CovidResearchTrials by Shray Alag


CovidResearchTrials Covid 19 Research using Clinical Trials (Home Page)


PlaceboWiki

Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation


Correlated Drug Terms (573)


Name (Synonyms) Correlation
drug1598 Nitazoxanide Wiki 0.14
drug1086 Hydroxychloroquine Wiki 0.13
drug1695 Ontamalimab Wiki 0.11
drug285 BCG vaccine Wiki 0.10
drug2620 VPM1002 Wiki 0.10
drug2059 Relamorelin Wiki 0.10
drug923 Favipiravir Wiki 0.10
drug1270 Ivermectin Wiki 0.09
drug1901 Presatovir Wiki 0.08
drug560 Chloroquine Wiki 0.08
drug1097 Hydroxychloroquine - Weekly Dosing Wiki 0.08
drug2422 TD-0903 Wiki 0.08
drug1592 Niclosamide Wiki 0.08
drug2665 Vitamin Super B-Complex Wiki 0.08
drug1331 Leronlimab (700mg) Wiki 0.08
drug1678 Olokizumab 64 mg Wiki 0.08
drug1114 Hydroxychloroquine Sulfate Regular dose Wiki 0.08
drug1788 Pentoxifylline Wiki 0.08
drug1316 LY3819253 Wiki 0.08
drug1998 REGN10933+REGN10987 combination therapy Wiki 0.08
drug1595 Nigella Sativa / Black Cumin Wiki 0.08
drug1279 Ivermectin Oral Product Wiki 0.08
drug2528 Tocilizumab (TCZ) Wiki 0.08
drug1374 Losartan Wiki 0.08
drug506 CYT107 Wiki 0.08
drug1113 Hydroxychloroquine Sulfate Loading Dose Wiki 0.08
drug2539 Tofacitinib 10 mg Wiki 0.08
drug1751 PUL-042 Inhalation Solution Wiki 0.08
drug2580 UC-MSCs Wiki 0.08
drug2067 Remdesivir Wiki 0.07
drug698 DAS181 Wiki 0.07
drug1860 Placebos Wiki 0.07
drug1696 Opaganib Wiki 0.07
drug2396 Suspension of heat killed (autoclaved) Mycobacterium w Wiki 0.07
drug284 BCG Vaccine Wiki 0.07
drug1324 Lanadelumab Wiki 0.07
drug315 Baricitinib Wiki 0.06
drug1853 Placebo oral tablet Wiki 0.06
drug2988 rhPTH(1-84) Wiki 0.06
drug1422 MVA-MERS-S_DF1 - Low Dose Wiki 0.06
drug912 FFP2 Wiki 0.06
drug2819 favipiravir Wiki 0.06
drug266 Azithromycin 500 milligram (mg) oral Tablet Wiki 0.06
drug2257 Silymarin Wiki 0.06
drug2437 Table Setting Training Wiki 0.06
drug65 ACT-541478 dose E1 Wiki 0.06
drug252 Auxora Wiki 0.06
drug418 C21 Wiki 0.06
drug1278 Ivermectin Injectable Solution Wiki 0.06
drug2481 Tezepelumab Wiki 0.06
drug278 BAY1817080 Wiki 0.06
drug1142 IC14 Wiki 0.06
drug2752 bacTRL-Spike Wiki 0.06
drug3040 vaccine candidate MVA-MERS-S Wiki 0.06
drug579 Clevudine Wiki 0.06
drug1081 Human umbilical cord mesenchymal stem cells + best supportive care Wiki 0.06
drug213 ArtemiC Wiki 0.06
drug2786 consultation Wiki 0.06
drug1838 Placebo Vaccine Wiki 0.06
drug2053 Regadenoson myocardial perfusion imaging stress test Wiki 0.06
drug26 2019-nCoV PCR Wiki 0.06
drug279 BBV152A Wiki 0.06
drug1387 Low nitrite/NDMA meals Wiki 0.06
drug1849 Placebo on a 0- and 14-day schedule Wiki 0.06
drug1378 Low Dose of KBP-COVID-19 Wiki 0.06
drug2559 Treadmill electrocardiographic stress test Wiki 0.06
drug2780 cholecalciferol 50,000 IU Wiki 0.06
drug2901 mouthrinse with bêta-cyclodextrin and citrox Wiki 0.06
drug1704 Organicell Flow Wiki 0.06
drug1477 Mesenchymal stem cells Wiki 0.06
drug60 ACT-541478 10 mg Wiki 0.06
drug1409 MK-5475 Wiki 0.06
drug2171 ST-2427 Wiki 0.06
drug597 Cognitive Training Wiki 0.06
drug504 CVnCoV Vaccine Wiki 0.06
drug1784 Peginterferon Lambda-1a Wiki 0.06
drug2815 exercise brochure Wiki 0.06
drug2331 Standard of care therapy Wiki 0.06
drug61 ACT-541478 100 mg Wiki 0.06
drug1737 PHR160 Spray Wiki 0.06
drug612 Combination of Lopinavir /Ritonavir and Interferon beta-1b Wiki 0.06
drug2837 hospitalized children with Covid19 Wiki 0.06
drug1400 M201-A Injection Wiki 0.06
drug844 Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet Wiki 0.06
drug1380 Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule Wiki 0.06
drug2124 SAR443122 Wiki 0.06
drug668 Coronary artery calcium score and cardiac computed tomographic angiography Wiki 0.06
drug1597 Nintedanib 150 MG Wiki 0.06
drug1891 Prasugrel Hydrochloride 10 MG Oral Tablet Wiki 0.06
drug400 Brief Behavioral Activation Treatment Wiki 0.06
drug66 ACT-541478 high or low dose (or placebo) Wiki 0.06
drug3052 zinc Wiki 0.06
drug1647 Normobaric oxygen therapy Wiki 0.06
drug1373 Lopinavir/ritonavir treatment Wiki 0.06
drug2556 Transplant patient Wiki 0.06
drug1231 Intermediate dose thromboprophylaxis Wiki 0.06
drug407 Bromhexine Hydrochloride Tablets Wiki 0.06
drug1888 Povidone-iodine Wiki 0.06
drug864 Enzalutamide Wiki 0.06
drug2211 Self-Compassion for Chronic Pain Virtual Group Treatment Program Wiki 0.06
drug1157 ION-827359 Wiki 0.06
drug1512 Monitoring Visit - Baseline Wiki 0.06
drug810 EIDD-2801 Wiki 0.06
drug704 DNL151 Wiki 0.06
drug2008 RSVPreF3 formulation 2 Wiki 0.06
drug2006 RS blend Wiki 0.06
drug2606 Urine Test Wiki 0.06
drug2189 Sample Collection/Performance Evaluation (A) Wiki 0.06
drug514 Canakinumab Wiki 0.06
drug1514 Monitoring Visit - Week 8 Wiki 0.06
drug2469 Telmisartan 40mg Wiki 0.06
drug2120 Ruxolitinib plus simvastatin Wiki 0.06
drug1116 Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets Wiki 0.06
drug355 Biological: mRNA-1273: 100 mcg Wiki 0.06
drug2048 Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) Wiki 0.06
drug429 CD24Fc Wiki 0.06
drug1095 Hydroxychloroquine - Daily Dosing Wiki 0.06
drug1093 Hydroxychloroquine + placebo Wiki 0.06
drug700 DAS181 OL Wiki 0.06
drug2289 Spironolactone 100mg Wiki 0.06
drug2430 TJ003234 Wiki 0.06
drug1017 Guanfacine hydrochloride (SPD503) Wiki 0.06
drug2009 RSVPreF3 formulation 3 Wiki 0.06
drug1654 Nutrition Wiki 0.06
drug1480 Metformin XR Wiki 0.06
drug2239 Serology Wiki 0.06
drug3024 telephone consult Wiki 0.06
drug2015 RTB101 Wiki 0.06
drug367 Blood Test Wiki 0.06
drug1855 Placebo solution Wiki 0.06
drug82 ASP7317 Wiki 0.06
drug2000 REGN3051 Wiki 0.06
drug2367 Study A Wiki 0.06
drug565 Chloroquine diphosphate Wiki 0.06
drug2165 SOC + Placebo Wiki 0.06
drug2564 Trivia Training Wiki 0.06
drug1338 Levilimab Wiki 0.06
drug1809 Phsyiotherapy Wiki 0.06
drug2164 SOC + Intravenous Famotidine Wiki 0.06
drug1708 Other drugs Wiki 0.06
drug974 GENUS device (Active Settings) Wiki 0.06
drug152 Aluminum hydroxide Wiki 0.06
drug1288 JNJ-53718678 2.5 mg/kg Wiki 0.06
drug247 Auto-questionnaires (patients co infected HIV Sras-CoV-2) Wiki 0.06
drug1431 Manremyc Wiki 0.06
drug1594 Nicotinamide riboside Wiki 0.06
drug1912 Probiotic and LC-PUFA Wiki 0.06
drug296 BM-Allo.MSC Wiki 0.06
drug256 Awake Proning Wiki 0.06
drug2428 TERN-101 Wiki 0.06
drug109 Acalabrutinib Treatment B Wiki 0.06
drug2914 newborns from covid 19 positive mothers Wiki 0.06
drug1221 Interferon beta 1a Wiki 0.06
drug62 ACT-541478 1000 mg Wiki 0.06
drug2714 Zilucoplan® Wiki 0.06
drug1743 PRV-015 Wiki 0.06
drug154 Ambrisentan Wiki 0.06
drug2701 XAV-19 Wiki 0.06
drug1314 LY3127804 Wiki 0.06
drug1100 Hydroxychloroquine Oral Product Wiki 0.06
drug1841 Placebo for Hydroxychloroquine Wiki 0.06
drug2870 liposomal lactoferrin Wiki 0.06
drug832 Electric pad for human external pain therapy Wiki 0.06
drug2998 sertraline Wiki 0.06
drug1568 Naltrexone Wiki 0.06
drug1292 JNJ-66525433 Wiki 0.06
drug281 BBV152C Wiki 0.06
drug2017 RUTI® vaccine Wiki 0.06
drug2443 Tap water Wiki 0.06
drug2126 SARS-CoV Wiki 0.06
drug1389 Low-Concentration Essential Oil Wiki 0.06
drug961 Follow-up at 14 days Wiki 0.06
drug140 Alferon LDO Wiki 0.06
drug783 Dociparastat sodium Wiki 0.06
drug91 ATYR1923 3 mg/kg Wiki 0.06
drug1325 Lateral Position (left and right lateral decubitus) Wiki 0.06
drug2621 VRC-SRSDNA015-00-VP Wiki 0.06
drug1956 Pyridostigmine Bromide Wiki 0.06
drug2163 SOC Wiki 0.06
drug2617 V-SARS Wiki 0.06
drug273 BACMUNE (MV130) Wiki 0.06
drug2543 Tradipitant Wiki 0.06
drug1339 Lianhua Qingwen Wiki 0.06
drug530 Cash transfer Wiki 0.06
drug2226 Sequencing Wiki 0.06
drug51 ABX464 Wiki 0.06
drug2456 Telehealth monitoring Wiki 0.06
drug807 EDP1815 Wiki 0.06
drug2148 SBI-101 Wiki 0.06
drug1313 LSALT peptide Wiki 0.06
drug191 Antibody Test Wiki 0.06
drug805 ECG-Holter Wiki 0.06
drug88 AT-527 Wiki 0.06
drug375 Blood group determination Wiki 0.06
drug2744 artus Influenza A/B RT-PCR Test Wiki 0.06
drug1810 Physical Exam Wiki 0.06
drug64 ACT-541478 300 mg Wiki 0.06
drug1096 Hydroxychloroquine - Daily dosing Wiki 0.06
drug2941 oxyhydrogen Wiki 0.06
drug1137 Hyperbaric oxygen therapy Wiki 0.06
drug1312 LRX712 Wiki 0.06
drug42 40mg of MitoQ Wiki 0.06
drug572 Ciclesonide Inhalation Aerosol Wiki 0.06
drug58 ACT-20-CM Wiki 0.06
drug291 BIIB091 Wiki 0.06
drug2005 RPH-104 80 mg Wiki 0.06
drug713 Dapagliflozin Wiki 0.06
drug1044 Helmet non-invasive ventilation (NIV) Wiki 0.06
drug1150 IMU-838 Wiki 0.06
drug714 Dapagliflozin 10 MG Wiki 0.06
drug2269 Sirukumab Wiki 0.06
drug976 GLS-1200 Wiki 0.06
drug1408 MFS Wiki 0.06
drug944 Fingolimod 0.5 mg Wiki 0.06
drug1968 Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) Wiki 0.06
drug2745 assessment of the sequelae after hospitalization for Sars-COV-2 Wiki 0.06
drug1371 Lopinavir/Ritonavir 400 mg/100 mg Wiki 0.06
drug148 Almitrine Wiki 0.06
drug881 Exercise Group Wiki 0.06
drug1924 Prone positioning (PP) Wiki 0.06
drug2749 avdoralimab Wiki 0.06
drug1440 Matched Placebo Hydroxychloroquine Wiki 0.06
drug1153 INOpulse Wiki 0.06
drug280 BBV152B Wiki 0.06
drug455 COVID-19 Convalescent Plasma (CCP) Wiki 0.06
drug999 Global Longitudinal Strain Wiki 0.06
drug2622 Vaccine Wiki 0.06
drug292 BIO101 Wiki 0.06
drug1457 Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule Wiki 0.06
drug1306 LB1148 Wiki 0.06
drug1522 Moxifloxacin Wiki 0.06
drug63 ACT-541478 30 mg Wiki 0.06
drug1318 Laboratory Analyses Wiki 0.06
drug310 Bacille Calmette-Guérin (BCG) Wiki 0.06
drug1171 IgG test Wiki 0.06
drug867 Ergoferon Wiki 0.06
drug1102 Hydroxychloroquine SAR321068 Wiki 0.06
drug1297 Ketamine Wiki 0.06
drug2435 TXA127 Wiki 0.06
drug1724 P2Et (Caesalpinia spinosa extract) Wiki 0.06
drug1675 Octagam 10% Wiki 0.06
drug356 Biological: mRNA-1273: 50 mcg Wiki 0.06
drug1513 Monitoring Visit - Week 4 Wiki 0.06
drug122 Ad26.COV2.S Wiki 0.06
drug1535 MySafeRx Inspire Flex Wiki 0.06
drug1827 Placebo 250 cc 24 hours continuous infusion for 15 days Wiki 0.06
drug868 Escin Wiki 0.06
drug108 Acalabrutinib Treatment A Wiki 0.06
drug1748 PTC299 Wiki 0.06
drug1658 OP-101 Wiki 0.06
drug829 Eicosapentaenoic acid gastro-resistant capsules Wiki 0.06
drug2764 blood draw Wiki 0.06
drug50 ABTL0812 Wiki 0.06
drug3044 vitamin d Wiki 0.06
drug2652 Virtual Care at Home Wiki 0.06
drug2604 Upadacitinib (ABT-494) Wiki 0.06
drug1907 Previfenon® Wiki 0.06
drug23 20 mg MitoQ Wiki 0.06
drug1053 High Dose of KBP-COVID-19 Wiki 0.06
drug2959 pre-operative screening Wiki 0.06
drug1167 Icosapent ethyl (IPE) Wiki 0.06
drug2751 azoximer bromide Wiki 0.06
drug1407 MEDI7219 Wiki 0.06
drug2779 cholecalciferol 200,000 IU Wiki 0.06
drug2897 molecular testing for virus RNA using RT-PCR Wiki 0.06
drug2366 Streptokinase Wiki 0.06
drug3039 vaccine BCG Wiki 0.06
drug189 Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients Wiki 0.06
drug2881 mavrilimumab Wiki 0.06
drug432 CERC-002 Wiki 0.06
drug1286 JNJ-53718678 Wiki 0.06
drug2820 favipiravir tablets+chloroquine phosphatetablets tablets Wiki 0.06
drug1593 Niclosamide Oral Tablet Wiki 0.06
drug2703 XPro1595 Wiki 0.06
drug921 Famotidine Wiki 0.06
drug1740 PLX-PAD Wiki 0.06
drug133 Aerosolized All trans retinoic acid Wiki 0.06
drug1026 HCQ+AZT Wiki 0.06
drug2371 Study D Wiki 0.06
drug3020 systemic treatment Wiki 0.06
drug1362 Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki 0.06
drug129 Aerolized Hydroxychloroquine Sulfate Wiki 0.06
drug1330 Lenzilumab Wiki 0.06
drug2007 RSV Mobile Application Wiki 0.06
drug1879 Positive Peer Journaling (PPJ) Wiki 0.06
drug147 Allopurinol Wiki 0.06
drug1940 Psychological and Behaviour Change Support Wiki 0.06
drug116 Acthar Gel Wiki 0.06
drug1291 JNJ-53718678 4.5 mg/kg Wiki 0.06
drug1572 NasoVAX Wiki 0.06
drug2841 hydroxychloroquine + azithromycin Wiki 0.06
drug2172 STC-19 score Wiki 0.06
drug96 AVM0703 Wiki 0.06
drug664 Cooking Training Wiki 0.06
drug2629 Vazegepant (BHV-3500) Wiki 0.06
drug1943 Psychosocial stimulation and healthy eating education Wiki 0.06
drug2741 anti-SARS-CoV-2 plasma Wiki 0.06
drug956 Fluvoxamine Wiki 0.06
drug1296 Kerecis Oral and Nasal Spray Wiki 0.06
drug157 Ampion Wiki 0.06
drug582 Clinical data Wiki 0.06
drug1273 Ivermectin + Doxycycline + Placebo Wiki 0.06
drug1605 Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki 0.06
drug1057 High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule Wiki 0.06
drug2857 intradermal injection of BCG Vaccine Wiki 0.06
drug1274 Ivermectin + Placebo Wiki 0.06
drug2094 Ringer solution Wiki 0.06
drug577 Clazakizumab 12.5 mg Wiki 0.06
drug1060 High nitrite/NDMA meals Wiki 0.06
drug410 Budesonide Wiki 0.06
drug706 DUR-928 Wiki 0.06
drug2702 XCEL-UMC-BETA Wiki 0.06
drug1164 Ibudilast Wiki 0.06
drug1414 MRx-4DP0004 Wiki 0.06
drug984 Galidesivir Wiki 0.06
drug986 Gam-COVID-Vac Lyo Wiki 0.06
drug1840 Placebo for Azithromycin Wiki 0.06
drug137 Airway pressure release ventilation Wiki 0.06
drug194 Antibody-Rich Plasma from COVID-19 recovered patients Wiki 0.06
drug913 FLOW intervention Wiki 0.06
drug414 Burnout Wiki 0.06
drug1307 LDAEP Wiki 0.06
drug2190 Sample Collection/Performance Evaluation (B) Wiki 0.06
drug2831 high flow nasal cannula (HFNC) Wiki 0.06
drug1750 PTSD Wiki 0.06
drug1818 Piclidenoson Wiki 0.06
drug1997 REGN10933+REGN10987 Wiki 0.06
drug2636 Verinurad Wiki 0.06
drug578 Clazakizumab 25 mg Wiki 0.06
drug2887 meplazumab for injection Wiki 0.06
drug784 Doctor Spot Wiki 0.06
drug791 Doxycycline Wiki 0.06
drug1301 Knowledge, Attitude, Practice, Awareness, Preference Wiki 0.06
drug2173 STI-1499 Wiki 0.06
drug677 Covid-19 Antibody testing (IgG and IgM) Wiki 0.06
drug2370 Study C Wiki 0.06
drug126 Adsorbed COVID-19 (inactivated) Vaccine Wiki 0.06
drug605 ColdZyme® mouth spray Wiki 0.06
drug1070 Honey Wiki 0.06
drug1830 Placebo Comparator Wiki 0.06
drug2041 Recombinant human alkaline phosphatase Wiki 0.06
drug1126 Hydroxychloroquine sulfate &Azithromycin Wiki 0.06
drug81 ASP0892 Wiki 0.06
drug2877 lung ultrasound (LUS) Wiki 0.06
drug2025 Ranitidine Wiki 0.06
drug958 Folfirinox Wiki 0.06
drug934 Fecal Microbiota Therapy (FMT) Wiki 0.06
drug1021 HB-adMSC Wiki 0.06
drug2418 TAK-981 Wiki 0.06
drug1423 Machine learning model Wiki 0.06
drug870 Essential oils Wiki 0.06
drug2407 T3 solution for injection Wiki 0.06
drug2325 Standard of Care thromboprophylaxis Wiki 0.06
drug2585 Ulinastatin Wiki 0.06
drug297 BM-MSCs Wiki 0.06
drug1663 Observation of behavior and COVID-19 infection will be conducted. Wiki 0.06
drug1317 LY3832479 Wiki 0.06
drug879 Exebacase Wiki 0.06
drug1536 MySafeRx Inspire Plus Wiki 0.06
drug1412 MR or M-M-R II ® vaccine Wiki 0.06
drug282 BCG Wiki 0.06
drug869 Esomeprazole 20mg Wiki 0.06
drug2523 Tissue plasminogen activator Wiki 0.06
drug113 Accuchek Inform II platform Wiki 0.06
drug2065 Relaxation Therapy Wiki 0.06
drug1526 Multi-tasking Training Wiki 0.06
drug3008 standard of care Wiki 0.06
drug780 Discontinuation of ARB/ACEI Wiki 0.06
drug209 Arbidol Hydrochloride Granules Wiki 0.06
drug1329 Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5. Wiki 0.06
drug1289 JNJ-53718678 250 mg Wiki 0.06
drug2591 Umbilical cord derived mesenchymal stem cells Wiki 0.06
drug2076 Repository Corticotropin Injection Wiki 0.06
drug1993 Quick Defense Wiki 0.06
drug1287 JNJ-53718678 125 mg Wiki 0.06
drug347 Biological collection (patients co infected HIV Sras-CoV-2) Wiki 0.06
drug989 Garadacimab, Factor XIIa Antagonist Monoclonal Antibody Wiki 0.06
drug1207 Inhaled beclomethasone Wiki 0.06
drug734 Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days Wiki 0.06
drug975 GENUS device (Sham Settings) Wiki 0.06
drug819 EUROIMMUN assay Wiki 0.06
drug193 Antibody titration Wiki 0.06
drug361 Biospecimen Collection Wiki 0.06
drug2369 Study B Wiki 0.06
drug2095 Rintatolimod Wiki 0.06
drug263 Azithromycin (Azithro) Wiki 0.06
drug919 Facial mask Wiki 0.06
drug1304 L-citrulline Wiki 0.06
drug90 ATYR1923 1 mg/kg Wiki 0.06
drug1973 Quantitative analysis of anti-SARS-CoV-2-antibodies Wiki 0.06
drug272 Açaí palm berry extract - natural product Wiki 0.06
drug2905 mycophenolate mofetil (MMF) Wiki 0.06
drug1298 Ketogenic diet Wiki 0.06
drug1556 NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells Wiki 0.06
drug2382 Surgery Wiki 0.06
drug59 ACT-20-MSC Wiki 0.06
drug1601 Nitazoxanide Tablets Wiki 0.06
drug1755 Pacritinib Wiki 0.06
drug97 AVP-786 Wiki 0.06
drug2037 Recombinant Human Interferon α2b Spray Wiki 0.06
drug1999 REGN3048 Wiki 0.06
drug2038 Recombinant Interferon Alfa-2b Wiki 0.06
drug1203 Infusion placebo Wiki 0.06
drug1358 Lopinavir / ritonavir tablets combined with Xiyanping injection Wiki 0.06
drug3022 tacrolimus Wiki 0.06
drug2656 Virtual Reality Pain Neuroscience Education Wiki 0.06
drug1101 Hydroxychloroquine Pre-Exposure Prophylaxis Wiki 0.06
drug1146 ID NOW vs. Accula Wiki 0.06
drug1579 Nebulized administration of RLF-100 or Placebo Wiki 0.06
drug657 Convalescent anti-SARS-CoV-2 plasma Wiki 0.06
drug655 Convalescent SARS COVID-19 plasma Wiki 0.06
drug2162 SNDX-6352 Wiki 0.06
drug211 Arm exercise electrocardiographic stress test Wiki 0.06
drug110 Acalabrutinib Treatment C Wiki 0.06
drug978 GM-CSF Wiki 0.06
drug2044 Recombinant human plasma gelsolin (Rhu-pGSN) Wiki 0.06
drug1290 JNJ-53718678 3 mg/kg Wiki 0.06
drug437 CK0802 Wiki 0.06
drug2268 Sirolimus 1 MG/ML Wiki 0.06
drug2690 Weekly Assessment Wiki 0.06
drug1540 N-Acetyl cysteine Wiki 0.06
drug201 Apilimod Dimesylate Capsule Wiki 0.06
drug289 BI 1569912 Wiki 0.06
drug1238 Intervention App Wiki 0.06
drug2902 mouthrinse without bêta-cyclodextrin and citrox Wiki 0.06
drug1315 LY3473329 Wiki 0.06
drug87 AT-001 Wiki 0.06
drug633 Continuation of ARB/ACEI Wiki 0.06
drug1061 High-Concentration Essential Oil Wiki 0.06
drug1710 Otilimab Wiki 0.06
drug1527 MultiStem Wiki 0.06
drug998 Gimsilumab Wiki 0.06
drug1681 Omnibiotic AAD Wiki 0.06
drug933 Favipiravir tablets Wiki 0.06
drug699 DAS181 COVID-19 Wiki 0.06
drug2712 Zanubrutinib Wiki 0.06
drug2004 RO6953958 Wiki 0.06
drug1421 MVA-MERS-S_DF1 - High Dose Wiki 0.06
drug646 Convalescent Immune Plasma Wiki 0.06
drug1367 Lopinavir/ Ritonavir Oral Tablet Wiki 0.06
drug132 Aerosolized 13 cis retinoic acid Wiki 0.06
drug1082 Humanistic Care Wiki 0.06
drug557 Chinese Herbal Medicine Wiki 0.06
drug539 Cerebrospinal fluid sampling, meningeal and brain parenchyma biopsies Wiki 0.06
drug1530 Multivitamin Wiki 0.06
drug2643 Video based exercise Wiki 0.06
drug1957 Pyronaridine-Artesunate Wiki 0.06
drug965 Formulation without Active Drug Wiki 0.06
drug100 Abatacept Wiki 0.06
drug2201 Sarilumab SAR153191 Wiki 0.06
drug524 Cardiac surgery Wiki 0.06
drug2948 photobiomodulation and photodynamic therapy Wiki 0.06
drug1869 Platelet count, platelet, mean platelet volume and platelet distribution Width in COVID-19 Wiki 0.06
drug1582 NestaCell® Wiki 0.06
drug800 Duvelisib Wiki 0.06
drug520 Capillary and salivary sampling Wiki 0.06
drug236 Atomoxetine hydrochloride Wiki 0.06
drug1578 Natural Honey Wiki 0.06
drug2839 hydrocortisone Wiki 0.06
drug866 Equipment with smartwatch throughout hospital stay on the general ward Wiki 0.06
drug968 Freestyle Libre 14 day CGM system Wiki 0.06
drug2942 pathogen reduced SARS-CoV-2 convalescent plasma Wiki 0.06
drug1757 Pamrevlumab Wiki 0.06
drug2527 Tocilizumab Wiki 0.05
drug2326 Standard of care Wiki 0.05
drug2767 blood sampling Wiki 0.05
drug576 Clazakizumab Wiki 0.05
drug512 Camostat Mesilate Wiki 0.05
drug262 Azithromycin Wiki 0.05
drug1103 Hydroxychloroquine Sulfate Wiki 0.05
drug3018 survey Wiki 0.05
drug2319 Standard of Care Wiki 0.04
drug2388 Survey Wiki 0.04
drug2663 Vitamin D Wiki 0.04
drug1090 Hydroxychloroquine + azithromycin Wiki 0.04
drug571 Ciclesonide Wiki 0.04
drug1107 Hydroxychloroquine Sulfate 200 MG Wiki 0.04
drug107 Acalabrutinib Wiki 0.04
drug1078 Human immunoglobulin Wiki 0.04
drug1260 Isavuconazonium sulfate Wiki 0.04
drug2031 Ravulizumab Wiki 0.04
drug1381 Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule Wiki 0.04
drug1058 High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule Wiki 0.04
drug717 Data Collection Wiki 0.04
drug2595 Unfractionated heparin Wiki 0.04
drug880 Exercise Wiki 0.04
drug1795 Peripheral blood draw Wiki 0.04
drug595 Cognitive Behavioral Therapy Wiki 0.04
drug1478 Mesenchymal stromal cells Wiki 0.04
drug305 BNT162b2 Wiki 0.04
drug1442 Matching placebo Wiki 0.04
drug1850 Placebo on a 0- and 28-day schedule Wiki 0.04
drug2221 Selinexor Wiki 0.04
drug1893 Prazosin Wiki 0.04
drug2332 Standard of care treatment Wiki 0.04
drug2441 Taking blood samples (capillary and venous), saliva sampling and nasopharyngeal sampling. Wiki 0.04
drug2039 Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki 0.04
drug1401 M5049 Wiki 0.04
drug24 200 mg EIDD-2801 Wiki 0.04
drug2018 Radiation therapy Wiki 0.04
drug1561 NORS (Nitric Oxide Releasing Solution) Wiki 0.04
drug1303 L-ascorbic acid Wiki 0.04
drug2267 Sirolimus Wiki 0.04
drug2129 SARS-CoV-2 Wiki 0.04
drug2003 RLF-100 (aviptadil) Wiki 0.04
drug2136 SARS-CoV-2 diagnostic rapid test Wiki 0.04
drug2092 Ribavirin Wiki 0.04
drug33 2D Telemedicine Wiki 0.04
drug1230 Interleukin-7 Wiki 0.04
drug1023 HCQ Wiki 0.04
drug1952 Pulmozyme Wiki 0.04
drug1618 No intervention, observational study Wiki 0.04
drug1783 Peginterferon Lambda-1A Wiki 0.04
drug1485 Methylprednisolone Sodium Succinate Wiki 0.04
drug2256 Siltuximab Wiki 0.04
drug1258 Iodine Complex Wiki 0.04
drug892 Exposure Wiki 0.04
drug2538 Tofacitinib Wiki 0.04
drug304 BNT162b1 Wiki 0.04
drug2068 Remdesivir placebo Wiki 0.04
drug1566 Nafamostat Mesilate Wiki 0.04
drug601 Colchicine Wiki 0.04
drug1163 Ibrutinib Wiki 0.04
drug2880 mRNA-1273 Wiki 0.04
drug1115 Hydroxychloroquine Sulfate Tablets Wiki 0.04
drug1458 Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule Wiki 0.04
drug2116 Ruxolitinib Wiki 0.04
drug1484 Methylprednisolone Wiki 0.03
drug2134 SARS-CoV-2 convalescent plasma Wiki 0.03
drug2069 Remestemcel-L Wiki 0.03
drug1911 Probiotic Wiki 0.03
drug566 Chloroquine or Hydroxychloroquine Wiki 0.03
drug1444 Mavrilimumab Wiki 0.03
drug1220 Interferon Beta-1B Wiki 0.03
drug1575 Nasopharyngeal swab Wiki 0.03
drug3012 standard therapy Wiki 0.03
drug1923 Prone positioning Wiki 0.03
drug1473 Mesenchymal Stromal Cells Wiki 0.03
drug2381 Supportive Care Wiki 0.03
drug2321 Standard of Care (SOC) Wiki 0.03
drug1715 Oxygen Wiki 0.03
drug41 3D Telemedicine Wiki 0.03
drug3005 standard care Wiki 0.03
drug1691 Online questionnaire Wiki 0.03
drug2950 placebo Wiki 0.03
drug2465 Telerehabilitation Wiki 0.03
drug1470 Mepolizumab Wiki 0.03
drug2739 anti-SARS-CoV-2 convalescent plasma Wiki 0.03
drug1687 Online Survey Wiki 0.03
drug1087 Hydroxychloroquine (HCQ) Wiki 0.03
drug1883 Povidone-Iodine Wiki 0.03
drug142 Alirocumab Wiki 0.03
drug1481 Methotrexate Wiki 0.03
drug2078 Reslizumab Wiki 0.03
drug876 Evolocumab Wiki 0.03
drug2300 Standard Care Wiki 0.03
drug1604 Nitric Oxide Wiki 0.03
drug1083 Hydrocortisone Wiki 0.03
drug1613 No intervention Wiki 0.03
drug2977 questionnaire assesment Wiki 0.03
drug2187 Saliva collection Wiki 0.03
drug2612 Usual Care Wiki 0.03
drug2197 Sarilumab Wiki 0.03
drug2715 Zinc Wiki 0.02
drug2348 Standard treatment Wiki 0.02
drug159 Anakinra Wiki 0.02
drug636 Control Wiki 0.02
drug852 Enoxaparin Wiki 0.02
drug1372 Lopinavir/ritonavir Wiki 0.02
drug2662 Vitamin C Wiki 0.02
drug658 Convalescent plasma Wiki 0.01
drug647 Convalescent Plasma Wiki 0.01
drug1978 Questionnaire Wiki 0.01

Correlated MeSH Terms (138)


Name (Synonyms) Correlation
D018352 Coronavirus Infections NIH 0.33
D045169 Severe Acute Respiratory Syndrome NIH 0.24
D007239 Infection NIH 0.22
D003141 Communicable Diseases NIH 0.19
D011014 Pneumonia NIH 0.18
D055371 Acute Lung Injury NIH 0.16
D012128 Respiratory Distress Syndrome, Adult NIH 0.16
D012127 Respiratory Distress Syndrome, Newborn NIH 0.13
D018357 Respiratory Syncytial Virus Infections NIH 0.12
D055370 Lung Injury NIH 0.11
D013577 Syndrome NIH 0.10
D014456 Ulcer NIH 0.09
D003092 Colitis NIH 0.09
D003093 Colitis, Ulcerative NIH 0.09
D014777 Virus Diseases NIH 0.09
D012141 Respiratory Tract Infections NIH 0.08
D000257 Adenoviridae Infections NIH 0.08
D008231 Lymphopenia NIH 0.08
D018589 Gastroparesis NIH 0.08
D059350 Chronic Pain NIH 0.07
D018184 Paramyxoviridae Infections NIH 0.07
D004417 Dyspnea NIH 0.06
D018450 Disease Progression NIH 0.06
D011024 Pneumonia, Viral NIH 0.06
D007249 Inflammation NIH 0.06
D019973 Alcohol-Related Disorders NIH 0.06
D001010 Anxiety, Separation NIH 0.06
D011236 Prediabetic State NIH 0.06
D012507 Sarcoidosis NIH 0.06
D029481 Bronchitis, Chronic NIH 0.06
D002446 Celiac Disease NIH 0.06
D009091 Mucormycosis NIH 0.06
D001991 Bronchitis NIH 0.06
D001982 Bronchial Diseases NIH 0.06
D017565 Sarcoidosis, Pulmonary NIH 0.06
D001238 Asphyxia Neonatorum NIH 0.06
D001228 Aspergillosis NIH 0.06
D000072861 Phobia, Social NIH 0.06
D009164 Mycobacterium Infections NIH 0.06
D053201 Urinary Bladder, Overactive NIH 0.06
D050197 Atherosclerosis NIH 0.06
D003015 Clostridium Infections NIH 0.06
D006969 Hypersensitivity, Immediate NIH 0.06
D001342 Autonomic Nervous System Diseases NIH 0.06
D011595 Psychomotor Agitation NIH 0.06
D002658 Developmental Disabilities NIH 0.06
D011565 Psoriasis NIH 0.06
D003928 Diabetic Nephropathies NIH 0.06
D020529 Multiple Sclerosis, Relapsing-Remitting NIH 0.06
D016470 Bacteremia NIH 0.06
D021821 Communicable Diseases, Emerging NIH 0.06
D012130 Respiratory Hypersensitivity NIH 0.06
D016584 Panic Disorder NIH 0.06
D063806 Myalgia NIH 0.06
D008173 Lung Diseases, Obstructive NIH 0.06
D003384 Coxsackievirus Infections NIH 0.06
D004696 Endocarditis NIH 0.06
D003424 Crohn Disease NIH 0.06
D000379 Agoraphobia NIH 0.06
D000374 Aggression NIH 0.06
D054969 Primary Dysautonomias NIH 0.06
D065626 Non-alcoholic Fatty Liver Disease NIH 0.06
D007011 Hypoparathyroidism NIH 0.06
D005234 Fatty Liver NIH 0.06
D020096 Zygomycosis NIH 0.06
D058186 Acute Kidney Injury NIH 0.05
D007674 Kidney Diseases NIH 0.05
D014947 Wounds and Injuries NIH 0.05
D013313 Stress Disorders, Post-Traumatic NIH 0.05
D012598 Scoliosi NIH 0.04
D065886 Neurodevelopmental Disorders NIH 0.04
D029424 Pulmonary Disease, Chronic Obstructive NIH 0.04
D006948 Hyperkinesis NIH 0.04
D058070 Asymptomatic Diseases NIH 0.04
D010149 Pain, Postoperative NIH 0.04
D000799 Angioedema NIH 0.04
D015004 Yellow Fever NIH 0.04
D016491 Peripheral Vascular Diseases NIH 0.04
D003139 Common Cold NIH 0.04
D021183 Peanut Hypersensitivity NIH 0.04
D000208 Acute Disease NIH 0.04
D054179 Angioedemas, Hereditary NIH 0.04
D004715 Endometriosis NIH 0.04
D008268 Macular Degeneration NIH 0.04
D000428 Alcohol Drinking NIH 0.04
D010698 Phobic Disorders NIH 0.04
D009369 Neoplasms, NIH 0.04
D009103 Multiple Sclerosis NIH 0.04
D007251 Influenza, Human NIH 0.03
D058729 Peripheral Arterial Disease NIH 0.03
D005334 Fever NIH 0.03
D000544 Alzheimer Disease NIH 0.03
D051436 Renal Insufficiency, Chronic NIH 0.03
D006967 Hypersensitivity, NIH 0.03
D002659 Child Development Disorders, Pervasive NIH 0.03
D009202 Cardiomyopathies NIH 0.03
D010300 Parkinsonian NIH 0.03
D005221 Fatigue NIH 0.03
D004194 Disease NIH 0.03
D008171 Lung Diseases, NIH 0.03
D001008 Anxiety Disorders NIH 0.03
D010003 Osteoarthritis, NIH 0.03
D001249 Asthma NIH 0.03
D001289 Attention Deficit Disorder with Hyperactivity NIH 0.03
D001321 Autistic Disorder NIH 0.03
D006331 Heart Diseases NIH 0.03
D003327 Coronary Disease NIH 0.03
D008175 Lung Neoplasms NIH 0.03
D008103 Liver Cirrhosis, NIH 0.03
D003333 Coronaviridae Infections NIH 0.03
D016739 Behavior, Addictive NIH 0.03
D000860 Hypoxia NIH 0.03
D005355 Fibrosis NIH 0.03
D000070642 Brain Injuries, Traumatic NIH 0.03
D018805 Sepsis NIH 0.03
D040921 Stress Disorders, Traumatic NIH 0.03
D011658 Pulmonary Fibrosis NIH 0.03
D002318 Cardiovascular Diseases NIH 0.02
D001523 Mental Disorders NIH 0.02
D007154 Immune System Diseases NIH 0.02
D000067877 Autism Spectrum Disorder NIH 0.02
D011665 Pulmonary Valve Insufficiency NIH 0.02
D001930 Brain Injuries, NIH 0.02
D053120 Respiratory Aspiration NIH 0.02
D019337 Hematologic Neoplasms NIH 0.02
D060825 Cognitive Dysfunction NIH 0.02
D053717 Pneumonia, Ventilator-Associated NIH 0.02
D020141 Hemostatic Disorders NIH 0.02
D001778 Blood Coagulation Disorders NIH 0.02
D000857 Olfaction Disorders NIH 0.02
D016638 Critical Illness NIH 0.02
D006973 Hypertension NIH 0.02
D003866 Depressive Disorder NIH 0.01
D012140 Respiratory Tract Diseases NIH 0.01
D013927 Thrombosis NIH 0.01
D013315 Stress, Psychological NIH 0.01
D004630 Emergencies NIH 0.01
D003863 Depression, NIH 0.01

Correlated HPO Terms (56)


Name (Synonyms) Correlation
HP:0002090 Pneumonia HPO 0.18
HP:0002583 Colitis HPO 0.09
HP:0100279 Ulcerative colitis HPO 0.09
HP:0011947 Respiratory tract infection HPO 0.08
HP:0001888 Lymphopenia HPO 0.08
HP:0002578 Gastroparesis HPO 0.08
HP:0012532 Chronic pain HPO 0.07
HP:0002098 Respiratory distress HPO 0.06
HP:0012387 Bronchitis HPO 0.06
HP:0003765 Psoriasiform dermatitis HPO 0.06
HP:0012768 Neonatal asphyxia HPO 0.06
HP:0100584 Endocarditis HPO 0.06
HP:0002608 Celiac disease HPO 0.06
HP:0006536 Pulmonary obstruction HPO 0.06
HP:0000829 Hypoparathyroidism HPO 0.06
HP:0003326 Myalgia HPO 0.06
HP:0004469 Chronic bronchitis HPO 0.06
HP:0000756 Agoraphobia HPO 0.06
HP:0001397 Hepatic steatosis HPO 0.06
HP:0000718 Aggressive behavior HPO 0.06
HP:0100280 Crohn's disease HPO 0.06
HP:0002621 Atherosclerosis HPO 0.06
HP:0001919 Acute kidney injury HPO 0.05
HP:0000077 Abnormality of the kidney HPO 0.05
HP:0030127 Endometriosis HPO 0.04
HP:0002487 Hyperkinetic movements HPO 0.04
HP:0100665 Angioedema HPO 0.04
HP:0006510 Chronic pulmonary obstruction HPO 0.04
HP:0002664 Neoplasm HPO 0.04
HP:0012378 Fatigue HPO 0.03
HP:0012393 Allergy HPO 0.03
HP:0001638 Cardiomyopathy HPO 0.03
HP:0001945 Fever HPO 0.03
HP:0002511 Alzheimer disease HPO 0.03
HP:0012622 Chronic kidney disease HPO 0.03
HP:0002088 Abnormal lung morphology HPO 0.03
HP:0002758 Osteoarthritis HPO 0.03
HP:0000717 Autism HPO 0.03
HP:0002099 Asthma HPO 0.03
HP:0007018 Attention deficit hyperactivity disorder HPO 0.03
HP:0030858 Addictive behavior HPO 0.03
HP:0001395 Hepatic fibrosis HPO 0.03
HP:0100526 Neoplasm of the lung HPO 0.03
HP:0012418 Hypoxemia HPO 0.03
HP:0100806 Sepsis HPO 0.03
HP:0004950 Peripheral arterial stenosis HPO 0.03
HP:0002206 Pulmonary fibrosis HPO 0.03
HP:0001626 Abnormality of the cardiovascular system HPO 0.02
HP:0010444 Pulmonary insufficiency HPO 0.02
HP:0000729 Autistic behavior HPO 0.02
HP:0001268 Mental deterioration HPO 0.02
HP:0001928 Abnormality of coagulation HPO 0.02
HP:0000458 Anosmia HPO 0.02
HP:0000822 Hypertension HPO 0.02
HP:0001909 Leukemia HPO 0.02
HP:0000716 Depressivity HPO 0.01

There are 315 clinical trials

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 Coronavirus (SARS-CoV) Drug: Aluminum hydroxide Drug: Placebo 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 Acute Respiratory Infections Dietary Supplement: Quick Defense 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 Respiratory Syncytial Virus Drug: Presatovir 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 Respiratory Syncytial Virus Infection Drug: Presatovir 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 Lung Transplant Infection Drug: Inhaled beclomethasone 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 Community Acquired Pneumonia Drug: Hydrocortisone 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 Common Cold Device: ColdZyme® mouth spray 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 Respiratory Syncytial Virus (RSV) Drug: Presatovir Drug: Placebo
MeSH: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 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b 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 Prediabetic State Atherosclerosis Metformin Drug: Metformin XR 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 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 Clostridium Difficile Infection Drug: Fecal Microbiota Therapy (FMT) 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

12 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 Ulcerative Colitis (UC) Drug: Upadacitinib (ABT-494) 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

13 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 Acute Respiratory Viral Infections Drug: Ergoferon 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.

14 A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Neurobehavioral Disinhibition Including Aggression, Agitation, and Irritability in Patients With Traumatic Brain Injury (TBI).

This is a multicenter, randomized, placebo-controlled study to evaluate AVP-786 for the treatment of neurobehavioral disinhibition including aggression, agitation, and irritability in participants with traumatic brain injury (TBI).

NCT03095066 Neurobehavioral Disinhibition Drug: AVP-786 Drug: Placebo
MeSH:Brain Injuries Brain Injuries, Traumatic Psychomotor Agitation Aggression
HPO:Aggressive behavior

Primary Outcomes

Description: The NPI-C can be used to rate the presence of neuropsychiatric symptoms across 14 domains. The scores for each item within an individual domain/subscale range from 0 to 3, with a higher score indicating increased severity. The NPI-C-3 is comprised of the aggression, agitation, and irritability/lability subscales. The scores for the three subscales are summed to create the total NPI-C-3 composite score, which ranges from 0 to 99, with a higher score indicating increased severity.

Measure: Change from Baseline to Week 12 in the Composite of the Clinical Impression Severity Scores on the Neuropsychiatric Inventory Clinician Rating Scale (NPI-C) Subscales of Aggression, Agitation, and Irritability/Lability (NPI-C-3)

Time: Baseline; Week 12

Secondary Outcomes

Description: The mCGI-C will be used to assess the clinician's general impression of the participant's treatment response. The mCGI-C is a 7-point (1 to 7) modified version of the CGI-C scale. A higher score represents worsening of symptoms.

Measure: Change from Baseline to Week 12 in Modified Clinical Global Impression of Change (mCGI-C) Raw Scores

Time: Baseline; Week 12

Description: The NPI-C is used to rate the presence of neuropsychiatric symptoms across 14 domains. The scores for each item within an individual domain/subscale range from 0 to 3, with a higher score indicating increased severity.

Measure: Change from Baseline to Week 12 in NPI-C Rating Scale Subscales Scores for Aggression, Agitation, Irritability/Lability, and Disinhibition

Time: Baseline; Week 12

Description: The mCGI-S will be used to assess the clinician's view of the participant's severity of aggression, agitation, and irritability symptoms. The mCGI-S is a 7-point (1 to 7) modified version of the CGI-S scale. In all cases, a higher score represents increased severity.

Measure: Change from Baseline to Week 12 in Modified Clinical Global Impression of Severity (mCGI-S) Scale Scores

Time: Baseline; Week 12

Description: The PGI-S is a single-question scale that specifically assesses the severity of symptoms of neurobehavioral disinhibition, including aggression, agitation, and irritability, on a 7-point scale : 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

Measure: Change from Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) Scores

Time: Baseline; Week 12

Description: The PGI-C is a 7-point (1 to 7) scale used to assess the participant's assessment of treatment response. A higher score indicates worsening of the symptoms.

Measure: Change from Baseline to Week 12 in Patient Global Impression of Change (PGI-C) Raw Scores

Time: Baseline; Week 12

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 Relapsing, Remitting Multiple Sclerosis Drug: Repository Corticotropin Injection 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 Age-Related Macular Degeneration Drug: ASP7317 Other: Placebo Drug: tacrolimus 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 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 Ulcerative Colitis Drug: Ontamalimab 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)

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 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 Ulcerative Colitis Drug: Ontamalimab 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)

19 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 Gastroparesis Diabetes Mellitus Drug: Relamorelin 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

20 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 Corona Virus Infection Other: Placebo Biological: REGN3048 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

21 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 Peripheral Artery Disease (PAD) Drug: GM-CSF 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

22 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 Sarcoidosis, Pulmonary Drug: Acthar Gel 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

23 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 Hypoparathyroidism Biological: rhPTH(1-84) 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

24 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 Healthy Volunteers Drug: MEDI7219 Drug: Placebo 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)

25 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 Gastroparesis Diabetes Mellitus Drug: Relamorelin 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

26 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 Gastroparesis Diabetes Mellitus Drug: Relamorelin 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

27 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 Posttraumatic Stress Disorder Drug: Prazosin 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

28 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 Crohn's Disease Biological: Ontamalimab 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

29 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 Crohn's Disease Biological: Ontamalimab 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

30 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 Diabetic Kidney Disease Drug: Pentoxifylline 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

31 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 Respiratory Syncytial Virus Infections Drug: JNJ-53718678 Drug: Placebo
MeSH:Infection Communicable Diseases Respiratory Syncytial Virus Infections Virus Diseases

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

32 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 Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Biological: Tezepelumab Other: Placebo
MeSH:Asthma Lung Diseases Lung Diseases, Obstructive Bronchial Diseases Respiratory Hypersensitivity Hypersensitivity Hypersensitivity, Immediate Inflammation Respiratory Tract Diseases Immune System Diseases
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.

33 A Phase 1, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability and Immune Response in Adolescents Allergic to Peanut After Receiving Intradermal Administration of ASP0892 (ARA-LAMP-vax), a Single Multivalent Peanut (Ara h1, h2, h3) Lysosomal Associated Membrane Protein DNA Plasmid Vaccine

The purpose of this study is to evaluate the safety and tolerability of ASP0892 after intradermal (ID) injection in adolescent participants with peanut allergy.

NCT03755713 Peanut Allergy Drug: ASP0892 Drug: Placebo
MeSH:Peanut Hypersensitivity

Primary Outcomes

Description: Adverse Events (AEs) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). AEs starting or worsening after the first dose of study drug up through study completion will be considered treatment-emergent.

Measure: Safety as assessed by Treatment Emergent Adverse Events (TEAEs)

Time: Up to Day 576

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: Safety as assessed by local reactogenicity reactions

Time: Up to Day 50

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: Safety as assessed by systemic reactogenicity reactions

Time: Up to Day 50

Description: Number of participants with potentially clinically significant vital sign values.

Measure: Number of participants with vital signs abnormalities and/or adverse events

Time: Up to Day 576

Description: Number of participants with potentially clinically significant laboratory values.

Measure: Number of participants with laboratory value abnormalities and/or adverse events

Time: Up to Day 576

Description: Anti-LAMP-1 antibody formation for all participants will be summarized for each treatment by visit using descriptive statistics.

Measure: Safety assessed by Anti-LAMP-1 antibody

Time: Up to Day 576

34 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 Lower Respiratory Tract Infection Parainfluenza Immunocompromised COVID-19 Drug: DAS181 Drug: Placebo Drug: DAS181 COVID-19 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

35 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 Maternal Exposure Health Behavior Infant Development Dietary Supplement: Probiotic and LC-PUFA Dietary Supplement: Placebo 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

36 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 COVID-19 Yellow Fever Drug: Galidesivir 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

37 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 Healthy Volunteer Drug: BIIB091 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

38 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 Quality of Life Health, Subjective Dietary Supplement: RS blend 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)

39 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 Respiratory Syncytial Virus Infections Drug: JNJ-53718678 250 mg Drug: Placebo Drug: JNJ-53718678 125 mg
MeSH:Infection Respiratory Syncytial Virus Infections Virus Diseases

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

40 A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL151 in Subjects With Parkinson's Disease

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL151 in subjects with Parkinson's disease.

NCT04056689 Parkinson's Disease Drug: DNL151 Drug: Placebo
MeSH:Parkinson Disease

Primary Outcomes

Measure: Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time: Randomization to Day 42

Measure: Number of Subjects with laboratory test abnormalities

Time: Randomization to Day 42

Measure: Number of Subjects with vital sign abnormalities

Time: Randomization to Day 42

Measure: Number of Subjects with electrocardiogram (ECG) abnormalities

Time: Randomization to Day 42

Measure: Number of Subjects with clinically significant neurological examination abnormalities

Time: Randomization to Day 42

Secondary Outcomes

Measure: Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL151

Time: Randomization to Day 28

Measure: Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL151

Time: Randomization to Day 28

Measure: Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL151

Time: Randomization to Day 28

Measure: Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL151

Time: Randomization to Day 28

Measure: Pharmacokinetic measure of CSF concentrations of DNL151

Time: Randomization to Day 28

Measure: Pharmacodynamic measure of pS935 in whole blood

Time: Randomization to Day 28

Measure: Pharmacodynamic measure of pRab10 in PBMCs

Time: Randomization to Day 28

41 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 Respiratory Syncytial Viruses Other: RSV Mobile Application Drug: Placebo Drug: JNJ-53718678 2.5 mg/kg Drug: JNJ-53718678 3 mg/kg 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

42 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 Attention Deficit Hyperactivity Disorder (ADHD) Drug: Guanfacine hydrochloride (SPD503) Drug: Atomoxetine hydrochloride 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

43 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 Osteoarthritis (OA) Drug: LRX712 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

44 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 Aging Stress Dietary Supplement: Multivitamin 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

45 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 MERS (Middle East Respiratory Syndrome) Biological: MVA-MERS-S_DF1 - Low Dose Biological: MVA-MERS-S_DF1 - High Dose 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)

46 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 Respiratory Syncytial Virus Infections Biological: RSVPreF3 formulation 2 Biological: RSVPreF3 formulation 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

47 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 Staphylococcus Aureus Bacteremia Staphylococcus Aureus Endocarditis Drug: Exebacase 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

48 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 Healthy Subjects Pharmacokinetics Pharmacodynamics Biological: Mepolizumab Biological: Mepolizumab Biological: Mepolizumab Biological: Mepolizumab Biological: Reslizumab Biological: Reslizumab Biological: Reslizumab Biological: Reslizumab 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

49 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 Posttraumatic Stress Disorder Diagnostic Test: LDAEP Drug: Placebo 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

50 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 Healthy Subjects Pharmacokinetics Pharmacodynamics Biological: Evolocumab Biological: Evolocumab Biological: Evolocumab Biological: Evolocumab Biological: Alirocumab Biological: Alirocumab Biological: Alirocumab Biological: Alirocumab 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

51 A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH) and Acquired Angioedema (AAE) Due to C1-INH Deficiency

The purpose of this study is to evaluate the safety and efficacy of repeated subcutaneous (SC) administrations of lanadelumab in preventing angioedema attacks in adolescents and adults with non-histaminergic angioedema with normal C1-INH and in adults with acquired angioedema (AAE) due to C1-INH deficiency.

NCT04206605 Angioedema Drug: Lanadelumab Other: Placebo
MeSH:Angioedema Angioedemas, Hereditary
HPO:Angioedema

Primary Outcomes

Description: An angioedema attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 will be assessed.

Measure: Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182

Secondary Outcomes

Description: Number of participants achieving attack-free status during the treatment period of day 0 through day 182 will be assessed.

Measure: Number of Participants Achieving Attack-Free Status During the Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182

Description: Moderate attack is defined as grade 2 (some assistance may be needed, no or minimal medical intervention/therapy required), Severe attack is defined as grade 3 (some assistance usually required, medical intervention/therapy required, hospitalizations possible). Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period of day 0 through day 182 will be assessed.

Measure: Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182

Time: Day 0 Through Day 182

Description: Number of investigator-confirmed angioedema attacks during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Investigator-Confirmed Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of participants achieving attack-free status during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Participants Achieving Attack-Free Status During the Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of investigator-confirmed moderate or severe angioedema attacks during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Investigator-Confirmed Moderate or Severe Angioedema Attacks During the Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of participants with maximum attack severity during the presumed steady state period of day 70 through day 182 will be assessed.

Measure: Number of Participants with Maximum Attack Severity During Presumed Steady State Period of Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Number of participants with maximum attack severity during treatment period of day 0 through day 182 will be assessed.

Measure: Number of Participants with Maximum Attack Severity During Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182

Description: The time to the first angioedema attack (days) after Day 0 for the efficacy evaluation period of Day 0 through Day 182 will be calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 0 through Day 182) to the date and time of the first in angioedema attack after the first dose for the efficacy evaluation period of Day 0 through Day 182.

Measure: Time to First Angioedema Attack After Day 0 Through Day 182

Time: Day 0 Through Day 182

Description: The time to the first angioedema attack (days) after Day 0 for the efficacy evaluation period of Day 70 through Day 182 will be calculated from the date and time of the first dose of lanadelumab for the efficacy evaluation period (Day 70 through Day 182) to the date and time of the first in angioedema attack after the first dose for the efficacy evaluation period of Day 70 through Day 182.

Measure: Time to First Angioedema Attack After Day 70 Through Day 182

Time: Day 70 through Day 182

Description: Efficacy evaluation period will consist of two periods: Day 0 (after study drug administration) through Day 182 (the end of treatment period), presumed steady-state period from Day 70 through Day 182. Run in period will be 4 weeks and may be extended up to 8 weeks to determine their baseline attack rate. The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period will be expressed as a monthly (28 days) angioedema attack rate. Number of participants achieving at least 50 percent (%), 70%, 90% and 100% reduction in the investigator-confirmed normalized number of attacks per 4 weeks during each of the efficacy evaluation periods relative to the observation period NNA will be assessed.

Measure: Number of Participants Achieving at Least 50 %, 70%, 90% and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) per 4 Weeks during each of the Efficacy Evaluation Periods Relative to the Observation Period NNA

Time: Day 0 Through Day 182

Description: The normalized number of investigator-confirmed angioedema attacks (NNA) during each efficacy evaluation period will be expressed as a monthly (28 days) angioedema attack rate. Number of participants achieving normalized number of attacks < 1.0 per 4 weeks during each of the efficacy evaluation periods will be assessed.

Measure: Number of Participants Achieving Normalized Number of Attacks (NNA) Less than (<)1.0 per 4 weeks During Each of the Efficacy Evaluation Periods

Time: Day 0 Through Day 182, Day 70 through Day 182

Description: A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. A 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 life-threatening, 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) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs)

Time: From start of the study up to follow up (Day 196)

Description: Plasma Concentrations of lanadelumab will be assessed.

Measure: Plasma Concentrations of Lanadelumab

Time: Day 0, 4, 28, 56, 84, 112, 140, 168 and 182

Description: Plasma Kallikrein activity will be measured by biomarker cleaved high molecular weight kininogen (cHMWK ) level to assess pharmacodynamics of lanadelumab.

Measure: Plasma Kallikrein (pKal) Activity

Time: Day 0, 4, 28, 56, 84, 112, 140, 168 and 182

Description: Number of participants with neutralizing or non-neutralizing antidrug antibodies in plasma will be assessed.

Measure: Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma

Time: Day 0, 28, 56, 84, 112, 140, 168 and 182

Description: The AE-QoL questionnaire is a self-administered validated instrument to assess health related (HR)QoL among participants with recurrent angioedema. The AE-QoL consists of 17 disease-specific quality-of-life items, to produce a total AEQoL score and 4 domain scores (functioning, fatigue/mood, fear/shame, and nutrition) and each of the 17 items has a five point response scale ranging from 1 (Never) to 5 (Very Often).

Measure: Change in Total Angioedema Quality of life (AE-QoL) Questionnaire Score During the Treatment Period of Day 0 Through Day 182

Time: Day 0 through Day 182

52 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 Healthy Volunteers (Intended Indication: Chronic Kidney Disease) Drug: Verinurad Drug: Placebo 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

53 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 Multiple Sclerosis Fatigue Drug: 20 mg MitoQ Drug: Placebo 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

54 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 2019 Novel Coronavirus Pneumonia COVID-19 Biological: UC-MSCs 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

55 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 COVID-19 Other: Placebo 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

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

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: 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: Clinical status using ordinal scale

Time: Day 3 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: For any reason.

Measure: Discontinuation or temporary suspension of investigational therapeutics

Time: Day 1 through Day 10

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

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: Percentage of subjects reporting each severity rating on an 8-point ordinal scale

Time: Day 15

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: 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

56 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 COVID-19 Biological: UC-MSCs 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

57 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 Influenza Infection SAD-RV Infection and COVID-19 Drug: DAS181 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

58 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 COVID19 Coronavirus Acute Respiratory Illnesses Drug: Chloroquine or Hydroxychloroquine 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

59 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 Corona Virus Infection Acute Respiratory Distress Syndrome SARS-CoV Infection Coronavirus Coronavirus Infections Drug: Hydroxychloroquine 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

60 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 Corona Virus Infection Acute Respiratory Distress Syndrome SARS-CoV Infection Drug: Losartan 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

61 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 Corona Virus Infection Acute Respiratory Distress Syndrome SARS-CoV Infection Drug: Losartan 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

62 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 COVID-19 Drug: PUL-042 Inhalation Solution 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

63 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 COVID-19 Drug: PUL-042 Inhalation Solution 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

64 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 COVID-19 Drug: Sarilumab 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

65 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 COVID COVID-19 Pneumonia Biological: NestaCell® 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.

66 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 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 230 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 Severe Coronavirus Disease (COVID-19) Drug: CD24Fc Drug: Placebo
MeSH:Coronavirus Infections

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 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.

Measure: Disease progression of COVID-19

Time: 29 days

Description: All cause of death

Measure: All cause of death

Time: 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

67 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 Novel Coronavirus Pnuemonia Drug: favipiravir tablets+chloroquine phosphatetablets tablets Drug: Favipiravir tablets 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

68 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 COVID-19 Pneumonia Drug: Tocilizumab (TCZ) 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

69 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 Coronavirus Drug: Hydroxychloroquine 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

70 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 Coronavirus Infection Drug: Tradipitant Drug: Placebo
MeSH:Infection Co 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

71 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 Corona Virus Infection Drug: Sarilumab SAR153191 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

72 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 NASH - Nonalcoholic Steatohepatitis Drug: TERN-101 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

73 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 COVID-19 Drug: BCG Vaccine Drug: Placebo

Primary Outcomes

Description: Number of days of unplanned absenteeism for any reason

Measure: Health Care Workers absenteeism

Time: Maximum of 180 days

Secondary Outcomes

Measure: the cumulative incidence of documented COVID-19

Time: Maximum of 180 days

Measure: the cumulative incidence of Hospital Admission due to documented COVID-19

Time: Maximum of 180 days

Measure: the number of days of unplanned absenteeism, because of documented COVID-19

Time: Maximum of 180 days

Measure: the cumulative incidence of self-reported acute respiratory symptoms or fever

Time: Maximum of 180 days

Measure: the cumulative incidence of death due to documented COVID-19

Time: Maximum of 180 days

Measure: the cumulative incidence of Intensive Care Admission due to documented COVID-19

Time: Maximum of 180 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 180 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 180 days

Description: Exploratory

Measure: the number of days of unplanned absenteeism because of self-reported acute respiratory symptoms

Time: Maximum of 180 days

Description: Exploratory

Measure: the number of days of self-reported fever (≥38 gr C)

Time: Maximum of 180 days

Description: Exploratory

Measure: the cumulative incidence of self-reported fever (≥38 gr C)

Time: Maximum of 180 days

Description: Exploratory

Measure: the number of days of self-reported acute respiratory symptoms

Time: Maximum of 180 days

Description: Exploratory

Measure: the cumulative incidence of self-reported acute respiratory symptoms

Time: Maximum of 180 days

Description: Exploratory

Measure: the cumulative incidence of death for any reason

Time: Maximum of 180 days

Description: Exploratory

Measure: the cumulative incidence of Intensive Care Admission for any reason

Time: Maximum of 180 days

Description: Exploratory

Measure: the cumulative incidence of Hospital Admission for any reason

Time: Maximum of 180 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 180 days

74 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 COVID-19 Corona Virus Infection ARDS Acute Respiratory Distress Syndrome Drug: Hydroxychloroquine 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

75 A Phase 2 Randomized, Single Blind Study of a Single Dose of Peginterferon Lambda-1a 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 COVID-19 Drug: Peginterferon Lambda-1a Other: Placebo

Primary Outcomes

Description: Time to first of two consecutive negative respiratory secretions obtained by nasopharyngeal and/or oropharyngeal and/or salivary swabs tests for SARS-CoV-2 by qRT-PCR.

Measure: Duration of Viral shedding of SARS-CoV-2 by qRT-PCR

Time: 28 days

76 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 Coronavirus Acute Respiratory Infection SARS-CoV Infection Drug: Hydroxychloroquine 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

77 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 COVID-19 Coronavirus Infection Drug: Piclidenoson Drug: Placebo
MeSH:Coronavirus Infections 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 a 7-point ordinal scale, where 1 = not hospitalized with resumption of normal activities; 2 = not hospitalized but unable to resume normal activities; 3 = hospitalized but not requiring supplemental oxygen; 4 = hospitalized and requiring supplemental oxygen; 5 = hospitalized and requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6 = hospitalized and requiring invasive mechanical ventilation and/or extra-corporeal membrane oxygenation; and 7 = 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

78 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 Coronavirus Infection Drug: Hydroxychloroquine SAR321068 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)

79 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 COVID 19 Drug: MR or M-M-R II ® vaccine 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

80 A Phase 1, Randomized, Observer-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Immunogenicity of the bacTRL-Spike Oral Candidate Vaccine for the Prevention of COVID-19 in Healthy Adults

Protocol bacTRL-Spike-1 will be the first-in-human study of bacTRL-Spike, and the first-in-human use of orally delivered bacTRL. Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1A), 3 billion (Group 2A) or 10 billion (Group 3A) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2. Placebo will consist of bacterial medium without bacteria.

NCT04334980 COVID-19 Biological: bacTRL-Spike Other: Placebo

Primary Outcomes

Description: Adverse events (specifically including incidence of gastrointestinal-associated events) following administration of oral bacTRL-Spike

Measure: Frequency of Adverse Events

Time: Up to12 months post-vaccination

Secondary Outcomes

Description: Antibody against SARS-CoV-2 Spike protein

Measure: Immune response against SARS-CoV-2 Spike protein

Time: Baseline (pre-vaccination), and 1, 3 and 12 months post-vaccination

Description: Incidence and clinical phenotype of confirmed and probable COVID-19 infection among vaccinated participants, based on current public health definitions

Measure: Incidence of COVID-19 infection

Time: Up to 12 months post-vaccination

Description: Isolation of viable bacTRL-Spike from stool post-vaccination

Measure: bacTRL-Spike in stool post-vaccination

Time: Days 7, 14, 21, and 1 and 3 months post-vaccination

Description: Collection of biological samples for future studies to understand immunity against SARS-CoV-2.

Measure: Seroconversion of circulating anti-Spike IgG antibodies & stability of serum IgG titers

Time: Up to 12 months post-vaccination

Description: Collection of biological samples for future studies to understand immunity against SARS-CoV-2.

Measure: Effectiveness of intestinal colonization of the probiotic-based bacTRL-Spike oral vaccine

Time: Up to 12 months post-vaccination

81 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 SARS-CoV-2 Infection Drug: Tocilizumab (TCZ) 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

82 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 COVID-19 Drug: Favipiravir 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

83 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 COVID-19 Nintedanib Safety Effect of Drugs Drug: Nintedanib 150 MG 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

84 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 COVID Drug: Camostat Mesilate Drug: Placebo 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

85 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 COVID-19 Biological: UC-MSCs 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

86 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 COVID-19 Respiratory Failure Drug: Azithromycin Drug: Hydroxychloroquine 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

87 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 COVID-19 Drug: Hydroxychloroquine 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

88 A Phase 1b/2, 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 Coronavirus Disease 2019 COVID-19 Drug: TJ003234 Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: 8-category ordinal scale

Measure: Proportion (%) of subjects experiencing deterioration in clinical status

Time: Changes from baseline on Day 14

Description: Per CTCAE

Measure: Treatment Emergent Adverse Events

Time: Up to 30 days after drug administration

Secondary Outcomes

Description: 8-category ordinal scale

Measure: Proportion (%) of subjects experiencing deterioration in clinical status

Time: Changes from baseline on Day 7 and Day 30

Description: 8-category ordinal scale: 8, Death; 7, ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT) or pressors; 6, Intubation and mechanical ventilation; 5, non-invasive mechanical ventilation (NIV) or high-flow oxygen; 4,Oxygen by mask or nasal prongs; 3, Hospitalization without oxygen supplementation; 2, Limitation of activities, discharge from hospital; and 1, No limitation of activities, discharge from hospital

Measure: Clinical status

Time: On Day 7, Day 14 and Day 30

Description: 8-category ordinal scale: 8, Death; 7, ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT) or pressors; 6, Intubation and mechanical ventilation; 5, non-invasive mechanical ventilation (NIV) or high-flow oxygen; 4,Oxygen by mask or nasal prongs; 3, Hospitalization without oxygen supplementation; 2, Limitation of activities, discharge from hospital; and 1, No limitation of activities, discharge from hospital

Measure: Improvement in clinical status

Time: On Day 7, Day 14 and Day 30

Description: The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. A higher score predicts a worse clinical outcome.

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: On Day 7 and Day 14

Measure: Change from baseline in PaO2/ FiO2

Time: On Day 7 and Day 14

Description: Defined as SpO2≥94% sustained minimum 24 hours

Measure: Length of time to normalization of oxygen saturation

Time: Up to 30 days after drug administration

Measure: Change from baseline in percentage of subjects requiring mechanical ventilation

Time: On Day 7 and Day 14

Measure: Change from baseline in Glucocorticoid use

Time: On Day 7 and Day 14

Measure: Mortality rate from any cause

Time: Up to 30 days after drug administration

Measure: Length of hospitalization

Time: Up to 30 days after drug administration

Measure: Change from baseline in D-dimer

Time: On Day 7 and Day 14

Measure: Serum concentration of TJ003234

Time: Day 1 predose, Day 1 End of Infusion, Day 7 and Day 14

Measure: Incidence and titer of anti-drug antibodies (ADA)

Time: Day 1 predose, Day 14

89 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 COVID-19 Biological: Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) 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

90 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 COVID-19 Drug: Sirolimus 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

91 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 COVID-19, Hydroxychloroquine Sulfate Drug: Hydroxychloroquine Sulfate 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

92 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 COVID 19 Coronavirus Drug: Fluvoxamine Drug: Placebo
MeSH: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)

93 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 COVID-19 Pneumonia Drug: LY3127804 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

94 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 COVID-19 Viral Respiratory Illnesses Drug: Nitazoxanide Drug: Placebo 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

95 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 COVID-19 SARS-CoV-2 Drug: Pyridostigmine Bromide 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

96 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 COVID-19 Drug: Clazakizumab 25 mg Drug: Clazakizumab 12.5 mg 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

97 Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (EVICT-CORONA-ALI)

This study will test to see if a 72-hour intravenous vitamin C infusion protocol (100 mg/kg every 8 hours) in patients with hypoxemia and suspected COVID-19 will reduce the lung injury caused by the SARS-Cov-2.

NCT04344184 COVID-19 Lung Injury, Acute Drug: L-ascorbic acid Other: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: Documented days free off mechanical ventilation the first 28 days post enrollment

Measure: Number of ventilator-free days

Time: Up to 28 days

Secondary Outcomes

Description: Mortality at 28-days by all causes

Measure: All-cause-mortality

Time: Up to 28 days

Description: Number of days free of acute inflammation (defined as CRP >= 10 mg/L)

Measure: Acute-inflammation-free days

Time: Up to 28 days

Description: Number of days that the participant is free of organ failure in ALL of the following organ systems: Cardiovascular, Respiratory, Neurological, Liver, Bone marrow organ, Renal

Measure: Organ-failure-free days

Time: Up to 1 year

98 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 101-200 will be stratified to ensure balanced randomization between the Auxora and placebo arms. 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. Both remdesivir and corticosteroids will be allowed. The infusion of Auxora will start within 12 hours from the time the patient or LAR provides informed consent.

NCT04345614 Pneumonia Drug: Auxora 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

99 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 Coronavirus Disease 2019 (COVID-19) Biological: BM-MSCs 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.

100 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 COVID-19 Infection Drug: Vazegepant (BHV-3500) Drug: Placebo

Primary Outcomes

Description: a. Efficacy will be measured by the average between group difference on a 6-point, ordinal, severity rating scale 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 evaluate efficacy of vazegepant (BHV-3500) compared with 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: The proportion of unique subjects alive and off of oxygen. These are subjects in categories 5 or 6 of the 6-point ordinal scale being used as the primary endpoint.

Time: Baseline to Day 29

Measure: A subject requiring initiation of invasive mechanical ventilation, non-invasive ventilation, or a high flow nasal cannula is a subject that has any eCRF showing the use of any such device on any day.

Time: Baseline to Day 60

Measure: The proportion of unique subjects admitted to an ICU verse those not admitted.

Time: Baseline to Day 60

Measure: Subjects are alive and respiratory-failure free if they are categorized as being in categories 3, 4, 5 or 6 of the 6-point ordinal scale being used as the primary endpoint.

Time: Baseline to Day 60

Measure: Subjects are alive and free of either invasive mechanical ventilation or non-invasive ventilation if they are categorized as being in categories 4, 5 or 6 of the 6-point ordinal scale being used as the primary endpoint.

Time: Baseline to Day 60

Measure: Efficacy on Day 29 will be evaluated using the same 6-point severity scales that is used at Day 15.

Time: Baseline at Day 15 and at Day 29

Measure: Time to improvement of one category on the 6-point severity scale will be determined as the number of days from baseline to the first day that an eCRF indicates a one category improvement in the scale.

Time: Baseline to Day 60

Measure: A 48-hour improvement in SpO2/FiO2 ratio consists of two consecutive days where the case report forms show a clinically meaningful increase from baseline.

Time: Baseline to Day 60

Measure: The time to improvement in the in the NEWS2 scale will be determined as the number of days from baseline to the first eCRF that shows an improvement.

Time: Baseline to Day 29

Measure: A score < 2 for 24 hours on the NEWS2 scale consists of a day where all of the reported NEWS2 scores are < 2.

Time: Baseline to Day 29

Measure: The change in NEWS2 scores will be determined as the change from baseline at Day 15 and at Day 29.

Time: Baseline at Day 15 and at Day 29.

Measure: The proportion of unique subjects alive and off of oxygen.

Time: Baseline to Day 60

Measure: The proportion of subjects discharged to home on supplemental oxygen will determined from the unique number of subjects have eCRF pages indicating they were discharged to home while still on supplemental oxygen.

Time: Baseline to Day 60

Measure: A day with a resting respiratory rate > 24 is a day in which all eCRFs collected for a subject indicate observed respiratory rates > 24 breaths per minute.

Time: Baseline to Day 29

Measure: A day with supplemental oxygen is one in which any case report form collected on that day indicates the use of any amount of supplemental oxygen.

Time: Baseline to Day 29

Measure: Time to saturation greater than or equal to 90% on room air is measured by the number of days from baseline to the first day on which an eCRF indicates saturation greater than or equal to 90% without any supplemental oxygenation.

Time: Baseline to Day 60

Measure: A ventilator free day is a day in which all of the eCRFs collected indicate that the subject was not using a ventilator.

Time: Baseline to Day 29

Measure: SOFA scores will be determined from eCRFs. Values will be determined for subjects at admission to an ICU and for all subjects still in an ICU at the end of the study (Day 29).

Time: Baseline to Day 29

Measure: The number of days of hospitalization will be determined from eCRFs. A hospitalization day is any day that it is shown that a subject spent at least spent part of the day in a hospital.

Time: First day of hospital admission to discharge from hospital (evaluated from Baseline to Day 60)

Measure: Time to fever resolution, without antipyretics, during two contiguous days .

Time: Screening to 48 hours fever free

Measure: The number of deaths, SAEs, severe AEs and Grade 3 or 4 laboratory abnormalities will be tabulated as the number of unique subjects meeting those criteria.

Time: Screening to Day 60

Measure: The incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infections will be tabulated as the number of unique subjects, reported in eCRFs, as having these conditions at any point in the study

Time: Screening to day 60

Measure: The incidence of intranasal administration reactions will be tabulated, from eCRFs, as the number of unique subjects having such a condition at any point in the study.

Time: Baseline to Day 60

Measure: The proportion of subjects who develop significant renal disease.

Time: Baseline to Day 60

101 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 Sars-CoV2 COVID-19 Drug: Favipiravir Drug: Placebo 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 will be assessed as the TCID50 (Median Tissue Culture Infectious Dose) 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)

102 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 SARS-CoV-2 Coronavirus Infection Asymptomatic Condition COVID-19 Drug: Hydroxychloroquine Sulfate Regular dose Drug: Hydroxychloroquine Sulfate Loading Dose Drug: Chloroquine 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

103 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 COVID-19 Drug: Clevudine 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

104 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 COVID-19 Drug: Nitazoxanide Tablets 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

105 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 Pulmonary Infection Covid-19 Drug: T3 solution for injection 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

106 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 Coronavirus Infection Drug: Selinexor 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

107 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 Acute Respiratory Distress Syndrome COVID-19 Drug: Human immunoglobulin Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syn 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

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

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

Measure: Occurrence of deep vein thrombosis or pulmonary embolism

Time: 28 days

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

108 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 COVID-19 Drug: Dapagliflozin 10 MG 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

109 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 Acute Lung Injury (ALI) Associated With COVID-19 Inflammatory Lung Conditions Associated With COVID-19 Drug: TD-0903 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

110 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 Sars-CoV2 Symptomatic Condition Covid-19 Drug: Hydroxychloroquine Sulfate Regular dose Drug: Hydroxychloroquine Sulfate Loading Dose Drug: Chloroquine 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

111 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 COVID-19 Drug: Gimsilumab 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

112 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 SARS-CoV 2 COVID-19 Drug: Hydroxychloroquine Other: Placebo

Primary Outcomes

Measure: ● Rate of hospitalization or death at day 7 after study inclusion

Time: 7 days

113 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 COVID19 Drug: Nafamostat Mesilate 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

114 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 Covid 19 Corona Virus Infection Drug: Hydroxychloroquine 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)

115 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 COVID-19 Drug: Camostat Mesilate 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

116 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 COVID-19 Drug: Suspension of heat killed (autoclaved) Mycobacterium w 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

117 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 COVID-19 Drug: DAS181 Drug: Placebo 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

118 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 Covid 19 Hypoxemic Respiratory Failure Drug: Almitrine 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

119 Use of a Medical Device, Kerecis Oral and Nasal Spray, for Treating the Symptoms of COVID-19 Via Application to the Naso- and Oropharyngeal Mucosa

Kerecis Oral and Nasal Spray is a Class I CE marked medical device manufactured by Kerecis hf (the "Device"). An 81-patient 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 81 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. 54 patients will be randomized into the Study Device group and 27 patients into the Control group. The Study Device group will be split into two with 27 patients administering the Device to both the oral and nasal passages and 27 patients to the oral only. 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 COVID-19 Device: Kerecis Oral and Nasal Spray 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

120 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 Covid-19 Drug: HCQ Drug: HCQ+AZT 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

121 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 Sars-CoV2 Drug: Recombinant human plasma gelsolin (Rhu-pGSN) 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

122 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 COVID-19 Drug: Suspension of heat killed (autoclaved) Mycobacterium w 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.

123 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 COVID 19 Drug: Hydroxychloroquine Sulfate 200 MG 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

124 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 (VRI) in Healthcare Workers

Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers

NCT04359680 COVID-19 Viral Respiratory Illnesses Drug: Nitazoxanide Drug: Placebo Dietary Supplement: Vitamin Super B-Complex

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

125 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 SARS-CoV 2 COVID ARDS ALI Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Dyspnea Drug: RLF-100 (aviptadil) Drug: Placebo Device: Nebulized administration of RLF-100 or Placebo
MeSH:Respiratory Distress Syndrome, Newborn 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

126 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 COVID-19 Drug: Telmisartan 40mg 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)

127 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 COVID-19 Drug: Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5. 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

128 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 COVID-19 Pneumonia Biological: Mesenchymal Stromal Cells 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

129 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 COVID-19 Biological: vaccine BCG 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

130 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 Cytokine Storm (Covid-19) Drug: Ruxolitinib 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

131 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 COVID-19 Coronavirus SARS-CoV-2 Biological: pathogen reduced SARS-CoV-2 convalescent plasma 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

132 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 COVID-19 Drug: HB-adMSC 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

133 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 Pneumonia and Cytokine Release Syndrome (Covid-19) Drug: Canakinumab Drug: Placebo
MeSH:Pneumonia Syndrome <