBS10 NOP10 HJV SPIB CSPP1 MPI ANKS6 SLC40A1 SDCCAG8 NEK8 BBS9 TMEM67 TTC37 CEP290 ASL DOLK DOCK6 SLC40A1 DGUOK IFT80 TTC8 EOGT WDPCP CEP55 ARL6 INVS MTTP B9D1 MPI TMEM216 PLIN1 RPGRIP1 IQCB1 NOTCH1 RBPJ
    Protein Mutations 7
    C282Y C677T G20210A H63D Q80K R506Q V617F
    SNP 0
    HP:0001397: Hepatic steatosis
    Genes 141
    TRMU AGPAT2 IARS1 HADH FOS ACADM CAV1 HFE LMNA CBS CPT2 CAV1 MRPL44 LMNA LIPA SLC25A13 SKI PPARG AKT2 LYRM4 TARS2 CYP7A1 HADHA HNF4A MRPS7 TYMP ACAD9 CAVIN1 TMEM199 ADK POLG BSCL2 ACOX1 BSCL2 PNPLA2 CYP19A1 LMNA PCK2 ETFDH GPD1 APOE PHKA2 RINT1 ETFA NGLY1 ABCG8 AGPAT2 PLIN1 DDOST HADH CIDEC TRAPPC11 LARS1 PHKG2 VCP ALMS1 HNRNPA1 CIDEC BCS1L TRAPPC11 LRPPRC PMM2 RMND1 IARS1 VPS33A COX15 ETFB EARS2 LMNA ABHD5 LDLR MCCC1 APOB TFAM HNRNPA2B1 LMNA RRM2B POLR3A PTRH2 CAVIN1 LIPE PNPLA2 CPT2 TKFC SLC25A13 SAR1B ATP6AP1 XRCC4 MPV17 ATP7B SLC25A13 CEP19 HNF1B BCS1L POLD1 NDUFAF1 PCSK9 FBP1 CPT2 ABHD5 SLC40A1 MARS1 BSCL2 POLG LIPE SLC40A1 DGUOK HADHB LMNB2 ACADM CPT2 FARSB ACADL NSMCE2 ABCG5 ALMS1 COA8 GABRD ALDOB PCK1 DNAJC19 DNAJC19 MTTP ACADVL PGM1 PPARG ACAD9 RERE PLIN1 LDLRAP1 PRDM16 PPARG CPT1A NSMCE2 KCNAB2 CLPB MPV17 ATP6AP2 SLC22A5 HSD17B4 CARS2
    Protein Mutations 4
    C282Y E167K H63D I148M
    SNP 10
    rs1260326 rs2281135 rs2293152 rs2294918 rs2854116 rs2854117 rs58542926 rs641738 rs73049 rs738409
    HP:0000752: Hyperactivity
    Genes 587
    LMAN2L ZIC2 KCNA2 SLC1A4 TRIO POGZ SLC25A22 PIGP TTI2 SETBP1 DYNC1I2 MID2 NODAL SPR LINS1 ZNF41 RAB39B LIMK1 CIC CNKSR2 SCN8A LHCGR UBTF USP27X EEF1A2 IGF1 NR2F1 NTRK1 CSGALNACT1 SIX3 STXBP1 ACTL6B CRADD SLITRK1 GP1BB GATA4 MTOR MLXIPL C12ORF4 PRKAR1A SEC24C PAH CHD2 SYNJ1 NSDHL DMD CRBN RLIM UBE3A FRMPD4 WWOX PIEZO2 TSHR DLL1 DISP1 FTSJ1 HCFC1 GAS1 ARF1 FOXH1 MANBA ELN IKBKG SETBP1 CXORF56 OCRL NF1 AFF2 TCF20 JMJD1C MAN1B1 UFD1 ZMIZ1 CREBBP FBXW11 CHRNA7 TSC1 DLL1 SIX3 GTF2I MBD5 MLH3 NECAP1 GNB5 C12ORF4 NSD1 GABRB2 FBXO11 PLA2G6 SATB2 FAN1 STS CXORF56 LNPK MSH2 FOXH1 SETD5 GABRA2 NAGLU SHROOM4 SLC2A1 CDON PTCH1 PPP2R1A TBX1 HERC2 MED12 NLGN1 TRAK1 GRIA4 USP9X TLK2 GAS1 SCN3A KIF11 TIMM8A PWAR1 HGSNAT TKT MBOAT7 AMT CACNA1H CUX2 CYFIP2 NODAL NBN CACNA1B CUL4B SLC1A4 KMT2A SHH DISP1 EBP RAD21 ABCD1 DDX6 CSNK2A1 PANK2 TRIO PPP1R12A GLI2 HIVEP2 PTCHD1 DYM NPAP1 TANC2 DISP1 KDM5B FGD1 SLC13A5 SLC6A8 SNORD116-1 SRPX2 FGF8 ARHGEF6 MAP1B GABRA5 TDGF1 TGFBR2 BCR GDI1 WDFY3 GLI2 FGF8 YY1 DDX3X HTT TUBB2B IFNG FGFR1 SYP CREBBP HERC2 GABRB3 BCORL1 NIPBL MKRN3 SNORD115-1 NDP CASK GAMT TSC1 TNIK AASS TSPAN7 FMR1 CDON WAC GRIN2D STAG2 PSMD12 DNM1 FLI1 ADSL SIX3 RAI1 GNE TMCO1 PRODH NSUN2 B3GALNT2 PIK3CA ZDHHC9 NKAP CAMTA1 RAI1 EZR MED12 RERE ZIC2 HDAC8 KMT2E ATRX RIC1 DCPS ASH1L PUF60 AUTS2 PAH SHOC2 RUSC2 GABRG2 KRAS ST3GAL3 DRD5 DOCK3 FGF8 PNKP CCBE1 SHH ARV1 STXBP1 GALC CNTNAP2 FMR1 STAG2 PCGF2 NODAL SLC1A2 TRMT1 PCDH19 PTCH1 ZIC2 NTRK1 SMC1A CLTC CC2D1A CPLX1 GAS1 PGAP1 TRAPPC9 GLDC SLC25A13 ARX NTRK2 PCNT KCNB1 PIGY TECR NDN MECP2 FLCN CDON DPF2 PTCHD1 PIGQ HCN1 KIF14 TRAPPC4 GRIN2A DNAJC21 PTCH1 FRRS1L DNAJC12 GLI2 MKRN3-AS1 NSUN2 YME1L1 AARS1 ANK3 GABRB3 FRMPD4 GABRA1 CHD7 CRKL DHCR7 ZMIZ1 TRAPPC14 ACSL4 CLTC SNRPN PHF21A DPH1 KDM6B SMC1A PRNP MLH1 LIG4 NTNG1 GRIK2 AIMP1 GNAQ DYRK1A UQCC2 HDC SH2B1 CDH2 ANK3 SMC1A PAK3 TCF20 IQSEC1 ADNP NRXN1 CDK19 TKT DHTKD1 SETD2 RREB1 MED25 BMPR1A ARVCF YWHAG NDST1 PANK2 PMS1 IQSEC2 PIGC CLIP2 SIM1 TBX1 SETD5 SYNGAP1 PPP3CA CNTNAP2 CC2D1A ODC1 SPG7 FBXO31 BAZ1B ZSWIM6 RSRC1 ACTL6A TBC1D24 PRSS12 METTL5 RAI1 STAG2 SHANK3 UPF3B NSDHL MED13 EBP RFC2 SIX3 KIF15 TUSC3 AP3B2 TDGF1 THRB ATR CACNA1A SGSH PRKCG PDE4D SCN2A HAL OPHN1 AFF2 USP7 FGF12 EP300 ARG1 SEMA3E ACTL6B SHANK3 DMXL2 ZNF711 GATAD2B CDON OPHN1 DLG3 MED23 TRIM8 KMT2A RPS6KA3 CDK8 PARS2 PPM1D DRD4 TAF6 JRK HNMT MED12 MED12L MYT1L RAI1 ZIC2 MYT1L ARID2 EPCAM CRBN SLC6A8 SMPD1 GABRG2 FOXH1 WDR62 CLCN4 UBA5 HUWE1 STS MCTP2 TRIP12 FGF8 WASHC4 MAGEL2 CORO1A SHROOM4 EP300 PHIP FMN2 TGIF1 WAC PSMD12 NTNG2 RAB39B GABRB3 UBE3A HDAC4 KRAS DHCR7 PTCH1 SH3KBP1 ADNP TDGF1 TSC2 SHH SMARCC2 CARS1 GLI2 CLCN4 RPS20 PNP DHDDS GAS1 TRAPPC9 KCNA1 NEXMIF BPTF RERE DNM1 GNE COMT TBX1 TGIF1 PAK3 SPRED1 GLUD1 BSCL2 WAC ACY1 GTF2IRD1 NEUROD2 STAG2 SCN8A ATRX NUS1 KCNA2 IQSEC1 NFIX DEAF1 MED13L PAH GABRG2 PTCH1 FGD1 DALRD3 SLC45A1 SATB2 SCN1A ADAT3 YWHAG SMC3 FOXH1 APC2 KCNK9 CUL4B TAF1 MAPK10 FLII BSCL2 SIK1 TSHR CNKSR2 HOXA2 TGIF1 SEMA4A CDKL5 MED13 AGTR2 ATP1A1 IPW VPS13A MECP2 APC2 ALDH5A1 ASPM SZT2 CLIP1 ALG13 IL1RAPL1 TDGF1 UPF3B TNIK DLL1 METTL23 BCORL1 DYRK1A TET3 SHH NOP56 TGIF1 MED12 SCN1B EP300 GATAD2B HSPG2 MSH6 INPP5E PWRN1 IGF1 ADAT3 FOXP1 GRIN2A FGFR1 TBX1 SIN3A IL1RAPL1 KANSL1 CREBBP SARS1 ELN EDC3 ALKBH8 TSC2 GCSH SLC9A7 POLA1 PUS7 MAPK1 NKX2-1 SOX5 ATP6V1A PNKP FOXP1 DDX3X KDM3B NODAL DPP6 BCAP31 KAT8 TSHR TBL2 DLL1 MID2 MED12 HIRA ZC3H14 IQSEC2 SVBP ZNF81 RSRC1 PMS2 DLL1 FGFR3 CNKSR2 ARX PDE4D TANC2 NBN GNS TBL1X TTI2 DPYD GNAO1 DISP1 SH2B1
    Protein Mutations 0
    SNP 0
    HP:0002487: Hyperkinetic movements
    Genes 32
    CACNA1B SYT1 PNKD NEUROD2 GNAO1 CACNA1E PTS SLC6A3 GNE NGLY1 FOXG1 PSAP THOC2 ZNF142 GCH1 SYT1 YME1L1 PRRT2 TRAPPC11 TRAPPC11 VPS13A NGLY1 RTTN ALDH5A1 PDE10A PYCR2 FRRS1L SLC9A6 IQSEC2 THOC2 GRIN1 SUCLA2
    Protein Mutations 1
    T380A
    SNP 0
    HP:0000822: Hypertension
    Genes 421
    ELN FBN1 SDCCAG8 PRKAR1A ALX4 LIMK1 PDE11A NR3C2 FBN1 KCTD1 VHL GP1BB ANGPTL6 ENPP1 MLXIPL NKX2-5 LEMD3 NOTCH2 SLC37A4 RET SEC24C BBS12 NPHP1 MMP14 EGFR HLA-DPB1 KCTD1 ABCG8 SCNN1A SLC25A11 COX3 CYTB TRAF3IP1 HGD MEF2A VHL PKD1 TRIP13 GANAB RPGRIP1L ITGA8 CDH23 BBS7 ELN DIS3L2 SMARCAL1 GATA5 PKD2 NPHP3 KIF1B JMJD1C UFD1 ARMC5 CCR6 SERPINA6 KLHL3 LMX1B BRCA2 GTF2I YY1AP1 TNFRSF11B LMNA CTLA4 G6PC NOTCH1 MDM2 WDR19 MAFB TRPC6 RET LMNA ERCC4 XYLT2 SDHB CACNA1D TMEM67 LZTFL1 ERCC4 COQ7 MYLK KIF1B PTPN22 COL4A5 NPHP1 DNMT3A SCNN1A CACNA1D BBS9 CDH23 WT1 FGFR2 TGFB2 GLA BICC1 TTC8 ND1 ADA2 WDPCP ARHGAP31 ARL6 AIP FGFR2 ALMS1 INVS FBN1 VHL WT1 IDUA SMAD4 CFHR3 PDE11A WNK1 NPHP1 WRN SLC2A10 SMAD6 OSGEP ABCC6 LRIG2 SDHB PRKACA FLT1 INVS HBB POU3F4 NOTCH3 LMNA MC4R PRKACA HLA-DRB1 TRNK MYH7 HSD11B2 MYH11 VANGL1 EDA2R PHF21A MDH2 MKS1 BBS2 DNAJB11 TSC1 CFB MTRR GNAS MTTP PRKAR1A LMNA NF1 MUC1 ND6 HPSE2 CYP11B1 CUL3 EDA NPHP4 ALMS1 VAC14 TRNK SMAD4 THBD OFD1 STAT2 BBS5 SDHD PRKAR1A HMBS APOB ECE1 KCNJ5 REST RET MKKS FMO3 PRTN3 ERCC6 PKHD1 CFHR1 LRP6 CYP11B2 BBS10 SDHD FN1 PCSK9 CBS ZMPSTE24 SDCCAG8 ERCC8 CDKN1A IRF5 C3 TRNL1 PKD1 FUZ COX1 HLA-DPA1 MGP PLIN1 LDLRAP1 CLCN2 SH2B3 LYZ LOX MFAP5 GNAS CYP17A1 CYP11B1 B2M TMEM127 KCNJ5 PAM16 NR3C1 ACAT1 TRNK CDKN1B MEN1 SDHAF2 WT1 STAT1 BNC2 TGFB3 HMBS USP8 BBIP1 LMX1B GANAB HLA-B PDE8B IFT27 LMNA RREB1 MMP2 CYP11B1 TRNL1 ARVCF MLX GCH1 ABCC6 CLIP2 C8ORF37 OFD1 TBX1 CEP164 JAK2 NFU1 FH GJA1 SDHC BAZ1B CFH CYP21A2 JAK2 CEP290 CD2AP TRNQ TRIM32 STOX1 RFC2 AIP RET CYP11B1 LDLR SPRY2 TMEM70 NDUFAF6 GUCY1A1 WT1 CDKN2C TRNF POU6F2 ADA2 IFT172 ADAMTSL4 TRIM28 GNAS BMPR2 TMEM127 PKD2 CORIN CAV1 PRKG1 ABCB6 VHL SLC25A11 EXT2 MAT2A NFIX XPNPEP3 KCNJ5 GBA SCNN1B MAX CACNA1H ENG AIP ACTA2 TRNW ARMC5 H19 SDHD TRNS2 TSC2 COL4A4 BRCC3 FGA PDE3A USP8 SCNN1B FIG4 COX2 ELP1 WDR35 INF2 GPC3 SDHC ACTN4 ABCC6 SCN2B SLC2A10 TRNV SDHA COMT CYP17A1 WNK4 TBX1 SMAD4 BSCL2 ENPP1 SCNN1G BBS1 SUGCT GTF2IRD1 GLA CFI ACVRL1 MPL NOS3 BBS1 APRT APOA1 FOXE3 MAX TGFBR2 XYLT1 TP53 CCDC28B NOD2 ADA2 PLIN1 DLST CC2D2A FN1 COL4A3 BANF1 TGFBR3 SCNN1G LARS2 GDNF SLC37A4 PPOX PKHD1 CEP290 ACP5 KRT18 DZIP1L CCND1 ERCC8 GUCY1A1 TRNC CCN2 SMAD3 KRT8 SDHB FBN1 TGFBR1 SDHD POR COL4A3 BBS4 SDHB IL12B MYMK FMR1 ELN NF1 CEP19 CPOX ARL6 NR3C1 TET2 EPAS1 ND5 DYRK1B PDE3A ELP1 TRIM28 YY1AP1 CD46 TMEM237 TBL2 ERCC6 THSD1 CDKN2B HIRA ACTA2 WT1 KIF1B VHL NSMCE2 GPR101 COL3A1 ABCG5 HSD11B2 PPARG PPARG TNFRSF11A COL3A1 LEMD3 TRNS1 IQCB1 TRNE
    Protein Mutations 18
    A1166C A118G C282Y C344T C677T D565H E298D G1051A G1691A G20210A G308A G3514C G389R H295R M235T S49G T393C V617F
    SNP 9
    rs1017783 rs10177833 rs13333226 rs1801133 rs2398162 rs2540923 rs254093 rs5068 rs7571842
    HP:0000829: Hypoparathyroidism
    Genes 55
    LIG4 DGCR8 FAM111A TRNW TRNL1 TRNS2 TBCE TRNS1 DGCR6 FAM111A ND6 HBB IRX5 HADHA HBB GP1BB TBX1 COMT TRNF TBX1 ND4 TBCE ND5 TRNH SEC24C PTH COL4A5 NKX2-1 RREB1 ARVCF GCM2 COX1 COX3 HADHB TBX1 PIGT HIRA ESS2 TBCE PTH1R ND1 GATA3 NSUN2 GATA3 HBB ATP7B TBX2 JMJD1C UFD1 TBCE AIRE AIRE DGCR2 TRNQ COX2
    Protein Mutations 0
    SNP 0
    HP:0012418: Hypoxemia
    Genes 21
    FGFR3 SFTPB PTRH2 CNOT1 BTNL2 HBB ASCL1 SFTPC CSF2RB ABCA3 PHOX2B EDN3 RET GDNF HBB ZFPM2 GATA6 SLC35A1 FBN1 HLA-DRB1 CSF2RA
    Protein Mutations 2
    P317R R200W
    SNP 0
    HP:0000794: IgA deposition in the glomerulus
    Genes 5
    NUP107 NUP107 SPRY2 COL7A1 MMP1
    Protein Mutations 0
    SNP 0
    HP:0006515: Interstitial pneumonitis
    Genes 9
    SFTPB TERC PLCG2 RAG1 TINF2 SFTPC TERT FOXP3 STAT3
    Protein Mutations 1
    S1009A
    SNP 0
    HP:0006530: Interstitial pulmonary abnormality
    Genes 161
    GAS8 TERT DNAL1 ZCCHC8 NUP107 BTNL2 RAG1 TERT CCDC40 RSPH4A DNAJB13 CCDC39 STAT3 ODAD3 DNAH9 HLA-DRB1 HLA-DRB1 SFTPA2 BACH2 TTC12 GBA MUC5B ABCA3 FAS DSP SCARB2 HLA-DRB1 ASAH1 DNAAF2 CCR6 TERT FAS DNAI2 CFAP221 GBA SPEF2 STING1 PLCG2 PLEC ODAD4 RNF168 HLA-DPB1 OFD1 ATP11A RTEL1 IL1RN HPS4 NME8 ODAD2 DRC1 DNAAF4 SFTPC DNAAF6 DNAH5 SP110 RTEL1 CSF2RB STN1 SPIDR POLR3H PARN IRF5 DNAAF3 FOXJ1 GAS2L2 CCDC103 ODAD1 CCR6 NHP2 ABCA3 STK36 DPP9 CYBC1 HPS1 SFTPA1 SFTPB CCDC65 FAM111B LRRC6 AP3D1 NDUFAF6 CLCA4 STX1A CCN2 ZMYND10 BNC1 CTLA4 COPA DNAI1 TERC TERC MUC5B ERF RAC2 SFTPA2 TERT DNAH11 DNAAF1 CCNO TGFB1 BMP15 AP3B1 CFTR PRTN3 PRKCD RCBTB1 FSHR BTNL2 PARN NOP10 PTPN22 NEK10 RPGR CSF2RA TERT NR5A1 NKX2-1 MARS1 RASGRP1 DNAH1 CAV1 DKC1 LRRC56 NSMCE3 DCTN4 IRF5 CCN2 SMPD1 HYDIN BMPR2 CAV1 SFTPB TINF2 RSPH9 SFTPC MRPS22 RSPH1 RNF168 TERC CFAP298 MCIDAS PSMC3IP TINF2 FARSB MARS1 GBA KIAA0319L HLA-DPA1 SPAG1 CFAP300 RSPH3 DNAAF5 FASLG UNC119 ITGA3 SFTPC HLA-DRB1 FOXP3 THOC2 CASP10 FAM13A
    Protein Mutations 0
    SNP 0
    HP:0100512: Low levels of vitamin D
    Genes 19
    RPS10 DZIP1L EFL1 FARSB SRP54 OCRL GPR35 SBDS MTTP COL7A1 ACOX2 MMP1 DNAJC21 GALNT2 RPL11 MST1 TCF4 PKHD1 COL7A1
    Protein Mutations 0
    SNP 4
    rs10766197 rs1790349 rs2060793 rs4588
    HP:0001888: Lymphopenia
    Genes 151
    MSN NHEJ1 CR2 RAG1 RFXANK LEPR IL2RA ATM CD81 CD3E WDR1 PGM3 IL2RG CD3G FOXN1 AK2 ZAP70 IL2RG PNP FOXN1 CD247 DOCK2 WIPF1 CD3D STAT1 ZBTB24 FAS DCLRE1C EXTL3 ELANE DNMT3B PSMB9 TERT FAS STAT4 PGM3 G6PC3 MS4A1 NFKB2 CD19 STK4 EXTL3 ADAMTS3 TCIRG1 NFKB1 TCF3 SAMD9 IKZF1 RFXAP CHD7 TNFRSF13B HELLS FAT4 MDM4 IL7 ATM SMARCAL1 SP110 XRCC4 TTC37 NFKB2 TRNT1 CD247 CTPS1 MYC PNP MYD88 ADA RAG1 ICOS RAG1 CDCA7 RFX5 GFI1 BCL11B CYBC1 RMRP CD3D PRKCD GATA2 PSMB4 SKIV2L IRAK1 WAS JAK3 RAG1 RAG2 SGPL1 SPP1 TERC PTEN ELANE RAG2 CXCR4 RAC2 CTLA4 DNMT3B MAGT1 CIITA MYSM1 LEP RAG1 PRKCD CCBE1 ACP5 MTHFD1 WAS KNSTRN LCK PTPRC SEMA3E RASGRP1 RAG2 ICOS IL7R CD3E GFI1 EPG5 NSMCE3 TCN2 PIK3CD TINF2 TNFSF12 RAG2 TPP2 RAC2 TFR2 IVNS1ABP IL7R TNFRSF13C RRAS2 CORO1A PIK3R1 PIK3CD WIPF1 SRP54 PTEN TNFSF12 IGHM ADA FASLG UNC119 SMARCAL1 DOCK8 TNFAIP3 NBN TTI2 FOXN1 CD8A STAT1 CASP10
    Protein Mutations 0
    SNP 0
    HP:0001268: Mental deterioration
    Genes 494
    PRDM8 KCNA2 VCP TRNL1 TBP SNCB DNAJC13 PNPLA6 MAPT RBM28 COMT PDE11A SCN8A PSEN2 ERCC8 PRNP ERCC6 GRN TREM2 EEF1A2 FTL HFE SNCA GBA2 ACTL6B TYMP SNCA HTT MAPT TTR CHD2 SYNJ1 TRNE C19ORF12 SYNJ1 NPC1 ABCC8 ATXN2 WFS1 C9ORF72 CSTB WWOX COX3 CYTB MFN2 ZFYVE26 PRKN NDP CHI3L1 ADH1C ACTB LRRK2 AUH TLR3 MAPT DNAJC6 GDAP2 SLC44A1 CHCHD10 TINF2 CREBBP C9ORF72 COX2 SDHA PMPCA CUBN NECAP1 PDGFB NHLRC1 GABRB2 PLA2G6 PINK1 GABRA2 WDR45 NAGLU CHMP2B NOTCH2NLC TOMM40 GALC TRAK1 CSF1R CHMP2B COL18A1 VCP SCN3A JAM2 ARSA TIMM8A HIBCH TREX1 TRNH MATR3 CHMP2B HGSNAT LYST GRN MPO PRNP APP TREM2 CUX2 PPP2R2B CYFIP2 NBN CACNA1B COASY ND1 ADA2 CLN6 CST3 ATP6V1A SQSTM1 CLN6 MECP2 ABCD1 DNAJC5 PDGFRB TREM2 PSAP SLC13A5 HNF4A ATP6V1E1 ATXN2 MYORG GBA SLC20A2 FMR1 COL4A1 HLA-DQB1 SLC13A5 ATXN7 PLP1 SCARB2 PSAP GABRA5 GRN PSEN1 TYROBP PSEN1 ATN1 RNF216 CHMP2B NRAS APOE TRNS2 TRNS1 NOTCH3 HTT XPR1 ROGDI NR4A2 TK2 SURF1 SNCA PSAP CREBBP SPG11 TRNK APP OPA1 MAPT RRM2B TBK1 DGUOK GBA2 ITM2B WFS1 TARDBP ND4 PDE10A POLG APP APOL2 GBA TUBA4A ND5 LRRK2 SLC6A1 SPG21 PANK2 UBAP1 PSEN2 GRIN2D MFSD8 PRKAR1A DNM1 CP COX1 PRNP SORL1 CLN8 UBQLN2 CYP27A1 ND6 RAB27A GALC HEXA PRDX1 MAPT A2M QDPR ATP6 APP MMACHC VCP CERS1 SNORD118 ALDH18A1 HNRNPA2B1 TRNK TBK1 TYROBP GABRG2 SQSTM1 HTRA1 AARS2 SUMF1 ARV1 STXBP1 GALC FA2H DCTN1 HTT SLC1A2 RRM2B TIMM8A CLN8 CLTC ASAH1 ASAH1 CPLX1 SLC2A3 HSD17B10 NDUFAF3 NTRK2 PPT1 TRNF GBE1 KCNB1 MAPT FTL VCP C9ORF72 PLA2G6 NHLRC1 DNM1L HEXB ERCC8 UCHL1 PSEN1 POLG MAPT HCN1 PSEN1 PLAU FBXO7 APOE MAPT CHCHD10 UCP2 MTHFR SNCAIP AARS1 TRNL1 ATP7B COX1 NDUFA6 DISC2 PARK7 PTS CTC1 AP2M1 GLB1 PRNP GIGYF2 PSAP GRN IRF6 C9ORF72 TREX1 APP PDGFRB KCNC1 ATP13A2 SMC1A PINK1 PPP2R2B HMBS PRNP MAPT FA2H PRNP CDK19 GLUD2 PSEN1 TRPM7 SCO2 GBA SYN2 ATP6V0A2 IDUA PSEN1 PANK2 MCOLN1 RNASEH1 SYNGAP1 ROGDI PPP3CA CNTNAP2 DNMT1 KCNJ11 FUS GCH1 SNCA ATP1A2 DAOA SPG11 SYNJ1 TBK1 MAPT SCN1A SNCA SERPINI1 HNRNPA1 SDHD TBC1D24 VPS13C GCDH GBA APP ATP6 CSF1R PDGFRB DRD3 TRNQ TRNQ SYNJ1 DCTN1 SPG21 AP3B2 CACNA1A AP5Z1 TIMMDC1 PRKCG RTN4R TBP PODXL FGF12 TRNF ATP13A2 ADA2 VCP PLEKHG4 CTSD ATXN7 PDGFB C9ORF72 JPH3 EPM2A TTPA GNAS KMT2A CLN5 NPC2 PARS2 DARS2 JPH3 HNF1A ERCC2 DCAF17 HTR2A LRRK2 EPM2A VCP TMEM106B COX3 ALDH18A1 PRNP MATR3 ATP13A2 VPS13C TMEM106B SNCA ND1 VPS35 UBA5 EIF4G1 EP300 PRNP XPA GRN SQSTM1 MTHFR DNMT1 NDUFB8 GABRB3 TRNW PRDM8 TRNS2 TREM2 SDHAF1 CSTB ERCC6 COX2 TWNK GM2A ERCC4 RNF216 GBA ATXN10 DHDDS PRKAR1B KCTD7 GALC PRICKLE1 NDUFS2 DNM1 APP TRNV RBM28 BSCL2 TARDBP ATP1A3 NUS1 KCNA2 MAPT PAH DALRD3 SCN1A YWHAG TREM2 PLA2G6 SQSTM1 MAPK10 GBA MBTPS2 BSCL2 FA2H CNKSR2 SPAST RAB39B VPS13A ATN1 VPS13A CTNS ARSA SZT2 ATXN3 CLN3 MAPT CTSF ATXN2 MAPT APOL4 TRNW CHMP2B TRNC HNRNPA2B1 SGPL1 TBP NOTCH3 DNMT1 ND6 WDR45 ATXN8OS SUMF1 CFAP43 ITM2B FMR1 APTX LMNB1 UBTF ND5 ATP6V1A TUBB4A TREM2 CISD2 RRM2B ARSA HTRA1 ATP13A2 NOTCH2NLC ABCA7 PSEN1 NOS3 DMPK C19ORF12 HEPACAM TMEM106B CHD2 HTRA2 TRNS1 GBA SDHB
    Protein Mutations 3
    K56M V158M V66M
    SNP 10
    rs10524523 rs11126727 rs11126731 rs12467815 rs12472215 rs429358 rs6739405 rs6971 rs7412 rs993607
    HP:0003560: Muscular dystrophy
    Genes 154
    FKTN FKTN LMNA DNAJB6 DAG1 POMT1 SGCB ANO5 DMD ITGA7 DPM1 POMT1 POMT2 POMK LARGE1 COL4A1 PSAT1 LMNA FKTN ANO5 RXYLT1 POMK CAVIN1 CHKB DPM3 DYSF RXYLT1 SELENON INPP5K FKRP POMGNT2 BVES CEP57 FKTN LMNA LIMS2 SYNE2 POMGNT1 COL6A1 CAV3 TMEM43 COL6A3 LMNA POMT1 HNRNPDL PIEZO2 FKRP TMEM43 POMGNT2 POMK SIL1 FKRP LAMA2 TRIP13 PLEC GMPPB ACTA1 GK POMT2 LARGE1 TRAPPC11 HNRNPA1 MYH7 EMD POMT2 GMPPB TTN TRAPPC11 TRAPPC11 POMT2 COL6A1 SMCHD1 FKRP HNRNPA2B1 CAPN3 GMPPB SGCD RYR1 TRIM32 FHL1 LMNA FRG1 COL12A1 FKRP TTN B4GAT1 PLEC B3GALNT2 DYSF FKTN BUB1B CRPPA SYNE1 POMGNT1 LAMA2 SGCG TTN DMD DAG1 RYR1 BUB1 TCAP FKRP TRIP4 HNRNPA1 DAG1 POMT1 PNKP FKTN NR0B1 B4GAT1 POMT2 POMT1 CRPPA B3GALNT2 POMGNT1 SGCA POMGNT1 CRPPA COL6A3 FKRP SYNE1 GMPPB CRPPA AHCY LMNA LARGE1 POMT1 LIPE FKRP ANO5 CAPN3 POMT1 DAG1 COL6A2 POMGNT1 POMT2 PHGDH CRYAB TNPO3 TOR1AIP1 LARGE1 SYNE2 SGCA SELENON POMT2 POMK BAG3 COL6A2 CRYAB FKTN COL12A1 DPM3 BUB3
    Protein Mutations 0
    SNP 4
    rs10835211 rs165599 rs17601696 rs6265
    HP:0001658: Myocardial infarction
    Genes 76
    PTPN11 WRN SLC2A10 TLR4 IKZF1 LDLR GTF2I APOB MEFV KLRC4 IL12A-AS1 LPL SCNN1G ERAP1 CYP27A1 CBS LIMK1 CTNNB1 CALR LMNA C4A MYH9 ABCC6 TET2 IL12B CFTR LRP6 ENPP1 CEP19 PCSK9 GTF2IRD1 GLA MEFV HLA-B FAS ZMPSTE24 TP53 BRAF DYRK1B PIGA SH2B3 IL12A UBAC2 MLX IL10 LMNA CYP27A1 TBL2 ABCG8 CLIP2 HGD CCR1 STAT4 MEF2A VHL HLA-B HLA-B ELN SCNN1A MYH9 BAZ1B ABCG5 BRAF MPL IL23R JAK2 LDLRAP1 SCNN1B RAF1 RFC2 THOC2 SH2B3 ABCA1 JAK2 ABCA1 BCHE
    Protein Mutations 20
    A1166C C282Y C344T C807T G1051A G20210A G3514C G681A G98T H63D I843S L28P L33P M235T Q192R Q222R R389G S49G T174M V34L
    SNP 11
    rs10153820 rs16969968 rs1761667 rs4244285 rs4986893 rs6434222 rs6971 rs7586970 rs7903146 rs8069645 rs8176528
    HP:0100582: Nasal polyposis
    Genes 63
    GAS8 ODAD4 DNAL1 STK11 CCDC40 CCDC65 LRRC6 RSPH4A PTGER2 DNAJB13 CCDC39 ODAD3 ZMYND10 DNAH9 DNAI1 ECM1 ZMYND10 TAPBP TTC12 DNAH11 DNAAF1 CCNO LRRC6 TAP1 MCIDAS DNAAF2 DNAAF3 NEK10 RPGR DNAI1 TBX21 DNAI2 DNAH1 CFAP221 SPEF2 ODAD4 LRRC56 OFD1 HYDIN HYDIN STK11 NME8 ODAD2 RSPH9 RSPH1 DRC1 CFAP298 MCIDAS ODAD3 DNAAF4 DNAAF6 DNAH5 SPAG1 CFAP300 RSPH3 DNAAF5 DNAAF3 FOXJ1 GAS2L2 CCDC103 ODAD1 TAP2 STK36
    Protein Mutations 0
    SNP 0
    HP:0003811: Neonatal death
    Genes 28
    FGFR3 FLNB ETFDH GLE1 SUCLG1 ATAD3A FOXF1 ETFA HSPG2 GBA FLNB QRSL1 NDUFB11 GLE1 CEP55 INTU GLI3 GATC MBTPS2 PIP5K1C PKHD1 GALT FGFR3 ETFB GLUL DSP LBR FAM20C
    Protein Mutations 0
    SNP 0
    HP:0040187: Neonatal sepsis
    Genes 3
    COG4 IL7R SERAC1
    Protein Mutations 0
    SNP 0
    HP:0000112: Nephropathy
    Genes 111
    VPS33B NPHP1 WT1 B2M TRNL1 TRNS2 FAM20A TRNS1 CCND1 FGA CC2D2A SCNN1B SCARB2 TREX1 IFT80 HIC1 WIPF1 DYNC2LI1 TMEM237 WFS1 KCNJ11 ND4 OSGEP TMEM138 SCNN1G ND5 SEC61A1 MEFV DYNC2H1 LAGE3 DYNC2I1 IFT172 IFT140 TMEM216 APOA1 ZNF423 COX1 HNF4A BLK TP53RK SCNN1A NOD2 PRDX1 ABCC8 DYNC2I2 UMOD TTC21B CEL TMEM237 MMACHC MYH9 PRODH PAX6 SLC26A4 APPL1 CLDN19 TRNQ LMX1B RPGRIP1L ALG1 TMEM231 TPRKB WDR19 COX2 EIF2AK3 NEUROD1 TRNW WAS WT1 IFT140 WDR4 RPGRIP1L WDR73 MAFB ND6 NUP133 TMEM67 PDX1 INPP5E TRNF CEP290 VIPAS39 TRNH WAS CC2D2A CEP120 TTR NLRP3 CISD2 INS MAFB COX3 GLA WDR19 HNF1A ADA2 COL4A1 PAFAH1B1 PAX4 ND1 HPRT1 YWHAE KLF11 FOXI1 CPOX NUP107 WT1 GCK SAA1 LYZ KCNJ10
    Protein Mutations 0
    SNP 0
    HP:0001513: Obesity
    Genes 490
    NR2E3 WT1 LMNA TBX3 POGZ PROK2 DCC MID2 SDCCAG8 ZNF41 RAB39B LIMK1 CNKSR2 PRPF4 PDE11A RP2 USP27X BBS10 CTNNB1 KIDINS220 FGFR3 XYLT1 PDE6B TOPORS GP1BB BBS7 GATA4 ARL2BP KCNJ11 MLXIPL HS6ST1 CEP290 GHRL EGF TAF1 PRKAR1A SEC24C PROM1 BBS12 POMC NPHP1 CARTPT C8ORF37 APOE DMD ZBTB20 BBS2 SYNE2 BLK UBE3A CCDC141 TMEM43 FTSJ1 HCFC1 FEZF1 SOX2 CACNA1S CDH23 BBS7 EMD ELN IFT172 CEL MAGEL2 TMEM67 JMJD1C UFD1 NIN ARMC5 CREBBP MKKS PDE6A BAP1 FHL1 GTF2I NEUROD1 USH2A SIN3A KIF7 RBMX PCARE CXORF56 EXOC6B MCM3AP LEP TBX1 HERC2 MED12 PDX1 OTX2 USP9X ARL6 LZTFL1 PWAR1 ADRB3 BBS9 RPE65 REEP6 RLBP1 HNF1A ERMARD TTC8 POMGNT1 INPP5E WDPCP CUL4B SAG SDCCAG8 SDC3 HESX1 KMT2A BLK RAD21 SEMA4A MOG ATP6AP2 CEP164 ARL6 BBS12 POMC MAN1B1 CTSH ALMS1 HSD11B1 NPAP1 CDHR1 RERE BLM HCRT ARNT2 FLRT3 BBS4 ROM1 SNORD116-1 ARHGEF6 ZNF711 ZNF513 GDI1 GNAS VPS13B RP1 FTO DDX6 PCNT POU3F4 TULP1 DUSP6 MC4R PNPLA6 SYP CREBBP SPATA7 LMNA GABRA3 H6PD CA4 NIPBL GNAS MKRN3 FMR1 SNORD115-1 RP9 MC3R MKS1 BBS2 PHF6 SUFU GNAS-AS1 WDR11 TSPAN7 MERTK GNAS MTTP PRPF6 NR0B2 GNAS BAP1 PRKAR1A MYT1L HNF4A RAI1 DYNC2I2 RPGR BBS9 SMARCB1 NKAP RAB23 GUCA1B LAS1L ZNF365 ALMS1 PAX6 HDAC8 ATRX TRAF3IP1 HDAC8 KIAA1549 CNNM2 PROKR2 MOG SEMA3A BBS5 PAX6 LEPR LZTFL1 SYNE1 SNRNP200 MKKS SMC1A PRMT7 CNGB1 MEGF8 CLRN1 TTC8 MAPK8IP3 TRAF7 AKT2 SETD2 IQSEC2 PCNT PPARG P2RY11 HESX1 BBS10 NDN POMC RAB23 MECP2 SOX10 PRPH2 PTCHD1 KCNJ18 BBS2 INS ACADVL LIPE KMT2D DHDDS WNT4 HLA-DQB1 MKRN3-AS1 KLF11 IDH3B TUB BBIP1 CCDC141 FRMPD4 CNGA1 ARL13B ADCY3 ACSL4 SNRPN PHF21A GNAS GNAS TBX3 STX16 ARL3 SH2B1 TUB SMO HUWE1 SHOX CYP7A1 NEK2 PRPF3 PAK3 RDH12 TCF20 USP8 IFT172 BBIP1 FGF8 ADNP IFT27 CYP19A1 ARHGEF18 RREB1 ABCA4 SLC10A7 PDGFB LRAT ARVCF PKDCC IQSEC2 MTFMT CLIP2 C8ORF37 SIM1 TBX1 BEST1 PIGT SETD5 PDSS1 EHMT1 SPG11 SCAPER ZNF408 RPS6KA3 SIM1 SH2B1 BAZ1B BRAF SLC25A4 P4HTM CEP290 C8ORF37 APPL1 UPF3B ENPP1 TRIM32 AFF4 SMARCE1 RFC2 AIP RNPC3 PRCD DHX38 UCP3 IFT172 BBS5 SLC7A14 PDE4D ATRX WT1 FAM161A ANOS1 SHANK3 IFT172 FGFR1 ZNF711 MC4R LEP DLG3 NSMF PNKP GNAS MAGEL2 RPS6KA3 KIZ SLC7A7 ADRB2 RAI1 MEGF8 AFF4 HDAC8 FXR1 GNAS CLCN4 PSMD12 PHF6 OFD1 PAX4 TRIP12 MAGEL2 GABRD EP300 TRAPPC9 SOX3 PHIP PTEN KCNAB2 WAC NDNF FGF17 ARMC5 HDAC4 SH3KBP1 IMPG2 LARS2 HACE1 ADNP AGRP LEPR PROK2 IL17RD AGBL5 USP8 TERT BPTF THOC2 PIK3CA SKI AHR TRAPPC9 CRX CRB1 PRMT7 KISS1R NF2 COMT TBX1 IMPDH1 SMAD4 BBS1 GTF2IRD1 EIF2S3 BBS1 PRPF31 PCSK1 KLHL7 DEAF1 COL10A1 AKT2 SMC3 CCDC28B CUL4B ABCC8 FLII DPYD PDE4D NRL PDE6G RBP3 MRAP2 AGTR2 VPS13B KDM6A IPW IGFALS PROKR2 MECP2 XRCC4 TRIM32 FGFR1 SPRY4 MKS1 ALG13 HGSNAT CERKL AKT1 RHO IDH3A RP1L1 EHMT1 EP300 PWRN1 IGF1 TACR3 SIN3A EYS EIF2S3 BBS4 IL1RAPL1 LAS1L IFT88 ARL6 CREBBP AHI1 CHD7 ELN CEP19 ARL6 PRPF8 SLC9A7 PCSK1 MAK SRY DNMT3A HACE1 HLA-DRB1 TTC8 TNFSF4 DYRK1B FOXP1 KIDINS220 OFD1 TBL2 BDNF RGR FSCN2 HIRA GHR NTRK2 IQSEC2 IFT74 ZNF81 XYLT1 ALB PRDM16 IFT140 IFT27 MAN1B1 ARX PDE4D SIM1 GCK IGF1R CANT1 SH2B1
    Protein Mutations 3
    G20210A P12A W64R
    SNP 17
    rs10163409 rs11548193 rs1544410 rs1558902 rs1761667 rs2075252 rs2228171 rs3755166 rs4343 rs45500792 rs571312 rs573112 rs58542926 rs731236 rs738409 rs7975232 rs9939609
    HP:0002758: Osteoarthritis
    Genes 84
    EXT2 COL2A1 TNFRSF11B MATN3 F8 AEBP1 KIF7 MMP13 CLCN7 CCN6 COL5A1 TRPS1 ZNF687 PHEX CLCN7 COL9A2 COMP KIF22 TRAPPC2 TGFB3 ACAN MATN3 COL2A1 GBA TRPV4 UFSP2 MATN3 ASPN HPGD COMP SCARB2 COL1A1 MIR140 MEFV TRAPPC2 COL11A2 ZMPSTE24 FGFR3 COL2A1 COL9A1 HLA-B COL2A1 COL5A2 FBN1 COL11A2 GNAS EXT1 COMP LMNA COL9A1 ANKH FRZB COL2A1 COL9A3 SLC40A1 HGD F9 SLC26A2 ACAN TRPV4 GHR COL9A2 COL11A1 SMAD3 ACAN GDF5 COMP PHEX AIP COL9A3 COL2A1 COL11A2 GPR101 COL3A1 COL1A1 CCN6 ATP7B COL5A1 UFSP2 SMAD3 MMP13 ANKH LMX1B CANT1
    Protein Mutations 1
    Q28D
    SNP 0
    HP:0100847: Palmoplantar pustulosis
    Protein Mutations 0
    SNP 0
    HP:0004950: Peripheral arterial stenosis
    Genes 31
    MFAP5 LMNA ELN LDLR PRKG1 FOXE3 APOB APOE TGFBR2 TGFB2 MYH11 JAK2 SMAD3 ABCG8 MAT2A TGFBR1 FBN1 MYH11 MPL ELN AGXT TGFB3 ABCG5 LDLRAP1 ABCC6 SMAD4 ACTA2 PCSK9 MYLK LOX THPO
    Protein Mutations 1
    G20210A
    SNP 0
    HP:0002090: Pneumonia
    Genes 272
    TBX20 DCLRE1C ZIC2 HLA-DQA1 GAS8 GRHL3 DNAI2 SFTPC CARD11 DNAJC21 CD81 NODAL PGM3 IL2RG GNPTAB ORC6 SFTPA2 CD247 NTRK1 TNFRSF13C SIX3 ACTA1 MUC5B LAMA3 IL2RG DNMT3B MED25 CHD7 TNFRSF13C EGFR ZBTB24 CACNA1C CYBB RNF125 NFKB1 CITED2 SMARCD2 SLC25A24 BLNK LRBA IRF8 DISP1 GAS1 KIAA0586 FOXH1 SFTPB CFTR KMT2D MAN2B1 LAMC2 P4HTM MASP2 CR2 CREBBP COL11A2 AFF4 ADA ICOS RAG1 FCGR2A CD3D SIX3 PRKCD DLL1 RANBP2 SIX3 TDGF1 PMM2 IL21R GATA4 WAS LTBP3 CFB KCNJ6 FOXH1 SGCG RNU4ATAC CDON TAF1 SLC35C1 LEP CDON EPM2A KDM6A UBB GAS1 FBLN5 ACP5 MCIDAS TBC1D24 CD79B MAN2B1 MTHFD1 TIMM8A SLC35A1 DNAI1 RAG2 ZIC2 BTK IL7R CD3E AFF4 PIK3CD NODAL NBN FOXH1 EFEMP2 NCF1 NFIX OFD1 RNF168 RAG2 SHH RAC1 DISP1 CD19 PANK2 TNFRSF13C FGF8 FANCF GLI2 IGLL1 ALMS1 SBDS EP300 CASP8 BLM ICOS DISP1 TGIF1 CRLF1 ADA UNC119 PIGN FOXP3 FGF8 TDGF1 PTCH1 NCF2 CR2 TDGF1 IL2RG GLI2 FGF8 NIPBL RAG2 WDR1 SHH BTK ZAP70 GLI2 TK2 FGFR1 CREBBP IL2RG GAS1 STAT3 DDR2 TGIF1 DCLRE1C GBA CFAP410 ELANE LAMB3 CDON IL7R MS4A1 NFKB2 STAG2 CD19 EXTL3 PTCH1 SIX3 TCIRG1 TBX20 PAFAH1B1 FOXH1 SAMD9 TNFRSF13B TGIF1 RAG1 ALMS1 NKX2-5 ZIC2 SP110 CD55 CYBA ACTC1 NFKB2 PEPD PNP PKHD1 FGF8 CYBC1 ACP5 TNFRSF11A CSPP1 WDR19 SHH DZIP1L TDGF1 DCLRE1C TLL1 JAK3 DLL1 STAG2 SHH NODAL POLA1 NOS1 TGIF1 PTCH1 ZIC2 ASAH1 TBCD CXCR4 RAC2 FGFR1 GAS1 EFL1 FMO3 HLA-DQB1 RYR1 SRP54 RAG1 BTK ABCA3 ZAP70 CARD11 SETBP1 USB1 SELENON RMRP KNSTRN NADK2 TERT CDON NHLRC1 NKX2-1 PTPRC GATA6 ICOS OSTM1 NODAL GFI1 ACADVL DLL1 PTCH1 TGFB1 TNFRSF13B KPTN TNFSF12 GLI2 ADA JAK3 LIG4 COL11A2 ODAD1 PLOD1 MYH6 DLL1 IFNGR1 SRP54 TNFSF12 IGHM RNU4ATAC SFTPC DOCK8 NBN FOXN1 DISP1 SMC1A
    Protein Mutations 6
    A2063G G551D K55R L460D R287Q S1009A
    SNP 0
    HP:0005764: Polyarticular arthritis
    Genes 21
    ANKRD55 ENPP1 PADI4 IL36RN PTPN22 NFKBIL1 SLC22A4 IL2RA IL10 MEFV STAT4 NOD2 NLRP1 TNFAIP3 IL2RB CIITA PTPN22 CD247 PTPN2 CD244 DMP1
    Protein Mutations 0
    SNP 0
    HP:0003765: Psoriasiform dermatitis
    Genes 26
    HLA-B HLA-DQB1 PIK3CD LIG4 HLA-C TTC7A FLI1 SLC29A3 NFKB2 HLA-DRB1 TP63 TTC7A ADAM17 CTLA4 IRF2BP2 GATA3 DSG1 AP1S3 IL36RN CARD14 CACNA1G EGFR NFKB2 MSMO1 KNSTRN FOXP3
    Protein Mutations 2
    V600E V66M
    SNP 1
    rs6265
    HP:0000709: Psychosis
    Genes 120
    WFS1 SPART PRDM8 TRNL1 TRNS2 DNASE1 TRNS1 MECP2 CACNA1A USP8 SH2B1 PDE11A FCGR2B TBC1D7 USP8 MKRN3 SNORD115-1 PANK2 C9ORF72 HFE PAK3 ND4 NDP ACADS ND5 STAT4 NPC1 PSEN1 PRKAR1A COX1 CLN8 WFS1 ZDHHC9 ZFYVE26 DNMT1 PUS3 NDP MED12 CDH23 RPS6KA3 SIM1 VPS13A DCAF17 ALDH18A1 PPOX IPW TWNK PAH ALDH5A1 PDGFRB C9ORF72 TTC19 TRNQ CLN3 AIP COX2 UPF3B HMBS IRAK1 TRNW PDGFB NHLRC1 SLC6A19 SPP1 PCDH19 SOBP ATP13A2 LMBRD1 PWRN1 PCDH19 ND6 ATXN7 PDGFB NAGS SLC25A13 TREX1 HERC2 ITM2B CHMP2B TRNF GNAS MAGEL2 ALAD VCP NDN NPC2 TRNH SLC7A7 PWAR1 CBS MED12 DCAF17 PARK7 GCLC MAPT PRNP FIG4 EPM2A COX3 GSS FCGR2A SQSTM1 ND1 MKRN3-AS1 ABCD1 TREM2 MTHFR MAGEL2 MYORG NPAP1 CPOX SLC12A6 SLC20A2 GRN TMEM106B CTLA4 KCNT1 PTPN22 SNORD116-1 SNRPN
    Protein Mutations 6
    D61804R N40D S311C S9G V158M V66M
    SNP 4
    rs1006737 rs1799732 rs3813929 rs6971
    HP:0002206: Pulmonary fibrosis
    Genes 86
    SFTPA1 TERT ZCCHC8 NUP107 BTNL2 TERT FAM111B NDUFAF6 CLCA4 STX1A CCN2 BNC1 CTLA4 TERC TERC MUC5B HLA-DRB1 HLA-DRB1 RAC2 SFTPA2 SFTPA2 TERT BACH2 TGFB1 BMP15 AP3B1 CFTR PRTN3 MUC5B FAS PRKCD DSP RCBTB1 HLA-DRB1 FSHR BTNL2 PARN NOP10 CCR6 PTPN22 TERT TERT NR5A1 FAS NKX2-1 RASGRP1 CAV1 DKC1 PLEC RNF168 HLA-DPB1 DCTN4 IRF5 CCN2 ATP11A RTEL1 CAV1 HPS4 TINF2 MRPS22 RNF168 TERC SFTPC PSMC3IP TINF2 SP110 KIAA0319L RTEL1 HLA-DPA1 STN1 SPIDR POLR3H PARN IRF5 FASLG SFTPC CCR6 HLA-DRB1 NHP2 ABCA3 DPP9 CYBC1 THOC2 CASP10 HPS1 FAM13A
    Protein Mutations 1
    V600E
    SNP 4
    rs35705950 rs3570920 rs3750920 rs6971
    HP:0006536: Pulmonary obstruction
    Genes 101
    TBX20 GAS8 DNAL1 SERPINA1 CCDC40 RSPH4A DNAJB13 CCDC39 ODAD3 DNAH9 CYBC1 MMP1 MYH7 TTC12 WIPF1 GP1BB COMT CFTR TBX1 DNAAF2 GLA SEC24C DNAI2 CFAP221 SPEF2 RREB1 ODAD4 ARVCF CITED2 HLA-DPB1 CITED2 OFD1 TBX20 TBX1 NME8 ODAD2 NCF4 DRC1 DNAAF4 DNAAF6 NCF2 DNAH5 SCNN1A ALMS1 NKX2-5 HMOX1 ACTC1 DNAAF3 JMJD1C FOXJ1 UFD1 GAS2L2 CCDC103 ODAD1 SCNN1B DNAAF4 STK36 NCF1 APC DNASE1L3 TLL1 CCDC65 GATA4 LRRC6 CYBA ZMYND10 CTLA4 SCNN1G DNAI1 NFKB1 RAC2 DNAH11 DNAAF1 CCNO PRTN3 MCIDAS PTPN22 WAS NEK10 RPGR VPS33A DNAH1 GATA6 CYBB TLL1 LRRC56 GLA HYDIN RSPH9 HIRA RSPH1 CFAP298 MCIDAS MYH6 HLA-DPA1 MGP BLM SPAG1 CFAP300 RSPH3 DNAAF5
    Protein Mutations 2
    A118G G551D
    SNP 6
    rs1051730 rs1800470 rs1828591 rs25331 rs4129267 rs7103572
    HP:0002098: Respiratory distress
    Genes 194
    ND4 TRNN CHAT AIFM1 SFTPC DPM2 EDA SLC18A3 USP9X FGFR2 PRRX1 COA3 XYLT1 COL2A1 LAMA3 ADNP ZIC3 DNAAF3 TRIP11 TRPV6 TRNE SCO2 SERPING1 SLC52A3 COX7B AIMP2 SFTPB MAPT LAMC2 COX20 EPHB4 ORC1 SIK1 MMUT TRNL1 ALDH7A1 VPS33A ETFB SFTPB ORC1 PMM2 BMPER TRNS1 ORC6 ZFPM2 RUNX2 ATP6 PET100 TRAK1 NAGS LAMB2 SCO2 LIFR TBC1D24 COQ7 FBP1 SLC35A1 SOX9 CSF2RA MMAA VPS33A CHRNE SCO1 DISC1 COL2A1 KAT6A DNAJC21 NUP214 POMT1 RPS28 VAMP1 SDCCAG8 NAGS SFTPC ORC4 HLCS EOMES ND6 COX8A FGFR2 MMAB TRNE EFTUD2 SLC12A3 SLC25A3 DMPK NDUFB8 FGFR2 FOXP3 COX14 PSAP COA8 ND5 SLC2A10 ADCY6 SRP54 AGRN TSC2 CLCNKB CDC6 HCCS COLQ NDUFB11 SNAP25 COX10 DPM1 DHX16 TK2 SURF1 TACO1 ND1 CDT1 UBE3B LYRM4 GALC GBA USP9X DYNC2LI1 NDUFS2 ABCA3 STT3B SSR4 GATA6 ASAH1 SBDS MPC1 TSC1 KRT6B LAMB3 COX6B1 SLC5A7 PLCB4 ETFDH CHAT ETFA CDC45 IL1RN IFT52 IFT81 TRNV FOXF1 GBA STAT5B GNAI3 ALMS1 CSF2RB NGLY1 PUF60 STT3B KCNA1 ADAMTS13 KRT16 BMPER KRT17 RPS26 OTX2 TRNW FAM20C LGI4 TRIP11 GATA6 EP300 TRNK PRRX1 ERF KRT6A GMNN MYO9A ND2 NDUFAF3 ABCA3 CREBBP KLHL7 SETBP1 TRMU MMUT NKX2-1 FGFR2 NKX2-1 TUBB4A SYT2 ACADVL MEGF10 MAPT EDN1 CPT2 SLC25A1 CNTNAP1 ITGA3 COL13A1 FGFR1 DPM2 RNF13 ND3
    Protein Mutations 1
    A118G
    SNP 1
    rs7103572
    HP:0011947: Respiratory tract infection
    Genes 785
    SMARCA4 TBC1D24 SNX10 SLC1A4 GRHL3 CFAP298 RSPH4A CARD11 CD3E COG4 PGM3 ECM1 GNPTAB LIMK1 CD247 NTRK1 ZBTB24 MANBA CLEC7A IL2RG TARS1 DNAAF2 NSD2 DNAJB13 DNAAF3 EXOSC9 NELFA EDARADD STING1 MAP3K20 HLA-DPB1 OFD1 SMARCD2 ABCA12 SCNN1G SLC25A24 BLNK GAS2L2 TYK2 HELLS FOXH1 DNAAF6 INPPL1 OCRL GTF2E2 MASP2 COL11A2 MYO5A FCGR2A PRKCD RANBP2 IL21R GATA4 TSC2 LTBP3 CYBA SPINK5 CTLA4 KCNJ6 FOXH1 NAGLU GUSB SHROOM4 LIPN RNU4ATAC TPM3 HERC2 EPG5 GAS1 FBLN5 NRAS ACP5 MCIDAS MAN2B1 TIMM8A COL13A1 PTPN22 SLC35A1 SLC46A1 HGSNAT LYST ZNF341 XIAP LRRC56 IGH NODAL LETM1 TRIP4 EFEMP2 NCF1 MCM4 SFTPC RSPH4A IL2RB RAG2 RAC1 DISP1 WRAP53 PANK2 TNFRSF13C ARID2 SBDS NPAP1 ACTA1 BLM CD40LG ICOS CCDC103 SNORD116-1 FOXP3 TDGF1 IL6R CIITA GLI2 FGF8 DNAJB13 CCDC39 IDUA GATA4 NOP10 GNPTAB TBX6 MKRN3 SNORD115-1 ELANE SMN1 KIF20A PGM3 PEX13 CDON IL7R SCNN1A STAG2 PLEC FLI1 SIX3 TCIRG1 ZNHIT3 LAMA2 CYP4F22 DNAAF4 FAT4 ZIC2 CSF2RB CD55 NFKB2 PEPD TNFRSF13B FGF8 STK36 RFX5 RYR1 SHH DCLRE1C SLC25A22 TLL1 AP3D1 NODAL ZMYND10 NOS1 TPM2 TRIP11 ZIC2 CTCF RAC2 CTLA4 PLP1 GAS1 EFL1 FMO3 RYR1 CIITA DLL3 PRTN3 ABCA3 AGA PCNT RSPH1 ZAP70 NDN NHLRC1 DNAH1 SCNN1G ACADVL DCTN4 PTCH1 DKC1 GMNN TNFRSF13B GLI2 MCIDAS SCN11A ROR2 IVNS1ABP ODAD1 MESP2 SLC12A6 MGP CFAP300 RSPH9 UMPS KRAS SFTPC COL13A1 SNRPN GAS8 CACNA1B AK2 INPPL1 CHAT CCDC40 IL2RG CD3G TASP1 SLC18A3 SCNN1G KAT6B STAT1 ACTA1 MUC5B SMN1 TAP1 MED25 CHD7 COG4 SULT2B1 GBA SPEF2 SDR9C7 CFI IDUA FUCA1 SAMD9L FLNC NCF4 LRBA DRC1 RFXAP KIAA0586 DNAH5 DOCK8 MAN2B1 ATM LAMC2 TRAF3IP2 CR2 GALNS TAP2 AFF4 UNG DNAAF4 RFC2 NCF1 CD3D RELB ODAD4 TDGF1 PMM2 RUNX2 SGSH WAS IL17F IL6ST IRAK4 LRRC8A TAPBP CCNO PLCG2 HK1 MYL2 LEP ERCC3 IGLL1 EPM2A CCDC65 CD79B FLNA XIAP CYBB CD3E AFF4 MESP2 POLE FOXH1 HYDIN TNNI3 NFIX BCL10 RNF168 NEU1 NPM1 IGLL1 TGIF1 WAC ADA UNC119 PIGN GAA CD8A IKZF1 TSC2 LEPR ARSB COG6 VPS51 COLQ WDR1 BTK GAS1 TTC12 WASHC5 CD3D STAT3 CCDC40 ASAH1 DNAI2 LAMB3 NFKB2 PTCH1 COL6A3 PAFAH1B1 FOXH1 MBTPS2 RYR1 TNFRSF13B TGIF1 CLCN7 SP110 COL6A1 TCTN3 SMARCC2 PNP GLUL PKHD1 ALPL ACP5 WDR19 TDGF1 TFRC MGP DLL1 SHH TGIF1 EHMT1 EP300 ITGA7 ERF DNMT3B FGFR1 HLA-DQB1 SPAG1 SRP54 UBE2A TINF2 CARD11 ARID1B SELENON RMRP WAS NEK10 MAPK1 GATA6 SCNN1B SYT2 USB1 DLL1 POLR3A PRPS1 RSPH1 TNFSF12 PIK3R1 IER3IP1 GSN NME8 LIG4 IL7R ALB COL11A2 TGFB1 DLL1 IFNGR1 LAMTOR2 DNAAF5 NXN PTPN22 TBX20 RAB3GAP2 ALOXE3 ZIC2 LRRC56 HLA-DQA1 KIF1A GAS8 PSAP DNAI2 NOTCH2 DPM2 CD81 NODAL DNAH9 TBC1D23 NFKB2 ORC6 SMARCB1 SIX3 LAMA3 DNAH5 ATP6V0A2 EGFR ZBTB24 LYST ODAD4 CACNA1C CYBB RNF125 DPF2 CITED2 GATA6 IRF8 DISP1 GAS1 ABCA12 ODAD3 DNAAF2 MECP2 BIRC3 SFTPB ELN CFTR SCNN1A KMT2D MDM4 IL17RA CCDC39 IL17RA FCGR3A VPS33A ODAD1 IKBKB RSPH3 CREBBP TNFSF11 SCNN1B AGA SCNN1A ADA RAG1 RAG1 TGM1 DLL1 SIX3 CARMIL2 GTF2I CCDC65 ARID1A CFB RAG2 SCNN1G SOX4 NECTIN1 ZMYND10 SGCG DNAAF6 CDON TAF1 IGHM LAMB2 LEP CD79A CFTR HPS6 CCBE1 PWAR1 RPGR VPS33A BTK SCNN1A IL7R EPG5 PIK3CD NBN HYDIN PSMB8 VAMP1 SDCCAG8 SHH RAC2 CD19 HLA-B GLI2 FLNA ALMS1 SCNN1B ITCH SPAG1 DISP1 DNAAF5 IDUA FGF8 MSN SMARCE1 BCR SERPINA1 PRPS1 NIPBL RAG2 ZAP70 TK2 FGFR1 CREBBP ALOX12B RFXANK IFIH1 GBA USP9X IKBKB MYOD1 CCNO TBCE GBA TSC1 PLCG2 G6PC3 MS4A1 CD19 EXTL3 GUSB DYNC2I2 NGLY1 SAMD9 NME8 TRAIP PYROXD1 SIK1 SLC26A2 RAG1 ALMS1 NKX2-5 IL21 FOXP1 LAMTOR2 ACTC1 FOXJ1 ARID1B SCNN1B CYBC1 CSPP1 SMARCD1 JAK3 STAG2 PCGF2 CXCR4 LEPR POLA1 PTCH1 RPGR ASAH1 ASAH1 RAG2 MYSM1 BTK DCLRE1C CFTR KNSTRN FOXJ1 PEPD TERT CDON TCF3 NKX2-1 ICOS DNAH11 OSTM1 ALG12 KATNIP TGFB1 KPTN ADA TPP2 MKRN3-AS1 SLC25A1 MYH6 HLA-DPA1 FBLN5 SRP54 TNFSF12 IGHM NEK10 RSPH3 TTC12 CRKL RASGRP1 SELENON DOCK8 GLI3 SMC1A DCLRE1C DNAL1 RIPK1 SFTPC CD79A TNNT2 DNAJC21 TSC1 CTSC USP9X SFTPA2 PIK3R1 TNFRSF13C NR2F2 CFTR ADNP DNMT3B TCIRG1 CFAP221 TNFRSF13C NFKBIA NFKB1 NEPRO SLC52A3 CLIP2 CRELD1 FCN3 NCF2 SIM1 BAZ1B P4HTM DNAAF3 GAS2L2 CCDC103 UGP2 GATA2 ICOS CDCA7 SIX3 JAGN1 CLCA4 STX1A MYH3 STAT3 DNAH11 LRRC6 SLC35C1 CDON IL17RC CD79B KDM6A UBB NHP2 NCF4 CCDC22 MAGEL2 TBC1D24 MTHFD1 MIR140 BLNK LCK NFE2L2 CSF2RA MYSM1 DNAI1 RAG2 ZIC2 HACD1 MPLKIP TLL1 COL6A2 OFD1 PARN SCN9A FGF8 MAGEL2 FANCF CORO1A PIK3R1 PRKDC CR2 EP300 PIK3CD CASP8 CRLF1 PTCH1 NCF2 SH3KBP1 CR2 DNAAF1 AGRN RFXANK TDGF1 IL2RA SOX11 IL2RG ATM ODAD3 CYBC1 SNAP25 SMPD1 TRPS1 SHH ELP1 GLI2 CHRM3 IL2RG PNP BACH2 CREBBP SH2D1A WIPF1 DDR2 CTC1 TGIF1 RFX5 DCLRE1C CFAP410 GTF2IRD1 SLC5A7 ERCC2 TERC ADAMTS3 TBX20 ODAD2 SLC29A3 MALT1 DSG1 TECPR2 IPW NGLY1 CYBA EP300 TNFRSF11A DZIP1L CD81 LRRC6 RTEL1 RAG1 DNAI1 MYPN NFKB1 ODAD2 TBCD ELANE CXCR4 PWRN1 TNFRSF1A FOXP1 MYO9A DNAAF1 TGFB1 RFXAP RAG1 SMPD1 CREBBP SETBP1 USB1 NADK2 MS4A1 CHAMP1 TERT NKX2-1 PTPRC SCN10A ELP1 POLR2A NODAL GFI1 PLG RNF113A TBL2 RSPH9 CFAP298 CD19 JAK3 AICDA GLB1 GTF2H5 NIPAL4 PLOD1 RNU4ATAC ITGA3 NBN GNS FOXN1 STAT1 DISP1 B2M
    Protein Mutations 1
    H275Y
    SNP 0
    HP:0001370: Rheumatoid arthritis
    Genes 29
    HLA-DRB1 ANKRD55 PADI4 STAT4 GCH1 IL2RA IL10 STAT4 IL2RB IL2RA PTPN2 PTPN22 CD244 CD247 ANKRD55 PTPN2 PTPN22 NFKBIL1 DCLRE1C SLC22A4 ACP5 LACC1 IL2RB CIITA IL6 PTPN22 MIF CD247 ACP5
    Protein Mutations 4
    A147T N363S R620W V600E
    SNP 10
    rs2246704 rs2853884 rs35705950 rs3747158 rs3790515 rs3828057 rs4820059 rs7291050 rs933226 rs9826
    HP:0001708: Right ventricular failure
    Genes 16
    TBX20 MYH7 GATA6 TTN NKX2-5 TLL1 GATA4 MYH6 SDHD CITED2 TBX20 ACTC1 BMPR2 SELENON ATRX DAXX
    Protein Mutations 0
    SNP 0
    HP:0100753: Schizophrenia
    Genes 72
    CIB2 APOL4 WFS1 UPF3B ADGRV1 MYO7A ARSG GIGYF2 RTN4R RBM12 DNAJC13 USH1C KRT83 COMT CAT PSAP MSTO1 PDZD7 TBX1 GP1BB HARS1 SNCA ESPN COMT TBX1 APOL2 ARSA DNMT3A SEC24C KRT81 WHRN TRNS2 MED12 NKX2-1 TRNE RREB1 CDH23 CLRN1 HTR2A CEP78 SYN2 LRRK2 ARVCF FLI1 KRT86 GJA5 TBX1 PRODH ATP2A2 ZDHHC9 HIRA USH1G CHI3L1 VPS35 DAOA EIF4G1 DSG4 PCDH15 USH2A MYO7A PRODH DISC2 GBA PRODH MTHFR JMJD1C SHANK3 GJA8 UFD1 DRD3 CHRNA7 MSTO1
    Protein Mutations 7
    D61804R N40D P50I S311C S9G V158M V66M
    SNP 14
    rs1006737 rs1256049 rs1799732 rs1801132 rs2023239 rs2069514 rs2234693 rs2494732 rs3813929 rs4244285 rs4680 rs6971 rs762551 rs9340799
    HP:0001250: Seizure
    Genes 2887
    SMARCA4 TBC1D24 ND4 PRDM8 SLC1A4 ZBTB18 GYS2 TMEM94 SCN1B SETBP1 GAD1 GPHN TXN2 COG4 LSS PGM3 FXYD2 TRIT1 POMT1 FOXG1 GRN BCL10 CTNNB1 EEF1A2 NR2F1 CRADD GP1BB ANGPTL6 ASS1 HS6ST1 GABRA1 ADRA2B EXTL3 GDNF NDUFS1 SLC25A19 SEC24C CALM1 SUCLA2 ANK2 PAH NELFA GABRB3 NOVA2 NCAPD3 KCNQ1 CHN1 COG2 AP4E1 PEX11B PEX11B RYR2 FKRP TDP1 FRMPD4 CCDC141 WWOX NSD2 CYTB FBXL4 PCYT1A KRAS ATP5F1D TSEN54 TRIP13 FTSJ1 ERCC1 FEZF1 KCNH1 ARF1 RNU4ATAC FOXH1 PERP IKBKG SETBP1 BTD MAGEL2 GTF2E2 PEX10 CDK19 NF1 HEPACAM PRF1 NDUFS6 HNRNPH2 ASXL1 AHDC1 KCNJ6 SEC31A IRF3 MLH3 NECAP1 FTSJ1 GCDH PIGG C12ORF4 NSD1 TSC2 PLA2G6 SPINK5 PRPS1 LAMA2 WDR45 NAGLU KMT2A DLD SHROOM4 EMC1 C12ORF57 PPP2R1A KIF2A COQ2 GRIA4 PGAP2 TMEM67 ARX ATP6V0A2 CSNK2B EFHC1 KIF11 JAM2 ARSA SYNJ1 TRNP CDH15 KIF5C SUCLA2 RASGRP1 LYST FKRP UFC1 TWNK GDF6 NEUROD2 TSFM TMEM67 SPOP CACNA1H CUX2 DPYS GPT2 LETM1 ACTL6B SCN2A ATP6V1A SQSTM1 FAM149B1 PEX19 ABCA2 TRNI ACADM APP PEX3 PANK2 TRIO GLI3 PEX13 MAN1B1 HNF4A SCN2A NPAP1 RERE TANC2 KLLN ARNT2 KDM5B SLC13A5 KIF7 SNORD116-1 SRPX2 PEX19 SEMA6B TGFBR2 OSGEP IARS1 SVBP VPS13B ENG FTO GLI2 TRAPPC12 HLCS ATIC NOTCH3 HIBCH RARS2 HIC1 ANKRD11 IFNG SURF1 ARL13B TACO1 HERC2 TRNK ZFP57 GFM2 COL4A1 SLC9A6 TBK1 STT3B MKRN3 KCNJ10 ATN1 MYO1H POLG VDR OCLN ND5 CASK PIGO FAR1 TSEN54 F8 NDUFS7 ARHGAP31 PIGH RFT1 CDON KCNQ1 SCN8A FGFR1 NEDD4L BAP1 SIX3 SERAC1 CYP27A1 GALC SMARCB1 LMNB2 PRDX1 INSR WDR11 LAMA2 KCNMA1 PHGDH TRNV QDPR ADAMTSL2 PEX14 TMEM165 FAT4 SCN2A PRODH SNORD118 ZIC2 KMT2E DHX37 TRNK TUBB3 GABRG2 NFKB2 CAV3 ALDH3A2 CNNM2 PEPD ST3GAL3 PIGQ FGF8 STAT2 SHH COL18A1 STXBP1 SON SLC25A22 GALC HMBS RET COG2 TPP1 NODAL JAK2 PCDH19 BUB1B EIF3F ERAP1 GRIA3 SMC1A CLN8 EIF2AK2 CC2D1A ADD3 MTFMT GAS1 SLC25A13 MAPK8IP3 TMEM231 ARX PRTN3 FLNA PIGN AKT2 NTRK2 RAB11B TRNF TDGF1 HTRA2 B4GAT1 VCP DYRK1A HCFC1 DNM1 BCOR FLCN NHLRC1 NAXE CTH PIGQ XK IL12A IDH2 PLK4 PLA2G6 CDKN1A HCN1 TUBB2A RORB ARL3 TBX19 CASQ2 TBCE NDUFV2 LMAN2L MTHFR GABRA1 TRNL1 GABRB3 ZEB2 RPL10 COX1 FRMPD4 ARCN1 TUBB2B NUP107 CENPJ COL13A1 ACSL4 MDH1 HSD17B4 EGF BUB3 GJA1 CACNA1B LIG4 LARP7 NTNG1 GRIK2 ANKRD11 ZBTB18 ALG11 TREX1 APP NF2 CCDC88C HUWE1 COA3 CD96 SEPSECS PSAT1 DLG4 COL4A1 TMEM237 EIF2B5 MSX2 SLC2A1 NRXN1 KCNQ2 CDKL5 TULP1 CTSA GBA SLC35A2 PIGK PQBP1 CPS1 PTS CIT ERLIN2 XPA ANKH RELN OFD1 CDK13 VARS1 SETD5 SYNGAP1 DPAGT1 PPP3CA CNTNAP2 COX7B APC2 GDF2 TRMT10A FBXO31 ALDH18A1 LAMC2 ACTL6A TBC1D24 D2HGDH PEX26 MMUT LRPPRC TRAF3IP2 GP9 KATNIP APP ALDH7A1 HCCS PIK3R2 SMARCB1 CTNNA2 PPM1B UPF3B PIGV NSDHL SLC33A1 STX1B GMPPB TRNQ RRM2B SYNJ1 GLI3 BCL11B ALG1 KIF15 TDGF1 ATR PMM2 SGSH KCNJ11 TANGO2 USP7 ARX TRNS1 MLYCD CTSA NLGN4X IL17F SCN10A SLC13A5 SHANK3 ACSF3 SLC35A2 ZNF711 PHOX2B HK1 NAGS ADPRS FLI1 ETHE1 CLCN4 TBR1 PEX19 PEX12 SETD1A CDK8 INS CC2D2A HNF1A MED12 MAP2K1 GJC2 PEX14 SYNGAP1 NFIA PAFAH1B1 PGK1 MOGS FIG4 EPM2A TBL1XR1 SMG9 SNRPN HSPD1 SLC6A8 VAMP2 FOXH1 NDUFAF5 EOGT PAFAH1B1 PHF6 FARS2 ACTA2 ND1 GPHN GPR161 NAXD NDUFS4 TRIP12 ARF1 PTEN PHOX2B SLC20A2 GUF1 SMAD4 EIF2B2 ACY1 PRNP SOX3 FMN2 WAC ADAM22 CHRNA2 PHACTR1 NTNG2 NDUFB8 SDHA FGFR2 FGF17 TRNW CARS2 WFS1 IFIH1 KRAS COA8 PSAP DHCR7 PEX1 PEX12 FBP1 AARS1 TREM2 PTCH1 MEN1 CLCNKB SLC35A1 PROK2 CKAP2L TRAPPC2L CC2D2A RAC3 AVPR2 BPTF COX10 PIK3CA UBA1 CLCN4 SAMD12 MED17 PLAGL1 ARMC9 GABRG2 ATXN10 GAS1 SMARCE1 LAMC3 GALC ERCC5 RERE LHX4 ERLIN2 TRNV HYMAI CACNA1C MKS1 ARHGEF9 SHH MEFV ACVRL1 ATP1A3 STAG2 CDON DOLK AKT1 FAM149B1 NNT CCDC88A RPE65 NFIX DEAF1 PEX2 HADHA PAH TRNF PIGL DALRD3 SATB2 PHGDH SLC12A5 PSAP PEX12 TAF1 NALCN PDE4D TRAPPC11 FA2H SDHAF1 ALDH7A1 PIGW TGFBR3 PODXL TGIF1 RAB39B COQ6 LARS2 ATN1 SMC3 RPS6KA3 LIPT2 PROKR2 MECP2 APC2 ARHGDIA GCK SMARCC2 FGFR1 ATAD3A PQBP1 PPOX EARS2 GLUL PET100 IL1RAPL1 TUBA8 TPRKB RAB3GAP1 ISCA1 GLRB TDGF1 MEIS2 GUCY1A1 KCNJ11 ASNS FARS2 PEX6 TSEN15 TRNW GLYCTK SCN9A METTL23 STRADA CERT1 ARX TGIF1 NOTCH3 WDR4 EHMT1 NOS1AP RPGRIP1L TRNK CEP120 WDR81 CNOT1 ANO10 CLCN2 MEF2C UBE2A ATP6AP1 RPGRIP1 TUBGCP6 CEP290 INTS8 CACNA1A WDR26 TMX2 DNMT3A UBTF TANGO2 CEP290 SDHB ADSL NUBPL SET MARCHF6 RARS1 CISD2 ATP5F1A DHCR24 GCM2 MFSD2A HTRA1 MID2 THSD1 SMC1A GOT2 KCNT2 HPRT1 TUBGCP4 NTRK2 SVBP ALDOB NSD1 DLL1 AP4M1 CPA6 GNB5 PUM1 CHD2 CNKSR2 PDE10A ENG TBCE TRNS2 KDM6A UNC80 CASP10 PPP3CA TUBG1 KCTD7 KIF1A TRNT POGZ FOXH1 PROK2 TRNL1 PIGP PEX11B DYNC1I2 KCNA1 NODAL HESX1 SPR MECP2 ANKRD11 CACNA1A ALX4 TBC1D23 RAB39B CIC COX10 SCN8A POMT2 LAMA2 RNU4ATAC SMARCB1 GRIN1 NDUFA2 STXBP1 BCOR HADHA ALG13 GRIN2B DNMT3A HTT KIF11 ADK MCCC2 CPS1 PCLO RAB18 PEX5 CHD2 CYP27B1 AVPR2 CPLX1 ATP6V0A2 CACNA1C NSDHL DMD GNB1 SRPX2 DPF2 STAG1 RLIM UBE3A ZFYVE26 CDK10 FKTN SCYL2 MSX2 DISP1 PEX13 GAS1 RPGRIP1L JAM3 AIMP2 TLR3 SCN11A TCTN3 CLCF1 CRADD ANKLE2 ISG15 TP53RK TCF20 IL17RA MAN1B1 UFD1 C9ORF72 GABRD FRA16E CPLANE1 TSC1 DLL1 TRMT10A TUBB4A TXNRD2 EIF2AK3 L1CAM AKT1 POLE ARID1A NACC1 NHLRC1 B3GALNT2 GABRB2 ABCC9 FBXO11 FAN1 FOXG1 PMPCB LNPK RORA RAB27A MSH2 DEGS1 HERC1 KCNA1 SYN1 SDHC CDON PTCH1 PDCD10 TBX1 PREPL MED12 TMEM67 INPP5E MYORG CHMP2B CCBE1 USP9X LRP2 PWAR1 SMARCA2 MECP2 TMTC3 SCO1 KIF5A DCC GFM1 PIK3CD ACTB PHOX2B BRAF CACNA1B ERMARD LHX4 PSMB8 VAMP1 NTRK2 DHDDS TCTN1 FCGR2A CLN6 MAPRE2 AKT3 EBP RAD21 LMNB2 GPC4 DNAJC5 ARHGAP31 CEP164 TREM2 YEATS2 CSNK2A1 TRPM6 GLI2 CPT1A SLC13A5 HIVEP2 TBCD PEX26 SCN9A WDR26 DISP1 SZT2 SIX3 FLRT3 TDP2 KATNB1 FGF8 AP4M1 PSAP GABRA5 SMARCE1 BCR POLG WDFY3 ATAD1 PRPS1 DCX GP1BA TRNS2 TK2 PIGB DNASE1 NIPBL KIF1A POU1F1 CEP41 TSEN54 PRRT2 AP4B1 ARMC9 CHD1 DDX3X SCN1A HTT SDHA DPM1 TUBB2B XPR1 IFIH1 ROGDI TK2 SYP SPG11 ND1 APP BCORL1 GPAA1 ZEB2 NODAL TUBGCP6 CLCN2 LETM1 RRM2B DNAJC6 USP9X CLDN16 MAFB BMP4 L1CAM GAMT PEX3 TBCK SLC13A5 FMR1 COX6B1 PLAA MFSD8 OCRL UBAC2 COX1 SORL1 CEP104 RAI1 NDE1 GNE NGLY1 SLC35A3 SAMD9 BUB1B HEXA EZR DDOST PIGW CRB2 PEX1 SIK1 GMPPB LAS1L DHDDS MMACHC MORC2 RERE LGI1 KCNQ3 ALMS1 AQP2 HDAC8 TRAPPC11 ALDH18A1 KCNQ2 ERCC6 JRK FKRP ASH1L TWNK PUF60 TBC1D24 TRNK RANBP2 SNTA1 CASR STT3B TYROBP ARID1B SPR FLVCR1 OCLN KRAS DOCK3 USP7 SUMF1 PROKR2 CCBE1 GCK PIK3CA STX11 DCX IRAK1 CPLANE1 ARX STAG2 PEX6 SLC6A19 SOX10 ECE1 KCNQ3 LRAT HTT POLA1 POLR3A GOSR2 MTOR PPP2CA SEC23B GJC2 TRNP SLC39A8 CLTC AMPD2 ASAH1 PIGP EML1 HYMAI ALG13 PIBF1 HMGCL HNRNPU KCNT1 NDUFA11 SLC25A12 PLA2G6 HSD17B10 SETD2 RPS6KA3 KCNB1 PPP2R1A L2HGDH CLPB TECR NDUFA12 ABCC8 CPT2 KNSTRN CBS TMEM216 CDON NDUFA4 SPTAN1 PACS1 PSEN1 NNT MAPT GUCY2D KMT2D GRIN2A NDUFB11 FRRS1L ATAD3A HAX1 NUS1 CTNNB1 MEGF10 GABBR2 AUH CKAP2L MKRN3-AS1 TCF4 SLC25A1 USP45 NOTCH1 ERCC4 AARS1 ANK3 AIFM1 LARGE1 SMPD4 HLA-DPA1 ABAT SURF1 GNAQ PTS PEX16 PTPN22 OTX2 CLPB NDUFA2 EPRS1 DPM2 COX7B THOC2 PIGN ND3 SMC1A SCN3A PEX1 AP2M1 GLB1 TRNN SUFU AIMP1 PSAP KLRC4 RHOBTB2 COG7 PCCA TSC1 USP9X KCNC1 PDCD10 PIGU SMC1A MEN1 ASCL1 NDUFAF6 HMBS CAMK2A GBA PPP1R15B FGF8 HLA-B CTU2 STAT4 SETD2 RELN ATP6V1B2 AMER1 TMEM216 MEN1 NDUFS1 BMPR1A PDGFB KIAA0753 ATP6V0A2 ZNF423 ARVCF ERCC5 AKT3 PMS1 IQSEC2 PEX16 MTFMT ALDOB PGAP2 CRB1 TMLHE GRM1 POGZ ROGDI NDUFS2 KCNJ11 EHMT1 ATP1A2 KLHL7 SCN1A ZIC2 RECQL4 RPS6KA3 KCNMA1 NDUFS8 SIM1 DLG3 LARS1 BRAT1 FUCA1 SERPINI1 CFH SLC25A20 SDHD KRIT1 COL3A1 ADAR WHCR SLC9A6 PEX26 DOCK7 TRNQ SMARCE1 LIAS ESCO2 TUSC3 SARS1 AP3B2 ATAD1 GLS CACNA1A TIMMDC1 POMT1 UBE2A MBTPS2 PSPH TBC1D24 FGFR3 OFD1 ARG1 ANOS1 SLC2A1 POMGNT1 NPRL3 MRPS22 KRIT1 FGFR1 CTSD DMXL2 EEF1A2 IL17RC FLNA DLG3 NSMF KDM6A TRIM8 ALG2 RPS6KA3 ALAD GABRA2 MTHFD1 FDFT1 DARS2 PHACTR1 CNPY3 PIK3R2 GLRA1 KCNMA1 GNAO1 GPSM2 GLI2 GLI2 VLDLR GTPBP2 IL10 COX3 SMPD1 GRIN2A POMT2 ECHS1 TRIP13 WWOX EZH2 PEX13 GABBR2 MCTP2 SCN8A FGF8 COX8A WASHC4 MAGEL2 SLC19A3 RAB18 NSUN2 DNAJC19 EP300 GLRA1 EFTUD2 NDUFB11 ENG NDUFAF6 TRAPPC4 CLP1 TUBA8 PRDM8 NDUFV1 PDE6D ZSWIM6 AP1S2 SDHAF1 GRM7 SLC19A3 HACE1 L1CAM CDH23 TDGF1 LGI4 SOX11 RUBCN HCN1 ERCC6 IL17RD CHRNA4 SMARCC2 TERT COX2 ARID1A MVK PURA CREBBP DHDDS NKX6-2 TRAPPC9 POMK EIF2B4 PEX3 CHRNA7 NEXMIF MTR SLC16A1 NANS NF2 ATP6V1B2 NADK2 DNM1 SLC19A3 GNE FAS RNASEH2A MPDZ TGIF1 OSGEP GLUD1 SMAD4 BSCL2 RNR1 HNRNPU L2HGDH NEUROD2 ARHGEF9 NLGN3 LAGE3 NEDD4L SLC25A15 FADD SLC5A7 NUS1 KCNA2 IQSEC1 AKT2 PGAP3 FIG4 PDX1 TDP2 HS6ST2 METTL23 CASQ2 TP53RK ADAT3 SMC3 POMT1 RAC1 STAG1 CUL4B STAT4 IREB2 POMGNT2 GBA PROKR2 GATA3 KLF13 GABRB2 GMPPB MEF2C KMT2C PEX1 VPS13A ALG11 AGTR2 ATP1A1 KDM6A ALDH5A1 SPRY4 SZT2 EFHC1 CUX2 TACO1 ALG13 CLN3 BCKDHA RPGRIP1L CTSF SLC6A5 KRAS TLR4 ERCC8 ETHE1 UPF3B ARV1 PEX19 XPR1 PEX3 MRM2 TRNC CACNA1E EDN3 ERCC6 MED12 SCN1B AIMP1 CTBP1 ADGRV1 IBA57 TBC1D20 TBCD CXCR4 PWRN1 ADAT3 TBX1 CENPE LAS1L MC1R MPL STX16 C4A ACSF3 TREX1 CAMKMT SLC25A22 TBX19 KANSL1 CHD8 CHD7 EDC3 PCCB TSC2 SLC9A7 SETBP1 STAMBP PEX10 VLDLR MVK IMPDH1 SLC17A5 TRAPPC11 FGFR2 TRIM71 PNKP DDX3X POLR2A RNF113A MECP2 SLC46A1 CLIC2 MAF SCN1A ALG9 KAT8 ARSA EMG1 NOTCH2NLC MED12 CDKN2B VPS11 ZC3H14 PGAP1 PEX10 STX1B ZNF81 ZC4H2 PEX5 DLD NAGA OTX2 RSRC1 GTF2H5 SCN9A PCK1 PRDM16 IDS ATP1A2 COL3A1 IKBKG GBA ITPA TRNS1 GBA CRIPT CAMK2A DPYD DOCK6 DISP1 LMAN2L IVD RNASEH2A KCNA2 TRIO NDUFA10 SLC25A22 PEX5 DCC ARX HERC1 NRAS SHANK3 MTHFR TRAF7 ECM1 CHRNB2 CNKSR2 NRAS EXT2 USP27X KCNH2 EEF1A2 CEP290 COX15 PIGO MMADHC FGFR3 MANBA SLC2A1 RALGAPA1 CLEC7A EGF WDR37 TARS1 SCN2A NSD2 FOXRED1 PTH STXBP1 FDXR POMC EXOSC9 SYNJ1 CNTN2 CAMK2B ATP1A3 NPC1 MYO5A PIGA DPAGT1 DHFR HLA-DPB1 UPB1 FTL POMK GPC1 SOX2 AUH SCN1B NFASC OCRL TMTC3 SPAST PTF1A TRAPPC6B GLS PSPH INPP5K LRP2 FBXW11 NAT8L CHRNA7 FCSK MYO5A KRAS ASXL3 RANBP2 SPATA5 LYST KIAA1109 ASPA TICAM1 MBD5 TUBB3 BTD SELENOI MED25 SNX14 SMS ATP5F1A CTLA4 ECM1 STS CXORF56 VPS11 NDUFAF4 KCNJ6 FOXH1 MECP2 GABRA2 LMBRD1 GLUD1 SYN1 STT3A NAGA PET100 ACTG1 SLC2A1 TRAK1 TRNQ TOE1 NOTCH2NLC AIP HERC2 TRAK1 CACNA1D WDR73 COL18A1 PTCH1 SCN1A EPG5 TLK2 ALG3 GAS1 BCS1L PLPBP STAG2 HIBCH TREX1 BCOR KCNJ1 TRNH FBP1 PTPN22 MRAP POMGNT1 SLC46A1 HGSNAT SLC2A1 ERCC3 FLVCR2 GM2A UFM1 CRPPA CDH23 TWIST1 GNAO1 AMT HMGCS2 FGFR1 TREM2 MIPEP NODAL NUP214 GBA ADA2 SCN3A ATP2A2 CLN6 NAGS HESX1 KMT2A GUF1 CPT2 RAC1 DISP1 ADGRG1 POU3F3 ATP6AP2 AHSG PIGM HCN1 TMEM70 NTRK2 RBM10 NDUFV1 PLCB1 PEX1 PIGG CYP2R1 NIPA1 ARID2 NRROS ST3GAL5 GDI1 PDGFRB ACADSB FASLG GABRD CFHR3 SLC6A8 PTEN PLP1 CARS2 MAP1B COX14 THPO TDGF1 AMACR PSEN1 KIF7 AQP2 MPDU1 NPHP1 GDI1 NDUFA13 NRAS CYTB PEX5 ATAD3A FGF8 PIGC STXBP1 BRAF NEU1 COQ2 POU3F4 CYB5R3 PCDH19 SCARB2 PDHA1 PRUNE1 MTHFS PSAP ERCC2 GABRB3 LARGE1 WDR73 ARX PHF21A NIPBL GABBR2 CYB5A SNORD115-1 POMK SRPX2 ACO2 PHF6 ACADS ACOX1 MBD5 SLC6A1 ATP1A3 RPL10 ZBTB20 DBT KCNB1 WDR11 MTRR PEX2 WAC STAG2 STXBP1 ARL6IP6 GNAS PSMD12 DNM1 FLI1 ADSL MYRF NDUFA1 ITGB6 HPD SLC12A6 RAB27A SON NSUN2 ABCC8 B3GALNT2 PIK3CA YEATS2 SLC17A5 ZNHIT3 CDK5 CAMTA1 DSTYK GRIK2 ATP6 ABCA5 HLA-B NARS2 CA8 MC2R RNASEH2C PLAA STXBP1 RBM8A ST3GAL3 FAM50A UGDH ATIC BCS1L TRMT1 HDAC8 TLR3 DCPS PAH GRIA3 LONP1 HADH RNU12 SC5D RPIA PNKP OFD1 TMEM231 RAPGEF2 TSC1 SURF1 ARV1 FMR1 HNF1B AP3D1 BCKDHB DHPS FA2H PEX6 ZIC2 WARS2 SC5D COQ8A PTEN SCN8A PRMT7 SLC2A3 FGFR2 ZIC2 GTPBP3 PGAP1 KCNC3 GLDC KCNJ10 CEP85L GPC3 NDUFAF3 AP3B2 PEX16 AGA PPT1 IQSEC2 PCNT CFHR1 B3GALNT2 PDSS2 PIK3R2 MFF NDN FOXP3 POMC COG5 BCKDK SOX10 DNM1L OSTM1 AKT1 DISP1 GSS TRAPPC4 RNF213 PTCH1 CRLF1 SCN2A ALDH3A2 NF1 COL1A2 GLI2 COL4A2 YWHAE NSUN2 TRRAP IL23R ALG6 BOLA3 SLC12A6 MGP SLC25A4 PRRT2 DOCK7 CTC1 DHCR7 ZMIZ1 PRRT2 XPC CLTC SNRPN DPH1 KDM6B GNAS FKTN SCN10A PRNP STT3A KCNMA1 CHAT ARX KCNQ3 TBCE GNAQ CNPY3 ALG2 SH2B1 CDC42 TASP1 FOXA2 CDH2 CYP27A1 SLC18A3 CBS LCA5 ANK3 ACAT1 KAT6B NDUFB8 RUBCN KCNA2 PROP1 PRKAG2 DHX30 RTTN CHKB CDK19 MED25 PEX10 CCND2 MVK COG4 PTPN23 ACTL6B SMS RREB1 KPTN MED25 RTTN PROP1 CEP57 B9D2 PSEN1 NEK9 YWHAG CILK1 FBLN1 TBCE MLX KMT5B ZNF592 FUCA1 CPLX1 CEP41 PIGC ZNHIT3 TBX1 PIGT ALG1 GEMIN4 CASK TUBA1A GCH1 ERMARD NIN PIK3CA GK CC2D2A CDH11 COLGALT1 EFHC1 NIPA1 PTEN PTRH2 ATM COX20 KDM5C FLNA RELA GCDH RAI1 RMND1 MED13 HRAS KAT6B POLA1 PNPO SCN2A TBP FAM111A SCN4B WDR4 PTRH2 PIGL SPP1 FKTN PEX7 TP53 ADA2 ACTL6B FAM111A CPT2 FGFR1 SLC45A1 GYS1 GATAD2B LBR ASPA KCNE1 NUP133 ERCC3 TRPV3 MED23 EPM2A PRKCD POMT1 TXN2 OTUD6B PNPLA8 ROBO3 MACF1 RAI1 SCN1B INSR CRLF1 PI4KA GNAS MYT1L HDAC8 EPCAM CRBN TP53 ATP6V1A SPATA5 KAT6A DGUOK GABRG2 IQCB1 WDR62 PSMD12 MAST1 ATP6AP2 SIN3A HLCS NEU1 UBA5 CACNB4 NAA10 SHROOM4 ATRX POLG2 MTOR PSAP SLC12A3 PIGA CLTCL1 CPT1A GABRG2 TGIF1 ARID1B PSMD12 POLG2 PIGN RAB39B UBE3A ERLIN2 GRIN1 CSPP1 ARFGEF2 FAM111A TSC2 CAD VPS51 HCCS BDNF CARS1 THOC2 PRRT2 CPT2 DHX16 GM2A SKI RPS20 NRAS SCN9A KCNA1 KCTD7 INPP5E BPTF TRNF AP4S1 FKTN NDUFS2 TFAP2A LAMB1 SSR4 COMT IFT140 INPP5E PAK3 ASAH1 DYNC1H1 FITM2 ACY1 GLA CACNA1A NOS3 BRAF PIGV ATRX KCNJ5 ATP1A2 LAMB3 PCSK1 DEPDC5 ANK1 PIEZO2 SLC25A15 NDUFS8 GABRG2 ACTB PTCH1 FGF12 CCM2 NPRL2 POMT2 UBA5 PHKA2 GABRA5 TBC1D20 GRIN2B DENND5A SNAP29 PAFAH1B1 FOXH1 TREM2 PEX6 PAX2 HADH MAPK10 MBTPS2 FLII PRRT2 ATP6V1A PHKG2 MDH2 SLC12A5 CDKL5 MED13 SMARCA4 SP110 VPS13B TCTN2 KCNK4 AP2M1 ARSA PMM2 BRAT1 CLIP1 ALPL ELMO2 ACP5 KCNQ2 POLG STAT3 PEX26 MGP TNIK SRD5A3 UNC93B1 DLL1 DYRK1A SHH SGPL1 NDUFAF3 EP300 TREX1 CLIC2 MSH6 FAR1 LSS TBCK GLI3 GRIN2A FGFR1 SIN3A SMARCA2 CCNQ BUB1 ALDH5A1 ABCC8 GLRX5 SARS1 GABRG2 ALKBH8 PC NF1 OTC POMT2 DHCR24 DNM1L ARID1B NDST1 NUP133 PEX6 POMGNT1 IQSEC2 MAPK1 MICOS13 GRIN2B SOX5 ATP6V1A COQ8A KCNJ11 ASPA SYT2 DOCK6 PIK3CA DLL1 CCR1 TRDN HIRA IER3IP1 JAM2 SARDH GMPPA HEPACAM NHLRC2 NECAP1 TGFB1 TBC1D24 MOCS2 TELO2 SSR4 FGFR3 COQ4 ADGRV1 TBK1 CTLA4 MAN1B1 KCNT1 ARX PYCR2 ERCC2 KDM5C MKS1 SH2B1 ZIC2 CDC42 TRNS1 CAMTA1 PTEN PSAP NONO DPM2 MID2 DMXL2 MICAL1 PRRT2 ACADM LINS1 ZNF41 POLG DLL4 PSAT1 UBTF ERCC8 LAGE3 SPTAN1 USP18 DDB2 BMP2 FCGR2B SIX3 CALM3 ACTL6B CYP27B1 DIAPH1 GATA4 LAMA3 KMT2E TIMM50 GMPPB MTOR CDON TMEM106B CILK1 KAT6A ALG3 TAF1 AVPR2 SLC1A3 STRADA GNAQ TTR PAK1 ABCC8 FOLR1 NUS1 RNF125 CRBN MTRR EXOSC3 COX3 MTO1 DLL1 DEAF1 FGF8 HCFC1 NDP LARGE1 MANBA MECP2 KMT2D PPP2R5D WARS2 CASK SLC44A1 NMNAT1 EFHC1 TRNL1 KCNE2 ELOVL4 JMJD1C IARS1 TRNT1 NIN FRRS1L FADD ZMIZ1 CREBBP GMPPB HECW2 DIS3L2 AGA HRAS HYLS1 BAP1 WDR45 COX2 SLC25A20 KIAA0586 SIX3 SDHA PLPBP TUBB2B MCCC1 SYNGAP1 PCDH12 EFTUD2 IRF2BPL MN1 ACTG1 SOX4 ALX4 MFF SETD5 ZNF142 ATP6 NECTIN1 SLC2A1 TWNK MGAT2 GABRD ERCC4 MOGS TOMM40 GTPBP3 TCF4 VPS53 OTX2 PEX2 SCN3A TRNK OTUD6B CCM2 MMAA GRIA2 CACNA1D PEX2 MBOAT7 AIFM1 SETBP1 ASL EPG5 SIX3 CYFIP2 FKRP GLA NDUFAF5 PEX13 SIK1 ND1 CUL4B SLC1A4 SHH SDHD CYP26C1 MECP2 ANTXR1 ABCD1 ND6 DDX6 PSAP SCN2A DEAF1 B3GLCT ATP6V1E1 ADGRG1 CPOX TRDN TWNK AKAP9 TBC1D24 DLL1 GABRB1 ARHGEF6 KCNQ2 NBAS DBH SCN1B FGFR3 TYROBP ATN1 LIPT1 FH SLC19A2 GRIN2A TRNS1 RAB39B MARCHF6 LINGO1 DUSP6 AHI1 ERMARD SPATA7 MECP2 FGFR1 PLAGL1 STAR CREBBP NDUFAF2 PDSS2 OPA1 GAL GBA MBTPS2 DALRD3 GNAS GAMT RXYLT1 GATA6 WFS1 CASK ATXN10 ND4 ALPL CDKL5 TBCE NDP GBA SUFU NF2 NAA10 ATP7A TSC1 FAS AASS TSPAN7 GJA1 GNAS MAF PSEN2 GRIN2D TBL1XR1 PROC WASF1 TCIRG1 EXTL3 CLN8 EIF2B1 ND6 PRODH BCAP31 ZDHHC9 MYO5A PUS3 ADARB1 MED12 NEU1 CDKL5 TRNH SLC3A1 CERS1 PDGFB RELN ATRX TRAPPC11 PLCB1 AUTS2 NFIX PEX12 NDUFS7 NEK1 TWNK RPL10 CHD2 RNASET2 SLC25A42 SMARCB1 SEMA3A SMARCD1 ALDH4A1 CNTNAP2 MOCS1 SLC5A6 SRPX2 ABCC8 SLC2A1 SLC1A2 TRMT1 PTCH1 ATP8A2 LMX1B ASAH1 CPLX1 NDE1 GAS1 NDUFS3 CNTNAP1 TRAPPC9 TRAF7 ROBO1 GJC2 TCF4 ERCC6 RNASEH2B FKTN PIGY NEU1 HESX1 GPT2 NEXMIF PGAP3 NDUFA9 SLC1A3 MECP2 TGIF1 CDKL5 PLA2G6 SCN1A KCNJ11 PTCHD1 TECPR2 ERCC8 OSTM1 ACVRL1 SLC1A2 POLG SAMHD1 MSL3 GP1BB PYCR2 PLK4 KPTN PCYT2 PIGY ATP7A FARSB UCP2 SALL4 CHD1 PACS1 GLI2 AHI1 CCDC141 GABRA1 PEX14 ND5 CRKL COX15 SLC12A3 LHX1 NDUFAF8 GLI3 ATP6AP2 TRNL1 PHF21A RBPJ AFG3L2 MLH1 MLC1 NALCN MC2R PNPO POLR3A DYRK1A IL12A-AS1 UQCC2 CNNM2 SIK3 SMO CDKN1B GABRA1 KIFBP SDHA DNM1L KCNH1 PAK3 KCNQ2 TCF20 SCN8A SLC25A10 FA2H TDP1 TMEM138 PARS2 IQSEC1 ADNP GNB1 NACC1 KCNN3 RDH12 SCO2 C11ORF95 CD96 NDST1 GPHN GALNT2 AP4B1 PROKR2 ADGRG1 PIGT PIGS FGFR3 KIF4A CLP1 TGDS ODC1 POMT2 SCN1A MYH14 CLPP CEP120 RSRC1 GYS2 BRAF PRSS12 AP4E1 METTL5 SIK1 TP53 TSC2 P4HTM ATP6 CSF1R TBCE ARX SLC25A1 UGP2 EBP CALM2 SIX3 ARSA EBF3 DNASE1L3 B4GAT1 SASS6 KLHL15 TMEM70 PLEKHG2 MTM1 FASTKD2 SLC6A1 CDKN2C OPHN1 DPM3 ATRX FGF12 GRIN2D DIP2B TRNF PRRT2 MYH3 KCNQ3 SLC39A8 ATP13A2 GLE1 SLC35C1 B9D1 CDON ADGRG1 RD3 OPHN1 KCNE1 TSEN2 KMT2A AMACR PDHA1 MAGEL2 TBC1D24 MAP1B SYP CLN5 NPC2 PARS2 JRK HNMT MED12L PDP1 MYT1L ZIC2 TBC1D24 MPLKIP HESX1 SLC22A5 ACOX1 GRM1 ST3GAL3 NONO DAG1 ASXL3 EXT2 HADHB EXT2 CLCN4 SPTBN4 FGFR3 GPAA1 XPNPEP3 NDUFS4 HUWE1 POLG COQ9 NAGA PRKDC GABRD TRAPPC9 ZSWIM6 GRN AIPL1 AP4S1 KCNAB2 ARX SNX14 USF3 POMGNT1 GCK NDNF ACOX1 GABRB3 NOTCH1 HDAC4 ND5 PTCH1 SCN5A FOXRED1 TRNS2 GFAP ADNP AGRN PDHX PEX16 SDHD MEFV TRNL1 CSTB ATM HADH NDUFB11 SNAP25 RAB3GAP2 SHH CTNND2 TREX1 ELP1 TWNK ASXL1 GLI2 IQSEC2 PRICKLE1 SCN2A FOXG1 ARX GATA6 SUOX PRMT7 CCDC115 KISS1R KCNJ13 FUT8 UNC80 TBX1 WAC WWOX MPC1 EIF2S3 PEX14 PPA2 PACS2 FAS AFG3L2 SLC6A19 LAMB1 ERCC2 COG6 ASXL2 ADAMTS3 PIGL CYFIP2 MMADHC SLC45A1 QARS1 DNAJC6 SCN1A YWHAG COG8 MRPL12 EIF2B3 CC2D2A BSCL2 PEX5 SIK1 SOX10 CNKSR2 TMEM237 SEMA4A SNIP1 MMACHC STARD7 SLC12A1 TECPR2 OAT KCNH1 IPW VPS13A NGLY1 PPP2R5D ASPM STUB1 SLC2A1 CACNB4 COG8 TNFRSF11A INTS1 FRG1 TNFRSF11B MCPH1 TRNW BCORL1 PEX5 SLC35A3 TET3 AKT1 ACVR1 ALG9 NSD1 WDR73 PCDH19 TRAF3 FOXP1 GNB5 ND6 WDR45 MYO9A HCN1 TACR3 EIF2S3 KCNQ5 TMEM237 FGFRL1 IL1RAPL1 ND2 POLG IVD IL12B FGFR2 CREBBP CPA6 HTT KCNMA1 NDUFAF2 VARS2 GCSH NDE1 HACE1 NADK2 ND5 AAAS CRX NTNG1 FAM126A KDM3B NODAL SAMD12 ERCC6 ARNT2 FMN2 RFT1 TAT ABCA7 TSEN54 KCNH1 CPT2 ARG1 CNTN2 IQSEC2 UGT1A1 PRRT2 TRAPPC12 HMGCL PMS2 COA8 TOE1 CLN8 STXBP1 TMEM106B MBOAT7 ZEB2 TANC2 MPDU1 GNS RNF13 ARFGEF2 GNAO1 PPP1R15B ABCC8 MSX2 TPK1 SDHB DPM1
    Protein Mutations 1
    A147T
    SNP 5
    rs1024611 rs1360780 rs222797 rs2297201 rs2298771
    HP:0100806: Sepsis
    Genes 92
    TGM1 DCLRE1C ALOXE3 IKZF1 SEMA3C TFRC AK2 LMOD1 RAG1 IL2RG SFTPC DNAJC21 CYBA RAG2 COG4 CYBC1 PGM3 IL2RG AK2 ELANE CTCF CXCR4 RAC2 LRRC8A CTLA4 ALOX12B LIPN EFL1 WIPF1 ECE1 IGHM SRP54 CD79A BTK ACTG2 GDNF IGLL1 LAMA3 CD79B ABCA3 HYOU1 APC GALT PLEC RMRP BLNK CHD7 WAS ATP7A EDN3 MMUT VPS33A SULT2B1 TCF3 LAMB3 SDR9C7 IL7R CYBB G6PC3 SERAC1 MYLK EDNRB MRTFA SAMD9 RET CTNNB1 NCF4 PIK3R1 ITGB4 ADA MNX1 ABCA12 CYP4F22 NCF2 SFTPB HLA-B LIG4 MYH11 IL7R RAG1 LAMC2 SBDS NIPAL4 CD40LG NFKB2 NRTN SEMA3D RNF13 FERMT3 MYD88 FOXP3 NCF1
    Protein Mutations 2
    G20210A N682S
    SNP 8
    rs150018775 rs2234237 rs2234237r25r rs2234246 rs3210140 rs4883263 rs4883264 rs61729512
    HP:0001257: Spasticity
    Genes 1210
    LMAN2L PMPCA RNASEH2A ND4 PRDM8 KCNA2 SLC1A4 NDUFA10 SLC25A22 PEX5 SCN1B GAD1 ARX GPHN ISCA2 RNASEH2C TXN2 CAPN1 TRIT1 LIMK1 ARL6IP1 BICD2 ERCC6 KIDINS220 EEF1A2 NR2F1 PSAT1 COX15 GAN GBA2 CRADD SLC30A10 SLC2A1 MARS2 RALGAPA1 TARS1 FDXR VPS13D EXOSC9 SYNJ1 SPG7 C19ORF12 NOVA2 NPC1 PIGA COG2 AP4E1 TDP1 FRMPD4 WWOX MFN2 SYNE1 AP5Z1 PRKN TARDBP ARF1 ATP6AP2 AUH FOXH1 IKBKG SOX4 DNAJC6 GDAP2 TMTC3 SPAST GTF2E2 HEPACAM INPP5K VCP MYO5A KRAS HPRT1 COASY KCNJ6 RANBP2 PMPCA SPATA5 SEC31A ASPA TUBB3 ATP6 SELENOI NECAP1 NUP62 MAG GCDH EZH2 MED25 C12ORF4 SNX14 ATXN8 PLA2G6 ERCC6 PRPS1 VPS11 NDUFAF4 KCNJ6 FOXH1 GABRA2 WDR45 DLD MCCC1 NAGA SLC2A1 TRAK1 TOE1 SIL1 UCHL1 KIF2A TRAK1 CACNA1D GRIA4 CSF1R WDR73 RARS1 TMEM67 GAS1 ARX ACP5 BCS1L ARSA BCOR KIF1A TRNP KIF5C SUCLA2 SLC2A1 LYST ERCC3 UFC1 HSD17B4 GM2A UFM1 NDUFV2 GNAO1 PRNP ALDH18A1 GPT2 NODAL NUP214 ACTL6B ATP6V1A ERCC4 DISP1 PHGDH POU3F3 TRNI PON1 NTRK2 OPA1 PANK2 NDUFV1 NIPA1 KDM5B SLC13A5 USP8 SLC6A8 PLP1 TDGF1 AMACR OSGEP NDUFA13 IARS1 SELENOI SVBP ATAD3A C12ORF65 GLI2 FGF8 STXBP1 TRAPPC12 OPTN CYB5R3 NOTCH3 REEP2 PRUNE1 ATXN8OS MTHFS RARS2 PAX3 HSPD1 SPG7 SURF1 PSAP ERCC2 SIX6 EDNRB GFM2 COL4A1 WDR73 VAMP1 RAB3GAP1 ARX CYB5A TARDBP SRPX2 OCLN CASK FAR1 CTNNB1 SPG21 RFT1 CDON ZFYVE27 STAG2 SLC18A2 STXBP1 FGFR1 DNM1 ADSL SIX3 SERAC1 CYP27A1 RAB27A NSUN2 GALC B3GALNT2 SLC17A5 SIL1 DSTYK PHGDH TRNV PEX14 NARS2 NEFH RNASEH2C SNORD118 ZIC2 UGDH BCS1L DCPS TRNK GRIA3 TUBB3 GABRG2 ALDH3A2 HTRA1 AARS2 RPIA ST3GAL3 FGF8 SHH CACNA1G LYRM7 SURF1 ARV1 STXBP1 SON GALC TRNW COG2 DHPS FA2H NODAL BSCL2 VWA3B TIMM8A ATXN2 ZIC2 WARS2 EIF2AK2 CC2D1A ANG ADD3 MTFMT PLP1 GAS1 TAF2 PGAP1 BEAN1 MAPK8IP3 TMEM231 ARX NDUFAF3 PEX16 NTRK2 PPT1 RAB11B PAX3 B4GAT1 MFF BCOR NHLRC1 DNM1L NSD1 PIGQ OSTM1 UCHL1 ANXA11 DAO HCN1 GSS CYP2U1 C19ORF12 PTCH1 SCN2A ALDH3A2 GSX2 STUB1 GLI2 COL4A2 CYP7B1 NDUFV2 MTHFR EPHA4 BOLA3 NDUFA6 PARK7 ENTPD1 SETX REEP1 CTC1 XPC CLTC HLA-DQB1 GJA1 SOD1 POLR3A GRIK2 ARX MAN2B1 CNPY3 ALG11 NEK1 ERLIN1 CYP27A1 ANK3 ACAT1 DSTYK SACS SEPSECS PSAT1 MRPS34 POLR3B EIF2B5 RAD50 RTTN SLC2A1 CDK19 HPRT1 MED25 CDKL5 PTPN23 TUBGCP2 SPTBN2 MED25 RTTN PQBP1 FBLN1 TBCE PTS CIT ERLIN2 ZNF592 FARS2 FUCA1 XPA PON3 PIGC KLC2 SYNGAP1 PPP3CA CNTNAP2 CASK TUBA1A TPI1 SNCA SUZ12 SPG11 SYNJ1 APC2 COLGALT1 CYP2U1 NIPA1 SPG7 MAN2B1 IBA57 FXN TRMT10A FBXO31 ATM TIMM50 KDM5C PEX3 FLNA CTNNA2 CYB5R3 OPA1 PDCD1 TTC19 AP1S2 SYNJ1 RFC2 BCL11B ERCC2 SPG21 TDGF1 POLA1 RAB3GAP2 SCN2A TANGO2 WDR4 ARX SOD1 PEX7 REPS1 SIGMAR1 PNPLA6 SLC13A5 PFN1 MARS2 EED SLC35A2 KANK1 GATAD2B CLCN4 SOX2 ERCC3 MED23 EPM2A NT5C2 PEX19 OTUD6B ABHD12 PNPLA8 MACF1 HIKESHI GJC2 CRLF1 PI4KA PAFAH1B1 FIG4 SPATA5 HSPD1 REEP1 ALDH18A1 FOXH1 NDUFAF5 WDR62 SACS ATP6AP2 SPTBN2 VPS13C GPHN NEU1 UBA5 PPARGC1A NDUFS4 GUF1 EIF2B2 ATRX PRNP PSAP XPA FMN2 DDHD1 TGIF1 ADAM22 NTNG2 NDUFB8 SDHA TFG ERLIN2 GRIN1 CARS2 IFIH1 PEX1 PEX12 NEFL AARS1 THOC2 GM2A CLCN4 MED17 HSPD1 HLA-DRB1 GAS1 TFG KCNA1 ALS2 GALC ERCC5 POLR3B ELP2 AP4S1 NDUFS2 LAMB1 CHCHD10 ASAH1 DYNC1H1 SPG11 AGTPBP1 POLR1C ATRX ZFR WDR48 MED13L SLC25A15 TRNF PTCH1 ATP2B3 UBA5 DALRD3 GABRA5 MATR3 TBC1D20 PHGDH DENND5A PAFAH1B1 FOXH1 CFAP410 TREM2 KIF1A TAF1 NALCN FA2H SDHAF1 ATP6V1A SLC33A1 CPT1C RNASEH2B TGIF1 SPAST CDKL5 C9ORF72 LIPT2 MECP2 ARSA NEFH ATAD3A PQBP1 CLIP1 PNP ATXN3 EARS2 PET100 ACP5 KCNQ2 RAB3GAP1 RAB3GAP2 ISCA1 GLRB TDGF1 PEX26 ASNS KIF1C TNIK FARS2 PEX6 TSEN15 TRNW DLL1 GLYCTK METTL23 OPA3 DDHD1 SHH PNPLA6 ARX TGIF1 TREX1 ACER3 TRNK CLIC2 ALS2 FAR1 CNOT1 FGFR1 GLT8D1 VAPB PNPLA6 ITM2B ABCC8 CACNA1G GLRX5 SARS1 ALS2 LMNB1 ERBB4 INTS8 ERCC3 UBQLN2 IDUA DHCR24 TMX2 LIPT1 POMGNT1 UBTF TREM2 MICOS13 GRIN2B ATP6V1A PQBP1 NUBPL RARS1 DHCR24 ASPA MFSD2A ATP13A2 DLL1 CAPN1 TPRKB GOT2 ANG GAN TCTN2 HEPACAM SLC39A14 SLC52A2 DLL1 MOCS2 TELO2 AP4M1 RTN2 PUM1 PRPH KIF5A PYCR2 KDM5C HTRA2 UNC80 KCNA4 PPP3CA TUBG1 ZIC2 TBP PIGP PEX11B DYNC1I2 PNPLA6 KCNA1 NODAL SPR MECP2 LINS1 TBC1D23 COX10 SCN8A UBTF LAGE3 GBA2 SPTAN1 NUP62 DDB2 FTL RNU4ATAC MECR GRIN1 SIX3 STXBP1 ACTL6B GRIN2B TIMM50 ALS2 KIF11 CHMP1A MCCC2 TAF1 KLC2 PCLO RAB18 TTR DARS1 CRBN ERCC8 EXOSC3 MTO1 ZFYVE26 TUFM KY SCYL2 DISP1 GAS1 RPGRIP1L JAM3 LRRK2 WASHC5 MECP2 NKX6-2 ELN WARS2 VCP ANKLE2 C12ORF65 TRNL1 TP53RK ELOVL4 IARS1 MAN1B1 FRRS1L AGA DLL1 TUBB4A SIX3 SDHA APC GTF2I L1CAM MCCC1 PCDH12 NACC1 GABRB2 DCTN1 IRF2BPL FOXG1 PMPCB ATXN8 MFF DEGS1 ATP6 CDON ERCC4 ADAR VPS53 GALC MAG PEX2 SCN3A TELO2 OTUD6B FIG4 PRPH FUS GRIA2 CACNA1D MBOAT7 SETBP1 GLRX5 RLIM GFM1 CYFIP2 PLP1 NDUFAF5 CACNA1B COASY SLC1A4 DHDDS SHH SDHD MECP2 ABCD1 ECHS1 ND6 PSAP GLI2 MARS1 SLC13A5 TBCD ATP6V1E1 SLC2A1 ATXN2 MICOS13 SLC33A1 WDR26 DISP1 LMNB1 REEP2 IDUA ATXN7 KATNB1 FGF8 AP4M1 PSAP GABRA5 BSCL2 TYROBP ATAD1 LIPT1 KIF1A OPA1 TSEN54 AP4B1 DDX3X LINGO1 SDHA IFIH1 KIF1C ROGDI FGFR1 SPG11 SCYL1 ND1 GPAA1 OPA1 ZEB2 MAPT GBA CACNA1G GBA2 ITM2B CASK ATXN10 SPG11 GBA ATXN3 L1CAM NAA10 ATP7A MTPAP FBXO7 GJA1 INPP5K PANK2 UBAP1 GRIN2D PLAA RETREG1 TAF15 EXTL3 EIF2B1 IBA57 OPA3 EZR CCT5 ADARB1 RERE ALDH18A1 CHP1 PLCB1 AUTS2 RANBP2 RUSC2 NDUFS7 TYROBP OCLN RNASET2 MRE11 DCX MOCS1 SLC5A6 ARX STAG2 ZC4H2 SOX10 SLC2A1 PEX6 SLC1A2 UNC13A POLR3A C19ORF12 PTCH1 GJC2 LMX1B CLTC AMPD2 ZNF335 EML1 NDE1 NDUFS3 CNTNAP1 HMGCL TRAPPC9 KCNT1 ELOVL4 SLC25A12 PLA2G6 HSD17B10 GJC2 RNASEH2B GBE1 RPS6KA3 KCNB1 L2HGDH NEU1 GPT2 SPART FTL CLPB TECR L1CAM NDUFA12 NDUFA9 CCNF PLA2G6 CDON TECPR2 NDUFA4 SOD1 PSEN1 PGAP1 FLRT1 TAF2 SLC1A2 SAMHD1 MSL3 FBXO7 FRRS1L ATAD3A PYCR2 NUS1 GFM2 STN1 CTNNB1 GABBR2 AUH CKAP2L PCYT2 ERCC5 ERCC4 AARS1 ANK3 DCTN1 SURF1 COX15 CLPB NDUFA2 EPRS1 KCNA1 THOC2 PIGN ND3 SMC1A AFG3L2 AFG3L2 SCN3A TRMT5 MLC1 B4GALNT1 NALCN GLB1 SPART DDHD2 AIMP1 PSAP POLR3A VPS37A SAMHD1 L1CAM ATP13A2 PIGU NDUFAF6 SDHA PINK1 PFN1 DDHD2 ARSI TCF20 HNRNPA1 ACP2 TBK1 SLC25A10 CAMK2A FA2H CCDC88C PPP1R15B PARS2 CCDC88C B4GALNT1 NACC1 SCO2 VAMP1 NDUFS1 ATP6V0A2 AMPD2 NDST1 PANK2 MCOLN1 AP4B1 CLIP2 ROGDI DNMT1 NDUFS2 GRM1 CLP1 ODC1 NDUFS8 BAZ1B FUCA1 SDHD RSRC1 PRSS12 AP4E1 METTL5 ADAR VPS13C ALS2 GJB1 CSF1R TBCE UGP2 FUS LIAS SIX3 ARSA TUSC3 BCL11B AP3B2 ERCC5 WASHC4 CACNA1A AP5Z1 PODXL ATL1 ATRX FGF12 COPB2 ARG1 PRRT2 SLC2A1 ATP13A2 MRPS22 CTSD DMXL2 CDON ADGRG1 ATXN3 OPHN1 TRIM8 TSEN2 ALDH18A1 PDHA1 GABRA2 NPC2 PARS2 DARS2 PHACTR1 WDR45B HNMT KMT2B GLRA1 ERCC2 ZIC2 ALDH18A1 MPLKIP GLE1 GTPBP2 ALS2 AMPD2 SNCA GPAA1 ECHS1 WWOX EZH2 PEX13 NDUFS4 PON2 HUWE1 POLG FGF8 WASHC4 RAB18 NSUN2 DNAJC19 MTPAP AP4S1 TRAPPC4 DNMT1 SNX14 CLP1 ENTPD1 CHMP2B PRDM8 ND5 PTCH1 FOXRED1 KIF5A AP1S2 ATXN3 SDHAF1 SLC19A3 HACE1 GFAP L1CAM SCYL1 PDHX TDGF1 TRNL1 WASHC5 RAB3GAP2 SHH SLC30A10 TREX1 RTN2 GLI2 PNP SLC39A14 DHDDS NKX6-2 FOXG1 EIF2B4 ARX PEX3 NEXMIF NADK2 SLC19A3 RNASEH2A UNC80 AFG3L2 PANK2 UBA5 TGIF1 BSCL2 WWOX GTF2IRD1 L2HGDH NEUROD2 AFG3L2 SLC25A15 NUS1 KCNA2 IQSEC1 ERCC2 EXOSC8 CYFIP2 SLC45A1 ATL1 DNAJC6 ADAT3 YWHAG IREB2 ATXN8OS ZFYVE26 PLA2G6 GBA EIF2B3 CC2D2A BSCL2 SIK1 SOX10 CNKSR2 GABRB2 CYP7B1 ALG11 NT5C2 STUB1 SQSTM1 SZT2 TACO1 FDX2 SLC6A5 ERCC8 GBE1 MRM2 CACNA1E CPT1C SCN1B AIMP1 PEX16 IBA57 TBC1D20 TBCD SLC16A2 C12ORF65 ADAT3 FOXP1 WDR45 ATXN1 EIF2S3 SUMF1 ERCC1 ERLIN1 DARS2 SYNE1 CCT5 SMPD1 ND2 SLC25A22 NDUFA13 HTT EDC3 NDUFAF2 SETBP1 NDE1 MTFMT STAMBP HACE1 NADK2 NTNG1 PNKP DDX3X ERLIN2 KIDINS220 NODAL RNF113A MECP2 CLIC2 ATP6 ARSA TBL2 ERCC6 ARNT2 VPS11 AIFM1 ZC3H14 SIGMAR1 TSEN54 PGAP1 ARG1 PEX10 C19ORF12 ZC4H2 L1CAM NAGA TRAPPC12 HMGCL GTF2H5 COA8 MCCC2 TOE1 STXBP1 ARL6IP1 ZEB2 IKBKG RNF13 GBA GNAO1 PPP1R15B DISP1 TPK1 SDHB
    Protein Mutations 0
    SNP 18
    rs1049522 rs1049524 rs137852620 rs2032892 rs2269272 rs2269273 rs2562582 rs2731886 rs377637047 rs4869675 rs4869676 rs529802001 rs544684689 rs547987105 rs549927573 rs550842646 rs562696473 rs573562920
    HP:0100651: Type I diabetes mellitus
    Genes 56
    PSTPIP1 INS TRNW KCNJ11 TRNL1 CLCNKB TRNS2 TRNS1 KCNJ11 FLT1 IL18BP CAT TTC7A TCF4 ITCH CNOT1 ND6 ABCC8 STAT1 KCTD1 EDA2R TRNF NEUROG3 ND4 FOXP3 ND5 TRNH CORIN TRNE TKT MMP2 MMP14 INS SLC16A2 ABCC8 COX1 COX3 MST1 GCK ND1 INS EDA GPR35 SLC29A3 DNAJC3 ITCH EIF2AK3 SLC12A3 HNF1A STUB1 AIRE PDX1 TRNQ FOXP3 STOX1 COX2
    Protein Mutations 7
    C1858T C282T I191V K1270A K3048A R620W S9C
    SNP 4
    rs35874116 rs35874116rs rs9701796 rs9939609
    HP:0005978: Type II diabetes mellitus
    Genes 186
    WRN NR2E3 IMPG2 ZNF513 RP1 TRNL1 CLCNKB TRNS2 PPARG TRNS1 PCNT AGBL5 ARL3 FBN1 TULP1 TUB CARS1 MC4R PNPLA6 LIMK1 PRPF4 RP2 TRNK MEN1 AHR KLF11 CTNNB1 CRX SPATA7 CRB1 DMXL2 PPP1R3A GLRX5 NEK2 ENPP1 PRPF3 LIG4 PDE6B CA4 TOPORS RDH12 MKRN3 IFT172 ARL2BP SNORD115-1 ABCC8 RP9 SLC30A8 IMPDH1 ND4 ND5 GTF2IRD1 HMGA1 PROM1 ABCC8 CYP19A1 NEUROD1 MERTK LMNA KCNJ11 ARHGEF18 SLC2A2 PRPF31 RETN ABCA4 KLHL7 PRPF6 LRAT C8ORF37 TRNL1 BBS2 COX1 WFS1 RPGR CLIP2 BEST1 XRCC4 GUCA1B SCAPER NRL PDE6G ZNF408 ELN RBP3 SIM1 ALMS1 PDX1 BAZ1B ATM BRAF IPW TCF7L2 KIAA1549 STUB1 IRS1 HNF1A TRNQ RFC2 BLM PDE6A PDX1 PRCD COX2 DHX38 GCK HGSNAT GTF2I IRS2 CERKL USH2A TRNW SLC7A14 POLR3A RHO PCARE IDH3A RP1L1 FAM161A SNRNP200 CAT PWRN1 CNGB1 AIP CLRN1 ND6 EYS GCK TTC8 PLCD1 HNF1A HERC2 IFT88 ARL6 AHI1 TRNF AMACR CEP19 MAGEL2 PRPF8 POLA1 NDN MAPK8IP1 MAK KIZ TRNH PWAR1 PRPH2 PAX4 LIPC RPE65 REEP6 HNF4A AR RLBP1 OFD1 COX3 IGF2BP2 MTNR1B TBL2 DHDDS POMGNT1 PEX10 RGR SAG FSCN2 GPD2 AKT2 ND1 SEMA4A MKRN3-AS1 INSR MOG IDH3B PTPN1 MAGEL2 NPAP1 CDHR1 SLC12A3 IFT140 HNF1B CNGA1 ROM1 SNORD116-1 SPINK1 SNRPN TRNE
    Protein Mutations 12
    A54T E158K E23K G174S G212A G401S G465R I349V K121Q P12A R230C R61C
    SNP 9
    rs10401969 rs13266634 rs2266782 rs2854275 rs35652124 rs780094 rs780094s rs78408340 rs7903146
    HP:0002635: Type IV atherosclerotic lesion
    Genes 1
    APOE
    Protein Mutations 0
    SNP 0
    HP:0100279: Ulcerative colitis
    Genes 11
    BACH2 MASP2 NOD2 MAP3K7 INAVA IL6 PLCG2 MST1 GPR35 TCF4 CYBC1
    Protein Mutations 2
    H180Q V600E
    SNP 1
    rs2097432

    Reports

    Data processed on September 26, 2020.

    An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.

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    691 reports on MeSH terms

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