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 (683)
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug1284 | Hydroxychloroquine Wiki | 0.13 |
| drug1869 | Nitazoxanide Wiki | 0.11 |
| drug1985 | Ontamalimab Wiki | 0.10 |
| drug1543 | LY3819253 Wiki | 0.10 |
| drug2413 | Remdesivir Wiki | 0.09 |
| drug2991 | UC-MSCs Wiki | 0.09 |
| drug1607 | Losartan Wiki | 0.09 |
| drug660 | Chloroquine or Hydroxychloroquine Wiki | 0.09 |
| drug336 | BCG vaccine Wiki | 0.09 |
| drug3039 | VPM1002 Wiki | 0.09 |
| drug150 | Ad26.COV2.S Wiki | 0.09 |
| drug2406 | Relamorelin Wiki | 0.09 |
| drug3090 | Vitamin Super B-Complex Wiki | 0.09 |
| drug675 | Clazakizumab Wiki | 0.08 |
| drug1489 | Ivermectin Wiki | 0.08 |
| drug2223 | Presatovir Wiki | 0.08 |
| drug1498 | Ivermectin Oral Product Wiki | 0.07 |
| drug2586 | Selinexor Wiki | 0.07 |
| drug1312 | Hydroxychloroquine Sulfate Regular dose Wiki | 0.07 |
| drug1964 | Olokizumab 64 mg Wiki | 0.07 |
| drug947 | EDP1815 Wiki | 0.07 |
| drug1529 | L-ascorbic acid Wiki | 0.07 |
| drug2045 | PUL-042 Inhalation Solution Wiki | 0.07 |
| drug2085 | Pentoxifylline Wiki | 0.07 |
| drug2713 | Standard of care treatment Wiki | 0.07 |
| drug2940 | Tofacitinib 10 mg Wiki | 0.07 |
| drug2929 | Tocilizumab (TCZ) Wiki | 0.07 |
| drug847 | Data record Wiki | 0.07 |
| drug605 | Canakinumab Wiki | 0.07 |
| drug2809 | TD-0903 Wiki | 0.07 |
| drug966 | Ebselen Wiki | 0.07 |
| drug593 | CYT107 Wiki | 0.07 |
| drug939 | Duvelisib Wiki | 0.07 |
| drug1311 | Hydroxychloroquine Sulfate Loading Dose Wiki | 0.07 |
| drug2337 | REGN10933+REGN10987 combination therapy Wiki | 0.07 |
| drug124 | Abatacept Wiki | 0.07 |
| drug2707 | Standard of care Wiki | 0.07 |
| drug603 | Camostat Mesilate Wiki | 0.07 |
| drug2458 | Rivaroxaban Wiki | 0.07 |
| drug2161 | Placebo oral tablet Wiki | 0.07 |
| drug812 | DAS181 Wiki | 0.06 |
| drug1552 | Lanadelumab Wiki | 0.06 |
| drug2765 | Supportive Care Wiki | 0.06 |
| drug259 | Aspirin Wiki | 0.06 |
| drug335 | BCG Vaccine Wiki | 0.06 |
| drug2782 | Suspension of heat killed (autoclaved) Mycobacterium w Wiki | 0.06 |
| drug1730 | Mesenchymal Stromal Cells Wiki | 0.06 |
| drug3086 | Vitamin D Wiki | 0.05 |
| drug3122 | White Sender in Acknowledgement Wiki | 0.05 |
| drug1482 | Isoprinosine Wiki | 0.05 |
| drug187 | Ambrisentan Wiki | 0.05 |
| drug157 | Aerolized Hydroxychloroquine Sulfate Wiki | 0.05 |
| drug591 | CVnCoV Vaccine Wiki | 0.05 |
| drug922 | Doxycycline Wiki | 0.05 |
| drug568 | COVID-19 swap test PCR Wiki | 0.05 |
| drug1112 | Fit test Wiki | 0.05 |
| drug1500 | Ivermectin Tablets Wiki | 0.05 |
| drug3254 | e-Psychotherapy Wiki | 0.05 |
| drug1961 | Odd/Even birth year intervention groups Wiki | 0.05 |
| drug3129 | Woebot Substance Use Disorder Wiki | 0.05 |
| drug3371 | non Wiki | 0.05 |
| drug2288 | Pyridostigmine Bromide Wiki | 0.05 |
| drug1169 | Garadacimab, Factor XIIa Antagonist Monoclonal Antibody Wiki | 0.05 |
| drug352 | BM-MSCs Wiki | 0.05 |
| drug1164 | Galidesivir Wiki | 0.05 |
| drug3244 | daily syndromic surveillance Wiki | 0.05 |
| drug331 | BBV152B Wiki | 0.05 |
| drug2564 | Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA] Wiki | 0.05 |
| drug1492 | Ivermectin + Doxycycline + Placebo Wiki | 0.05 |
| drug1655 | MR or M-M-R II ® vaccine Wiki | 0.05 |
| drug715 | Combination of Lopinavir /Ritonavir and Interferon beta-1b Wiki | 0.05 |
| drug872 | Dexamethasone and Hydroxychloroquine Wiki | 0.05 |
| drug1244 | High Dose of KBP-COVID-19 Wiki | 0.05 |
| drug363 | BRII-196 Wiki | 0.05 |
| drug1627 | Low-Concentration Essential Oil Wiki | 0.05 |
| drug2525 | SNDX-6352 Wiki | 0.05 |
| drug83 | AMA Acknowledgement Drug Pricing Wiki | 0.05 |
| drug817 | DAXI for injection dose MEDIUM DOSE Wiki | 0.05 |
| drug1314 | Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets Wiki | 0.05 |
| drug1666 | MVA-MERS-S_DF1 - High Dose Wiki | 0.05 |
| drug1462 | Interview by psychologists Wiki | 0.05 |
| drug882 | Diagnostic test Wiki | 0.05 |
| drug2481 | SARS-CoV Wiki | 0.05 |
| drug148 | Activity Wiki | 0.05 |
| drug347 | BIO101 Wiki | 0.05 |
| drug3207 | blood sample for seroepidemiological investigation Wiki | 0.05 |
| drug1719 | Melatonin 2mg Wiki | 0.05 |
| drug2469 | Routine standard of care Wiki | 0.05 |
| drug943 | ECCO2R Wiki | 0.05 |
| drug1175 | General health education Wiki | 0.05 |
| drug721 | Community interest message Wiki | 0.05 |
| drug364 | BRII-198 Wiki | 0.05 |
| drug329 | BAY1817080 Wiki | 0.05 |
| drug3073 | Virtual Care at Home Wiki | 0.05 |
| drug2623 | Sildenafil Wiki | 0.05 |
| drug508 | CERC-002 Wiki | 0.05 |
| drug2323 | Questionnaires for specific phobia Wiki | 0.05 |
| drug1624 | Low nitrite/NDMA meals Wiki | 0.05 |
| drug1161 | GSK3882347 Wiki | 0.05 |
| drug324 | BACMUNE (MV130) Wiki | 0.05 |
| drug3372 | non applicable Wiki | 0.05 |
| drug3323 | lopinavir/ritonavir group Wiki | 0.05 |
| drug3185 | attendance by ambulance crew Wiki | 0.05 |
| drug1107 | FilmArray PCR on respiratory samples Wiki | 0.05 |
| drug1508 | JNJ-53718678 125 mg Wiki | 0.05 |
| drug1593 | Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki | 0.05 |
| drug2661 | Spartan COVID-19 System Wiki | 0.05 |
| drug2359 | Racial Inequality Highlighted Wiki | 0.05 |
| drug1657 | MRx-4DP0004 Wiki | 0.05 |
| drug1396 | Impact Event Score Wiki | 0.05 |
| drug238 | Apilimod Dimesylate Capsule Wiki | 0.05 |
| drug2142 | Placebo Subcutaneous Solution Wiki | 0.05 |
| drug1817 | NIVOLUMAB Wiki | 0.05 |
| drug3232 | conjunctival RT PCR Wiki | 0.05 |
| drug337 | BCG vaccine (Freeze-dried) Wiki | 0.05 |
| drug3461 | sertraline Wiki | 0.05 |
| drug3433 | quesionnair Wiki | 0.05 |
| drug920 | Double-Blind Placebo Wiki | 0.05 |
| drug181 | Almitrine Wiki | 0.05 |
| drug3136 | XC221 Wiki | 0.05 |
| drug108 | ATI-450 Wiki | 0.05 |
| drug1785 | Moxifloxacin Wiki | 0.05 |
| drug2211 | Prasugrel Hydrochloride 10 MG Oral Tablet Wiki | 0.05 |
| drug3101 | WHO recommendations (waiting condition) Wiki | 0.05 |
| drug1128 | Folfirinox Wiki | 0.05 |
| drug418 | Biological: mRNA-1273: 100 mcg Wiki | 0.05 |
| drug479 | Bromhexine Hydrochloride Wiki | 0.05 |
| drug1416 | Infusion placebo Wiki | 0.05 |
| drug2195 | Positive Peer Journaling (PPJ) Wiki | 0.05 |
| drug938 | Dutasteride Wiki | 0.05 |
| drug2563 | Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA] Wiki | 0.05 |
| drug1793 | Multivitamin Wiki | 0.05 |
| drug3149 | Zilucoplan® Wiki | 0.05 |
| drug840 | Data collection and clinical testing of subjects Wiki | 0.05 |
| drug2864 | Telmisartan 40mg Wiki | 0.05 |
| drug2758 | Sulodexide Wiki | 0.05 |
| drug2974 | Trust in science message Wiki | 0.05 |
| drug815 | DAXI for injection Dose HIGH DOSE Wiki | 0.05 |
| drug988 | Embarrassment message Wiki | 0.05 |
| drug2531 | SOC: Temozolomide Wiki | 0.05 |
| drug814 | DAS181 OL Wiki | 0.05 |
| drug712 | Collection of samples Wiki | 0.05 |
| drug3293 | hyperbaric oxygen therapy (HBOT) Wiki | 0.05 |
| drug536 | COVID-19 Convalescent Plasma (CCP) Wiki | 0.05 |
| drug3161 | [TIMP-2]*[IGFBP-7] Wiki | 0.05 |
| drug3270 | favipiravir tablets+chloroquine phosphatetablets tablets Wiki | 0.05 |
| drug1435 | Interferon beta 1a Wiki | 0.05 |
| drug1476 | Invasive mechanical ventilation using the Unisabana-Herons Ventilator during 24 hours Wiki | 0.05 |
| drug2344 | RO6953958 Wiki | 0.05 |
| drug2752 | Study C Wiki | 0.05 |
| drug2232 | Primary care professionals reports of potential patient safety incidents, non-COVID-19 related Wiki | 0.05 |
| drug1648 | MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg Wiki | 0.05 |
| drug3488 | tacrolimus Wiki | 0.05 |
| drug521 | COPAN swabbing and blood sample collection Wiki | 0.05 |
| drug1254 | High-Concentration Essential Oil Wiki | 0.05 |
| drug2002 | Otilimab Wiki | 0.05 |
| drug1324 | Hydroxychloroquine sulfate &Azithromycin Wiki | 0.05 |
| drug11 | 0.9%NaCl Wiki | 0.05 |
| drug2347 | RSV Mobile Application Wiki | 0.05 |
| drug106 | AT-527 Wiki | 0.05 |
| drug677 | Clazakizumab 25 mg Wiki | 0.05 |
| drug392 | Berzosertib Wiki | 0.05 |
| drug98 | ASC09/ritonavir group Wiki | 0.05 |
| drug2383 | Recombinant Human Interferon α2b Spray Wiki | 0.05 |
| drug1098 | Fecal Microbiota Therapy (FMT) Wiki | 0.05 |
| drug1513 | JNJ-66525433 Wiki | 0.05 |
| drug303 | Avdoralimab Wiki | 0.05 |
| drug119 | AZD5718 Wiki | 0.05 |
| drug342 | BI 706321 Wiki | 0.05 |
| drug1203 | Guanfacine hydrochloride (SPD503) Wiki | 0.05 |
| drug1837 | NasoVAX Wiki | 0.05 |
| drug2163 | Placebo solution Wiki | 0.05 |
| drug2346 | RS blend Wiki | 0.05 |
| drug1497 | Ivermectin Injectable Solution Wiki | 0.05 |
| drug3366 | newborns from covid 19 positive mothers Wiki | 0.05 |
| drug2815 | TERN-101 Wiki | 0.05 |
| drug2353 | RT-PCR SARS-Cov2 Wiki | 0.05 |
| drug330 | BBV152A Wiki | 0.05 |
| drug1079 | FTC/TAF Wiki | 0.05 |
| drug1738 | Metformin Wiki | 0.05 |
| drug3291 | hydroxychloroquine sulfate 200 MG Wiki | 0.05 |
| drug1533 | LDAEP Wiki | 0.05 |
| drug1909 | Non-convalescent Plasma (control plasma) Wiki | 0.05 |
| drug970 | Economic freedom message Wiki | 0.05 |
| drug224 | Anti-Sars-CoV-2 Convalescent Plasma Wiki | 0.05 |
| drug1337 | Hyperbaric oxygen Wiki | 0.05 |
| drug317 | Azithromycin 500 milligram (mg) oral Tablet Wiki | 0.05 |
| drug2051 | Pamrevlumab Wiki | 0.05 |
| drug172 | Alferon LDO Wiki | 0.05 |
| drug3410 | placebo for clazakizumab Wiki | 0.05 |
| drug393 | Best Available Therapy Wiki | 0.05 |
| drug457 | Bolus vitamin D3 Wiki | 0.05 |
| drug494 | C21 Wiki | 0.05 |
| drug2807 | TCC-COVID mHealth solution Wiki | 0.05 |
| drug3189 | avdoralimab Wiki | 0.05 |
| drug122 | AZD8154 Placebo Monodose DPI presented in capsules Wiki | 0.05 |
| drug3286 | hydrocortisone Wiki | 0.05 |
| drug2348 | RSVPreF3 formulation 2 Wiki | 0.05 |
| drug630 | Cenicriviroc (CVC) Wiki | 0.05 |
| drug1589 | Lopinavir / ritonavir tablets combined with Xiyanping injection Wiki | 0.05 |
| drug2236 | Probiotic and LC-PUFA Wiki | 0.05 |
| drug2125 | Placebo (Plasma-Lyte 148) Wiki | 0.05 |
| drug2425 | Repository Corticotropin Injection Wiki | 0.05 |
| drug159 | Aerosol-reducing Mask Wiki | 0.05 |
| drug3216 | captopril 25mg Wiki | 0.05 |
| drug1530 | L-citrulline Wiki | 0.05 |
| drug1436 | Interferon beta-1a Wiki | 0.05 |
| drug345 | BIIB091 Wiki | 0.05 |
| drug383 | Baseline message Wiki | 0.05 |
| drug2355 | RTB101 Wiki | 0.05 |
| drug3025 | Use of Remote Pulse Oximeter Wiki | 0.05 |
| drug998 | Endoscopic intervention Wiki | 0.05 |
| drug1886 | No Racial Inequality Highlighting Wiki | 0.05 |
| drug3299 | imaging, blood tests Wiki | 0.05 |
| drug2958 | Transfusion of SARS-CoV-2 Convalescent Plasma. Wiki | 0.05 |
| drug61 | ABX464 Wiki | 0.05 |
| drug1205 | Guided online support program Wiki | 0.05 |
| drug2301 | Quality of Life Wiki | 0.05 |
| drug832 | Dapagliflozin Wiki | 0.05 |
| drug182 | Alteplase 100 MG [Activase] Wiki | 0.05 |
| drug813 | DAS181 COVID-19 Wiki | 0.05 |
| drug2477 | SAB-301 Wiki | 0.05 |
| drug3191 | azoximer bromide Wiki | 0.05 |
| drug2049 | Pacritinib Wiki | 0.05 |
| drug497 | CAG length >=22 Wiki | 0.05 |
| drug307 | Awake prone positioning Wiki | 0.05 |
| drug3024 | Use of Doctorgram Patient Kit Wiki | 0.05 |
| drug1278 | Human umbilical cord derived CD362 enriched MSCs Wiki | 0.05 |
| drug515 | CK0802 Wiki | 0.05 |
| drug1474 | Intubation Box Wiki | 0.05 |
| drug1206 | Guilt message Wiki | 0.05 |
| drug2632 | Simultaneous EGD and colonoscopy Wiki | 0.05 |
| drug1507 | JNJ-53718678 Wiki | 0.05 |
| drug180 | Allopurinol Wiki | 0.05 |
| drug1043 | Experimental Group Wiki | 0.05 |
| drug1097 | Favipiravir tablets Wiki | 0.05 |
| drug190 | Ampion Wiki | 0.05 |
| drug579 | CPI-006 Wiki | 0.05 |
| drug2305 | Quantitative analysis of anti-SARS-CoV-2-antibodies Wiki | 0.05 |
| drug1941 | OP-101 Wiki | 0.05 |
| drug1606 | Lopinavir/ritonavir treatment Wiki | 0.05 |
| drug1375 | Icosapent ethyl (IPE) Wiki | 0.05 |
| drug1304 | Hydroxychloroquine Sulfate + Azythromycin Wiki | 0.05 |
| drug2526 | SOC Wiki | 0.05 |
| drug1044 | Experimental drug Wiki | 0.05 |
| drug486 | Budesonide Wiki | 0.05 |
| drug2356 | RTLS data Wiki | 0.05 |
| drug3056 | Verinurad Wiki | 0.05 |
| drug1986 | Opaganib Wiki | 0.05 |
| drug1649 | MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg Wiki | 0.05 |
| drug2264 | Proxalutamide Wiki | 0.05 |
| drug2705 | Standard of Care Triple IS Wiki | 0.05 |
| drug3138 | XPro1595 Wiki | 0.05 |
| drug3036 | V591 Wiki | 0.05 |
| drug120 | AZD7442 Wiki | 0.05 |
| drug45 | 40mg of MitoQ Wiki | 0.05 |
| drug3288 | hydroxychloroquine + azithromycin Wiki | 0.05 |
| drug2839 | Tele-Yoga Therapy Wiki | 0.05 |
| drug2626 | Silymarin Wiki | 0.05 |
| drug676 | Clazakizumab 12.5 mg Wiki | 0.05 |
| drug910 | Dociparastat sodium Wiki | 0.05 |
| drug585 | CT-imaging Wiki | 0.05 |
| drug2390 | Recombinant human plasma gelsolin (Rhu-pGSN) Wiki | 0.05 |
| drug2042 | PTC299 Wiki | 0.05 |
| drug3137 | XCEL-UMC-BETA Wiki | 0.05 |
| drug1493 | Ivermectin + Placebo Wiki | 0.05 |
| drug116 | AVM0703 Wiki | 0.05 |
| drug185 | Aluminum hydroxide Wiki | 0.05 |
| drug2959 | Transfusion of standard Plasma. Wiki | 0.05 |
| drug1790 | MultiStem Wiki | 0.05 |
| drug2703 | Standard of Care (SOC): Radiation Therapy Wiki | 0.05 |
| drug3135 | XAV-19 Wiki | 0.05 |
| drug95 | ARCT-021 Dose Regimen 2 Wiki | 0.05 |
| drug3350 | monthly serologic IgM/G test Wiki | 0.05 |
| drug747 | Control message Wiki | 0.05 |
| drug2997 | Ulinastatin Wiki | 0.05 |
| drug183 | Alteplase 50 MG [Activase] Wiki | 0.05 |
| drug2700 | Standard of Care (SOC) Wiki | 0.05 |
| drug2096 | Personal freedom message Wiki | 0.05 |
| drug1294 | Hydroxychloroquine - Daily dosing Wiki | 0.05 |
| drug1868 | Nintedanib 150 MG Wiki | 0.05 |
| drug1421 | Inhaled budesonide Wiki | 0.05 |
| drug2278 | Pulmonary Vascular Permeability Index Wiki | 0.05 |
| drug1872 | Nitazoxanide Tablets Wiki | 0.05 |
| drug3384 | observation Wiki | 0.05 |
| drug1907 | Non-contact ECG Wiki | 0.05 |
| drug2168 | Placebo videos Wiki | 0.05 |
| drug2753 | Study D Wiki | 0.05 |
| drug1064 | F-652 Wiki | 0.05 |
| drug1739 | Metformin XR Wiki | 0.05 |
| drug254 | ArtemiC Wiki | 0.05 |
| drug2315 | Questionnaire for evaluation of confinement on deviant sexual fantasies Wiki | 0.05 |
| drug1512 | JNJ-53718678 4.5 mg/kg Wiki | 0.05 |
| drug2917 | Thromboprophylaxis Wiki | 0.05 |
| drug3399 | oxyhydrogen Wiki | 0.05 |
| drug2318 | Questionnaire with precaution information Wiki | 0.05 |
| drug92 | ARCT-021 Dose 2 Wiki | 0.05 |
| drug302 | Auxora Wiki | 0.05 |
| drug1356 | INM005 Wiki | 0.05 |
| drug762 | Convalescent anti-SARS-CoV-2 plasma Wiki | 0.05 |
| drug438 | Blood for anti-drug antibody (ADA) Wiki | 0.05 |
| drug2331 | RAPA-501-Allo off-the-shelf Therapy of COVID-19 Wiki | 0.05 |
| drug3005 | Umbilical cord derived mesenchymal stem cells Wiki | 0.05 |
| drug1351 | IGV-001 Cell Immunotherapy Wiki | 0.05 |
| drug1509 | JNJ-53718678 2.5 mg/kg Wiki | 0.05 |
| drug1612 | Low Dose of KBP-COVID-19 Wiki | 0.05 |
| drug1025 | Estradiol patch Wiki | 0.05 |
| drug1542 | LY3473329 Wiki | 0.05 |
| drug2682 | Standard Mask Wiki | 0.05 |
| drug1863 | Niclosamide Oral Tablet Wiki | 0.05 |
| drug3221 | chlorine dioxide 3000 ppm Wiki | 0.05 |
| drug3028 | Use of virus (Covid-19) genome sequence report to inform infection prevention control procedures Wiki | 0.05 |
| drug1253 | High nitrite/NDMA meals Wiki | 0.05 |
| drug161 | Aerosolized All trans retinoic acid Wiki | 0.05 |
| drug1568 | Lianhua Qingwen Wiki | 0.05 |
| drug2941 | Toraymyxin PMX-20R (PMX Cartridge) Wiki | 0.05 |
| drug1022 | Esomeprazole 20mg Wiki | 0.05 |
| drug1652 | MK-5475 Wiki | 0.05 |
| drug2368 | Rapamycin Wiki | 0.05 |
| drug1650 | MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg Wiki | 0.05 |
| drug1371 | Ibudilast Wiki | 0.05 |
| drug2794 | T3 solution for injection Wiki | 0.05 |
| drug3196 | bidirectional oxygenation mouthpiece Wiki | 0.05 |
| drug440 | Blood for research purposes Wiki | 0.05 |
| drug1170 | Gargle/Mouthwash Wiki | 0.05 |
| drug919 | Double-Blind NT-I7 Wiki | 0.05 |
| drug2336 | REGN10933+REGN10987 Wiki | 0.05 |
| drug913 | Dolutegravir Wiki | 0.05 |
| drug658 | Chloroquine analog (GNS651) Wiki | 0.05 |
| drug244 | Apple Watch Series 5 Wiki | 0.05 |
| drug1034 | Exebacase Wiki | 0.05 |
| drug2879 | Tezepelumab Wiki | 0.05 |
| drug121 | AZD8154 Monodose DPI presented in capsules Wiki | 0.05 |
| drug2030 | PHR160 Spray Wiki | 0.05 |
| drug1960 | Octagam 10% Wiki | 0.05 |
| drug1567 | Levilimab Wiki | 0.05 |
| drug140 | Acknowledgement Racial Injustice AMA Wiki | 0.05 |
| drug2992 | UCMSCs Wiki | 0.05 |
| drug2479 | SAR443122 Wiki | 0.05 |
| drug64 | ACE inhibitor, angiotensin receptor blocker Wiki | 0.05 |
| drug3246 | decisions of limitations and stop processing Wiki | 0.05 |
| drug908 | Disulfiram Wiki | 0.05 |
| drug2568 | Sars-Cov2 serology Wiki | 0.05 |
| drug2349 | RSVPreF3 formulation 3 Wiki | 0.05 |
| drug111 | ATYR1923 3 mg/kg Wiki | 0.05 |
| drug1565 | Levamisole and Isoprinosine Wiki | 0.05 |
| drug2289 | Pyronaridine-Artesunate Wiki | 0.05 |
| drug2273 | Psychosocial stimulation and healthy eating education Wiki | 0.05 |
| drug1563 | Levamisole Wiki | 0.05 |
| drug351 | BM-Allo.MSC Wiki | 0.05 |
| drug609 | Candesartan Wiki | 0.05 |
| drug3407 | pirfenidone Wiki | 0.05 |
| drug909 | Docetaxel Wiki | 0.05 |
| drug101 | ASP7317 Wiki | 0.05 |
| drug1852 | NestaCell® Wiki | 0.05 |
| drug2582 | Self-interest message Wiki | 0.05 |
| drug110 | ATYR1923 1 mg/kg Wiki | 0.05 |
| drug1735 | Mesenchymal stem cells Wiki | 0.05 |
| drug830 | Daily placebo Wiki | 0.05 |
| drug901 | Dipyridamole 100 Milligram(mg) Wiki | 0.05 |
| drug1358 | INOpulse Wiki | 0.05 |
| drug618 | Caring Contacts Wiki | 0.05 |
| drug823 | DUR-928 Wiki | 0.05 |
| drug1803 | N-Acetyl cysteine Wiki | 0.05 |
| drug2660 | Sonclot Coagulation and platelet function Analyzer SCP1, Sienco, USA Wiki | 0.05 |
| drug1522 | Ketamine Wiki | 0.05 |
| drug1182 | Glucose tablets Wiki | 0.05 |
| drug2808 | TCM prescriptions Wiki | 0.05 |
| drug1844 | Nasopharyngeal, oropharyngeal, or saliva swab Wiki | 0.05 |
| drug3231 | congenital malformation Wiki | 0.05 |
| drug399 | Best available treatment Wiki | 0.05 |
| drug93 | ARCT-021 Dose 3 Wiki | 0.05 |
| drug1996 | Organicell Flow Wiki | 0.05 |
| drug2638 | Sirolimus 1 MG/ML Wiki | 0.05 |
| drug1968 | Omnibiotic AAD Wiki | 0.05 |
| drug94 | ARCT-021 Dose Regimen 1 Wiki | 0.05 |
| drug60 | ABTL0812 Wiki | 0.05 |
| drug2180 | Plasma Donation Wiki | 0.05 |
| drug834 | Dapagliflozin 10 mg Wiki | 0.05 |
| drug2367 | Ranitidine Wiki | 0.05 |
| drug1692 | Mavrilimumab Wiki | 0.05 |
| drug1532 | LB1148 Wiki | 0.05 |
| drug3049 | Vazegepant (BHV-3500) Wiki | 0.05 |
| drug1260 | Home Sleep Apnea Testing or In-hospital Polysomnography Wiki | 0.05 |
| drug323 | Açaí palm berry extract - natural product Wiki | 0.05 |
| drug2817 | TJ003234 Wiki | 0.05 |
| drug1135 | Formulation without Active Drug Wiki | 0.05 |
| drug374 | Bardoxolone methyl Wiki | 0.05 |
| drug634 | Certified cloth face mask plus preventive information Wiki | 0.05 |
| drug1678 | Manremyc Wiki | 0.05 |
| drug1362 | ION-827359 Wiki | 0.05 |
| drug2338 | REGN3048 Wiki | 0.05 |
| drug154 | Adsorbed COVID-19 (inactivated) Vaccine Wiki | 0.05 |
| drug3450 | rhPTH(1-84) Wiki | 0.05 |
| drug1056 | Extra blood sample Wiki | 0.05 |
| drug2339 | REGN3051 Wiki | 0.05 |
| drug2033 | PLX-PAD Wiki | 0.05 |
| drug3011 | Unfractionated heparin nebulized Wiki | 0.05 |
| drug1156 | GSK3494245 Wiki | 0.05 |
| drug3164 | acetylsalicylic acid Wiki | 0.05 |
| drug304 | Aviptadil by intravenous infusion + standard of care Wiki | 0.05 |
| drug1639 | M201-A Injection Wiki | 0.05 |
| drug2229 | Preventive information Wiki | 0.05 |
| drug2899 | Therapeutic plasma exchange (TPE) Wiki | 0.05 |
| drug240 | Apixaban 2.5 MG Wiki | 0.05 |
| drug1773 | Monalizumab Wiki | 0.05 |
| drug3167 | additional blood tubes Wiki | 0.05 |
| drug68 | ACT-20-CM Wiki | 0.05 |
| drug2736 | Standardized crisis management and coping protocol plan toward Coronavirus disease 2019 (COVID-19) Wiki | 0.05 |
| drug2118 | Piclidenoson Wiki | 0.05 |
| drug204 | Anger message Wiki | 0.05 |
| drug950 | EIDD-2801 Wiki | 0.05 |
| drug221 | Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) Wiki | 0.05 |
| drug3023 | Use of Doctorgram Mobile Application Wiki | 0.05 |
| drug1300 | Hydroxychloroquine SAR321068 Wiki | 0.05 |
| drug2590 | SensiumVitals wearable sensor Wiki | 0.05 |
| drug1667 | MVA-MERS-S_DF1 - Low Dose Wiki | 0.05 |
| drug995 | Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet Wiki | 0.05 |
| drug771 | Cooking Training Wiki | 0.05 |
| drug2666 | Spironolactone 100mg Wiki | 0.05 |
| drug2387 | Recombinant human alkaline phosphatase Wiki | 0.05 |
| drug2535 | ST-2427 Wiki | 0.05 |
| drug2429 | Respiratory Mechanics Wiki | 0.05 |
| drug3068 | Views and experiences of health care professionals working in intensive care units during the COVID-19 pandemic Wiki | 0.05 |
| drug2836 | Technology based social interactions Wiki | 0.05 |
| drug496 | CAG length <22 Wiki | 0.05 |
| drug3517 | washed microbiota transplantation Wiki | 0.05 |
| drug333 | BCG Wiki | 0.05 |
| drug2527 | SOC + Intravenous Famotidine Wiki | 0.05 |
| drug1157 | GSK3640254 Wiki | 0.05 |
| drug1298 | Hydroxychloroquine Oral Product Wiki | 0.05 |
| drug141 | Acthar Gel Wiki | 0.05 |
| drug2100 | Personalized health education Wiki | 0.05 |
| drug1544 | LY3832479 Wiki | 0.05 |
| drug1299 | Hydroxychloroquine Pre-Exposure Prophylaxis Wiki | 0.05 |
| drug3466 | sodium chloride 0.9% Wiki | 0.05 |
| drug1193 | Group B Control Wiki | 0.05 |
| drug2016 | P2Et (Caesalpinia spinosa extract) Wiki | 0.05 |
| drug456 | Bolus placebo Wiki | 0.05 |
| drug2690 | Standard Ventilation Strategy Wiki | 0.05 |
| drug1379 | IgG test Wiki | 0.05 |
| drug1292 | Hydroxychloroquine , Sofosbuvir, daclatasvir Wiki | 0.05 |
| drug346 | BIO 300 Oral Suspension Wiki | 0.05 |
| drug1209 | HB-adMSC Wiki | 0.05 |
| drug160 | Aerosolized 13 cis retinoic acid Wiki | 0.05 |
| drug2749 | Study A Wiki | 0.05 |
| drug760 | Convalescent SARS COVID-19 plasma Wiki | 0.05 |
| drug2824 | Table Setting Training Wiki | 0.05 |
| drug340 | BI 1569912 Wiki | 0.05 |
| drug2137 | Placebo Group Wiki | 0.05 |
| drug969 | Economic benefit message Wiki | 0.05 |
| drug2977 | Two COVID-19 vaccine candidate (TMV-083) administrations - Low dose Wiki | 0.05 |
| drug3062 | Video based aerobic exercise Wiki | 0.05 |
| drug3506 | vaccine BCG Wiki | 0.05 |
| drug69 | ACT-20-MSC Wiki | 0.05 |
| drug2394 | Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) Wiki | 0.05 |
| drug3179 | anti-SARS-CoV-2 plasma Wiki | 0.05 |
| drug1733 | Mesenchymal cells Wiki | 0.05 |
| drug2976 | Two COVID-19 vaccine candidate (TMV-083) administrations - High dose Wiki | 0.05 |
| drug1972 | One COVID-19 vaccine candidate (TMV-083) administration - High dose Wiki | 0.05 |
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| drug1934 | Nutrition support Wiki | 0.05 |
| drug2328 | Quick Defense Wiki | 0.05 |
| drug1111 | Fisetin Wiki | 0.05 |
| drug2528 | SOC + Placebo Wiki | 0.05 |
| drug91 | ARCT-021 Dose 1 Wiki | 0.05 |
| drug2439 | Retrospective data collection Wiki | 0.05 |
| drug816 | DAXI for injection dose LOW DOSE Wiki | 0.05 |
| drug2036 | PRV-015 Wiki | 0.05 |
| drug1377 | IgG Wiki | 0.05 |
| drug2537 | STI-1499 Wiki | 0.05 |
| drug3357 | mycophenolate mofetil (MMF) Wiki | 0.05 |
| drug3243 | daily room disinfection Wiki | 0.05 |
| drug2207 | Povidone-iodine Wiki | 0.05 |
| drug3123 | White Sender in Informational Videos Wiki | 0.05 |
| drug439 | Blood for pharmacokinetic samples Wiki | 0.05 |
| drug2221 | Pregnant women under investigation for Coronavirus or diagnosed with COVID-19 Wiki | 0.05 |
| drug2849 | Telehealth monitoring Wiki | 0.05 |
| drug1895 | No research related technology based social interactions Wiki | 0.05 |
| drug3440 | rapid salivary test Wiki | 0.05 |
| drug163 | African American Sender Acknowledgement Wiki | 0.05 |
| drug2821 | TRV027 Wiki | 0.05 |
| drug2199 | Postpartum women under investigation for Coronavirus or diagnosed with COVID-19 Wiki | 0.05 |
| drug3348 | molecular testing for virus RNA using RT-PCR Wiki | 0.05 |
| drug1849 | Nebulized administration of RLF-100 or Placebo Wiki | 0.05 |
| drug2514 | SCTA01 Wiki | 0.05 |
| drug100 | ASP0892 Wiki | 0.05 |
| drug3169 | after-each-case room disinfection Wiki | 0.05 |
| drug1540 | LSALT peptide Wiki | 0.05 |
| drug341 | BI 474121 Wiki | 0.05 |
| drug1150 | GLS-1200 Wiki | 0.05 |
| drug1345 | IC14 Wiki | 0.05 |
| drug2884 | The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care: Wiki | 0.05 |
| drug2869 | Tenecteplase Wiki | 0.05 |
| drug1355 | INC424 / Ruxolitinib Wiki | 0.05 |
| drug1646 | MEDI7219 Wiki | 0.05 |
| drug419 | Biological: mRNA-1273: 50 mcg Wiki | 0.05 |
| drug164 | African American Sender in Informational Videos. Wiki | 0.05 |
| drug1045 | Experimental: Questionnaire without precaution information Wiki | 0.05 |
| drug2715 | Standard oxygen therapy Wiki | 0.05 |
| drug3087 | Vitamin D 1000 IU Wiki | 0.05 |
| drug158 | Aerosol Box Wiki | 0.05 |
| drug1541 | LY3127804 Wiki | 0.05 |
| drug2544 | Saline containing 1% Human serum albumin（solution without UC-MSCs） Wiki | 0.05 |
| drug2639 | Sirukumab Wiki | 0.05 |
| drug2080 | Peginterferon Lambda-1a Wiki | 0.05 |
| drug893 | DigiVis visual acuity app Wiki | 0.05 |
| drug1291 | Hydroxychloroquine + placebo Wiki | 0.05 |
| drug945 | ECG-Holter Wiki | 0.05 |
| drug505 | CD24Fc Wiki | 0.05 |
| drug559 | COVID-19 e-package: Psychological wellbeing for healthcare workers Wiki | 0.05 |
| drug2751 | Study B Wiki | 0.05 |
| drug1152 | GM-CSF Wiki | 0.05 |
| drug1599 | Lopinavir/ Ritonavir Oral Tablet Wiki | 0.05 |
| drug3416 | prayer Wiki | 0.05 |
| drug480 | Bromhexine Hydrochloride Tablets Wiki | 0.05 |
| drug1815 | NHANES smell and taste tests Wiki | 0.05 |
| drug1511 | JNJ-53718678 3 mg/kg Wiki | 0.05 |
| drug1272 | Human Amniotic Fluid Wiki | 0.05 |
| drug678 | Clevudine Wiki | 0.05 |
| drug3162 | a specifically designed self-administered questionnaire Wiki | 0.05 |
| drug1687 | Matched Placebo Hydroxychloroquine Wiki | 0.05 |
| drug3329 | mHealth Assessments Wiki | 0.05 |
| drug2566 | Sarilumab SAR153191 Wiki | 0.05 |
| drug1539 | LRX712 Wiki | 0.05 |
| drug250 | Arbidol Hydrochloride Granules Wiki | 0.05 |
| drug282 | Atomoxetine hydrochloride Wiki | 0.05 |
| drug1864 | Nicotinamide riboside Wiki | 0.05 |
| drug2178 | Plaquenil 200Mg Tablet Wiki | 0.05 |
| drug332 | BBV152C Wiki | 0.05 |
| drug2767 | Suramin Wiki | 0.05 |
| drug1420 | Inhaled beclomethasone Wiki | 0.05 |
| drug1055 | Extended sampling and procedures Wiki | 0.05 |
| drug1354 | IMU-838 Wiki | 0.05 |
| drug1191 | Group A HCQ Wiki | 0.05 |
| drug1456 | Intervention App Wiki | 0.05 |
| drug1125 | Fluvoxamine Wiki | 0.05 |
| drug319 | Azithromycin Capsule Wiki | 0.05 |
| drug1160 | GSK3739937 Wiki | 0.05 |
| drug3297 | iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System Wiki | 0.05 |
| drug1546 | Laboratory Biomarker Analysis Wiki | 0.05 |
| drug2411 | Relaxation Therapy Wiki | 0.05 |
| drug572 | COVID-surgRES questionaire Wiki | 0.05 |
| drug1558 | Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5. Wiki | 0.05 |
| drug318 | Azithromycin 500Mg Oral Tablet Wiki | 0.05 |
| drug2499 | SARS-CoV-2 vaccine (inactivated) Wiki | 0.05 |
| drug241 | Apixaban 5MG Wiki | 0.05 |
| drug829 | Daily Vitamin D3 Wiki | 0.05 |
| drug1061 | Extravascular Lung Water Index Wiki | 0.05 |
| drug1832 | Naltrexone Wiki | 0.05 |
| drug3332 | mavrilimumab Wiki | 0.05 |
| drug400 | Best standard of care Wiki | 0.05 |
| drug1921 | Normal Saline Infusion + standard of care Wiki | 0.05 |
| drug1827 | NT-I7 Wiki | 0.05 |
| drug2332 | RBA-2 Wiki | 0.05 |
| drug3192 | bacTRL-Spike Wiki | 0.05 |
| drug3273 | fsfi survey Wiki | 0.05 |
| drug1515 | Janus Kinase Inhibitor (ruxolitinib) Wiki | 0.05 |
| drug1214 | HCQ+AZT Wiki | 0.05 |
| drug1109 | Filtration Test Wiki | 0.05 |
| drug1928 | Not bravery message Wiki | 0.05 |
| drug2230 | Previfenon® Wiki | 0.05 |
| drug1677 | Mannitol Wiki | 0.05 |
| drug3183 | artus Influenza A/B RT-PCR Test Wiki | 0.05 |
| drug833 | Dapagliflozin 10 MG Wiki | 0.05 |
| drug3338 | meplazumab for injection Wiki | 0.05 |
| drug1559 | Lenzilumab Wiki | 0.05 |
| drug3375 | non-RAS blocking antihypertensives Wiki | 0.05 |
| drug1273 | Human Biological samples Wiki | 0.05 |
| drug2945 | Tradipitant Wiki | 0.05 |
| drug2345 | RPH-104 80 mg Wiki | 0.05 |
| drug707 | ColdZyme® mouth spray Wiki | 0.05 |
| drug1760 | Mindfulness Rounds Wiki | 0.05 |
| drug1918 | Normal (9%) Saline Wiki | 0.05 |
| drug1510 | JNJ-53718678 250 mg Wiki | 0.05 |
| drug1789 | Multi-tasking Training Wiki | 0.05 |
| drug3170 | airway management during sedation or general anesthesia Wiki | 0.05 |
| drug3400 | pathogen reduced SARS-CoV-2 convalescent plasma Wiki | 0.05 |
| drug1604 | Lopinavir/Ritonavir 400 mg/100 mg Wiki | 0.05 |
| drug2822 | TXA127 Wiki | 0.05 |
| drug1269 | Hospital anxiety and depression scale Wiki | 0.05 |
| drug2073 | Patients admitted to Intensive Care Unit with SARS-CoV2 Wiki | 0.05 |
| drug3147 | Zanubrutinib Wiki | 0.05 |
| drug1180 | Gimsilumab Wiki | 0.05 |
| drug25 | 20 mg MitoQ Wiki | 0.05 |
| drug123 | AZD8154 nebuliser Wiki | 0.05 |
| drug1019 | Ergoferon Wiki | 0.05 |
| drug1521 | Kerecis Oral and Nasal Spray Wiki | 0.05 |
| drug2357 | RUTI® vaccine Wiki | 0.05 |
| drug3018 | Upadacitinib (ABT-494) Wiki | 0.05 |
| drug2376 | Razuprotafib Subcutaneous Solution Wiki | 0.05 |
| drug58 | ABC/3TC Wiki | 0.05 |
| drug1887 | No intervention Wiki | 0.05 |
| drug1087 | Favipiravir Wiki | 0.05 |
| drug2928 | Tocilizumab Wiki | 0.05 |
| drug376 | Baricitinib Wiki | 0.04 |
| drug1744 | Methylprednisolone Sodium Succinate Wiki | 0.04 |
| drug2213 | Prazosin Wiki | 0.04 |
| drug2093 | Peripheral blood draw Wiki | 0.04 |
| drug754 | Convalescent Plasma (anti-SARS-CoV-2 plasma) Wiki | 0.04 |
| drug2939 | Tofacitinib Wiki | 0.04 |
| drug3448 | retrospective analysis Wiki | 0.04 |
| drug359 | BNT162b1 Wiki | 0.04 |
| drug1296 | Hydroxychloroquine 200 Mg Oral Tablet Wiki | 0.04 |
| drug614 | Carboplatin Wiki | 0.04 |
| drug1560 | Leronlimab (700mg) Wiki | 0.04 |
| drug1830 | Nafamostat Mesilate Wiki | 0.04 |
| drug1478 | Iodine Complex Wiki | 0.04 |
| drug360 | BNT162b2 Wiki | 0.04 |
| drug3485 | survey work Wiki | 0.04 |
| drug669 | Ciclesonide Wiki | 0.04 |
| drug3331 | mRNA-1273 Wiki | 0.04 |
| drug654 | Chloroquine Wiki | 0.04 |
| drug696 | Cognitive Behavioral Therapy Wiki | 0.04 |
| drug2385 | Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki | 0.04 |
| drug1313 | Hydroxychloroquine Sulfate Tablets Wiki | 0.04 |
| drug406 | Bicalutamide 150 Mg Oral Tablet Wiki | 0.04 |
| drug1640 | M5049 Wiki | 0.04 |
| drug583 | CT-Scan Wiki | 0.04 |
| drug1305 | Hydroxychloroquine Sulfate 200 MG Wiki | 0.04 |
| drug485 | Bucillamine Wiki | 0.04 |
| drug1370 | Ibrutinib Wiki | 0.04 |
| drug2637 | Sirolimus Wiki | 0.04 |
| drug2343 | RLF-100 (aviptadil) Wiki | 0.04 |
| drug1862 | Niclosamide Wiki | 0.04 |
| drug35 | 2D Telemedicine Wiki | 0.04 |
| drug1276 | Human immunoglobulin Wiki | 0.04 |
| drug26 | 200 mg EIDD-2801 Wiki | 0.04 |
| drug2283 | Pulmozyme Wiki | 0.04 |
| drug1865 | Nigella Sativa / Black Cumin Wiki | 0.04 |
| drug1736 | Mesenchymal stromal cells Wiki | 0.04 |
| drug2493 | SARS-CoV-2 diagnostic rapid test Wiki | 0.04 |
| drug1288 | Hydroxychloroquine + azithromycin Wiki | 0.04 |
| drug3498 | tocilizumab Wiki | 0.04 |
| drug1101 | Fiberoptic Endoscopic Evaluation of Swallowing Wiki | 0.04 |
| drug3504 | unfractionated Heparin Wiki | 0.04 |
| drug2360 | Radiation therapy Wiki | 0.04 |
| drug1295 | Hydroxychloroquine - Weekly Dosing Wiki | 0.04 |
| drug1401 | Inactivated SARS-CoV-2 Vaccine (Vero cell) Wiki | 0.04 |
| drug309 | Ayurveda Wiki | 0.04 |
| drug1447 | Interleukin-7 Wiki | 0.04 |
| drug2633 | Simvastatin Wiki | 0.04 |
| drug313 | Azithromycin Wiki | 0.03 |
| drug2471 | Ruxolitinib Wiki | 0.03 |
| drug752 | Convalescent Plasma Wiki | 0.03 |
| drug2415 | Remestemcel-L Wiki | 0.03 |
| drug1877 | Nitric Oxide Gas Wiki | 0.03 |
| drug1211 | HCQ Wiki | 0.03 |
| drug44 | 3D Telemedicine Wiki | 0.03 |
| drug1601 | Lopinavir/Ritonavir Wiki | 0.03 |
| drug1883 | Nivolumab Wiki | 0.03 |
| drug2251 | Prone positioning Wiki | 0.03 |
| drug2179 | Plasma Wiki | 0.03 |
| drug3204 | blood donation SMS Wiki | 0.03 |
| drug1004 | Enoxaparin Wiki | 0.03 |
| drug1301 | Hydroxychloroquine Sulfate Wiki | 0.03 |
| drug2698 | Standard of Care Wiki | 0.03 |
| drug131 | Acalabrutinib Wiki | 0.03 |
| drug1875 | Nitric Oxide Wiki | 0.03 |
| drug556 | COVID-19 convalescent plasma Wiki | 0.03 |
| drug1981 | Online questionnaire Wiki | 0.03 |
| drug1281 | Hydrocortisone Wiki | 0.03 |
| drug1433 | Interferon Beta-1A Wiki | 0.03 |
| drug174 | Alirocumab Wiki | 0.03 |
| drug1031 | Evolocumab Wiki | 0.03 |
| drug257 | Ascorbic Acid Wiki | 0.03 |
| drug3235 | convalescent plasma Wiki | 0.03 |
| drug2427 | Reslizumab Wiki | 0.03 |
| drug1727 | Mepolizumab Wiki | 0.03 |
| drug2007 | Oxygen Wiki | 0.03 |
| drug763 | Convalescent plasma Wiki | 0.02 |
| drug2562 | Sarilumab Wiki | 0.02 |
| drug3209 | blood sampling Wiki | 0.02 |
| drug1638 | Lung ultrasound Wiki | 0.02 |
| drug870 | Dexamethasone Wiki | 0.02 |
| drug2730 | Standard treatment Wiki | 0.02 |
| drug2311 | Questionnaire Wiki | 0.02 |
| drug3150 | Zinc Wiki | 0.02 |
| drug703 | Colchicine Wiki | 0.02 |
| drug1605 | Lopinavir/ritonavir Wiki | 0.02 |
| drug1743 | Methylprednisolone Wiki | 0.01 |
| drug3408 | placebo Wiki | 0.01 |
| drug2176 | Placebos Wiki | 0.01 |
Correlated MeSH Terms (173)
| Name (Synonyms) | Correlation | |
|---|---|---|
| D018352 | Coronavirus Infections NIH | 0.33 |
| D045169 | Severe Acute Respiratory Syndrome NIH | 0.28 |
| D007239 | Infection NIH | 0.23 |
| D003141 | Communicable Diseases NIH | 0.20 |
| D011014 | Pneumonia NIH | 0.18 |
| D055371 | Acute Lung Injury NIH | 0.15 |
| D012128 | Respiratory Distress Syndrome, Adult NIH | 0.14 |
| D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.13 |
| D018357 | Respiratory Syncytial Virus Infections NIH | 0.11 |
| D001289 | Attention Deficit Disorder with Hyperactivity NIH | 0.10 |
| D055370 | Lung Injury NIH | 0.10 |
| D013577 | Syndrome NIH | 0.10 |
| D014777 | Virus Diseases NIH | 0.10 |
| D014456 | Ulcer NIH | 0.08 |
| D003092 | Colitis NIH | 0.08 |
| D003093 | Colitis, Ulcerative NIH | 0.08 |
| D012141 | Respiratory Tract Infections NIH | 0.08 |
| D000505 | Alopecia NIH | 0.07 |
| D006948 | Hyperkinesis NIH | 0.07 |
| D014552 | Urinary Tract Infections NIH | 0.07 |
| D000257 | Adenoviridae Infections NIH | 0.07 |
| D000428 | Alcohol Drinking NIH | 0.07 |
| D004194 | Disease NIH | 0.07 |
| D008231 | Lymphopenia NIH | 0.07 |
| D018589 | Gastroparesis NIH | 0.07 |
| D002659 | Child Development Disorders, Pervasive NIH | 0.06 |
| D018184 | Paramyxoviridae Infections NIH | 0.06 |
| D007249 | Inflammation NIH | 0.06 |
| D058186 | Acute Kidney Injury NIH | 0.06 |
| D007674 | Kidney Diseases NIH | 0.05 |
| D019973 | Alcohol-Related Disorders NIH | 0.05 |
| D000550 | Amblyopia NIH | 0.05 |
| D012507 | Sarcoidosis NIH | 0.05 |
| D008569 | Memory Disorders NIH | 0.05 |
| D000067877 | Autism Spectrum Disorder NIH | 0.05 |
| D029481 | Bronchitis, Chronic NIH | 0.05 |
| D001049 | Apnea NIH | 0.05 |
| D002446 | Celiac Disease NIH | 0.05 |
| D001997 | Bronchopulmonary Dysplasia NIH | 0.05 |
| D001991 | Bronchitis NIH | 0.05 |
| D001982 | Bronchial Diseases NIH | 0.05 |
| D008595 | Menorrhagia NIH | 0.05 |
| D017565 | Sarcoidosis, Pulmonary NIH | 0.05 |
| D006929 | Hyperaldosteronism NIH | 0.05 |
| D009164 | Mycobacterium Infections NIH | 0.05 |
| D011470 | Prostatic Hyperplasia NIH | 0.05 |
| D009128 | Muscle Spasticity NIH | 0.05 |
| D053201 | Urinary Bladder, Overactive NIH | 0.05 |
| D012772 | Shock, Septic NIH | 0.05 |
| D054559 | Hyperphosphatemia NIH | 0.05 |
| D019446 | Endotoxemia NIH | 0.05 |
| D003015 | Clostridium Infections NIH | 0.05 |
| D006969 | Hypersensitivity, Immediate NIH | 0.05 |
| D006965 | Hyperplasia NIH | 0.05 |
| D004314 | Down Syndrome NIH | 0.05 |
| D001342 | Autonomic Nervous System Diseases NIH | 0.05 |
| D002658 | Developmental Disabilities NIH | 0.05 |
| D003928 | Diabetic Nephropathies NIH | 0.05 |
| D020529 | Multiple Sclerosis, Relapsing-Remitting NIH | 0.05 |
| D016470 | Bacteremia NIH | 0.05 |
| D012130 | Respiratory Hypersensitivity NIH | 0.05 |
| D000230 | Adenocarcinoma NIH | 0.05 |
| D008173 | Lung Diseases, Obstructive NIH | 0.05 |
| D003384 | Coxsackievirus Infections NIH | 0.05 |
| D004696 | Endocarditis NIH | 0.05 |
| D000370 | Ageusia NIH | 0.05 |
| D054969 | Primary Dysautonomias NIH | 0.05 |
| D065626 | Non-alcoholic Fatty Liver Disease NIH | 0.05 |
| D000309 | Adrenal Insufficiency NIH | 0.05 |
| D007008 | Hypokalemia NIH | 0.05 |
| D007011 | Hypoparathyroidism NIH | 0.05 |
| D007896 | Leishmaniasis NIH | 0.05 |
| D005234 | Fatty Liver NIH | 0.05 |
| D004827 | Epilepsy NIH | 0.05 |
| D000435 | Alcoholic Intoxication NIH | 0.05 |
| D018450 | Disease Progression NIH | 0.05 |
| D011024 | Pneumonia, Viral NIH | 0.05 |
| D060825 | Cognitive Dysfunction NIH | 0.05 |
| D018805 | Sepsis NIH | 0.05 |
| D051436 | Renal Insufficiency, Chronic NIH | 0.05 |
| D003424 | Crohn Disease NIH | 0.05 |
| D007251 | Influenza, Human NIH | 0.04 |
| D020141 | Hemostatic Disorders NIH | 0.04 |
| D001778 | Blood Coagulation Disorders NIH | 0.04 |
| D001008 | Anxiety Disorders NIH | 0.04 |
| D014947 | Wounds and Injuries NIH | 0.04 |
| D001321 | Autistic Disorder NIH | 0.04 |
| D011658 | Pulmonary Fibrosis NIH | 0.04 |
| D014808 | Vitamin D Deficiency NIH | 0.04 |
| D013313 | Stress Disorders, Post-Traumatic NIH | 0.04 |
| D030341 | Nidovirales Infections NIH | 0.04 |
| D019964 | Mood Disorders NIH | 0.04 |
| D001010 | Anxiety, Separation NIH | 0.04 |
| D011236 | Prediabetic State NIH | 0.04 |
| D065886 | Neurodevelopmental Disorders NIH | 0.04 |
| D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.04 |
| D009080 | Mucocutaneous Lymph Node Syndrome NIH | 0.04 |
| D012640 | Seizures NIH | 0.04 |
| D000072861 | Phobia, Social NIH | 0.04 |
| D010149 | Pain, Postoperative NIH | 0.04 |
| D000799 | Angioedema NIH | 0.04 |
| D050197 | Atherosclerosis NIH | 0.04 |
| D003072 | Cognition Disorders NIH | 0.04 |
| D015004 | Yellow Fever NIH | 0.04 |
| D004417 | Dyspnea NIH | 0.04 |
| D016491 | Peripheral Vascular Diseases NIH | 0.04 |
| D003139 | Common Cold NIH | 0.04 |
| D058345 | Asymptomatic Infections NIH | 0.04 |
| D014786 | Vision Disorders NIH | 0.04 |
| D011654 | Pulmonary Edema NIH | 0.04 |
| D021183 | Peanut Hypersensitivity NIH | 0.04 |
| D000208 | Acute Disease NIH | 0.04 |
| D005909 | Glioblastoma NIH | 0.04 |
| D054179 | Angioedemas, Hereditary NIH | 0.04 |
| D015354 | Vision, Low NIH | 0.04 |
| D000379 | Agoraphobia NIH | 0.04 |
| D004715 | Endometriosis NIH | 0.04 |
| D008268 | Macular Degeneration NIH | 0.04 |
| D010698 | Phobic Disorders NIH | 0.04 |
| D016638 | Critical Illness NIH | 0.03 |
| D012140 | Respiratory Tract Diseases NIH | 0.03 |
| D015658 | HIV Infections NIH | 0.03 |
| D012598 | Scoliosi NIH | 0.03 |
| D058729 | Peripheral Arterial Disease NIH | 0.03 |
| D005334 | Fever NIH | 0.03 |
| D020181 | Sleep Apnea, Obstructive NIH | 0.03 |
| D058070 | Asymptomatic Diseases NIH | 0.03 |
| D009103 | Multiple Sclerosis NIH | 0.03 |
| D009422 | Nervous System Diseases NIH | 0.03 |
| D016584 | Panic Disorder NIH | 0.03 |
| D014029 | Tobacco Use Disorder NIH | 0.03 |
| D003428 | Cross Infection NIH | 0.03 |
| D005221 | Fatigue NIH | 0.03 |
| D000437 | Alcoholism NIH | 0.03 |
| D002318 | Cardiovascular Diseases NIH | 0.03 |
| D000857 | Olfaction Disorders NIH | 0.03 |
| D003680 | Deglutition Disorders NIH | 0.03 |
| D000544 | Alzheimer Disease NIH | 0.03 |
| D010003 | Osteoarthritis, NIH | 0.03 |
| D001249 | Asthma NIH | 0.03 |
| D011471 | Prostatic Neoplasms NIH | 0.03 |
| D012891 | Sleep Apnea, NIH | 0.03 |
| D009362 | Neoplasm Metastasis NIH | 0.03 |
| D008103 | Liver Cirrhosis, NIH | 0.03 |
| D006470 | Hemorrhage NIH | 0.03 |
| D016739 | Behavior, Addictive NIH | 0.03 |
| D008171 | Lung Diseases, NIH | 0.02 |
| D002277 | Carcinoma NIH | 0.02 |
| D006967 | Hypersensitivity, NIH | 0.02 |
| D003289 | Convalescence NIH | 0.02 |
| D008175 | Lung Neoplasms NIH | 0.02 |
| D003333 | Coronaviridae Infections NIH | 0.02 |
| D012327 | RNA Virus Infections NIH | 0.02 |
| D013927 | Thrombosis NIH | 0.02 |
| D000860 | Hypoxia NIH | 0.02 |
| D007154 | Immune System Diseases NIH | 0.02 |
| D012769 | Shock, NIH | 0.02 |
| D003327 | Coronary Disease NIH | 0.02 |
| D001523 | Mental Disorders NIH | 0.02 |
| D005355 | Fibrosis NIH | 0.02 |
| D004630 | Emergencies NIH | 0.02 |
| D059350 | Chronic Pain NIH | 0.02 |
| D006331 | Heart Diseases NIH | 0.02 |
| D019966 | Substance-Related Disorders NIH | 0.02 |
| D053120 | Respiratory Aspiration NIH | 0.02 |
| D003924 | Diabetes Mellitus, Type 2 NIH | 0.02 |
| D020521 | Stroke NIH | 0.01 |
| D006973 | Hypertension NIH | 0.01 |
| D012120 | Respiration Disorders NIH | 0.01 |
| D003920 | Diabetes Mellitus, NIH | 0.01 |
| D013315 | Stress, Psychological NIH | 0.01 |
| D040921 | Stress Disorders, Traumatic NIH | 0.01 |
| D003863 | Depression, NIH | 0.01 |
Correlated HPO Terms (73)
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0002090 | Pneumonia HPO | 0.18 |
| HP:0007018 | Attention deficit hyperactivity disorder HPO | 0.10 |
| HP:0002583 | Colitis HPO | 0.08 |
| HP:0100279 | Ulcerative colitis HPO | 0.08 |
| HP:0011947 | Respiratory tract infection HPO | 0.08 |
| HP:0002487 | Hyperkinetic movements HPO | 0.07 |
| HP:0002293 | Alopecia of scalp HPO | 0.07 |
| HP:0001888 | Lymphopenia HPO | 0.07 |
| HP:0002578 | Gastroparesis HPO | 0.07 |
| HP:0001919 | Acute kidney injury HPO | 0.06 |
| HP:0000077 | Abnormality of the kidney HPO | 0.05 |
| HP:0012387 | Bronchitis HPO | 0.05 |
| HP:0002905 | Hyperphosphatemia HPO | 0.05 |
| HP:0002900 | Hypokalemia HPO | 0.05 |
| HP:0002104 | Apnea HPO | 0.05 |
| HP:0000846 | Adrenal insufficiency HPO | 0.05 |
| HP:0000646 | Amblyopia HPO | 0.05 |
| HP:0001257 | Spasticity HPO | 0.05 |
| HP:0002354 | Memory impairment HPO | 0.05 |
| HP:0008711 | Benign prostatic hyperplasia HPO | 0.05 |
| HP:0100584 | Endocarditis HPO | 0.05 |
| HP:0000132 | Menorrhagia HPO | 0.05 |
| HP:0002608 | Celiac disease HPO | 0.05 |
| HP:0006536 | Pulmonary obstruction HPO | 0.05 |
| HP:0000829 | Hypoparathyroidism HPO | 0.05 |
| HP:0000224 | Hypogeusia HPO | 0.05 |
| HP:0004469 | Chronic bronchitis HPO | 0.05 |
| HP:0001397 | Hepatic steatosis HPO | 0.05 |
| HP:0000859 | Hyperaldosteronism HPO | 0.05 |
| HP:0000729 | Autistic behavior HPO | 0.05 |
| HP:0001268 | Mental deterioration HPO | 0.05 |
| HP:0100806 | Sepsis HPO | 0.05 |
| HP:0012622 | Chronic kidney disease HPO | 0.05 |
| HP:0100280 | Crohn's disease HPO | 0.05 |
| HP:0001928 | Abnormality of coagulation HPO | 0.04 |
| HP:0000717 | Autism HPO | 0.04 |
| HP:0002206 | Pulmonary fibrosis HPO | 0.04 |
| HP:0100512 | Low levels of vitamin D HPO | 0.04 |
| HP:0030127 | Endometriosis HPO | 0.04 |
| HP:0012174 | Glioblastoma multiforme HPO | 0.04 |
| HP:0000505 | Visual impairment HPO | 0.04 |
| HP:0100598 | Pulmonary edema HPO | 0.04 |
| HP:0012047 | Hemeralopia HPO | 0.04 |
| HP:0100665 | Angioedema HPO | 0.04 |
| HP:0000756 | Agoraphobia HPO | 0.04 |
| HP:0002621 | Atherosclerosis HPO | 0.04 |
| HP:0006510 | Chronic pulmonary obstruction HPO | 0.04 |
| HP:0002098 | Respiratory distress HPO | 0.04 |
| HP:0012378 | Fatigue HPO | 0.03 |
| HP:0001250 | Seizure HPO | 0.03 |
| HP:0001945 | Fever HPO | 0.03 |
| HP:0002870 | Obstructive sleep apnea HPO | 0.03 |
| HP:0001626 | Abnormality of the cardiovascular system HPO | 0.03 |
| HP:0000458 | Anosmia HPO | 0.03 |
| HP:0002758 | Osteoarthritis HPO | 0.03 |
| HP:0012125 | Prostate cancer HPO | 0.03 |
| HP:0002015 | Dysphagia HPO | 0.03 |
| HP:0002099 | Asthma HPO | 0.03 |
| HP:0002511 | Alzheimer disease HPO | 0.03 |
| HP:0010535 | Sleep apnea HPO | 0.03 |
| HP:0030858 | Addictive behavior HPO | 0.03 |
| HP:0001395 | Hepatic fibrosis HPO | 0.03 |
| HP:0002088 | Abnormal lung morphology HPO | 0.02 |
| HP:0012393 | Allergy HPO | 0.02 |
| HP:0004950 | Peripheral arterial stenosis HPO | 0.02 |
| HP:0030731 | Carcinoma HPO | 0.02 |
| HP:0100526 | Neoplasm of the lung HPO | 0.02 |
| HP:0012418 | Hypoxemia HPO | 0.02 |
| HP:0012532 | Chronic pain HPO | 0.02 |
| HP:0005978 | Type II diabetes mellitus HPO | 0.02 |
| HP:0001297 | Stroke HPO | 0.01 |
| HP:0000822 | Hypertension HPO | 0.01 |
| HP:0000819 | Diabetes mellitus HPO | 0.01 |
There are 374 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
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-weeksThe 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 9Description: 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 28Secondary 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 284 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 9Secondary Outcomes
Measure: Number of Supplemental O2-Free Days Through Day 28 Time: Up to Day 28Measure: 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 daysMeasure: Death Time: 180 days
Secondary Outcomes
Measure: Respiratory virus symptom score Time: 7 daysMeasure: 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
Primary Outcomes
Measure: Day 28 all causes mortality Time: at day 28Description: 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 21Secondary 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 daysMeasure: 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-stayDescription: Sub-group of patients included with COVID19
Measure: Proportion of patients needing endotracheal intubation Time: at day 21Description: Sub-group of patients included with COVID19
Measure: Proportion of patients experiencing secondary infection during their ICU-stay Time: From baseline to day 21This 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 daysSecondary 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysMeasure: 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 daysMeasure: 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 daysDescription: FEV1 is defined as forced expiratory volume in the first second.
Measure: Percent Change From Study Baseline in FEV1% Predicted Value Time: Baseline; Day 289 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-daySecondary Outcomes
Measure: Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors) Time: 28 daysMeasure: 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)
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 yearsSecondary 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 yearsDescription: 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 yearsDescription: 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 yearsThe 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 randomizationSecondary 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: The incidence of death within 56 days of randomization.
Measure: Death Time: Within 56 days of randomizationDescription: 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 randomizationOther 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 randomization12 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
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 WeeksThe 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 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 42Description: 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 42Description: Data will be summarized for each visit.
Measure: Change from Baseline in diastolic/systolic blood pressures Time: Baseline and Up to Day 42Measure: 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 42Description: 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 21Description: 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 4215 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 26Description: 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 MonthsDescription: 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 MonthsDescription: 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 MonthsDescription: 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 MonthsDescription: 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 MonthsDescription: 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 MonthsDescription: 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 WeeksDescription: 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 WeeksDescription: 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 WeeksDescription: 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 WeeksDescription: 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 WeeksDescription: 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 MonthsSecondary 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 2616 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)
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 301)
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 12Secondary 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 12Description: 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, 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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, 12Description: 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 12Description: 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, 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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, 12Description: 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 12Description: 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)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)
18 A 12-week, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis
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 12Secondary 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 12Description: 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, 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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, 12Description: 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 12Description: 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, 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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, 12Description: 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 12Description: 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)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
19 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
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 WeeksDescription: 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 WeeksSecondary 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12This 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 1-2Measure: 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 121Measure: 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
20 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
21 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
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 9Secondary 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 9Description: 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 3Description: 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 3Description: 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 3Description: 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 3Description: 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 9Description: 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 9Description: 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 9The 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeks22 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
23 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
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 26Secondary 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 24Description: 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 24Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 26Description: 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 30This 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 visitDescription: 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-doseDescription: 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 visitDescription: 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 visitDescription: 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 visitDescription: 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 visitDescription: 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)24 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
25 A 12-week, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic 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 12Description: 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 52Description: Incidence of AEs
Measure: Number of participants with adverse events (AEs) Time: Baseline to Week 52Description: 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 52Description: 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 52Description: The number of participants who experienced CS ECG values during the 52 week treatment period
Measure: Electrocardiogram (ECG) Heart Rate Time: Baseline to Week 52Description: The number of participants who experienced CS ECG values during the 52 week treatment period
Measure: ECG PR Interval Time: Baseline to Week 52Description: The number of participants who experienced CS ECG values during the 52 week treatment period
Measure: ECG QRS Interval Time: Baseline to Week 52Description: The number of participants who experienced CS ECG values during the 52 week treatment period
Measure: ECG QT Interval Time: Baseline to Week 52Description: The number of participants who experienced CS ECG values during the 52 week treatment period
Measure: ECG QTc Interval Time: Baseline to Week 52Description: 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 52Description: 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 52This 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
26 Noradrenergic Biomarkers in PTSD: Precision Medicine & Mechanisms
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 12Description: 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 12Secondary 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 12Description: 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 12Description: 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 12Description: 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 12Description: 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 12Posttraumatic 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 weeks27 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
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 306)
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 16Description: 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 16Secondary 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 terminationDescription: 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 16Description: Incidence of all cause hospitalizations will be assessed.
Measure: Incidence of Hospitalizations Time: Baseline up to Week 32Description: Incidence of total inpatient days will be assessed.
Measure: Incidence of Total Inpatient Days Time: Baseline up to Week 32Description: 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 32The 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
29 CSP #2008 - Pentoxifylline in Diabetic Kidney 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 16Description: 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 16Secondary 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 16Description: 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 terminationDescription: 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 16Description: Incidence of all cause hospitalizations will be assessed.
Measure: Incidence of Hospitalizations Time: Baseline up to Week 32Description: Incidence of total inpatient days will be assessed.
Measure: Incidence of Total Inpatient Days Time: Baseline up to Week 32Description: 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 32Pentoxifylline (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
30 Targeting Inflammation and Alloimmunity in Heart Transplant Recipients With Tocilizumab (RTB-004)
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 yearsSecondary 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 yearsDescription: Time until doubling of serum creatinine
Measure: Time until doubling of serum creatinine Time: 5 to 9 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsThe purpose of this research study is to see if a study drug called Tocilizumab will, when given with standard anti-rejection medicines, lead to better heart transplantation outcomes at 1 year after the transplant. Specifically, the investigators will evaluate whether taking tocilizumab leads to less rejection, less development of unwanted antibodies, and better heart function.
NCT03644667 Heart Transplant Biological: tocilizumab Biological: Placebo Drug: Standard of Care Triple IS
Primary Outcomes
Description: This outcome is defined by a composite 1 year post-transplant endpoint of: detection of de novo donor-specific antibodies (dnDSA) (Core Laboratory), acute cellular rejection (ACR) ≥ ISHLT 2R rejection (Core Laboratory), antibody mediated rejection (AMR) ≥ ISHLT AMR 1 (Core Laboratory), hemodynamic compromise rejection in the absence of a biopsy or histological rejection, death, or re-transplantation.
Measure: Proportion of Participants Positive for Event of dnDSA, ACR, AMR, Hemodynamic Compromise, Death or Re-Transplantation - By Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Secondary Outcomes
Description: A comparison by treatment group of the incidence of freedom from development of de novo donor-specific antibodies (dnDSA). dnDSA is a newly developed alloantibody that is against the donor organ.
Measure: Freedom of Detection of de Novo Donor-Specific Antibodies (dnDSA) - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: A comparison by treatment group of the incidence of freedom from development of acute cellular rejection ≥2R (Reference: International Society of Heart and Lung Transplantation [ISHLT] acute cellular rejection-grade 2R or greater severity).
Measure: Freedom from Acute Cellular Rejection (ACR) ≥ International Society of Heart and Lung Transplantation (ISHLT) 2R Rejection - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: A comparison by treatment group of the incidence of freedom from development of antibody-mediated rejection defined as ISHLT grade AMR 1 or greater severity.
Measure: Freedom from Antibody Mediated Rejection (AMR) ≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1 - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: A comparison by treatment group of the incidence of freedom from development of hemodynamic compromise (HDC). Hemodynamic compromise is defined by: - Need for inotropic agents due to a Cardiac Index (CI) <2.0 L/min/m^2 or a 25% decrease from baseline, in addition to one of the following: ejection fraction of <40% or a 20% decrease from baseline, and the need for inotropic agents OR fractional shortening of <20% or a 25% decrease from baseline, and the need for inotropic agents.
Measure: Freedom from Hemodynamic Compromise Rejection in the Absence of a Biopsy or Histological Rejection - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: A comparison by treatment group of the incidence of freedom from development of episode of rejection requiring treatment. Reference: Acute cellular rejection as defined by the 2004 International Society of Heart and Lung Transplantation (ISHLT) grading scale.
Measure: Freedom from Any-Treated Rejection - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: A comparison by treatment group of the incidence of freedom from acute cellular rejection (ACR) ≥ ISHLT 2R rejection. Reference: 2004 International Society of Heart and Lung Transplantation [ISHLT [ grading scale).
Measure: Freedom from Acute Cellular Rejection (ACR) ≥ International Society of Heart and Lung Transplantation (ISHLT) 2R Per Patient - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: Time from transplant, free of antibody mediated rejection, defined as ISHLT grade AMR 1 or greater will be compared between the treatment groups. Hemodynamic compromise is defined as the need for inotropic agents due to a Cardiac Index (CI) <2.0 L/min/m2 or a 25% decrease from baseline in addition to one of the following: Ejection fraction of <40% or a 20% decrease from baseline, and the need for inotropic agents Fractional shortening of <20% or a 25% decrease from baseline, and the need for inotropic agents
Measure: Freedom from Antibody Mediated Rejection (AMR) (≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1) Per Participant - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)]Description: Time from transplant, free of antibody mediated rejection, defined as ISHLT grade AMR 1 or greater will be compared between the treatment groups
Measure: Freedom from Hemodynamic Compromise Rejection in the Absence of a Biopsy or Histological Rejection Per Participant - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: Incidence of all-cause mortality will be compared between the treatment groups.
Measure: Occurrence of Death - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: Incidence of participant(s) being re-listed for transplant will be compared between the treatment groups.
Measure: Occurrence of Re-Listed for Transplantation - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)Description: Incidence of participant(s) re-transplantation will be compared between the treatment groups.
Measure: Occurrence of Re-Transplantation - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)]Description: The frequency of events will be compared between the treatment groups.
Measure: Number of Acute Cellular Rejection (≥ International Society of Heart and Lung Transplantation (ISHLT) 2R) Per Patient - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)]Description: The frequency of events will be compared between the treatment groups.
Measure: Number of Antibody Mediated Rejection (AMR) (≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1) Per Participant - by Treatment Group Time: 12 months post-transplantationDescription: The frequency of events will be compared between the treatment groups.
Measure: Number of Rejection Episodes Associated with Hemodynamic Compromise (HDC) Per Participant - by Treatment Group Time: From transplant through 12 months post transplant surgery (12 months)]Description: Per protocol, per clinical research site standard of care.
Measure: Change in Intravascular Ultrasound (IVUS) Measurements From Baseline to 1 Year Post-Transplant- by Treatment Group Time: Baseline (4 to 8 weeks post-transplant), 1 year post-transplantDescription: In accordance with the International Society of Heart and Lung Transplantation (ISHLT) Cardiac Allograft Vasculopathy (CAV) angiographic grading scale.
Measure: Angiographic Evidence of Cardiac Allograft Vasculopathy (CAV) - by Treatment Group Time: 12 months post-transplantationDescription: Incidence of participant loss to follow up will be compared between the treatment groups.
Measure: Participant Loss to follow up - by Treatment Group Time: 12 months post-transplantationDescription: The frequency of serious infections requiring intravenous antimicrobial therapy and need for hospitalization will be compared between treatment groups.
Measure: Occurrence of Serious Infections Requiring Intravenous Antimicrobial Therapy and Need for Hospitalization - by Treatment Group Time: Through 24 months post transplant surgeryDescription: The incidence of tuberculosis will be compared between treatment groups.
Measure: Incidence of Tuberculosis - by Treatment Group Time: Through 24 months post transplant surgeryDescription: The incidence of CMV infection will be compared between treatment groups.
Measure: Incidence of Cytomegalovirus (CMV) Infection - by Treatment Group Time: Through 24 months post transplant surgeryDescription: The incidence of PTLD will be compared between treatment groups.
Measure: Incidence of Post-Transplant Lymphoproliferative Disease (PTLD) - by Treatment Group Time: Through 24 months post transplant surgeryDescription: The number of participants who discontinue study drug, per protocol, will be compared between treatment groups.
Measure: Tolerability (Discontinuation of Study Drug) of Tocilizumab (TCZ) - by Treatment Group Time: Through 24 months post transplant surgery31 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 5Secondary 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 21Description: 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 14Description: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Time to improvement based on general questions on overall health will be reported.
Measure: Time to Improvement on Overall Health Time: Up to 21 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Percentage of participants with abnormal ECGs findings will be reported.
Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings Time: Up to 21 daysDescription: 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 3Description: 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 daysDescription: 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 8Description: 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 days32 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
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.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 576Description: 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 50Description: 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 50Description: 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 576Description: 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 576Description: 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 57634 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 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging, Multi-Center Trial to Evaluate the Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Upper Limb Spasticity in Adults After Stroke or Traumatic Brain Injury
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 28Measure: 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 28Measure: 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
This is a randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging, trial to Evaluate the Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Upper Limb Spasticity in Adults After Stroke or Traumatic Brain Injury. The study will be conducted in the U.S.A. , approximately 128 adult subjects from approximately 30 study centers will be randomly assigned (1:1:1:1) to one of four treatment groups. The study consists of a 21-day screening period, a treatment visit and follow-up visits.The study enrollment is discontinued early due to the impact of COVID-19 on enrollment.
NCT03821402 Upper Limb Spasticity Biological: DAXI for injection dose LOW DOSE Biological: DAXI for injection dose MEDIUM DOSE Biological: DAXI for injection Dose HIGH DOSE Other: Placebo MeSH:Muscle Spasticity
HPO:Spasticity
Primary Outcomes
Description: Mean change from baseline in muscle tone measured with the Modified Ashworth Scale (MAS) in the suprahypertonic muscle group (SMG) of the elbow, wrist, OR finger flexors at Week 6. Score range: 0 (Normal tone, no in tone) to 4 (Affected part{s} rigid in flexion or extension)
Measure: Change from Baseline from suprahypertonic muscle group (SMG) score Time: Week 6
Description: Mean score on of the the Physician Global Impression of Change (PGIC) at Week 6. Score range: -4 (Markedly worse) to +4 (Markedly improved).
Measure: Change from Baseline Physician Global Impression of Change (PGIC) score Time: Week 6
Secondary Outcomes
Description: Proportion of subjects who improve by a full point on the Modified Ashworth Scale (MAS) in the suprahypertonic muscle group (SMG). Score range: 0 (Normal tone, no increase in tone) to 4 (Affected part{s} rigid in flexion or extension)
Measure: Muscle tone improvement Time: Weeks 6 and 12
Description: Proportion of subjects with improvement (score ≥ 1) on the Physician Global Impression of Change (PGIC). Score range: 0 (Normal tone, no increase in tone) to 4 (Affected part{s} rigid in flexion or extension)
Measure: Physician Global Impression of Change (PGIC) improvement Time: Weeks 6 and 12
Description: Change in functional impairment as measured by the Disability Assessment Scale (DAS) for the principal treatment target (PTT). Score range: 0 (No disability) to 3 (Severe disability - normal activities limited).
Measure: Disability Assessment Scale (DAS) functional impairment Time: Weeks 6 and 12
Description: Duration of effect
Measure: Duration of effect Time: Up to 36 weeks
Description: Number of subjects with potential Botulinum Toxin type A distant spread of toxin adverse events, and number of subjects who develop neutralizing antibodies to Botulinum Toxin Type A will be assessed.
Measure: Safety and immunogenicity assessment Time: Up to 36 weeks
36 Promotion of Maternal Gut Microbiota and Psychological Stimulation on Child Cognitive Development at 6 Months of Age
Primary Outcomes
Description: Mean change from baseline in muscle tone measured with the Modified Ashworth Scale (MAS) in the suprahypertonic muscle group (SMG) of the elbow, wrist, OR finger flexors at Week 6. Score range: 0 (Normal tone, no in tone) to 4 (Affected part{s} rigid in flexion or extension)
Measure: Change from Baseline from suprahypertonic muscle group (SMG) score Time: Week 6Description: Mean score on of the the Physician Global Impression of Change (PGIC) at Week 6. Score range: -4 (Markedly worse) to +4 (Markedly improved).
Measure: Change from Baseline Physician Global Impression of Change (PGIC) score Time: Week 6Secondary Outcomes
Description: Proportion of subjects who improve by a full point on the Modified Ashworth Scale (MAS) in the suprahypertonic muscle group (SMG). Score range: 0 (Normal tone, no increase in tone) to 4 (Affected part{s} rigid in flexion or extension)
Measure: Muscle tone improvement Time: Weeks 6 and 12Description: Proportion of subjects with improvement (score ≥ 1) on the Physician Global Impression of Change (PGIC). Score range: 0 (Normal tone, no increase in tone) to 4 (Affected part{s} rigid in flexion or extension)
Measure: Physician Global Impression of Change (PGIC) improvement Time: Weeks 6 and 12Description: Change in functional impairment as measured by the Disability Assessment Scale (DAS) for the principal treatment target (PTT). Score range: 0 (No disability) to 3 (Severe disability - normal activities limited).
Measure: Disability Assessment Scale (DAS) functional impairment Time: Weeks 6 and 12Description: Duration of effect
Measure: Duration of effect Time: Up to 36 weeksDescription: Number of subjects with potential Botulinum Toxin type A distant spread of toxin adverse events, and number of subjects who develop neutralizing antibodies to Botulinum Toxin Type A will be assessed.
Measure: Safety and immunogenicity assessment Time: Up to 36 weeksProbiotics 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 yearDescription: Myelination index
Measure: Fetal brain development Time: 1 yearDescription: 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 yearDescription: BSID-III
Measure: Child cognitive at 6 months of age Time: 1 monthDescription: BERA
Measure: Brain function at 6 months of age Time: 1 monthSecondary Outcomes
Description: Edinburgh Postnatal Depression Scale (EPDS)
Measure: Mother depression scale Time: 1 yearDescription: Visual acuity
Measure: Cognitive development and brain function at 4-months of age Time: 1 yearDescription: Baby weighing scale
Measure: Birth weight Time: 1 monthDescription: Change in weight-for-age z-score
Measure: Child's Growth Time: 6 monthsDescription: Change in Length-for-age z-score
Measure: Child's linear growth Time: 6 monthsDescription: Change in Head-circumference-for-age
Measure: Head circumference Time: 6 monthsDescription: Change in weight-for-length z score
Measure: Child nutritional status Time: 6 monthsDescription: Maternal involvement using HOME inventory questionnaires
Measure: Quality of interaction with parents Time: 1 yearDescription: Zinc, iron, folate blood level
Measure: Maternal micronutrient status Time: 1 yearDescription: Blood glucose
Measure: Gestational diabetes Time: 1 yearDescription: Diagnosed by doctor
Measure: Pre-eclampsia Time: 1 yearDescription: Gestational age
Measure: Preterm birth Time: 1 yearDescription: actual dietary intake, dietary pattern and quality
Measure: Mother's dietary quality Time: 1 yearDescription: Microbiota composition by S16rRNA analysis
Measure: Fecal microbiota composition Time: 1 year37 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
38 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
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 daysMeasure: 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 21Measure: 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
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 CohortsSecondary 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 CohortsMeasure: 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
39 Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 706321 in Healthy Male Subjects (Single-blind, Randomised, Placebo-controlled, Parallel Group Design)
The main objectives are: - Part I: To investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy male subjects following oral administration of single rising doses. - Part II: The relative bioavailability of BI 706321 after administration of tablets and capsules under fasted conditions will be compared with each other and the effect of food on the tablet bioavailability will be investigated.
NCT03971695 Healthy Drug: BI 706321 Drug: Placebo
Primary Outcomes
Measure: Part I: Safety and tolerability of BI 706321 is the percentage of subjects with drug-related adverse events Time: Up to 22 DaysMeasure: Part II: AUC0-tz (area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 to the last quantifiable data point) Time: Up to 22 Days
Measure: Part II: Cmax (maximum measured concentration of BI 706321 in plasma) Time: Up to 22 Days
Secondary Outcomes
Measure: Part I: AUC0-∞ (area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity) Time: Up to 22 DaysMeasure: Part I: Cmax (maximum measured concentration of BI 706321 in plasma) Time: Up to 22 Days
Measure: Part I: tmax (time from dosing to the maximum measured concentration of BI 706321 in plasma) Time: Up to 22 Days
Measure: Part II: AUC0-∞ (area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity) Time: Up to 22 Days
40 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 weeksSecondary 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)41 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 28Secondary 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 28Description: 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 daysDescription: Percentage of participants with abnormal clinical laboratory findings will be reported.
Measure: Percentage of Participants with Abnormal Clinical Laboratory Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal ECGs findings will be reported.
Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal vital signs findings will be reported.
Measure: Percentage of Participants with Abnormal Vital Signs Findings Time: Up to 49 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 yearDescription: 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 daysDescription: 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 daysDescription: Number of supplemental O2 free days will be reported.
Measure: Number of Supplemental Oxygen (O2) Free Days Through Day 28 Time: Through Day 28Description: Incidence of supplemental oxygen requirement in participants will be reported.
Measure: Incidence of Supplemental Oxygen Requirement Time: Up to 28 daysDescription: Duration of supplemental oxygen requirement in participants will be reported.
Measure: Duration of Supplemental Oxygen Time: Up to 28 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 yearDescription: 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 yearDescription: Total length of hospital stay (time in hospital from first dosing) will be reported.
Measure: Total Length of Hospital Stay Time: Up to 49 daysDescription: 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 daysDescription: 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 daysDescription: Incidence of respiratory AEs will be reported.
Measure: Incidence of Respiratory AEs Time: Up to 49 daysDescription: Incidence of thoracic-related AEs will be reported.
Measure: Incidence of Thoracic-related AEs Time: Up to 49 daysDescription: 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 daysDescription: 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 daysDescription: 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 28Description: 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 daysDescription: 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 28Description: 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 28Description: 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 8Description: 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 1Description: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 28Description: 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 28Description: 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 daysDescription: 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 daysDescription: 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 28Description: 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 28Description: 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 days42 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 stageSecondary 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 stageDescription: 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 stageDescription: 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 1Description: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stageDescription: 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 stage43 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
44 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
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 10Description: 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 18Description: 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 49Secondary 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 49Description: 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 49Description: 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 49Description: 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 49Description: 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 49Description: 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 49Description: 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 52Description: 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 52Description: 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 49Description: 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 49Description: 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 49Description: 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 49Description: 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 49This 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
45 Improving Everyday Functioning in Adults Aged 70 and Over Using a Multivitamin Supplement
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 28Secondary 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 52Description: 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 52Description: 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 weeksDescription: The observed maximum (Cmax) plasma concentration following drug administration
Measure: Maximum Observed Plasma Concentration (Cmax) Time: Pre-dose to 28 weeksDescription: The observed minimum (Cmin) plasma concentration following drug administration
Measure: Minimum Observed Plasma Concentration (Cmin) Time: Pre-dose to 28 weeksDescription: The observed synovial concentration following drug administration
Measure: Concentration in synovial fluid Time: Day 1; week 4; week 8Investigation 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) treatmentSecondary 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) treatmentDescription: 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) treatmentDescription: C-Reactive Protein (CRP)
Measure: Immune/inflammatory response (change from baseline) Time: Measured at baseline and then following chronic (12 weeks) treatmentDescription: Secretory Immunoglobulin-A (s-IgA)
Measure: Immune/inflammatory response(change from baseline) Time: Measured at baseline and then following chronic (12 weeks) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: Task performance on the Multi-Tasking Framework (MTF),
Measure: Cognitive function (change from baseline) Time: Measured at baseline and then following chronic (12 weeks) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatmentDescription: 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) treatment46 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, 364Measure: 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)47 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 7Description: 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 7Description: 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 30Description: 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-deliveryDescription: 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-deliveryDescription: 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-deliveryDescription: 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-deliveryDescription: 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-deliveryDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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 31Description: 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 31Description: 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-deliveryDescription: 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-deliveryDescription: 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-deliveryDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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-deliveryDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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-birthDescription: 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-deliveryDescription: 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-deliveryDescription: 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 31Description: 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-deliveryDescription: 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 birthDescription: 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 birthDescription: 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 birthDescription: 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 birthDescription: 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 birthDescription: 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 birthDescription: 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 birthDescription: 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 birthDescription: 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 birth48 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
49 Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 1: Interleukin-5 Antagonists - Mepolizumab and Reslizumab
Primary Outcomes
Measure: Clinical responder rate at Day 14 in the methicillin-resistant Staphylococcus aureus (MRSA) population Time: Day 14Description: TEAEs will be summarized by treatment group.
Measure: Treatment-emergent adverse events (TEAEs) through Day 60 Time: Through Day 60Secondary Outcomes
Measure: Clinical responder rate at Day 14 in all S. aureus patients Time: Day 14Measure: 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
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 armSecondary 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 armDescription: 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 arm50 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 14Secondary 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 14Description: 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 14Description: 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 14Description: 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 14Description: 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 14Description: 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 1451 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 armDescription: 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 armSecondary 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 armDescription: 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 armDescription: 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 armDescription: 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 armDescription: 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 armDescription: 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 arm52 A Randomised, Single-blind, Placebo-controlled Trial to Investigate Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 474121 Administered as Oral Solution and Tablets to Healthy Male Subjects (SRD Part), and a Randomised, Open-label, Single-dose, Three-way Cross-over Bioavailability Comparison of BI 474121 as Tablet Versus Oral Solution and Tablet With and Without Food (BA Part)
The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 474121 in healthy male subjects following oral administration of single rising doses.
NCT04194645 Healthy Drug: BI 474121 Drug: Placebo
Primary Outcomes
Measure: Percentage of subjects with drug-related adverse events (Single-rising dose (SRD) part) Time: Up to 15 daysMeasure: BA part: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) Time: Up to 96 hours
Measure: BA part: Cmax (maximum measured concentration of the analyte in plasma) Time: Up to 96 hours
Secondary Outcomes
Measure: SRD part: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) Time: Up to 96 hoursMeasure: SRD part: Cmax (maximum measured concentration of the analyte in plasma) Time: Up to 96 hours
Measure: BA part: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) Time: Up to 96 hours
53 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
54 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
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 182Secondary 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182Description: 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 182This 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
55 MitoQ for Fatigue in Multiple Sclerosis: A Placebo Controlled Trial
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-doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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-doseDescription: 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 doseDescription: 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 doseDescription: 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-doseDescription: 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-doseDescription: 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-doseDescription: 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-doseDescription: 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-doseDescription: 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-doseDescription: 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-doseDescription: 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-doseDescription: 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 periodDescription: 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 visitThe 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
56 Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe COVID-19
Primary Outcomes
Description: MFIS is a self -reported fatigue survey. Scale 0 - 84
Measure: Modified Fatigue Inventory Scale (MFIS) Time: 12 weeksSecondary Outcomes
Description: SDMT measures cognitive function. Scale 0-110
Measure: Symbol Digit Modalities Test (SDMT) Time: 12 weeksDescription: EDSS measures neurological function. Scale 0-10
Measure: Expanded Disability Status Scale (EDSS) Time: 12 weeksDescription: BDI is a self-reported questionnaire measuring depression. Scale 0-21
Measure: Beck's Depression Inventory (BDI) Time: 12 weeksThe 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
57 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
Primary Outcomes
Description: Evaluation of Pneumonia Improvement
Measure: Pneumonia severity index Time: From Baseline (0W) to 12 week after treatmentDescription: Evaluation of Pneumonia Improvement
Measure: Oxygenation index (PaO2/FiO2) Time: From Baseline (0W) to 12 week after treatmentSecondary 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 treatmentDescription: Marker for efficacy of treatment
Measure: 28-days survival Time: Day 28Description: 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 28Description: Markers of Infection
Measure: C-reactive protein Time: From Baseline (0W) to 12 week after treatmentDescription: Markers of Infection
Measure: Procalcitonin Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: Lymphocyte count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD3+, CD4+ and CD8+ T celll count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD4+/CD8+ratio Time: From Baseline (0W) to 12 week after treatmentThis 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 29Secondary Outcomes
Measure: Change from baseline in alanine transaminase (ALT) Time: Day 1 through Day 29Measure: 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 29Description: 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 29Description: 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 29Description: 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 29Description: For any reason.
Measure: Discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Measure: 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 29Description: 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 15Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 29-day mortality Time: Day 1 through Day 29Description: 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 29Description: 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 29Description: 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 2958 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
59 A Phase IIb Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Severe Influenza Infection
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 8Description: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Secondary 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 8Description: 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 8Description: 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 8Description: 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 8Description: 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 8Description: Marker of Immunology and inflammation
Measure: CD4+ and CD8+ T cells count Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: 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 8Description: Markers of the heart function
Measure: Concentration of the myocardial enzymes Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8This 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 daysDescription: 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 days60 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 daysSecondary 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysOther 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 days61 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 daysDescription: 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 daysSecondary 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 daysDescription: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Measure: Incidence of Death Time: 90 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 days62 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 daysSecondary 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Outcome reported as the mean number of days participants in each arm did not require ventilator use.
Measure: Ventilator-Free Days Time: 28 daysDescription: 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 daysDescription: 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 daysDescription: 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 days63 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 daysSecondary 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 daysDescription: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Measure: Hypotension Requiring Vasopressors Time: 10 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Outcome reported as the number of participants who have expired at 28 days post enrollment.
Measure: 28-Day Mortality Time: 28 daysDescription: Outcome reported as the number of participants who have expired at 90 days post enrollment.
Measure: 90-Day Mortality Time: 90 daysDescription: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Measure: ICU Admission Time: 10 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 days64 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 daysSecondary Outcomes
Description: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy
Measure: SARS-CoV-2 infection Time: 28 daysDescription: 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 daysDescription: 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 daysDescription: The requirement for ICU admission within 28 days from the start of the experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.
Measure: Mechanical Ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy
Measure: Mortality Time: 28 days65 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 daysSecondary 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 daysDescription: 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 daysDescription: 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 daysDescription: The requirement for ICU admission within 28 days from the start of experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of experimental therapy.
Measure: Mechanical ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy.
Measure: Mortality Time: 28 days66 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 4Description: 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 22Description: 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 22Secondary 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: Phase 2
Measure: Mean change in the 7-point ordinal scale Time: Up to day 29Description: Phase 2
Measure: Percentage of patients in each clinical status category using the 7-point ordinal scale Time: Up to day 29Description: 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 29Description: Phase 2
Measure: Change from baseline in NEWS2 scoring system Time: Up to day 29Description: 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 29Description: Phase 2
Measure: Proportion of patients alive, off oxygen Time: At day 29Description: Phase 2
Measure: Number of days of resting respiratory rate >24 breaths/min Time: Up to day 29Description: Phase 2
Measure: Number of days with hypoxemia Time: Up to day 29Description: Phase 2
Measure: Number of days of supplemental oxygen use Time: Up to day 29Description: Phase 2
Measure: Time to saturation ≥94% on room air Time: Up to day 29Description: Phase 2
Measure: Number of ventilator free days in the first 28 days Time: Baseline to day 29Description: Phase 2
Measure: Number of patients requiring initiation of mechanical ventilation Time: Up to day 29Description: Phase 2
Measure: Number of patients requiring non-invasive ventilation Time: Up to day 29Description: Phase 2
Measure: Number of patients requiring the use of high flow nasal cannula Time: Up to day 29Description: Phase 2
Measure: Number of patients admitted into an intensive care unit (ICU) Time: Up to day 29Description: Phase 2
Measure: Number of days of hospitalization among survivors Time: Up to day 29Description: Phase 2
Measure: Number of deaths due to any cause Time: Up to day 60Description: 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 22Description: 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 22Description: Phase 3
Measure: Proportion of deaths Time: Through day 29Description: Phase 3
Measure: Proportion of patients alive not receiving mechanical ventilation Time: At day 22Description: Phase 3
Measure: Proportion of patients alive not requiring extracorporeal membrane oxygenation (ECMO) Time: At day 22Description: Phase 3
Measure: Proportion of patients with a 2-point improvement in clinical status on the 7-point ordinal scale Time: Up to day 22Description: Phase 3
Measure: Time to at least 1-point improvement in clinical status assessment on the 7-point ordinal scale Time: Up to day 29Description: Phase 3
Measure: Time to at least 2-point improvement in clinical status assessment on the 7-point ordinal scale Time: Up to day 29Description: Phase 3
Measure: Proportion of patients receiving mechanical ventilation Time: Up to day 22Description: Phase 3
Measure: Proportion of patients receiving ECMO Time: Up to day 22Description: Phase 3
Measure: Proportion of patients discharged and alive Time: At day 22Description: 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 29Description: Phase 3
Measure: Proportion of deaths Time: Through day 60Description: Phase 3
Measure: Time to death due to any cause Time: Through day 60Description: Phase 3
Measure: Number of ventilator free days Time: Up to day 29Description: Phase 3
Measure: Number of days of hospitalization among survivors Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with serious adverse events Time: Up to Day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with Grade 4 neutropenia (ANC <500/mm3) Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection Time: Up to day 29Description: 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 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with hypersensitivity reactions Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with infusion reactions Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with gastrointestinal perforation Time: Up to day 29Description: Phase 2 and Phase 3
Measure: White blood cell count Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Hemoglobin levels Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Platelet count Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Creatinine levels Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Total bilirubin level Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Alanine aminotransferase (ALT) level Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Aspartate aminotransferase (AST) level Time: Up to day 29 if still hospitalized67 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.
68 A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment
Primary Outcomes
Description: Ordinal scale (WHO ordinal scale that measures illness severity over time)
Measure: Change in Clinical Condition Time: 10 daysSecondary Outcomes
Description: Evaluation of Pneumonia change
Measure: Rate of mortality within 10-days Time: 10 daysDescription: Evaluation of Pneumonia change
Measure: Change of Clinical symptoms - respiratory rate Time: 10 daysDescription: oxygen saturation
Measure: Hypoxia Time: 10 daysDescription: oxygen saturation
Measure: PaO2 / FiO2 ratio Time: 10 daysDescription: 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 daysDescription: Number of participants with treatment-related adverse events
Measure: Side effects in the treatment group Time: 10 daysDescription: 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.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 daysSecondary 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 daysDescription: 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 daysDescription: All cause of death
Measure: All cause of death Time: 29 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: The discharge time, calculated after the randomization.
Measure: Hospital discharge time Time: 29 daysDescription: Duration of mechanical ventilation (IMV, NIV) (days)
Measure: Duration of mechanical ventilation Time: 29 daysDescription: Duration of pressors (days)
Measure: Duration of pressors Time: 29 daysDescription: Duration of extracorporeal membrane oxygenation (days)
Measure: Duration of ECMO Time: 29 daysDescription: Duration of oxygen therapy (oxygen inhalation by high flow nasal cannula or mask) (days)
Measure: Duration of high flow oxygen therapy Time: 29 daysDescription: Changes of absolute lymphocyte count in peripheral blood
Measure: Absolute lymphocyte count Time: 29 daysDescription: The changes of plasma concentration of D-dimers
Measure: Change of D-dimers Time: 15 and 29 days69 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
70 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 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 periodDescription: 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 periodDescription: Frequency of improvement or recovery of respiratory symptoms
Measure: Frequency of Improvement or recovery of respiratory symptoms Time: 10 days during the intervention periodSecondary Outcomes
Description: Duration of fever after recruitment
Measure: Duration of fever Time: 10 days during the intervention periodDescription: 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 periodDescription: Time of improvement of pulmonary imaging
Measure: Time of improvement of pulmonary imaging Time: 10 days during the intervention periodDescription: Peripheral blood c-reactive protein concentration
Measure: Peripheral blood c-reactive protein concentration Time: day-1,3,7,14 after the intervention periodDescription: Absolute value of peripheral blood lymphocytes
Measure: Absolute value of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodDescription: percentage of peripheral blood lymphocytes
Measure: percentage of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodThis 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
71 Hydroxychloroquine Versus Placebo in Patients Presenting COVID-19 Infection and at Risk of Secondary Complication: a Prospective, Multicentre, Randomised, Double-blind Study
Primary Outcomes
Measure: Clinical Status Assessed Using a 7-Category Ordinal Scale Time: Day 28Secondary Outcomes
Measure: Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of Time: Up to 60 daysMeasure: 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
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 14Secondary 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 28Description: 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 14Description: 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 28Measure: 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
72 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 dischargeSecondary Outcomes
Measure: Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6) Time: 14 days or dischargeMeasure: 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
73 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 29Secondary Outcomes
Measure: Percent of patients alive at Day 29 Time: Day 29Description: 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, 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 29Measure: 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 60Measure: 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 60Measure: 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
74 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
75 Reducing Health Care Workers Absenteeism in COVID-19 Pandemic by Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial.
Primary Outcomes
Measure: Subject incidence of adverse events for TERN-101 versus placebo Time: 16 weeksSecondary Outcomes
Measure: Percent change from baseline in ALT for TERN-101 versus placebo at 12 weeks Time: 12 weeksDescription: Area under the curve
Measure: Plasma concentration of TERN-101 - AUC Time: 12 weeksDescription: Maximum observed concentration
Measure: Plasma concentration of TERN-101 - Cmax Time: 12 weeksDescription: Time to reach maximum measured plasma concentration
Measure: Plasma concentration of TERN-101 - Tmax Time: 12 weeksDescription: Determination of half-life
Measure: Plasma concentration of TERN-101 - t1/2 Time: 12 weeksRationale: 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 daysSecondary Outcomes
Measure: the cumulative incidence of documented COVID-19 Time: Maximum of 180 daysMeasure: 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 daysDescription: 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 daysDescription: Exploratory
Measure: the number of days of unplanned absenteeism because of self-reported acute respiratory symptoms Time: Maximum of 180 daysDescription: Exploratory
Measure: the number of days of self-reported fever (≥38 gr C) Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of self-reported fever (≥38 gr C) Time: Maximum of 180 daysDescription: Exploratory
Measure: the number of days of self-reported acute respiratory symptoms Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of self-reported acute respiratory symptoms Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of death for any reason Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of Intensive Care Admission for any reason Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of Hospital Admission for any reason Time: Maximum of 180 daysDescription: 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 days76 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 weeksSecondary 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeks77 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 days78 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
79 Piclidenoson for Treatment of COVID-19 - A Randomized, Double-Blind, Placebo-Controlled Trial
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 15Secondary 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 15Description: 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 29Description: 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 3Description: 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 8Description: 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 29Description: 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 28Description: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: The number of days spent out of the ICU to day 28.
Measure: ICU-free days to Day 28 Time: 28 days after randomizationDescription: 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 randomizationOther 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationDescription: 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 randomizationPatients 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 daysDescription: 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 daysDescription: Proportion of patients experiencing AEs
Measure: Treatment-emergent adverse events (AEs) Time: 29 daysSecondary 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 daysDescription: Time (days) to improvement of 2 points on 7-point ordinal clinical scale
Measure: Time to improvement Time: 29 daysDescription: Proportion of patients who require mechanical ventilation
Measure: Incidence of mechanical ventilation Time: 29 daysDescription: Ventilator-free days to Day 29
Measure: Ventilator-free days Time: 29 daysDescription: Proportion of patients who require ICU admission
Measure: Incidence of Intensive Care Unit (ICU) admission Time: 29 daysDescription: Duration (days) of ICU stay
Measure: Duration of ICU stay Time: 29 daysDescription: Time (days) to hospital discharge
Measure: Time to hospital discharge Time: 29 daysDescription: Duration (days) of need for supplemental oxygen
Measure: Duration of need for supplemental oxygen Time: 29 daysDescription: 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 daysDescription: SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR
Measure: SARS-CoV-2 viral load Time: 29 daysDescription: Proportion of patients experiencing AEs leading to early discontinuation of trial treatment
Measure: AEs leading to withdrawal Time: 29 daysDescription: Proportion of patients experiencing SAEs
Measure: Treatment-emergent serious AEs (SAEs) Time: 29 daysDescription: 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 daysDescription: Proportion of patients who meet study safety-related stopping rules
Measure: Incidence of meeting safety-related stopping rules Time: 29 daysDescription: Plasma concentrations over time of piclidenoson
Measure: Pharmacokinetics of piclidenoson in this patient population Time: 5 days80 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 3Description: 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 3Secondary 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 5Description: 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)
81 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 daysSecondary 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 daysDescription: 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 months82 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-vaccinationSecondary 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-vaccinationDescription: 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-vaccinationDescription: 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-vaccinationDescription: 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-vaccinationDescription: 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-vaccination83 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 randomisationMeasure: 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 randomisationDescription: 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 randomisationDescription: 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 randomisationMeasure: 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 randomisationMeasure: 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 randomisationMeasure: Number of patients with SAEs considered by the investigator to be at least probably related to the IMP Time: Within 28 days after randomisation
84 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 daysSecondary 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 6. Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization
Measure: Rate of auxiliary oxygen therapy Time: 28 daysDescription: ICU admission rate within 28 days of randomization
Measure: ICU admission rate Time: 28 daysDescription: All-cause mortality within 28 days of randomization
Measure: Mortality Time: 28 days85 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
86 Evaluation of the Efficacy and Safety of Camostat Mesilate + Hydroxychloroquine Combination Therapy in Hospitalized Patients With Moderate COVID-19 Infection
Primary Outcomes
Description: Changes in forced vital capacity (FVC) after treatment compared to baseline.
Measure: Changes in forced vital capacity (FVC) Time: 8 weeksSecondary Outcomes
Description: Changes incarbon monoxide dispersion (DLco%) after treatment compared to baseline.
Measure: Changes in carbon monoxide dispersion (DLco%) Time: 8 weeksDescription: Changes in the six-minute walk test (6MWT) after treatment compared to baseline.
Measure: Changes in the six-minute walk test (6MWT) Time: 8 weeksDescription: 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 weeksEvaluation 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 baselineSecondary Outcomes
Measure: Time to improvement of 2 categories from admission on a 7-point ordinal scale Time: day 14Measure: 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
87 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
88 Azithromycin Added to Hydrochloroquine in Patients Admitted to Intensive Care Due to Coronavirus Disease 2019 (COVID-19)- Randomised Controlled Trial
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 weeksDescription: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: Monitor blood oxygen saturation of the participants within 4 weeksSecondary 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 4Description: 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 4Description: 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 4Description: Degree of infection
Measure: Peripheral blood count recovery time Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: 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 4Description: 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 4Trial 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 enrolmentSecondary 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 daysDescription: Length of stay in intensive care unit
Measure: ICU LOS Time: 28 daysDescription: Proportion of patients who died by day 28
Measure: Mortality28 Time: 28 daysDescription: Proportion of patients who died by day 90
Measure: Mortality90 Time: 90 days89 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 daysSecondary 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 daysMeasure: 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 daysMeasure: Change in COVID-19 virus load from baseline to day 14 Time: 28±2 days
90 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 14Description: Per CTCAE
Measure: Treatment Emergent Adverse Events Time: Up to 30 days after drug administrationSecondary Outcomes
Description: 8-category ordinal scale
Measure: Proportion (%) of subjects experiencing deterioration in clinical status Time: Changes from baseline on Day 7 and Day 30Description: 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 30Description: 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 30Description: 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 14Measure: 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 administrationMeasure: 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
91 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 vaccinationMeasure: 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 vaccinationMeasure: 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
92 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
93 Randomized Controlled Trial of Hydroxychloroquine Versus Placebo for the Treatment of Adult Patients With Acute Coronavirus Disease 2019 - COVID-19
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 daysSecondary Outcomes
Description: Progression to a higher level of care, e.g. ICU
Measure: Proportion of patients who require escalation in care Time: 14 daysDescription: 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 daysDescription: Survival to hospital discharge
Measure: Proportion of patients surviving to hospital discharge Time: daysDescription: Incidence and type of adverse events
Measure: Drug safety profile Time: 14 daysDescription: Number of days spent on advanced respiratory support measures
Measure: Duration of advanced respiratory support Time: daysDescription: Length of hospitalization (in patients who survive to discharge)
Measure: Duration of hospital stay Time: daysDescription: 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: daysDescription: Time (in days) to resolution of fever
Measure: Time to resolution of fever Time: 14 daysDescription: 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 daysThe 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 monthsOther Outcomes
Measure: In-hospital mortality Time: 60 daysMeasure: 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
94 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)95 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
96 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)
Primary Outcomes
Description: Number of days on which a participant breathes without assistance
Measure: Number of Ventilator Free Days Time: Day 1 to Day 28Secondary 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 28Description: Survival without Respiratory Failure
Measure: Percentage of Participants who are Alive and Respiratory Failure Free Time: Day 1 to Day 28Description: Mortality
Measure: Mortality Time: Day 1 to Day 28Description: Days of Hospitalization
Measure: Length of Hospitalization Time: Day 1 to Day 28Description: Number of Participants with any Serious Adverse Event (SAE)
Measure: Number of Participants with any Serious Adverse Event (SAE) Time: Day 1 to Day 28Description: 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 28Trial 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 weeksDescription: 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 weeks97 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 daysDescription: Kinetics of circulating IL-6
Measure: IL-6 Time: 14 days in-hospital, hospital discharge, or death98 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 daysSecondary Outcomes
Measure: Cumulative incidence of intubation Time: 14 daysMeasure: 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 daysDescription: Number of patients who remain alive at end of study.
Measure: Patient Survival Time: 60 days99 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 daysSecondary Outcomes
Description: Mortality at 28-days by all causes
Measure: All-cause-mortality Time: Up to 28 daysDescription: Number of days free of acute inflammation (defined as CRP >= 10 mg/L)
Measure: Acute-inflammation-free days Time: Up to 28 daysDescription: 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 year100 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
101 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
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 30Secondary 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 30Measure: 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 30Measure: 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 hoursCoronavirus 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 monthsSecondary 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 monthsDescription: 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 28Description: 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 6.102 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 15Secondary 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 29Measure: 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
103 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 daysSecondary 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 daysDescription: Clinical worsening will be determined by clinician assessment.
Measure: Count of participants with clinical worsening of COVID-19 disease Time: Up to 28 daysMeasure: 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 daysDescription: 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)104 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 daysSecondary Outcomes
Description: Time to progression to next stage of SARS-CoV-2 disease severity index
Measure: Progression of symptoms Time: 7 daysDescription: 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 daysDescription: Drug related adverse events as determined by data safety and monitoring board (DSMB)
Measure: Adverse events Time: 7 days105 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 15daysSecondary 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 baselineMeasure: 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
106 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 21Secondary Outcomes
Description: Time to wean off oxygen supplementation
Measure: Evolution of acute respiratory syndrome Time: 21 daysDescription: 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 daysDescription: Time to be discharged from hospital
Measure: Hospital discharge Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Rate of mortality within 21-days Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Need of mechanical ventilation Time: 21 days107 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 daysSecondary Outcomes
Description: Hemodynamic status will be assessed by continuous blood pressure measurements (systolic BP in mmHg)
Measure: Assessment of hemodynamic status Time: 30 daysDescription: Hemodynamic status will be assessed by continuous blood pressure measurements (diastolic BP in mmHg)
Measure: Assessment of hemodynamic status Time: 30 daysDescription: Hemodynamic status will be assessed by continuous blood pressure measurements (mean BP in mmHg)
Measure: Assessment of hemodynamic status Time: 30 daysDescription: Hemodynamic status will be assessed by the number of participants with use of inotropic and vasoactive drugs
Measure: Assessment of hemodynamic status Time: 30 daysDescription: 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 daysDescription: 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 daysDescription: Pulmonary function will be assessed by arterial measurement of lactate levels (in mmol/L)
Measure: Assessment of pulmonary function Time: 30 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Urine volume during 24 hours (in ml) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Changes in urea (in mg/dL) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Changes in uric acid (in mg/dL) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Changes in creatinine (in mg/dL) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Echocardiographic assessment of cardiac left ventricular ejection fraction (LVEF, %)
Measure: Assessment of cardiac function Time: 30 daysDescription: Measurements of cardiac troponin I (in μg/L) will be used to assess myocardial injury
Measure: Assessment of cardiac injury Time: 30 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: COVID-19 infection will be assessed by temperature monitoring (in degrees Celsius)
Measure: Assessment of the course of COVID-19 infection Time: 30 daysDescription: 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 daysDescription: 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 daysDescription: 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 days108 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 14Secondary Outcomes
Measure: Time to Clinical Improvement (TTCI) Time: Up to Day 28Measure: 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
109 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 daysSecondary Outcomes
Measure: Mortality Time: 28 and 90 daysDescription: 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 28Description: 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 28Measure: 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 28Description: Concentration in mg/L
Measure: Biological efficacy endpoints - C-reactive protein Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in microgram/L
Measure: Biological efficacy endpoints - Procalcitonin Time: Days 1, 3, 7, 14, 21 and 28Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes
Measure: Immunological profile Time: Up to 28 daysDescription: Use of corticosteroids, antiretroviral, chloroquine
Measure: Number of patients using other treatments for COVID-19 related ARDS Time: Up to 28 daysMeasure: 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 daysDescription: 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 daysDescription: Medical research council sum score on awakening
Measure: Occurrence of critical illness neuromyopathy Time: Up to 28 daysDescription: 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 days110 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 30Secondary 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 30Description: Time to hospital discharge
Measure: Time to hospital discharge Time: Randomization through Day 30Description: 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 30Description: 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 30Description: Time to death from any cause
Measure: Time to death from any cause Time: Randomization through Day 30Description: Time to new/worsened organ dysfunction
Measure: Time to new/worsened organ dysfunction Time: Randomization through Day 30Description: 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 30111 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 8Description: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events Time: Day 1 to Day 14Secondary 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 4Description: 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 4Description: 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 4Description: 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 9Description: 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 9Description: 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 9112 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 daySecondary Outcomes
Description: Time to progression to next stage of SARS-CoV-2 disease severity index
Measure: Progression of symptoms Time: 7 daysDescription: Death
Measure: Mortality Time: 30 days113 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 43Secondary Outcomes
Measure: Incidence of subjects who are alive and not on mechanical ventilation Time: Day 29Description: Subjects who die will be assigned "0" ventilator-free days
Measure: Number of ventilator-free days Time: Baseline to Day 29Measure: Time to hospital discharge Time: Baseline to Day 43
114 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 days115 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 28Secondary 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 28Description: Proportion of patients who will progress to critical illness/death
Measure: Critical or dead patients Time: day 1 until day 28Description: Change in pO2/FiO2 ratio over time
Measure: pO2/FiO2 ratio Time: day 1 until day 28Description: 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 28Description: Duration of hospitalization in survivors (days)
Measure: Hospitalization Time: day 1 until day 28Description: Number of patients who require ventilation
Measure: Mechanical ventilation Time: day 1 until day 28Description: Duration of ventilation (days)
Measure: Mechanical ventilation duration Time: day 1 until day 28Description: 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 28116 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 trialDescription: 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 daysSecondary Outcomes
Description: Number of subjects in each arm who are hospitalized for Covid 19 infection
Measure: Incidence of hospitalization Time: 14 daysDescription: 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 daysDescription: 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 daysDescription: Blood tests to determine level of immunity in each subject
Measure: Immunity to Covid-19 Time: 70 days (10 weeks)117 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 daysSecondary 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 days118 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 weeksDescription: 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 dosing119 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 14Secondary 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, 28Description: time to Improved COVID-19 Clinical Classification 1 to 6 (where higher score means worse outcome)
Measure: Improved COVID-19 Clinical Classification Time: Day 28Description: Percent of subjects RTRA
Measure: Return To Room Air (RTRA) Time: Day 10, 21, 28Measure: Percent of subjects who achieve clinical stability Time: Day 28
Description: Time to
Measure: SARS-CoV-2 RNA undetectable Time: Day 28Description: Time to
Measure: Clinical Deterioration Time: Day 28Description: Percent of subjects discharge
Measure: Percent of subjects discharged Time: Day 14, 21, 28Description: Time to
Measure: Death (all cause) Time: Day 28120 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
121 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
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 daysSecondary Outcomes
Measure: 28-day mortality Time: 28 daysMeasure: 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 daysKerecis 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 daysDescription: 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 daysSecondary 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 daysDescription: The number of adverse events reported will be compared between groups.
Measure: Number of adverse events per group Time: 28 days122 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 daysSecondary 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 DaysDescription: 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 days123 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
124 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.
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 14Description: 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 28Secondary 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 14Description: 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 90Description: 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 90Description: 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 28Description: 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 28Description: Proportion of subjects readmitted to the hospital
Measure: Efficacy: Proportion of subjects readmitted to the hospital Time: Up to 90 daysDescription: 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 28Description: 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 28Description: Proportion of subjects with rhu-pGSN antibodies
Measure: Immunogenicity: Proportion of subjects with rhu-pGSN antibodies Time: Days 1, 28, and 90Description: 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 3Description: 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 3Description: 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 3Description: 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 3Description: 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 3This 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 28Description: 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.125 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 weeksSecondary 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: Outcome reported as the percent of participants experiencing any possible adverse events from Hydroxychloroquine
Measure: Incidence of study medication-related adverse events Time: 12 weeks126 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 weeksMeasure: 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
127 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
128 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
Primary Outcomes
Description: Progression to ARDS is defined as the need for mechanical ventilation
Measure: Progression to ARDS Time: 28 daysSecondary Outcomes
Description: Blood PO2 as measured by pulse oximetry
Measure: Blood oxygenation Time: 28 daysDescription: 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 daysDescription: Distance walked in six minutes
Measure: Distance walked in six minutes Time: 28 daysThis 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 studySecondary 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 studyDescription: 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)129 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 daysDescription: o Improvement of the neutrophil-to-lymphocyte ratio (NLR)
Measure: Immune-inflammatory improvement Time: 30 daysSecondary Outcomes
Description: All-cause mortality at 30 days after enrollment
Measure: Mortality Time: 30 days130 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
131 Performance Evaluation of BCG Vaccination in Healthcare Personnel to Reduce the Severity of SARS-COV-2 Infection in Medellín, Colombia, 2020
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 daysDescription: To measure global success
Measure: Rate of mortality Time: 28 daysSecondary 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: 0-7daysDescription: Evaluation of pneumonia changes
Measure: Proportion of patients who have achieved radiological responses Time: 0-28 daysOther Outcomes
Description: Haemogram and cell subpopulations
Measure: Blood white cell counts and their subpopulations. Time: 0-180 daysDescription: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs
Measure: Cellular markers of inflammation Time: 0-180 daysDescription: IL-10, IL-6, IP-10, TNF-alpha
Measure: Cytokines and chemokines in peripheral blood Time: 0-180 daysUntil 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 studySecondary Outcomes
Description: Incidence of severe or critical infection in COVID-19 cases
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: Lethality of the infection in both groups
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: 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 studyDescription: Prevalence of SARS-Cov-2 infection
Measure: Secondary outcome Time: At baseline evaluation132 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 daysSecondary 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 29Description: 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 29Description: 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 29Description: 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 29Description: 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 daysDescription: Mean change from baseline in the 9-point ordinal scale.
Measure: Mean change from baseline in the clinical status Time: Baseline, Day 15, Day 29Description: Mortality rate at Day 15 and at Day 29
Measure: Mortality rate Time: Day 15, Day 29Description: Proportion of patients requiring mechanical ventilation
Measure: Proportion of patients requiring mechanical ventilation Time: 29 daysDescription: Duration of hospitalization
Measure: Duration of hospitalization Time: 29 daysDescription: 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 daysDescription: 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 29Description: 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 29Description: 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 29133 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 15Secondary Outcomes
Description: All-location, all-cause 14-day mortality
Measure: All-location, all-cause 14-day mortality Time: Baseline to Study Day 14Description: All-location, all-cause 28-day mortality
Measure: All-location, all-cause 28-day mortality Time: Baseline to Study Day 28Description: 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 3Description: 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 8Description: 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 29Description: Number of participants that died or received ECMO
Measure: Composite of death or receipt of ECMO through Day 28 Time: Baseline to Day 28Description: Number of days without use of oxygen
Measure: Oxygen-free days through Day 28 Time: Baseline to Day 28Description: Number of days without use of vasopressors
Measure: Vasopressor-free days through Day 28 Time: Baseline to Day 28Description: Number of days without use of a ventilator
Measure: Ventilator-free days through Day 28 Time: Baseline to Day 28Description: Number of days outside of ICU
Measure: ICU-free days through Day 28 Time: Baseline to Day 28Description: Number of days outside of the hospital
Measure: Hospital-free days through Day 28 Time: Baseline to Day 28Other Outcomes
Description: Number of participants with Acute kidney injury
Measure: Acute kidney injury Time: Baseline to Day 28Description: Number of participants requiring renal replacement therapy
Measure: Renal replacement therapy Time: Baseline to Day 28Description: Number of participants with documented venous thromboembolic disease (DVT or PE)
Measure: Documented venous thromboembolic disease (DVT or PE) Time: Baseline to Day 28Description: Number of Participants with myocardial infarction or ischemic stroke
Measure: Documented cardiovascular event (myocardial infarction or ischemic stroke) Time: Baseline to Day 28Description: Number of participants with transfusion reaction (fever/rash)
Measure: Transfusion reaction Time: Baseline to Day 28Description: Number of participants with transfusion related acute lung injury (TRALI)
Measure: Transfusion related acute lung injury (TRALI) Time: Baseline to Day 28Description: Number of participants with transfusion associated circulatory overload (TACO)
Measure: Transfusion associated circulatory overload (TACO) Time: Baseline to Day 28Description: Number of participants with transfusion related infection
Measure: Transfusion related infection Time: Baseline to Day 28134 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, 10Description: Change from baseline in C Reactive protein
Measure: C Reactive protein Time: screening, day 0, 7, 10Description: change from baseline oxygenation (%)
Measure: Oxygenation Time: screening, day 0, 7, 10Description: change from baseline in TNF alpha
Measure: TNF alpha Time: screening, day 0, 7, 10Description: change from baseline level of IL-10 in the blood (pg/mL)
Measure: IL-10 Time: screening, day 0, 7. 10Description: Time to return to room air
Measure: Return to room air (RTRA) Time: Day 0, 3, 7, 10, 28Secondary Outcomes
Description: Monitoring for changes in qt interval
Measure: EKG qt interval Time: screening, day 0, 3, 7, 10Description: change from baseline in leukocyte differential
Measure: Leukocyte differential Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of glucose in the blood (mg/dL)
Measure: Glucose Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of calcium in the blood (mg/dL)
Measure: Calcium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of albumin in the blood (g/dL)
Measure: Albumin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total protein in the blood (g/dL)
Measure: Total protein Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of sodium in the blood (mol/L)
Measure: Sodium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)
Measure: Total carbon dioxide Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of potassium in the blood (mmol/L)
Measure: Potassium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of chloride in the blood (mmol/L)
Measure: Chloride Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of BUN in the blood (mg/dL)
Measure: BUN Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of creatinine in the blood (mg/dL)
Measure: Creatinine Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)
Measure: Alkaline phosphatase Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)
Measure: Alanine aminotransferase Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total bilirubin in the blood (mg/dL)
Measure: Total bilirubin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of white blood cells in the blood (x10^3/uL)
Measure: White blood cells Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of red blood cells in the blood (x10^6/uL)
Measure: Red blood cells Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of hemoglobin in the blood (g/dL)
Measure: Hemoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of hematocrit in the blood (%)
Measure: Hematocrit Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular volume in the blood (fL)
Measure: Mean corpuscular volume Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular hemoglobin in the blood (pg)
Measure: Mean corpuscular hemoglobin Time: screening, day 0, 7, 10Description: 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, 10Description: clinical lab evaluation of level of red cell distribution width in the blood (%)
Measure: Red cell distribution width Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of neutrophils in the blood (%)
Measure: Neutrophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of lymphocytes in the blood (%)
Measure: Lymphs Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of monocytes in the blood (%)
Measure: Monocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of eosinophils in the blood (%)
Measure: Eosinophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of basophils in the blood (%)
Measure: Basophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute neutrophils in the blood (x10^3/uL)
Measure: Absolute neutrophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute lymphocytes in the blood (x10^3/uL)
Measure: Absolute lymphs Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute monocytes in the blood (x10^3/uL)
Measure: Absolute monocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute eosinophils in the blood (x10^3/uL)
Measure: Absolute eosinophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute basophils in the blood (x10^3/uL)
Measure: Absolute basophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of immature granulocytes in the blood (x10^3/uL)
Measure: Immature granulocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of platelets in the blood (x10^3/uL)
Measure: Platelets Time: screening, day 0, 7, 10Description: clinical lab evaluation of time for blood to coagulate (seconds)
Measure: Prothrombin time Time: screening, day 0, 7, 10Description: clinical lab evaluation of international normalized ratio of blood coagulation (no unit)
Measure: INR Time: screening, day 0, 7, 10Description: clinical lab evaluation of percentage of cells CD3- and CD54+ (%)
Measure: NK cell surface antigen (CD3-CD54+) Time: screening, day 0, 7, 10Description: clinical lab evaluation of ratio of CD4+ cells to CD8+ cells (no unit)
Measure: CD4+/CD8+ ratio Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)
Measure: Myoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)
Measure: Troponin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of creatinine kinase in the blood (U/L)
Measure: Creatinine kinase MB Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of serum ferritin in the blood (ng/mL)
Measure: Serum ferritin Time: screening, day 0, 7, 10Description: incidence of adverse events
Measure: Adverse events Time: screening through day 28Description: 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, 28Description: change from baseline in D-dimer
Measure: D-dimer Time: screening, day 0, 7, 10Description: change from baseline chest x-ray result
Measure: Chest X-ray Time: Day 0, Day 28Description: change from baseline CT scan result
Measure: CT scan Time: Day 0, Day 28Description: time to achieve negative PCR test results
Measure: PCR test for SARS-CoV-2 Time: day 0, 3, 7, 10135 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
HPO:Pneumonia
Primary Outcomes
Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8.
Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.
Measure: Number of patients with clinical response Time: Day 3 to Day 29
Secondary Outcomes
Description: COVID-19-related death during the 4-week period after study treatment.
Measure: COVID-19-related death rate during the 4-week period after study treatment Time: 4 weeks
Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the C-reactive protein (CRP) Time: Baseline, Day 29
Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the serum ferritin Time: Baseline, Day 29
Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the D-dimer Time: Baseline, Day 29
Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).
Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs Time: 127 days
136 A Pilot, Multiple Dose Study to Evaluate the Efficacy and Safety of MRx-4DP0004 in Hospitalised Patients With Symptoms of COVID-19 (SARS-CoV-2 Infection)
Primary Outcomes
Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.
Measure: Number of patients with clinical response Time: Day 3 to Day 29Secondary Outcomes
Description: COVID-19-related death during the 4-week period after study treatment.
Measure: COVID-19-related death rate during the 4-week period after study treatment Time: 4 weeksDescription: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the C-reactive protein (CRP) Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the serum ferritin Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the D-dimer Time: Baseline, Day 29Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).
Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs Time: 127 daysThis is a randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of MRx-4DP0004 in patients with COVID-19. 90 hospitalised patients will be enrolled and randomised (2:1) to receive MRx-4DP0004 or placebo for up to 14 days. MRx-4DP0004 is an immunomodulating Live Biotherapeutic Product (LBP) which is expected to prevent or reduce the hyperinflammatory response to SARS-CoV-2 infection without impairing viral clearance.
NCT04363372 COVID-19 Drug: MRx-4DP0004 Drug: Placebo
Primary Outcomes
Description: Clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement where patients are scored on a scale of 0-8 with 0 being uninfected and 8 being dead
Measure: Change in mean clinical status score in each treatment arm Time: Baseline to Day 42Secondary Outcomes
Description: Safety and tolerability will be determined according to clinically relevant reported adverse events
Measure: Number of adverse events in each treatment arm Time: Baseline to Day 42Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement
Measure: Number of patients with an improvement in clinical status score in each treatment arm Time: Day 1 to Day 42Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement
Measure: Number of patients with a deterioration in clinical status score in each treatment arm Time: Day 1 to Day 42Description: Oxygen saturation will be measured as per local standard procedures
Measure: Number of patients with at least 95% oxygen saturation on room air in each treatment arm Time: Day 1 to Day 14Description: Oxygen saturation will be recorded daily during hospitalisation to determine the mean time for each arm to reach at least 95% saturation
Measure: Time to patients with at least 95% oxygen saturation on room air in each treatment arm Time: Day 1 to Day 14Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature
Measure: Number of patients with an improvement in the National Early Warning Score (NEWS) 2 in each treatment arm Time: Day 1 to Day 14Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature
Measure: Number of patients with an deterioration in the National Early Warning Score (NEWS) 2 in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout hospitalisation
Measure: Number of patients requiring Continuous Positive Airway Pressure in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Number of patients requiring Intermittent Positive Pressure Ventilation in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Time to patients requiring Continuous Positive Airway Pressure in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Time to patients requiring Intermittent Positive Pressure Ventilation in each treatment arm Time: Day 1 to Day 14Description: Length of hospital stay will be compared
Measure: Time to discharge in each treatment arm Time: Day 1 to Day 42Description: All cause mortality will be compared
Measure: Number of deaths in each treatment arm Time: Day 1 to Day 42137 Hydroxychloroquine as Primary Prophylaxis for COVID-19 in Healthcare Workers (HCQPreP)
This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.
NCT04363450 COVID-19 Corona Virus Infection Wuhan Coronavirus Prophylaxis Healthcare Worker Sars-CoV2 Hydroxychloroquine Drug: Hydroxychloroquine Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay
Measure: Incidence of symptomatic COVID-19 infection in healthcare workers Time: 12 weeksSecondary Outcomes
Description: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection
Measure: Absenteeism from work due to COVID-19 Time: 12 weeksDescription: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)
Measure: Severity of COVID-19 infection Time: 12 weeks138 A Randomized Placebo-controlled Safety and Dose-finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
In this study Investigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.
NCT04363502 COVID Drug: Clazakizumab Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Serum CRP (measured in mg/dl) will be evaluated at baseline and on days 1 and 2 following clazakizumab or placebo administration to assess response
Measure: Change in C-reactive protein (CRP) level Time: Up to 3 days139 A Randomized-Control Pilot Study to Assess Hydroxychloroquine in Patients Infected With SARS-CoV-2 (COVID-19)
This is a prospective, randomized, participant-blinded, placebo-controlled, pilot study to assess the preliminary efficacy and safety of hydroxychloroquine for the treatment of patients with lower respiratory tract SARS-CoV-2 infection.
NCT04363866 COVID-19 SARS-CoV-2 Drug: Hydroxychloroquine Drug: Placebo
Primary Outcomes
Description: A 6-point ordinal scale ranging from "Death" to "Not hospitalized with full resumption of normal activities" is used to evaluate differences in the clinical status between participants that receive placebo vs hydroxychloroquine
Measure: Clinical Status at Day 5 Assessed by a 6-Point Ordinal Scale Time: Day 5Secondary Outcomes
Description: Assess differences in SARS-CoV-2 viral shedding between participants that receive placebo vs hydroxychloroquine
Measure: Number of Participants with Detectable SARS-CoV-2 Virus from Day 0 to Day 28 and at Day 5 Time: Day 0 to Day 28 and at Day 5Description: Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)
Measure: Toxicity of Study Drug Assessed by Incidence of Adverse Events Time: Day 0 to Day 28Other Outcomes
Description: Assess length of hospitalization
Measure: Duration of Initial Hospitalization Time: Day 0 to Day 28Description: Assess number of deaths during study follow-up
Measure: Mortality During Follow-Up Time: Day 0 to Day 28Description: Assess number of deaths in the hospital during initial hospitalization
Measure: Mortality During Initial Hospitalization Time: Day 0 to Day 28Description: Assessing utilization of hospital resources
Measure: Incidence of New Hospital Resource Utilization Time: Day 0 to Day 28Description: Assessing duration of hospital resource utilization
Measure: Duration of Hospital Resource Utilization Time: Day 0 to Day 28Description: Provide preliminary characterization of differences in inflammatory response between participants that receive placebo vs hydroxychloroquine
Measure: Changes in Cytokine Profile Time: Day 0 to Day 28140 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19
Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.
NCT04365985 COVID-19 Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome (SARS) Coronavirus Infections Drug: Naltrexone Drug: Ketamine Other: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
Primary Outcomes
Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)
Measure: Progression of oxygenation needs Time: up to 1 monthSecondary Outcomes
Description: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.
Measure: Renal failure Time: up to 1 monthDescription: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits
Measure: Liver failure Time: up to 1 monthDescription: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)
Measure: Cytokine Storm Time: up to 1 monthDescription: Count of participants who die from COVID-19
Measure: Mortality Time: up to 1 month post hospital dischargeDescription: Length of hospital stay in days
Measure: Length of hospital stay Time: up to 1 monthDescription: Count of patients admitted to the ICU at any time during index hospitalization
Measure: Intensive Care Unit (ICU) admission Time: up to 1 monthDescription: Length of ICU stay in days
Measure: Intensive Care Unit (ICU) duration Time: up to 1 monthDescription: Count of participants requiring intubation
Measure: Intubation Time: up to 1 monthDescription: Length of intubation, measured in days
Measure: Intubation duration Time: up to 1 monthDescription: Time measured in days from hospital admission to determination patient is stable for discharge
Measure: Time until recovery Time: up to 1 month141 A Randomized, Double-Blind, Placebo-Controlled, Phase 1/2 Study Evaluating AVM0703 in Patients With COVID-19
This is a randomized, double-blind, placebo-controlled, single-ascending dose study of AVM0703 administered as a single intravenous (IV) infusion to patients with COVID-19. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single-ascending dosing of AVM0703 in patients with COVID-19.
NCT04366115 COVID-19 Drug: AVM0703 Drug: Placebo Drug: hydrocortisone
Primary Outcomes
Description: The primary endpoint of the Phase 1 portion of the study is to evaluate the safety of AVM0703 in subjects with severe or life-threatening COVID-19 infection, and to identify the RP2D.
Measure: Dose-Limiting Toxicities Time: 0-12 monthsDescription: The primary endpoint of the Phase 1/2 portion of the study is to evaluate the efficacy of AVM0703 in subjects with severe or life-threatening COVID-19 infection.
Measure: 28 day all-cause mortality will be a primary end point for Phase 1 and 2 Time: 0-12 months142 A Phase 2/3 Study to Assess the Safety and Efficacy of MultiStem® Therapy in Subjects With Acute Respiratory Distress Syndrome (ARDS) Due to Coronavirus Disease (COVID-19)
Multicenter investigation featuring an open-label lead-in followed by a double blinded, randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy of MultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.
NCT04367077 ARDS Biological: MultiStem Biological: Placebo
Primary Outcomes
Measure: Ventilator-Free Days Time: Day 0 through Day 28.Measure: Safety and Tolerability as measured by the incidence of treatment-emergent adverse events as assessed by CTCAE v5.0. Time: Day 28
Secondary Outcomes
Measure: All-cause mortality Time: Day 60Measure: Ranked hierarchical composite outcome of alive and ventilator-free Time: Day 28
Measure: Ventilator-free days Time: Day 0 through Day 60
143 A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY ADULTS
This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy adults. The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part. The study will evaluate the safety, tolerability, and immunogenicity of 2 different SARS CoV 2 RNA vaccine candidates against COVID 19 and the efficacy of 1 candidate: - As a 2-dose (separated by 21 days) schedule; - At various different dose levels in Phase 1; - In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: 18 to 85 years of age [stratified as ≤55 or >55 years of age]). The candidate selected for evaluation in Phase 2/3 is BNT162b2 (mid-dose).
NCT04368728 SARS-CoV-2 Infection COVID-19 Biological: BNT162b1 Biological: BNT162b2 Other: Placebo
Primary Outcomes
Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Measure: Percentage of participants in Phase 1 reporting local reactions Time: For 7 days after dose 1 and dose 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: Percentage of participants in Phase 1 reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As elicited by investigational site staff
Measure: Percentage of participants in Phase 1 reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: Percentage of participants in Phase 1 reporting serious adverse events Time: From dose 1 through 6 months after the last doseDescription: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values Time: 1 day after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values Time: 7 days after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values Time: 7 days after dose 2Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments Time: Between baseline and 1 day after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments Time: Between baseline and 7 days after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments Time: Between before dose 2 and 7 days after dose 2Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions Time: For 7 days after dose 1 and dose 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As elicited by investigational site staff
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting serious adverse events Time: From dose 1 through 6 months after the last doseDescription: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions Time: For 7 days after dose 1 and dose 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As elicited by investigational site staff
Measure: Percentage of participants in Phase 2/3 reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: Percentage of participants in Phase 2/3 reporting serious adverse events Time: From dose 1 through 6 months after the last doseDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination Time: From 7 days after the last dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 7 days after the last dose of study intervention to the end of the study, up to 2 yearsSecondary Outcomes
Description: As measured at the central laboratory
Measure: In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, expressed as GMCs Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, GMFR in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels from before vaccination to each subsequent time point Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 (anti-S1 and anti-RBD) binding antibody levels Time: Through 2 years after the final doseDescription: Per 1000 person-years of follow-up
Measure: Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination Time: From 7 days after the last dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 7 days after the last dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination Time: From 7 days after the last dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 7 days after the last dose of study intervention to the end of the study, up to 2 years144 A Single-blinded, Randomized, Placebo Controlled Phase II Trial of Prophylactic Treatment With Oral Azithromycin Versus Placebo in Cancer Patients Undergoing Antineoplastic Treatment During the Corona Virus Disease 19 (COVID-19) Pandemic
Prophylactic treatment in cancer patients undergoing antineoplastic therapy during the COVID-19 pandemic.
NCT04369365 COVID Drug: Azithromycin 500 milligram (mg) oral Tablet Drug: Placebo MeSH:Coronavirus Infections Virus Diseases
Primary Outcomes
Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)
Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections Time: 12 weeks after initiation of therapySecondary Outcomes
Description: defined as combined endpoint of hospitalization rate or death
Measure: Number of severe COVID-19 cases Time: 12 weeks after initiation of therapyDescription: grading as outlined by the world health organization (WHO)
Measure: Severity of COVID-19 cases Time: 12 weeks after initiation of therapyDescription: significant clinical and laboratory abnormalities according to CTCAE criteria
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: 12 weeks after initiation of therapyDescription: other than COVID-19
Measure: Number of viral and bacterial infections Time: 12 weeks after initiation of therapyDescription: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test
Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test Time: 12 weeks after initiation of therapy145 A Single Center, Double-blinded, ,Placebo-controlled Phase I Clinical Trial in Healthy Volunteer to Evaluate Tolerance and Pharmacokinetics of Meplazumab of Injection
This is a single center, double-blinded, placebo-controlled phase I clinical trail in healthy volunteer of meplazumab for injection. The primary objective of this phase I trial is to evaluate the safety, tolerability, pharmacokinetic characteristics and occupancy characteristics of peripheral blood cell receptors of meplazumab in healthy volunteer, and provide a reference for the dosage of meplazumab in phase II clinical trial.
NCT04369586 Healthy Volunteers Drug: meplazumab for injection Drug: Placebo
Primary Outcomes
Description: Nature, incidence, and severity of AEs/SAEs, and the relationship to meplazumab treatment.
Measure: Incidence rate of treatment-related adverse events as assessed by CTCAE v5.0 Time: 0-28 daysSecondary Outcomes
Description: AUC0-tn
Measure: Pharmacokinetic assessments of meplazumab- AUC0-tn Time: 0-28 daysDescription: AUC0-∞
Measure: Pharmacokinetic assessments of meplazumab- AUC0-∞ Time: 0-28 daysMeasure: Pharmacokinetic assessments of meplazumab-half life time Time: 0-28 days
Description: Maximum observed plasma concentration of meplazumab (Cmax)
Measure: Pharmacokinetic assessments of meplazumab-Cmax Time: 0-28 days146 COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement
To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).
NCT04369794 COVID-19 Therapeutic Vaccine BCG SARS-CoV 2 Transmission Biological: BCG Biological: Placebo
Primary Outcomes
Description: Classified as mild, moderate and severe
Measure: Clinical evolution of COVID-19 Time: 45 days of symptoms onset or diagnosisDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 7 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate and titration Time: 7 days of symptoms onset or diagnosisSecondary Outcomes
Description: Classified according to type and severity
Measure: Local and systemic adverse events to BCG vaccination Time: 3 monthsOther Outcomes
Description: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 21 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate Time: 21 days of symptoms onset or diagnosisDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 45 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate and titration Time: 45 days of symptoms onset or diagnosis147 A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of XPro1595 in the Treatment of Participants With Pulmonary Complications From Coronavirus Disease (COVID-19)
The purpose of this study is to determine whether XPro1595 can prevent the progression of respiratory complications in COVID19 patients.
NCT04370236 COVID-19 Drug: XPro1595 Drug: Placebo
Primary Outcomes
Description: Disease progression is defined by the development of need for mechanical ventilation or death. Mechanical ventilation includes CPAP, BIPAP or mechanical ventilation requiring intubation.
Measure: Proportion of participants with disease progression from randomization to 28 days post-randomization Time: 28 daysSecondary Outcomes
Measure: Proportion of participants with all-cause mortality Time: 28 daysMeasure: Proportion of participants who transfer to ICU level care by Day 28 (ICU level care is defined as a hospital setting where patient to nurse ratio is < 4); Time: 28 days
Measure: Proportion of participants with a new onset of neurologic disease (requiring medical intervention), including stroke by Day 28; Time: 28 days
Measure: Proportion of participants with evidence of new CHF or new MI requiring medical intervention by Day 28; Time: 28 days
Measure: Proportion of participants with a new onset embolus or thrombus by Day 28; Time: 28 days
Measure: Proportion of participants who develop a need for renal replacement therapy (defined as need for any type of dialysis including intermittent or continuous peritoneal or hemodialysis) by Day 28; Time: 28 days
Measure: Proportion of participants with an increase in the WHO Ordinal Scale of Clinical Improvement score at any time during the study; Time: 28 days
Measure: Length of hospital stay defined as the number of days in hospital from time of randomization to time of discharge or death, whichever occurs first; Time: 28 days
Measure: Change from baseline in inflammation markers over time. Time: 28 days
Other Outcomes
Measure: Incidence of adverse events and serious adverse events not due to underlying disease Time: 28 daysMeasure: Incidence of abnormal findings in clinical safety laboratory parameters, vital signs, and ECGs. Time: 28 days
148 A Double-blind, Randomized Study Versus Placebo of Avdoralimab (IPH5401), an Anti-C5aR Antibody, in Patients With COVID-19 Severe Pneumonia
The primary objective of this trial is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by acute respiratory distress syndrome (ARDS).
NCT04371367 COVID Biological: avdoralimab Other: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: number of patients alive and discharged from the hospital at Day 14 for COVID-19 severe pneumonia patients who don't require hospitalization in ICU
Measure: Number of patients alive and no longer hospitalized at D14 Time: day 14
Description: Number of days without mechanical ventilation at Day 28 for COVID-19 related Acute Respiratory Distress Syndrome (ARDS) Patients hospitalized in ICU
Measure: Number of ventilator-free days at Day 28 (VFD28) Time: day 28
Secondary Outcomes
Measure: Number of participants with treatment-related adverse events Time: day 28
149 Mesenchymal Stem Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome
Primary Outcomes
Description: number of patients alive and discharged from the hospital at Day 14 for COVID-19 severe pneumonia patients who don't require hospitalization in ICU
Measure: Number of patients alive and no longer hospitalized at D14 Time: day 14Description: Number of days without mechanical ventilation at Day 28 for COVID-19 related Acute Respiratory Distress Syndrome (ARDS) Patients hospitalized in ICU
Measure: Number of ventilator-free days at Day 28 (VFD28) Time: day 28Secondary Outcomes
Measure: Number of participants with treatment-related adverse events Time: day 28The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.
NCT04371393 Mesenchymal Stromal Cells Remestemcel-L Acute Respiratory Distress Syndrome COVID Biological: Remestemcel-L Drug: Placebo MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
Primary Outcomes
Description: Number of all-cause mortality within 30 days of randomization.
Measure: Number of all-cause mortality Time: 30 daysSecondary Outcomes
Description: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.
Measure: Number of days alive off mechanical ventilatory support Time: 60 daysDescription: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.
Measure: Number of adverse events Time: 30 daysMeasure: Number of participants alive at day 7 Time: 7 days
Measure: Number of participants alive at day 14 Time: 14 days
Measure: Number of participants alive at day 60 Time: 60 days
Measure: Number of participants alive at day 90 Time: 90 days
Description: The number and percent of patients with resolution and/or improvement of ARDS at day 7
Measure: Number of participants with resolution and/or improvement of ARDS Time: 7 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 14
Measure: Number of participants with resolution and/or improvement of ARDS Time: 14 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 21
Measure: Number of participants with resolution and/or improvement of ARDS Time: 21 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 30
Measure: Number of participants with resolution and/or improvement of ARDS Time: 30 daysDescription: Change from baseline of the severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Change from baseline of the severity of ARDS Time: baseline and 7 daysDescription: Change from baseline of the severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Change from baseline of the severity of ARDS Time: baseline and 14 daysDescription: Change from baseline of the severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Change from baseline of the severity of ARDS Time: baseline and 21 daysDescription: Change from baseline of the severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Change from baseline of the severity of ARDS Time: baseline and 30 daysDescription: Hospital length of stay
Measure: Length of stay Time: 12 monthsDescription: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 7 daysDescription: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 14 daysDescription: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 21 daysDescription: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 30 daysDescription: Changes from baseline in serum hs-CRP concentration at days 7
Measure: Change in serum hs-CRP concentration Time: baseline and 7 daysDescription: Changes from baseline in serum hs-CRP concentration at days 14
Measure: Change in serum hs-CRP concentration Time: baseline and 14 daysDescription: Changes from baseline in serum hs-CRP concentration at days 21
Measure: Change in serum hs-CRP concentration Time: baseline and 21 daysDescription: Changes from baseline in serum hs-CRP concentration at days 30
Measure: Change in serum hs-CRP concentration Time: baseline and 30 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 7 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 14 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 21 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 30 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 30 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 7 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 14 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 21 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 30 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 30 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 7 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 14 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 21 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 30 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 30 days150 A Randomized, Double-Blinded, Placebo-Controlled Trial Evaluating the Virological Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sirolimus Adjuvant Therapy in Patients With Coronavirus Disease (COVID-19)
This is a double-blinded, two-arm, randomized, placebo controlled study comparing the virological efficacy of add-on sirolimus with standard care to placebo and standard care. Virological efficacy is defined as the change from baseline to day 7 in SARS-CoV-2 viral burden measured by quantitative real-time polymerase chain reaction.
NCT04371640 SARS-CoV-2 Covid-19 Drug: Sirolimus 1 MG/ML Drug: Placebo
Primary Outcomes
Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR
Measure: Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment Time: Baseline, and days 1, 2, 3, 4, 5, 6, & 7 post-dose for all patientsSecondary Outcomes
Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR
Measure: Change in SARS-CoV-2 viral burden at days 1-6 Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patientsDescription: Safety and tolerability of sirolimus in patients with COVID-19
Measure: Rate of treatment emergent adverse events Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patients151 Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study
The aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of reducing or even abolishing the cytokine explosion and thus the evolution towards a serious form of the disease which can lead to death. Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival. Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may also be able to inhibit the replication of positive-polarity single-stranded RNA viruses, such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property used in the treatment of inflammatory skin diseases for many years. These modulating effects are noted on several targets of innate immunity: They can decrease the expression of NFKB, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and free radical release. Tetracyclines could therefore participate in limiting the cytokine release induced by COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to inhibit viral replication.
NCT04371952 COVID19 Drug: Doxycycline Drug: Placebo
Primary Outcomes
Description: Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment
Measure: Percentage of Patients with Clinical Respiratory Aggravation Time: after at least 48 hours of treatmentDescription: Percentage of patients hospitalized after at least 48 hours of experimental treatment
Measure: Percentage of patients hospitalized Time: after at least 48 hours of experimental treatmentDescription: Percentage of patients requiring ventilatory assistance
Measure: Percentage of patients requiring ventilatory assistance Time: Day 0 to Day 28Secondary Outcomes
Description: Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)
Measure: Positive SARS-CoV-2 PCR Test Time: Day -1 or day 0 AND Day 7Description: Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)
Measure: Duration of symptoms Time: Day 0 to Day 28Description: Total duration of hospitalization
Measure: Duration of hospitalization Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0Description: Duration of hospitalization in intensive care or reanimation
Measure: Hospitalization intensive care or reanimation Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0Description: Duration of mechanical ventilatory assistance
Measure: Duration of mechanical ventilatory assistance Time: to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0Description: Percentage of deaths related to SARS-CoV-2 infection
Measure: Percentage of deaths related to SARS-CoV-2 Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)Description: Number of AE / SAE in both arms
Measure: AE / SAE in both arms Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)152 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia
This study will evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia.
NCT04372186 COVID-19 Pneumonia Drug: Placebo Drug: Tocilizumab MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Measure: Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28 Time: Up to Day 28
Secondary Outcomes
Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status Time: Up to Day 28
Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) Time: Up to Day 28
Measure: Mortality Rate by Day 28 Time: Up to Day 28
Measure: Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen) Time: Up to Day 28
Measure: Percentage of Participants with Adverse Events Time: Up to Day 60
Measure: Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection Time: Up to Day 60
Measure: Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline) Time: Up to Day 60
153 A Pilot Study of Duvelisib to Combat COVID-19
Primary Outcomes
Measure: Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28 Time: Up to Day 28Secondary Outcomes
Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status Time: Up to Day 28Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) Time: Up to Day 28
Measure: Mortality Rate by Day 28 Time: Up to Day 28
Measure: Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen) Time: Up to Day 28
Measure: Percentage of Participants with Adverse Events Time: Up to Day 60
Measure: Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection Time: Up to Day 60
Measure: Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline) Time: Up to Day 60
The exceedingly high mortality rates of severe and critical COVID-19 warrant the identification and evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. Based on preclinical data from this institution and others, the investigators hypothesize that PI3K inhibition with duvelisib could potentially quell aberrant hyperactivtation of the innate immune system, preferentially polarize macrophages, reduce pulmonary inflammation, and limit viral persistence, thereby improving patient outcomes.
NCT04372602 COVID-19 Drug: Duvelisib Procedure: Peripheral blood draw Drug: Placebo
Primary Outcomes
Measure: Overall survival Time: Through 28 daysSecondary Outcomes
Measure: Length of hospital stay Time: Through completion of follow-up (estimated to be 7 months)Measure: Length of ICU stay Time: Through completion of follow-up (estimated to be 7 months)
Description: -For those on a ventilator at the time of randomization
Measure: Duration of ventilator use Time: Through completion of follow-up (estimated to be 7 months)Measure: Duration of vasopressors use Time: Through completion of follow-up (estimated to be 7 months)
Measure: Duration on renal replacement therapy Time: Through completion of follow-up (estimated to be 7 months)
Description: -Defined as increase in viral load of >0.5 log on two consecutive days, or >1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing
Measure: Viral kinetics as measured by virologic failure Time: Through completion of follow-up (estimated to be 7 months)Measure: Number of adverse events as measured by CTCAE v. 5.0 Time: Through completion of follow-up (estimated to be 7 months)
154 Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19
Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
NCT04372628 COVID-19 Drug: Lopinavir/Ritonavir 400 mg/100 mg Other: Placebo
Primary Outcomes
Description: Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial
Measure: Modified COVID Ordinal Outcomes Scale: Study Day 15 Time: Day 15Secondary Outcomes
Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity
Measure: Modified COVID Ordinal Outcome Scale: Study Day 8 Time: Day 8Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale
Measure: Modified COVID Ordinal Outcome Scale: Study Day 29 Time: Day 29Description: Proportion hospitalized
Measure: Proportion of patients hospitalized: Day 1 to 29 Time: Day 1 to Day 29Description: Number of days from enrollment to hospitalization
Measure: Time to hospitalization Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days from enrollment to resolution of COVID-19 symptoms
Measure: Time to symptom resolution: Day 1 to Day 29 Time: Day 1 to Day 29Description: Survival status
Measure: All-cause, all-location mortality: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of Days without oxygen
Measure: Oxygen-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without fever
Measure: Fever-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without ventilator use
Measure: Ventilator-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the ICU
Measure: ICU-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the hospital
Measure: Hospital-free days: Day 1 to Day 29 Time: Day 1 to Day 29155 RCT in Asymptomatic Volunteers With COVID-19 Comparing Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone vs Standard of Care Without Antibiotics
The coronavirus disease-2019 (COVID-19) is spreading throughout the United States. While there are no known therapies to treat those who have become sick, there have been some reports that a medication currently used to treat rheumatoid arthritis, lupus, and malaria (Hydroxychloroquine sulfate, also known as Plaquenil) may help to lessen the chance or severity of illness, especially if combined with a medicine that treats other kinds of infections (Azithromycin, also known as Zithromax or Zmax or Zpak). There are some people who test positive for the virus but who are otherwise not ill. Current standard of care is to advise these people to self-monitor but no treatment is offered. It is not known how many of these individuals will remain symptom free, and how many will become sick or how severe those symptoms will be. This study will randomize those people who do not have symptoms into one of three treatment plans 1) Hydroxycholoquine and Azithromycin, or 2) no active medication (placebo). All participants will be followed for 2 months. The study will determine if there is any benefit to those who are asymptomatic to taking taking Hydroxychloroquine sulfate in combination with Azithromycin, or if there is no benefit from taking these medications.
NCT04374552 SARS-CoV-2 Infection Drug: Hydroxychloroquine sulfate &Azithromycin Drug: Placebo
Primary Outcomes
Description: Change in SARS-CoV-2 viral from baseline to day 6
Measure: The primary outcome is the rate of decline in viral load over the 10 days after randomization Time: 10 days156 IbrutiNib in SARS CoV-2 Induced Pulmonary Injury and Respiratory Failure (iNSPIRE)
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection. Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States. Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care. There may be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.
NCT04375397 CoronaVirus Induced Disease-2019 (COVID-19) Drug: Ibrutinib Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Insufficiency Lung Injury
Primary Outcomes
Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.
Measure: Percentage of Participants Alive and Without Respiratory Failure Time: Day 28Secondary Outcomes
Description: WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).
Measure: Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline Time: Day 14Description: Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.
Measure: Median Reduction in Days Spent on Supplemental Oxygen Time: Up to Day 28Description: Percentage of participants with mortality from any cause.
Measure: All-Cause Mortality Time: Up to Day 28Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.
Measure: Percentage of Participants Experiencing Respiratory Failure or Death Time: Up to Day 28Description: Percentage of participants alive and not requiring mechanical ventilation.
Measure: Mechanical Ventilation-Free Survival Time: Up to Day 56Description: Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.
Measure: Days on Mechanical Ventilation Time: Up to Day 56Description: The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.
Measure: Duration of hospitalization Time: Up to Day 56Description: Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.
Measure: Time to Discharge Time: Up to Day 56Description: PaO2:FiO2 ratio is an index of respiratory distress.
Measure: Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio Time: Up to Day 56Description: Oxygenation Index is a parameter of pulmonary function of participants.
Measure: Oxygenation Index Time: Up to Day 56Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Measure: Number of Participants With Adverse Events Time: Up to Day 56Description: Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure: Number of Participants With Abnormal Laboratory Findings Time: Up to Day 56157 A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease
This is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. Otilimab is a human monoclonal anti-GM-CSF antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of patients with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.
NCT04376684 Severe Acute Respiratory Syndrome Biological: Otilimab Biological: Placebo Drug: Standard of care MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections
Primary Outcomes
Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 28 Time: Day 28Secondary Outcomes
Description: Number of deaths due to all causes will be assessed.
Measure: Number of deaths due to all causes at Day 60 Time: Day 60Description: Time to death due to all causes will be assessed.
Measure: Time to number of deaths due to all causes at Day 60 Time: Day 60Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 7 Time: Day 7Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 14 Time: Day 14Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 42 Time: Day 42Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 60 Time: Day 60Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Time to recovery from respiratory failure Time: Day 28Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 7 Time: Day 7Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 14 Time: Day 14Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 28 Time: Day 28Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 42 Time: Day 42Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 60 Time: Day 60Description: Time will be recorded from dosing to last dependence on supplementary oxygen. Participants are dependent on supplementary oxygen if they are in category 4 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Time to last dependence on supplementary oxygen Time: Day 28Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.
Measure: Proportion of participants admitted to Intensive Care Unit (ICU) Time: Day 28Description: Defined as the time from dosing to when the participant is discharged from the ICU.
Measure: Time to final Intensive Care Unit (ICU) discharge Time: Day 28Description: Time from dosing to when a participant is discharged from the hospital.
Measure: Time to final hospital discharge Time: Day 28Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence, that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.
Measure: Number of participants with Adverse events (AEs) and Serious adverse events (SAEs) Time: Up to Day 60158 A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.
NCT04377620 COVID-19 Drug: Placebo Drug: Ruxolitinib
Primary Outcomes
Description: To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.
Measure: Proportion of participants who have died due to any cause Time: Up to Day 29Secondary Outcomes
Description: Number of days participant did not require mechanical ventilation
Measure: Number of Ventilator free days Time: Day 29Description: Number of days participant is out of the ICU
Measure: Number of ICU free days Time: Day 29Description: Number of days participant did not receive supplemental oxygen
Measure: Oxygen free days Time: Day 29Description: Number of days without use of vasopressor therapy
Measure: Vasopressor free days Time: Day 29Description: Number of days Partcipant is out of the hospital
Measure: Hospital free days Time: Day 29Description: Clinical status of participant at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Measure: Improvement in the COVID-19 ordinal scale Time: Day 15 and 29Description: SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems.
Measure: Change in SOFA Score Time: from baseline to Days 3, 5, 8, 11, 15, and 29Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Measure: Number of treatment-related adverse events Time: Day 29159 A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Ciclesonide Metered-Dose Inhaler in Non-hospitalized Patients 12 Years of Age and Older With Symptomatic COVID-19 Infection
The purpose of this study is to assess the safety and efficacy of Alvesco (ciclesonide) Inhalation Aerosol in non hospitalized patients with symptomatic COVID-19 infection in a multicenter, randomized, double-blind, placebo controlled study
NCT04377711 COVID-19 Drug: Ciclesonide Drug: Placebo
Primary Outcomes
Measure: Percentage of patients hospital admission or death by day 30 Time: Day 30Secondary Outcomes
Measure: All-cause mortality by day 30 Time: Day 30Measure: COVID-19-related mortality by day 30 Time: Day 30
Measure: Percentage of patients with subsequent emergency department visit or hospital admission for reasons attributable to COVID 19 by day 30 Time: Day 30
Measure: Time to hospital admission or death Time: Day 30
Measure: Time to alleviation of COVID-19-related symptoms of cough, dyspnea, chills, and feeling feverish, defined as symptom-free for a continuous period of more than 24 hours (ie, > 3 AM/PM assessments) Time: Day 30
Measure: Change from baseline in oxygen saturation levels Time: Day 30
Measure: Change from baseline in COVID-19 viral load in nasopharyngel sample nasal secretions at day 30 Time: Day 30
Measure: Safety will be assessed based on adverse events. Time: Day 60
160 A Prospective, Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19
At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood. Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.
NCT04379271 COVID-19 Drug: IMU-838 Other: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Description: Clinical
Measure: Proportion of patients without any need* for INV until end-of-study (EoS) Time: Throughout the Study (Day 0 to Day 28)Secondary Outcomes
Description: Key Secondary
Measure: Duration of ICU treatment until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Key Secondary
Measure: 28-day all-cause mortality Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy: defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9 category ordinal scale , or live discharge from hospital without oxygen supplementation, whichever comes first
Measure: Time to clinical improvement Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy: Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)
Measure: Duration of hospitalization Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients both for all patients and surviving patients free of renal-replacement therapy (RRT)* until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)* until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients free of INV until Days 6 and 14* Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients free of RRT until Days 6 and 14* Time: Day 0 to Days 6 and 14Description: Efficacy
Measure: Proportion of patients free ECMO until Days 6 and 14* Time: Day 0 to Days 6 and 14Description: Efficacy
Measure: Proportion of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Proportion of patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Proportion of patients with clinical recovery: Axillary temperature ≤36.6 ℃, or oral temperature ≤37.2 ℃, or rectal or tympanic temperature ≤37.8 ℃; Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical recovery: Respiratory frequency ≤24 times/min without oxygen inhalation; and Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical recovery: Oxygen saturation ≥98% without oxygen inhalation Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Duration of INV Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Duration of ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of RRT Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of auxiliary oxygen therapy (including all types of oxygen therapy) Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of hospitalization for survivors Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: The rate of ICU* admission on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Hospital-free days Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time from IMP treatment initiation to death Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of INV Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of RRT Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of INV, RRT, and ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to ICU admission Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Cumulative dose of vasoactive therapies and days with vasoactive therapies (daily until Day 14) Time: Day 0 to day 14Description: Efficacy
Measure: Time to clinical recovery Time: Throughout the Study (Day 0 to Day 28)Description: Pharmacokinetics
Measure: Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28 Time: on Days 0, 1, 2, 3, 6, 14, and 28Description: Pharmacokinetics
Measure: Correlation of trough levels (quartiles) to selected clinical outcomes (Clinical improvement accoding to WHO criteria) Time: on Days 0, 1, 2, 3, 6, 14, and 28Description: Safety
Measure: Adverse events (AEs) and serious AEs Time: Throughout the Study (Day 0 to Day 28)Description: Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: height Time: only at ScreeningDescription: Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: weight Time: Throughout the Study (Day 0 to Day 28)Description: Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: body temperature (ºC) Time: Throughout the Study (Day 0 to Day 28)Description: Safety Pulse must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: pulse rates, Time: Throughout the Study (Day 0 to Day 28)Description: Safety Blood pressure (systolic and diastolic) must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: systolic and diastolic blood pressures Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: blood chemistry Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: hematology Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: urinalysis Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: 12-lead electrocardiogram: heart rate Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: PQ-interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: QRS-interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: QT interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: the heart rate-corrected QTc interval (according to Bazett's formula) Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: Temperature Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: D-dimer Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Lactate dehydrogenase (LDH) Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: C-reactive protein Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Troponin I Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Procalcitonin Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Correlation of disease markers to selected clinical outcomes (Clinical improvement accoding to WHO criteria) Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Decrease of SARS-CoV-2 viral load Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Qualitative virologic clearance in spontaneous sputum and nasopharyngeal swab samples (= 2 consecutive negative SARS-CoV-2 reverse transcriptase polymerase chain reaction tests at least 24 hours apart) Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Rate of conversion to a negative SARS-CoV-2 (qualitative) test on Days 6, 14 and 28 Time: on Days 6, 14 and 28Description: Virologic markers
Measure: Time to conversion to a negative SARS-CoV-2 (qualitative) test Time: Throughout the Study (Day 0 to Day 28)Description: Biomarkers
Measure: Interleukin (IL)-17 Time: Day 0, 6, 14 and Day 28Description: Biomarkers
Measure: Interleukin (IL)-1ß Time: Day 0, 6, 14 and Day 28Description: Biomarkers
Measure: Interleukin (IL)-6 Time: Day 0, 6, 14 and 28Description: Biomarkers
Measure: interferon gamma (IFNγ) Time: Day 0, 6, 14 and 28Description: Biomarkers
Measure: tumor necrosis factor alpha Time: Day 0, 6, 14 and 28Description: Serologic markers
Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Time to appearance of IgA and/or IgG antibodies Time: Day 0, 6, 14 and 28Description: Serologic markers
Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Proportion of patients with IgA and/or IgG antibodies on Days 6, 14, and 28 Time: Day 0, 6, 14 and 28161 Single-center, Phase II, Randomized Double-blind, Placebo-controlled Study of Hydroxychloroquine Compared to Placebo as Treatment for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection
This study is being done to see if hydroxychloroquine is an effective treatment for COVID-19.
NCT04379492 COVID-19 COVID19 Sars-CoV2 SARS-Cov-2 Drug: Hydroxychloroquine Other: Placebo
Primary Outcomes
Description: Clinical improvement is defined as a composite endpoint of a two-point clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19
Measure: Clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI) Time: 14 daysDescription: Clinical improvement is defined as no mechanical ventilation for respiratory failure attributed to SARS-CoV-2 within 14 days of randomization.
Measure: Number of participants requiring mechanical ventilation for respiratory failure Time: 14 days162 An International, Multicenter, Randomized, Double-blind, Adaptive Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe SARS-CoV-2 Infection (COVID-19)
The primary objective of the study is to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study
NCT04380519 COVID-19 Biological: RPH-104 80 mg Drug: Olokizumab 64 mg Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Proportion of patients, responded to the study therapy, in each of the treatment groups. The patient can be considered as the therapy responder, in case tocilizumab or sarilumab were not administered and there is an improvement of a clinical status at least by 1 point on a 6-points COVID-19 scale, where 1 point means most favorable outcome, 6 points means most undesirable outcome.
Measure: Proportion of patients, responded to the study therapy, in each of the treatment groups Time: Day 15Secondary Outcomes
Description: Changes of patients' clinical status on a 6 points ordinal scale over time
Measure: Changes of patients' clinical status on a 6 points ordinal scale over time Time: from Day 2 until Day 15, Day 29Description: Mortality rate over the follow-up period
Measure: Mortality rate over the follow-up period Time: from Day 1 until Day 29Description: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.
Measure: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration. Time: on screening and then from Day 1 until Day 29Description: Proportion of patients received tocilizumab or sarilumab due to COVID-19
Measure: Proportion of patients received tocilizumab or sarilumab due to COVID-19 Time: from Day 1 until the Day 29Other Outcomes
Description: Proportion of patients having National Early Warning Score 2 (NEWS2) of ≤ 4 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 4 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 2 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 2 maintained for two consecutive days Time: from day 1 until day 15Description: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, CRP, ferritin (if applicable), D-dimer (if applicable)
Measure: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable) Time: Day 2, Day 3, Day5, Day 7, Day 15Description: Mortality during an ICU stay, on days 7, 15, 29 of the study
Measure: Mortality during an ICU stay, on days 7, 15, 29 of the study Time: On Day 7, Day 15, Day 29Description: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days
Measure: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days Time: from Day 2 until Day 15Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period
Measure: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period Time: On Day 1 and from Day 2 until Day 15Description: Duration of ICU stay measured in days
Measure: Duration of ICU stay measured in days Time: from Day 2 until Day 15Description: Changes from baseline (if applicable) in severity of ARDS according to WHO criteria
Measure: Changes from baseline (if applicable) in severity of Acute Respiratory Distress Syndrome (ARDS) according to World Health Organization (WHO) criteria Time: from Day 1 until Day 15Description: Duration of mechanical ventilation and EMO (if applicable) measured in days
Measure: Duration of mechanical ventilation and Extracorporeal Membrane Oxygenation (EMO) (if applicable) measured in days Time: from Day 2 until Day 15Description: Duration of oxygen support (if applicable) measured in days
Measure: Duration of oxygen support (if applicable) measured in days Time: from Day 1 until Day 15Description: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 4 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 4 maintained for two consecutive days Time: from day 1 until day 15Description: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)
Measure: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable) Time: On Day 1 and from Day 2 until Day 15Description: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)
Measure: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable) Time: from day 1 until day 15Description: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study Time: from Day 1 until Day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable Time: from Day 1 until Day 29Description: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)
Measure: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable) Time: from Day 1 until Day 29163 Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical COVID-19 Disease
The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.
NCT04380961 Severe or Critical Confirmed Coronavirus Disease (COVID)-19 Drug: Sirukumab Drug: Placebo Other: Standard of Care (SOC) MeSH:Coronavirus Infections
Primary Outcomes
Description: Time to improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale. The 6-point ordinal clinical recovery scale provides 6 mutually exclusive conditions ordered from best to worst, and the score reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are : not hospitalized (category 1); Hospitalization; not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO (category 5); death (category 6).
Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale Time: Up to Day 28Secondary Outcomes
Description: Percentage of participants with an improvement of at Least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.
Measure: Percentage of Participants with an Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28 Time: Day 28Description: Percentage of participants with all-cause mortality will be reported.
Measure: Percentage of Participants with All-cause Mortality Time: Up to Day 28Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Measure: Percentage of Participants with Serious Adverse Events (SAEs) Time: Up to Day 28Description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
Measure: Percentage of Participants with Related Adverse Events Time: Up to Day 28Description: Percentage of participants with severe or life-threatening, bacterial, invasive fungal, viral or opportunistic infections (other than severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) will be reported.
Measure: Percentage of Participants with Severe or Life Threatening Bacterial, Invasive Fungal, Viral or Opportunistic Infections Time: Up to Day 28Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) neutropenia will be reported.
Measure: Percentage of Participants with Grade 3 and 4 Neutropenia Time: Up to Day 28Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) lymphocytopenia will be reported.
Measure: Percentage of Participants with Grade 3 and 4 Lymphocytopenia Time: Up to Day 28Description: Percentage of participants with increased ALT >=3 times ULN combined with increased bilirubin >2 times ULN (up to Day 28) will be reported.
Measure: Percentage of Participants with Increased Alanine Aminotransferase (ALT) Greater than or equal to 3 Times Upper Limit of Normal (ULN) Combined with Increased Bilirubin > 2 Times ULN Time: Up to Day 28Description: Time to improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale will be reported.
Measure: Time to Improvement of at least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale Time: Up to Day 28Description: Percentage of participants with an improvement of at Least 1 category relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.
Measure: Percentage of Participants with an Improvement of at Least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28 Time: Day 28Description: Time from study intervention to end of oxygen supplementation is defined as achieving category 1 or 2 on the 6-point ordinal clinical recovery scale.
Measure: Time from Study Intervention to end of Oxygen Supplementation Time: Up to Day 28Description: Time from study intervention to hospital discharge among the surviving participants will be reported.
Measure: Time from Study Intervention to Hospital Discharge Among the Surviving Participants Time: Up to Day 28Description: Total length of hospitalization (days from admission to hospital discharge) among the surviving participants will be reported.
Measure: Total Length of Hospitalization Time: Up to Day 28Description: Number of Ventilation free Days will be reported.
Measure: Number of Ventilation Free Days Time: Up to Day 28Description: Participant's clinical status at Day 7, 14, 21, 28 will be assessed by 6-point ordinal clinical recovery scale.
Measure: Participant's Clinical Status at Day 7, 14, 21, 28 as Assessed by 6-Point Ordinal Clinical Recovery Scale Time: Day 7, 14, 21, 28Description: Total time on invasive mechanical ventilation will be reported.
Measure: Total Time on Invasive Mechanical Ventilation Time: Up to Day 28Description: Percentage of participants with a worsening of at least 1 category on the 6-point ordinal clinical recovery scale over time (between Day 5 and Day 28) will be reported.
Measure: Percentage of Participants with a Worse Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale over Time Time: From Day 5 up to Day 28Description: Percentage participants on ECMO over time will be reported.
Measure: Percentage of Participants on Extracorporeal Membrane Oxygenation (ECMO) Over Time Time: Up to Day 28Description: Total time on ECMO will be reported.
Measure: Total Time on ECMO Time: Up to Day 28Description: Percentage of alive participants at Day 28, Week 8 and Week 16 will be reported.
Measure: Percentage of Alive Participants at Day 28, Week 8 and Week 16 Time: Day 28, Week 8 and Week 16Description: Percentage of alive participants that required readmission (if previously discharged) at Week 8 and Week 16 will be reported.
Measure: Percentage of Alive Participants that Required Readmission at Week 8 and Week 16 Time: Week 8 and Week 16Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Measure: Percentage of Participants with Serious Adverse Events (SAEs) Time: Up to Week 16164 A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.
NCT04381052 COVID-19 Drug: Clazakizumab Other: Placebo MeSH:Infection
Primary Outcomes
Measure: Cumulative incidence of serious adverse events associated with clazakizumab or placebo Time: 60 daysSecondary Outcomes
Measure: Cumulative Incidence of Intubation Time: 14 daysMeasure: Time to Extubation Time: 14 days
Measure: Length of Intensive Care Unit (ICU) stay Time: 14 days
Measure: Number of Patients who Present a Decrease in C-reactive protein (CRP) Time: 14 days
Measure: Number of Patients with Acute Kidney Injury (AKI) Time: 14 days
Measure: Number of Patients with a Need for Renal Replacement Therapy (RRT) Time: 14 days
Measure: Duration of Renal Replacement Therapy (RRT) Time: 60 days
Description: Number of participants alive at day 28.
Measure: Patient Survival Time: 28 daysDescription: Number of participants alive at day 60, end of study.
Measure: Patient Survival Time: 60 daysMeasure: Number of Patients with Hemodialysis Time: 60 days
Measure: Number of Patients with Continuous Renal Replacement Therapies (CRRT) Time: 60 days
Measure: Number of Patients with Peritoneal Dialysis Time: 60 days
165 A Multi-centre, Adaptive, Randomized, Double-blind, Placebo-controlled Comparative Clinical Study of the Safety and Efficacy of Polyoxidonium®, Lyophilizate for Solution for Injections and Topical Application, 6 mg (NPO Petrovax Pharm LLC, Russia) in Patients With Coronavirus Disease (COVID-19).
The purpose of this study is to demonstrate the superiority of Polyoxidonium®, lyophilizate for solution for injections and topical application, 6 mg over placebo in hospitalized patients with coronavirus disease (COVID-19). This is a multicentre prospective, randomized, double-blind, placebo-controlled, parallel-group phase IIb\IIIa clinical trial.
NCT04381377 Infections, Coronavirus Drug: azoximer bromide Other: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Description: The primary efficacy outcome will be defined based on the blinded analysis of data of the first 100 patients in the 1st part of the study. There is uncertainty about the clinical course and potential different trajectories according to baseline disease severity, so the day of the primary endpoint may be modified based on a blinded evaluation of the primary efficacy outcome in various days.
Measure: Clinical status of the patient (according to 7-point ordinal scale) Time: Day 15Secondary Outcomes
Description: Time to improvement by one category from admission on the ordinal scale. Clinical status of the patient. Average change in the ordinal scale from baseline.
Measure: Clinical status of the patient (according to 7-point ordinal scale) Time: Clinical status of the patient and the average change in the ordinal scale from baseline, both on days 3, 5, 8, 11, 29.Description: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Change in NEWS from baseline.
Measure: NEWS Time: Change in NEWS from baseline on days 3, 5, 8, 11, 15, 29.Description: Oxygenation free days. Incidence and duration of new oxygen use.
Measure: Oxygenation Time: Oxygenation free days in the first 28 days (to day 29). Incidence and duration of new oxygen use during the study.Description: Ventilator free days. Incidence and duration of new mechanical ventilation use.
Measure: Mechanical Ventilation Time: Ventilator free days in the first 28 days (to day 29). Incidence and duration of new mechanical ventilation use during the trial.Measure: Mortality Time: 28-day mortality
166 A Phase II Randomized Double-Blind Placebo-Controlled Clinical Trial Of Hydroxychloroquine For Prophylaxis Against Covid-19 In Patients Receiving Radiotherapy (COVID)
The researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.
NCT04381988 COVID-19 Cancer Drug: Hydroxychloroquine Other: Placebo Radiation: Radiation therapy
Primary Outcomes
Description: Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint.
Measure: cumulative incidence of SARS-CoV-2 infection Time: within 9 weeks from randomizationSecondary Outcomes
Description: Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19.
Measure: cumulative incidence of severe COVID-19 or death Time: within 12 weeks of randomization167 A Phase II, Controlled Clinical Study Designed to Evaluate the Effect of ArtemiC in Patients Diagnosed With COVID-19
Agent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.
NCT04382040 COVID-19 Corona Virus Infection SARS-CoV 2 Coronavirus Coronavirus Infection Drug: ArtemiC Drug: Placebo MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: patient will be assessed using a scoring table for changes in clinical signs
Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of Time: 24 hoursDescription: Adverse events caused by the study drug will be assessed
Measure: Percentage of participants with definite or probable drug related adverse events Time: 14 daysSecondary Outcomes
Measure: Time to negative COVID-19 PCR Time: 14 daysMeasure: Proportion of participants with normalization of fever and oxygen saturation through day 14 since onset of symptoms Time: 14 days
Measure: COVID-19 related survival Time: 14 days
Measure: Incidence and duration of mechanical ventilation Time: 14 days
Measure: Incidence of Intensive Care Init (ICU) stay Time: 14 days
Measure: Duration of ICU stay Time: 14 days
Measure: Duration of time on supplemental oxygen Time: 14 days
168 A Phase 2, Randomized, Double Blind, Placebo-Controlled Study of Zanubrutinib Treatment in Patients Hospitalized for COVID-19 Infection and Pulmonary Distress
The primary objective of this study is to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress.
NCT04382586 COVID-19 Pulmonary Complications COVID-19 Drug: Zanubrutinib Drug: Supportive Care Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Respiratory failure-free survival rate 28 is defined as the proportion of patients who have not had respiratory failure nor died <= 28 days from randomization.
Measure: Respiratory failure-free survival rate at day 28 Time: 28 DaysSecondary Outcomes
Measure: Median reduction in days spent on supplemental oxygen Time: Up to 28 DaysMeasure: All-cause mortality Time: Up to 28 Days
Measure: Proportion of participants experiencing respiratory failure or death Time: Up to 28 Days
Measure: Mechanical ventilation-free survival Time: Up to 28 Days
Measure: Days on mechanical ventilation Time: Up to 28 Days
Measure: Duration of hospitalization Time: Up to 28 Days
Measure: Time to discharge Time: Up to 28 Days
Measure: PaO2:FiO2 and/or oxygenation index Time: Up to 28 Days
Description: This scale evaluates the safety and efficacy of investigational therapeutic agents in combination with care for the treatment of hospitalized participants suffering from COVID-19 infections on a scale of scores from 0 to 8, with higher scores indicating higher level of severity of the disease. (0 = No clinical or virological evidence of disease, and 8 = Death)
Measure: Change from Baseline to Day 14 in WHO - 8 Point Ordinal Scale Time: Up to 28 Days169 A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Complement C5 Inhibition With Zilucoplan® in Improving Oxygenation and short-and Long-term Outcome of COVID-19 Patients With Acute Hypoxic Respiratory Failure
The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury. Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.
NCT04382755 COVID-19 Drug: Zilucoplan® Drug: Placebo MeSH:Respiratory Insufficiency
Primary Outcomes
Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Mean change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Median change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Secondary Outcomes
Measure: number of AE's (Adverse Events) Time: during hospital admission (up to 28 days)Measure: number of SAE's (Serious Adverse Events) Time: during hospital admission (up to 28 days)]
Description: 6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: mean change in 6-point ordinal scale change Time: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).Description: defined as independence from supplemental oxygen
Measure: Time since randomization until improvement in oxygenation Time: during hospital admission (up to 28 days)Description: defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen
Measure: Number of days with hypoxia Time: during hospital admission (up to 28 days)Measure: Number of days of supplemental oxygen use Time: during hospital admission (up to 28 days)
Measure: Time to absence of fever (defined as 37.1°C or more) for more than 48h without antipyretic Time: during hospital admission (up to 28 days)
Description: defined as 37.1°C or more
Measure: Number of days with fever Time: during hospital admission (up to 28 days)Measure: Mean change in CRP levels between day 1 and day 6 Time: day 1, day 6
Measure: Mean change in CRP levels between day 1 and day 15 (or discharge whichever comes first) Time: day 1, day 15
Measure: Mean change in ferritin levels between day 1 and day 6 Time: day 1, day 6
Measure: Mean change in ferritin levels between day 1 and day 15 (or discharge, whichever comes first) Time: day 1, day 15
Measure: Incidence of AE's Time: during hospital admission (up to 28 days)
Measure: Incidence of SAE's Time: at 10-20 weeks follow-up
Measure: Incidence of SUSAR's (Suspected Unexpected Serious Adverse Reaction) Time: during hospital admission (up to 28 days)
Measure: Incidence of SAR's (Serious Adverse Reaction) Time: during hospital admission (up to 28 days)
Measure: Duration of hospital stay Time: during hospital admission (up to 28 days)
Measure: Duration of hospital stay in survivors Time: during hospital admission (up to 28 days)
Description: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 6 (or on discharge, whichever is first) Time: day 1, day 6 or on discharge, whichever is firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 15 or on discharge, whichever is first) Time: day 1, day 15 or on discharge, whichever is firstDescription: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale at randomization, day 6 and 15 (or discharge, whichever comes first) and day 28 (phone call) Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: 6-point Ordinal Scale at 6 and 15 days (or discharge whichever comes first) and day 28 (phone call), in relation to serum D-dimers and complement C5a levels at randomization Time: day 1, day 6, day 15 (or discharge, whichever comes first)Measure: Incidence of nosocomial bacterial or invasive fungal infection for 28 days (phone call) after enrolment in trial Time: day 28
Measure: Time since randomization until first use of high-flow oxygen devices in non-ventilated patients Time: during hospital admission (up to 28 days)
Measure: Time since randomization until first use of non-invasive mechanical ventilation in non-ventilated patients Time: during hospital admission (up to 28 days)
Measure: Time since randomization until first use of invasive mechanical ventilation in non-ventilated patients Time: during hospital admission (up to 28 days)
Measure: Number of ventilator-free days Time: day 1, day 28 or discharge whichever comes first
Measure: Duration of invasive and non-invasive mechanical ventilation in ventilated patients Time: during hospital admission (up to 28 days)
Measure: Duration of ICU stay in patients that enrolled in trial on invasive or non-invasive mechanical ventilation for less than 24h prior to or after randomization Time: during hospital admission (up to 28 days)
Description: criteria-defined ARDS criteria-defined ARDS according to the adapted Berlin criteria as follow: within 1 week of a known Clinical insult or new or worsening respiratory symptoms bilateral infiltrates not supposed to be of cardiac origin or fluid overload PaO2/FiO2 < 300 mmHg
Measure: Time since randomization to progression to ARDS (Acute Respiratory Distress Syndrome) Time: during hospital admission (up to 28 days)Measure: Time to progression to ARDS in ventilated patients according to D-dimers at randomization Time: during hospital admission (up to 28 days)
Measure: Time to progression to ARDS in ventilated patients according to complement C5a at randomization Time: during hospital admission (up to 28 days)
Measure: All-cause mortality rate (excluding group that entered during ventilation) Time: at day 28
Measure: All-cause mortality rate (including group that entered during ventilation) Time: at day 28
Measure: Percentage of patients in clinical status on 6-point Ordinal Scale Time: at 12-22 weeks follow-up
Measure: Incidence of lung function abnormalities at follow up Time: at 12-22 weeks follow-up
Measure: Incidence of lung fibrosis on chest CT scan at follow up Time: at 12-22 weeks follow-up
Measure: All cause mortality for the entire study population Time: at follow up 12-22 weeks
170 Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria
A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.
NCT04383535 SARS Virus SARS-CoV-2 COVID-19 Other: Convalescent SARS COVID-19 plasma Other: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 30th day Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary Outcomes
Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 7th day Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 14th day Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Description: Hospital discharge or intrahospital death
Measure: Time until hospital discharge (days). Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission
Description: ICU discharge or ICU death
Measure: Time until discharge from ICU (days) Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission
Description: Death and time to death
Measure: Time to death Time: In a 30 days follow up period
Description: Time until complete functional recovery (according to basal status).
Measure: Time until complete functional recovery Time: Whenever the patient returns to basal functional status until 1 month from discharge
Description: Percentage of participants with adverse events / serious adverse events
Measure: Percentage of participants with adverse events / serious adverse events Time: In a 30 days follow up period
Description: Percentage of patients with negative SARS-CoV-3 PCR
Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Description: D Dimer plasma concentration
Measure: D Dimer plasma concentration at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Description: Ferritin plasma concentration
Measure: Ferritin plasma concentration at Day 13th Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 2nd Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 7th Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Description: Post-transfusion adverse reactions between study groups
Measure: Post-transfusion adverse reactions Time: In a 30 days follow up period
171 A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Organicell Flow for the Treatment of Moderate to SARS Related to COVID-19 Infection vs Placebo
Primary Outcomes
Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 30th day Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Secondary Outcomes
Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 7th day Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 14th day Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Hospital discharge or intrahospital death
Measure: Time until hospital discharge (days). Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admissionDescription: ICU discharge or ICU death
Measure: Time until discharge from ICU (days) Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admissionDescription: Death and time to death
Measure: Time to death Time: In a 30 days follow up periodDescription: Time until complete functional recovery (according to basal status).
Measure: Time until complete functional recovery Time: Whenever the patient returns to basal functional status until 1 month from dischargeDescription: Percentage of participants with adverse events / serious adverse events
Measure: Percentage of participants with adverse events / serious adverse events Time: In a 30 days follow up periodDescription: Percentage of patients with negative SARS-CoV-3 PCR
Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: D Dimer plasma concentration
Measure: D Dimer plasma concentration at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ferritin plasma concentration
Measure: Ferritin plasma concentration at Day 13th Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 2nd Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 7th Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Post-transfusion adverse reactions between study groups
Measure: Post-transfusion adverse reactions Time: In a 30 days follow up periodThe purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Organicell Flow for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.
NCT04384445 Corona Virus Infection COVID-19 SARS Acute Respiratory Distress Syndrome Biological: Organicell Flow Other: Placebo MeSH:Infection Corona Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
Primary Outcomes
Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician
Measure: Incidence of any infusion associated adverse events Time: 60 DaysDescription: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 60 DaysSecondary Outcomes
Description: Measured at day 60 or at hospital discharge, whichever comes first.
Measure: All Cause Mortality Time: 60 DaysDescription: Number of participants that are alive at 60 days post first infusion follow up
Measure: Survival Rate Time: 60 DaysDescription: Measure IL-6, IL-2, TNF-alpha from serum of blood samples
Measure: Cytokine Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab
Measure: D-dimer Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: CRP from serum of blood samples
Measure: C-reactive protein Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: Viral load by real time RT methodology using blood samples or nose / throat swab
Measure: Quantification of the COVID-19 Time: Day 0, Day 4, Day 8Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.
Measure: Improved Organ Failure Time: Day 30Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.
Measure: Chest Imaging Changes Time: Day o, Day 30172 A Randomised Double-blind Placebo-controlled Trial to Determine the Safety and Efficacy of Inhaled SNG001 (IFN-β1a for Nebulisation) for the Treatment of Patients With Confirmed SARS-CoV-2 Infection
SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.
NCT04385095 SARS-CoV-2 Drug: Interferon beta 1a Drug: Placebo MeSH:Infe Infection
Primary Outcomes
Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)
Measure: Ordinal Scale for Clinical Improvement Time: Day 1 to day 28Secondary Outcomes
Description: Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment
Measure: Progression to pneumonia Time: Day 2 to day 28Description: Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment
Measure: Progression to pneumonia Time: Day 1 to day 28Description: Time to clinical improvement
Measure: Time to clinical improvement Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hoursDescription: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)
Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity Time: Day 1 to day 28Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)
Measure: Changes in daily breathlessness, cough and sputum scale (BCSS) Time: Day 1 to day 28Description: Looking at blood pressure measured in mmHg
Measure: Safety and tolerability - blood pressure II. Viral load Time: Day 1 to day 28Description: Looking at heart rate measured in beats per minute
Measure: Safety and tolerability - heart rate II. Viral load Time: Day 1 to day 28Description: Looking at temperature measured in degrees Celsius
Measure: Safety and tolerability - temperature II. Viral load Time: Day 1 to day 28Description: Looking at respiratory rate measure in breaths per minute
Measure: Safety and tolerability - respiratory rate II. Viral load Time: Day 1 to day 28Description: Looking at oxygen levels measured in a %
Measure: Safety and tolerability - oxygen saturation II. Viral load Time: Day 1 to day 28Description: Looking at adverse events (numbers and terms)
Measure: Safety and tolerability - adverse events II. Viral load Time: Day 1 to day 28Description: Looking at concomitant medications given during treatment
Measure: Safety and tolerability - concomitant medications II. Viral load Time: Day 1 to day 28173 A Phase III, Double-blind, Randomized, Placebo-controlled Multicentre Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Healthcare Professionals' Absenteeism in the SARS-CoV-2 Pandemic by Modulating the Immune System
The aim of this study is to investigate whether vaccination of healthcare professionals with VPM1002 could reduce the number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection). VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the new corona virus "SARS-CoV 2". A total of 1200 health care professionals (doctors, nurses and paramedical staff) with high expected exposure to SARSCoV-2 infected patients will receive a single dose of either VPM1002 or Placebo. All subjects will be requested to enter data regarding absenteeism, adverse events / serious adverse events, hospitalizations, intensive care unit admissions into an online questionnaire.
NCT04387409 Infection, Respiratory Tract Biological: VPM1002 Biological: Placebo MeSH:Respiratory Tract Infections
HPO:Respiratory tract infection
Primary Outcomes
Measure: Number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection) Time: From day 0 to day 240
Secondary Outcomes
Measure: Cumulative incidence of documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Number of days absent from work due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Number of days absent from work due to exposure to person with documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Number of days absent from work due to symptoms of respiratory disease, documented SARS-CoV-2 infection, or fever (≥ 38 °C) Time: From day 0 to day 240
Measure: Number of days of self-reported fever (≥ 38 °C) Time: From day 0 to day 240
Measure: Number of days of self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of death for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of hospital admission for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of hospital admission due to documented SARS-CoV-2 infection Time: From day 0 to day 240
174 A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase II Study to Evaluate the Efficacy and Safety of Intramuscular Injections of PLX PAD for the Treatment of Severe COVID-19
Primary Outcomes
Measure: Number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection) Time: From day 0 to day 240Secondary Outcomes
Measure: Cumulative incidence of documented SARS-CoV-2 infection Time: From day 0 to day 240Measure: Number of days absent from work due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Number of days absent from work due to exposure to person with documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Number of days absent from work due to symptoms of respiratory disease, documented SARS-CoV-2 infection, or fever (≥ 38 °C) Time: From day 0 to day 240
Measure: Number of days of self-reported fever (≥ 38 °C) Time: From day 0 to day 240
Measure: Number of days of self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of death for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of hospital admission for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of hospital admission due to documented SARS-CoV-2 infection Time: From day 0 to day 240
This clinical trial will examine if a new treatment of Mesenchymal Stems Cells (called PLX-PAD) can help patients intubated and mechanically ventilated due to COVID-19 to recover more quickly with less complications.
NCT04389450 COVID ARDS Biological: PLX-PAD Biological: Placebo
Primary Outcomes
Measure: Number of ventilator free days Time: 28 daysSecondary Outcomes
Measure: All-cause mortality Time: 28 daysMeasure: Duration of mechanical ventilation Time: 8 weeks
175 A Phase 2/3 Study to Evaluate the Safety and Efficacy of Dociparstat Sodium for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure
A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
NCT04389840 COVID-19 Acute Lung Injury SARS-CoV-2 Drug: Dociparastat sodium Drug: Placebo MeSH:Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult
Primary Outcomes
Description: Alive and free of invasive mechanical ventilation
Measure: Proportion of participants who are alive and free of invasive mechanical ventilation Time: Through Day 28Secondary Outcomes
Description: Time to all-cause mortality
Measure: All-cause mortality Time: Through Day 28176 Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission
SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.
NCT04390022 Covid-19 Coronavirus Infection SARS-CoV-2 Infection Drug: Ivermectin Drug: Placebo MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment
Measure: Proportion of patients with a positive SARS-CoV-2 PCR Time: 7 days post-treatmentSecondary Outcomes
Description: Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab
Measure: Mean viral load Time: Baseline and on days 4, 7, 14 and 21Description: Proportion of patients with fever and cough at days 4, 7, 14 and 21 as well as proportion of patients progressing to severe disease or death during the trial
Measure: Fever and cough progression Time: Up to and including day 21Description: Proportion of participants with positive IgG at day 21
Measure: Seroconversion at day 21 Time: Up to and including day 21Description: Proportion of drug-related adverse events
Measure: Proportion of drug-related adverse events Time: 7 days post treatmentDescription: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay
Measure: Levels of IgG, IgM and IgA Time: Up to and including day 28Description: Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry
Measure: Frequency of innate immune cells Time: Up to and including day 7Description: Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry
Measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells Time: Up to and including day 7Description: Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher)
Measure: Results from cytokine Human Magnetic 30-Plex Panel Time: Up to and including day 28177 A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19
Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.
NCT04390139 COVID-19 SARS-CoV 2 Adult Respiratory Distress Syndrome Drug: XCEL-UMC-BETA Other: Placebo MeSH:Respiratory Distress Syndrome, Newborn Respi Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
Primary Outcomes
Description: Number of patients who died, by treatment group
Measure: All-cause mortality at day 28 Time: Day 28Secondary Outcomes
Description: Number of patients with treatment-emergent adverse events, by treatment group
Measure: Safety of WJ-MSC Time: Day 28Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group
Measure: Need for treatment with rescue medication Time: Day 28Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group
Measure: Need and duration of mechanical ventilation Time: Day 28Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.
Measure: Ventilator free days Time: Day 28Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.
Measure: Evolution of PaO2 / FiO2 ratio Time: Day 28Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.
Measure: Evolution of the SOFA index Time: Day 28Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.
Measure: Evolution of the APACHE II score Time: Day 28Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.
Measure: Duration of hospitalization Time: Day 28Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.
Measure: Evolution of markers of immune response (leucocyte count, neutrophils) Time: Day 28Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date
Measure: Feasibility of WJ-MSC administration Time: Day 28Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.
Measure: Feasibility of WJ-MSC administration Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: D-dimer Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: Ferritin Time: Day 28Other Outcomes
Description: Blood sample analysis
Measure: Analysis of subpopulations of lymphocytes and immunoglobulins Time: Day 28Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)
Measure: Evaluation of the in vitro response of the receptor lymphocytes Time: Day 28Description: Reactivity will be assessed using ELISPOT
Measure: Study of reactivity against SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis
Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis for the patient's genomic sequencing
Measure: Genetic variability of patient's genotype in response to treatment Time: Day 28Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample
Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment Time: Day 28178 A Phase 2 Study to Evaluate LB1148 for the Treatment of Pulmonary Dysfunction Associated With COVID-19 Pneumonia
This is a Phase 2, proof of concept, randomized, placebo-controlled, multicenter study to evaluate the ability of LB1148 to attenuate pulmonary dysfunction associated with COVID-19 pneumonia. The primary objective of this study is to determine if enteral administration of LB1148 will effect disease progression in hospitalized patients with moderate to severe COVID-19 via measurement of the proportion of subjects alive and free of respiratory failure at Day 28.
NCT04390217 COVID-19 Coronavirus Disease 2019 Covid19 COVID-19 Pneumonia Drug: LB1148 Drug: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: The proportion of subjects alive and free of respiratory failure at Day 28.
Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure. Time: 28 Days
Secondary Outcomes
Description: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)
Measure: Clinical status at fixed time points Time: Measured at 3, 5, 7, 8, 10, 14 and 28 Days
Description: Length of hospital stay (live discharge)
Measure: Duration of hospital stay Time: 28 Days
Description: Number and proportion of patients requiring admission to the intensive care unit
Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization Time: 28 Days
Description: Length of ICU stay
Measure: Duration of ICU stay Time: 28 Days
Description: Number and proportion of patients requiring invasive mechanical ventilation
Measure: Invasive mechanical ventilation requirements Time: 28 Days
Description: Length of time patients require invasive mechanical ventilation
Measure: Duration of invasive mechanical ventilation Time: 28 Days
Description: The number and proportion of patients deceased at Day 28
Measure: All-cause 28-day mortality Time: 28 Days
Description: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Measure: Safety and tolerability of LB1148 Time: 28 Days
179 Efficacy and Safety of Hydroxychloroquine and Ivermectin in Hospitalized no Critical Patients Secondary to COVID-19 Infection: Randomized Controlled Trial
Primary Outcomes
Description: The proportion of subjects alive and free of respiratory failure at Day 28.
Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure. Time: 28 DaysSecondary Outcomes
Description: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)
Measure: Clinical status at fixed time points Time: Measured at 3, 5, 7, 8, 10, 14 and 28 DaysDescription: Length of hospital stay (live discharge)
Measure: Duration of hospital stay Time: 28 DaysDescription: Number and proportion of patients requiring admission to the intensive care unit
Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization Time: 28 DaysDescription: Length of ICU stay
Measure: Duration of ICU stay Time: 28 DaysDescription: Number and proportion of patients requiring invasive mechanical ventilation
Measure: Invasive mechanical ventilation requirements Time: 28 DaysDescription: Length of time patients require invasive mechanical ventilation
Measure: Duration of invasive mechanical ventilation Time: 28 DaysDescription: The number and proportion of patients deceased at Day 28
Measure: All-cause 28-day mortality Time: 28 DaysDescription: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Measure: Safety and tolerability of LB1148 Time: 28 DaysBackground: In December 2019, patients with pneumonia secondary to a new subtype of Coronavirus (COVID-19) were identified in China. In a few weeks the virus spread and cases started practically all over the world. In February 2020, the WHO declared a pandemic. Severe symptoms have been found in patients mainly with comorbidities and over 50 years of age. At this time there is no proven therapeutic alternative. In vitro studies and observational experiences showed that antimalarial drugs (Chloroquine and hydroxychloroquine) had antiviral activity and increased viral clearance. Ivermectin, on the other hand, has been shown in vitro to reduce viral replication and in an observational cohort, greater viral clearance with promising clinical results. So far there is no standard of treatment and clinical trials are needed to find effective treatment alternatives. Objective: To evaluate the safety and efficacy of treatment with hydroxychloroquine and ivermectin for serious COVID-19 infections in no critical hospitalized patients. Material and methods: Randomized controlled trial of patients diagnosed with respiratory infection by COVID-19, who present criteria for hospitalization. Randomization will be performed to receive hydroxychloroquine at a dose of 400 mg every 12 hours for one day and then 200 mg every 12 hours, to complete a 5-day treatment schedule. Group 2: Ivermectin 12 mg every 24 hours for one day (less than 80 kg) or Ivermectin 18 mg every 24 hours for one day (greater than 80 kg) + placebo until the fifth day. Group 3: Placebo. Prior to randomization, the risk of cardiovascular complications determined by corrected QT interval, related to hydroxychloroquine intake will be assessed. If the patient is at high risk, the allocation will be to ivermectin only or to placebo in an independent randomization, if the risk is low, any of the three groups could be assigned. Outcomes: The primary outcome will be discharge from hospital for improvement. The safety outcomes will be requirement of mechanical intubation, septic shock or death. Viral clearance will also be evaluated by means of PCR, which will be taken on the 5th day after admission, day 14 and 21.
NCT04391127 COVID-19 Drug: Hydroxychloroquine Drug: Ivermectin Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Days from admission as a suspected case of COVID with hospitalization criteria until discharge
Measure: Mean days of hospital stay Time: Three monthsDescription: Respiratory deterioration defined by respiratory rate > 25 per minute, requirement of high oxygen supply (FiO2 > 80% ) to maintain oxygen saturation > 90 %, invasive mechanical ventilation or dead.
Measure: Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead Time: Three monthsDescription: Daily delta of oxygenation index during the hospitalization
Measure: Mean of oxygenation index delta Time: Three monthsSecondary Outcomes
Description: Mean time to viral negativization of RT-qPCR SARS-CoV-2. Pre Specified time: 5, 14, 21 and 28 days after the first positive PCR.
Measure: Mean time to viral PCR negativization Time: 5, 14, 21 and 28 days after the first positive PCR180 Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)
This is a multicenter, randomized, double-blind, placebo-controlled phase 2 study of IC14, an antibody to CD14, in reducing the severity of respiratory disease in hospitalized COVID-19 patients.
NCT04391309 SARS-CoV2 Biological: IC14 Other: Placebo
Primary Outcomes
Description: Days alive and free of any episodes of acute respiratory failure through Day 22 defined by need for high-flow nasal cannula, noninvasive positive-pressure ventilation, endotracheal intubation and mechanical ventilation, and extracorporeal membrane oxygenation
Measure: Acute respiratory failure Time: Day 1-22Secondary Outcomes
Description: Defined as time to the first day that a subject is in categories 6, 7, or 8 on the Eight-Point Ordinal Scale. The Eight-Point Ordinal Scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen—requiring ongoing medical care (COVID-19-related or otherwise); 6) Hospitalized, not requiring supplemental oxygen—no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to clinical improvement Time: Day 1-29Description: Proportion of patients alive and free of any episode of acute respiratory failure through Days 8, 15, 22, and 29
Measure: Acute respiratory failure Time: Days 1-8, 1-15, 1-22, 1-29Description: Proportion of patients alive and free of invasive mechanical ventilation through Days 8, 15, 22, and 29
Measure: Invasive mechanical ventilation Time: Days 1-8, 1-15, 1-22, 1-29Description: Days alive and free of acute respiratory failure through Days 15 and 29
Measure: Acute respiratory failure Time: Days 1-15 and 1-29Description: Days alive and free of invasive mechanical ventilation through Days 15, 22, and 29
Measure: Invasive mechanical ventilation Time: Days 1-15, 1-22, 1-29Description: Days alive and hospitalized through Day 29
Measure: Hospitalization Time: Days 1-29Description: Change in Sequential Organ Failure Assessment (SOFA) score (range 0 [best] to 24 [worst]) from baseline to Day 8, Day 15, and Day 22
Measure: Sequential Organ Failure Assessment Time: Days 1-8, 1-15, 1-22Description: Worst SOFA score from baseline to Day 22
Measure: Sequential Organ Failure Assessment Time: Days 1-22Description: Proportion of patients alive and discharged from the hospital at Days 15 and 29.
Measure: Hospitalization Time: Days 1-15, 1-29Description: Mean change in the eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29
Measure: Ordinal Scale Time: Days 1-29Description: Time to improvement in one category from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.
Measure: Time to clinical improvement Time: Days 1-29Description: Time to improvement in two categories from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.
Measure: Time to clinical improvment Time: Days 1-29Description: Time to recovery through Day 29. Day of recovery is defined as the first day on which the subject satisfies one of categories 6-8 from the ordinal scale.
Measure: Time to recovery Time: Days 1-29Description: Change in C-reactive protein in blood on Days 4 and 8 compared to baseline (from normal < 10 mg/L [normal] to >10 mg/L [worse])
Measure: Change in C-reactive protein Time: Day 4 compared to baseline; Day 8 compared to baselineDescription: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events
Measure: Adverse events Time: Days 1-60Description: Cumulative incidence of serious adverse events
Measure: Serious adverse events Time: Days 1-60181 A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of EIDD-2801 Following Oral Administration to Healthy Volunteers
This is a First In Human study designed to assess the safety, tolerability and pharmacokinetics of EIDD-2801 in healthy human volunteers.
NCT04392219 Coronavirus Drug: EIDD-2801 Drug: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Description: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of Single Ascending Dose (SAD) of EIDD-2801 (Part 1): Adverse Events Time: From screening through study completion, up to 15 daysDescription: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of Multiple Ascending Dose (MAD) of EIDD-2801 (Part 3): Adverse Events Time: From screening through study completion, up to 20 daysDescription: Multiple pharmacokinetic variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax
Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Doses (Part 2): Maximum observed concentration Cmax Time: Day 1 through Day 18Secondary Outcomes
Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax
Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Ascending Dose (SAD) (Part 1): Maximum observed concentration Cmax Time: Day 1 up to Day 4Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax
Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Multiple Ascending Dose (MAD) (Part 3): Maximum observed concentration Cmax Time: Day 1 up to Day 14Description: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of Single Doses of EIDD-2801 (Part 2): Adverse Events Time: From screening through study completion, up to 30 days182 A Phase 2/3, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ABX464 in Treating Inflammation and Preventing COVID-19 Associated Acute Respiratory Failure in Patients Aged ≥ 65 and Patients Aged ≥18 With at Least One Additional Risk Factor Who Are Infected With SARS-CoV-2.
A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).
NCT04393038 COVID-19 Drug: ABX464 Drug: Placebo MeSH:Respiratory Insufficiency Inflammation
Primary Outcomes
Measure: Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive Time: at the end of the 28-day treatment periodSecondary Outcomes
Measure: Rate of patients hospitalized Time: 28-day treatment periodDescription: 7-point ordinal scale is defined as Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death
Measure: Percentage of patients reporting each severity rating on a 7-point ordinal scale Time: 28-day treatment periodMeasure: Change from enrolment in inflammatory markers in plasma and in immune phenotype and assessment of cell-activation markers in PBMCs Time: at each study visit during the 28-day treatment period
Measure: Rate of patients requiring oxygen supplementation Time: 28-day treatment period
Measure: Time to hospitalization Time: 28-day treatment period
Measure: Time to assisted ventilation and oxygen supplementation Time: 28-day treatment period
Measure: Change from baseline in microRNA-124 levels Time: at each study visit during the 28-day treatment period
Measure: Change from baseline in CRP, Troponin I & T and D-dimer Time: at each study visit during the 28-day treatment period
Description: Nasopharyngeal sample and/or in blood
Measure: SARS-CoV-2 viral load Time: at each study visit during the 28-day treatment periodMeasure: Number and rates of participants with Treatment Emergent Adverse Event Time: 28-day treatment period
183 A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Ulinastatin for the Treatment of COVID-19 in Hospitalized Patients
The primary objective of this study is to evaluate the safety and efficacy of intravenous (IV) infusion of ulinastatin compared to placebo with respect to time to recovery, disease severity, need for ventilator support, and mortality in patients with COVID 19.
NCT04393311 COVID-19 Drug: Ulinastatin Drug: Placebo
Primary Outcomes
Description: Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities
Measure: Time to recovery Time: Up to 29 daysSecondary Outcomes
Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).
Measure: COVID-19 disease severity scale score on Day 8 Time: Day 8Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).
Measure: COVID-19 disease severity scale score on Day 15 Time: Day 15Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).
Measure: COVID-19 disease severity scale score on Day 22 Time: Day 22Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).
Measure: COVID-19 disease severity scale score on Day 29 Time: Day 29Measure: Incidence of mortality at Day 29 Time: 29 days
Measure: Incidence of in-hospital mortality Time: Up to 29 days
Measure: Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose Time: Up to 29 days
Measure: Number of patients with resolution of symptoms defined as score of 8 on the 8-point ordinal scale at Day 29 Time: Day 29
Measure: Number of patients alive and free of respiratory failure defined as score of 4, 5, 6, 7, or 8 on the 8-point ordinal scale at Day 29 Time: Day 29
Description: For patients requiring mechanical ventilation.
Measure: Duration of mechanical ventilation Time: Up to 29 daysDescription: For patients requiring mechanical ECMO.
Measure: Duration of ECMO Time: Up to 29 daysDescription: For patients requiring non-invasive ventilation
Measure: Duration of noninvasive ventilation Time: Up to 29 daysDescription: For patients admitted to ICU
Measure: Duration of ICU stay Time: Up to 29 daysMeasure: Duration of hospital stay Time: Up to 29 days
Measure: Change in oxygen saturation Time: Between screening and 24 hours after last dose (up to 11 days)
184 Trial of Silymarin in Adults With COVID-19 Pneumonia
A randomized placebo controlled trial to assess the clinical outcome in COVID-19 Pneumonia following administration of Silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and anti-oxidant effects
NCT04394208 COVID-19 Viral Pneumonia Human Coronavirus Drug: Silymarin Drug: Placebo MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.
Measure: Time to clinical improvement Time: 7-28 days
Secondary Outcomes
Description: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14
Measure: Clinical outcome Time: 7-14 days
Description: Time in days patient was intubated
Measure: Duration of Mechanical Ventilation Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days
Description: Total days of hospitalization
Measure: Hospitalization Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days
Description: number of days patient remained with positive RT-PCR SARS-CoV-2 swab
Measure: Virologic Response Time: Randomization till discharge, up to 28 days
Description: Any adverse events whether related to medication or not
Measure: Adverse events Time: Randomization till hospital discharge, up to 28 days
185 Combination With Inhibitor of Neutrophil Elastase (All-trans Retinoic Acid ) and Isotretinoin May Enhances Neutralizing Antibodies in COVID -19 Infected Patients Better Than COVID-19 Inactivated Vaccines
Primary Outcomes
Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.
Measure: Time to clinical improvement Time: 7-28 daysSecondary Outcomes
Description: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14
Measure: Clinical outcome Time: 7-14 daysDescription: Time in days patient was intubated
Measure: Duration of Mechanical Ventilation Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 daysDescription: Total days of hospitalization
Measure: Hospitalization Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 daysDescription: number of days patient remained with positive RT-PCR SARS-CoV-2 swab
Measure: Virologic Response Time: Randomization till discharge, up to 28 daysDescription: Any adverse events whether related to medication or not
Measure: Adverse events Time: Randomization till hospital discharge, up to 28 daysUnfortunately, All of the vaccinated monkeys treated with the Oxford vaccine known as ChAdOx1 nCoV-19, is undergoing trials in Britain.became infected when challenged as judged by recovery of virus RNA from nasal secretions," said Dr William Haseltine, a former Harvard Medical School professor who had a role in the development of early Aids treatments. and in general future COVID-19 vaccination which depends on inactivated viral vaccine will be restricted to healthy people with strong immunity and It will not be given to patients with History of contact with COVID-19 infection. In addition to the COVID-19 antigens with hyper mutation lead to (ADE) phenomenon in which IgG antibodies facilitate viral entry and fusion with infected cell through uptake of the virus-IgG complex via the Fc receptors and later viral fusion with antigen presenting cells like macrophages and B cells via FcR , through the neonatal FcR instead of antibodies induced viral agglutination and this is known as antibody dependent enhancement (ADE)(2) There are various hypotheses on how ADE happens and there is a likelihood that more than one mechanism exists. In one such pathway, some cells of the immune system lack the usual receptors on their surfaces that the virus uses to gain entry, but they have Fc R that bind to one end of antibodies. The virus binds to the antigen-binding site at the other end, and in this way gains entry to and infects the immune cell. Dengue virus can use this mechanism to infect human macrophages.(3) An ongoing question in the COVID-19 pandemic is whether—and if so, to what extent—COVID-19 receives ADE from prior infection with other COVID-19. ADE can hamper vaccine development, as a vaccine may cause the production of antibodies which, via ADE, worsen the disease the vaccine is designed to protect against. Vaccine candidates for Dengue virus and feline infectious peritonitis virus had to be stopped because they elicited ADE.(4) ADE in COVID-19 infection can be caused by high mutation rate of the gene that encodes spike (S) protein. A thorough analysis of amino acid variability in COVID-19 virus proteins, that included the S-protein, revealed that least conservative amino acids are in most exposed fragments of S-protein including receptor binding domain (RBD).(5) A study reported that Inhibitors of NET stimulate murine B lymphocyte differentiation into IgG- and IgA-producing cells via immunoglobulin class switching . A study demonstrated that depletion of NET improves the production of mucosal IgA and IgG after sublingual immunization with Bacillus anthracis edema toxin as adjuvant and also, another study demonstrated that extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19 and also reported that there is aberrant linking between NET formation and pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19. So,the principal investigator expects that High NETs in covid-19 infection may be the reason of delayed antibody response and severe complications.Currently, only limited information is available on the host innate immune status of COVID-19 infected patients. In one report where 99 cases in Wuhan were investigated, increased total NETs (38%), reduced total lymphocytes (35%) and increased serum IL-6 (52%) .25 In a separate report also from Wuhan, it revealed that in 41 patients, increased total NETs, decreased total lymphocytes in patients of ICU vs. non-ICU care were found to be statistically different. Increased NETs and decreased lymphocytes also correlate with disease severity .(10) B cells/plasma cells produce COVID-19 specific Abs that may help neutralize viruses.(11) Humoral immune response, especially production of neutralizing antibody, plays a protective role by limiting infection at later phase and prevents reinfection in the future. In Covid-19, both T and B cell epitopes were extensively mapped for the structural proteins, S, N, M and E protein.(12) ,(14) Delayed antibodies response and secretion after covid -19 symptoms onset may be responsible for antibody dependent enhancement (ADE) Because this immune response takes a while to show up, antibody tests will be negative for those newly infected with COVID-19, which is why they're not used for diagnosis. "If it's the beginning of the infection, you don't pick it up, it's something that only develops later," Dr. Melanie Ott, a virologist at the Gladstone Institutes Finally, according to this protocol the investigator will treat with potent inhibitor of NET elastase plus Isotretinoin and the mechanism of action will be discussed in Detailed Description
NCT04396067 COVID -19 Drug: Aerosolized 13 cis retinoic acid Drug: Aerosolized All trans retinoic acid Other: Placebo
Primary Outcomes
Description: Proportion of lung injury score decreased or increased after treatment
Measure: lung injury score Time: at 7 daysSecondary Outcomes
Description: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon
Measure: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon Time: at day 7 and 14 after randimizationDescription: Serum level of COVID19 RNA
Measure: Serum level of COVID19 RNA Time: at day 7 and 14Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample
Measure: d-dimers Time: within 14 daysDescription: lymphocyte counts
Measure: Absolute lymphocyte counts Time: at day 7 and 14 after randimizationDescription: To determine the immune correlates of viral clearance (Antibody Titres sufficient for viral clearance and neutralizing ) against future exposure to SARS-CoV-2
Measure: The immune correlates of protection against future exposure to SARS-CoV-2 Time: within 14 daysDescription: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes
Measure: Immunological profile Time: within 14 daysMeasure: Total duration of mechanical ventilation, ventilatory weaning and curarisation Time: at day 7 and 14
Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)
Measure: Occurrence of adverse event related to immunoglobulins Time: at day 14Description: serum levels of IgG and IgM against COVID-19
Measure: IgG, IgA and IgM against COVID-19 Time: at day 7 and 14Description: ACE2 expression in patients with COVID-19 infection
Measure: ACE2 expression in patients with COVID-19 infection Time: at day 7 and 14Measure: All cause mortality rate [ Time: at day 7 and 14
Measure: Ventilation free days Time: at 14 days
Measure: ICU free days Time: at 14 days
186 A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-527 in Subjects With Moderate COVID-19
The objectives of this study are to evaluate the safety, tolerability and efficacy of AT-527 in older subjects (ages 45-80 years) with moderate COVID-19 and risk factors for poor outcomes (such as obesity (BMI>30), hypertension, diabetes or asthma). Eligible subjects will be randomized to blinded AT-527 (nucleotide analog) tablets or matching placebo tablets to be administered orally for 5 days. Local supportive standard of care (SOC) will be allowed for all subjects. Efficacy and safety observations will be compared for treatment with active AT-527 tablets + SOC vs. placebo tablets + SOC.
NCT04396106 COVID-19 Drug: AT-527 Other: Placebo
Primary Outcomes
Description: Progressive respiratory insufficiency defined as a ≥ 2-tier increase in respiratory support methods required to maintain satisfactory oxygenation (SpO2 ≥ 93%), using the 6-tier hierarchical scale of respiratory support methods
Measure: Proportions (active vs. placebo) of subjects with progressive respiratory insufficiency. Time: Day 14Measure: Proportions (active vs. placebo) of subjects experiencing treatment-emergent adverse events Time: Day 14
Secondary Outcomes
Description: Clinical recovery defined as time from randomization to disease resolution status on an 8 point Clinical Status scale
Measure: Time to clinical recovery Time: Day 14Measure: Proportions (active vs. placebo) of subjects with respiratory failure or death Time: Day 28
187 Safety and Efficacy of Post-exposure Prophylaxis With Hydroxychloroquine (HCQ) for the Prevention of COVID-19 in High-risk Older Individuals in Long-term and Specialized Care: A Double-blind Randomized Control Trial
Older adults are at the highest risk of complications and severe illness for 2019-nCoV infections. Hydroxychloroquine (HCQ), an emerging chemoprophylaxis, which holds clinical and mechanistic plausibility, will help to reduce disease incidence and mitigate disease severity across in-patient settings. This study is designed to assess the safety and efficacy of post-exposure prophylaxis with hydroxychloroquine (HCQ) for the prevention of Coronavirus Infectious Disease-19 (COVID-19) in high-risk older individuals in long-term and specialized care.
NCT04397328 COVID-19 Drug: Hydroxychloroquine Drug: Placebo
Primary Outcomes
Measure: Incidence of symptomatic fever >37.8, dry cough, or shortness of breath (resident/patient report or nurse observation) respiratory infection with confirmed PCR+ result for SARS-CoV-2. Time: baseline through day 90Secondary Outcomes
Measure: Requirement for admission to acute care hospital and/or ICU admission or death Time: baseline through day 90Measure: Asymptomatic PCR+ SARS-CoV-2 test result Time: baseline, days 2, 5, 12, and 19
Measure: Time to clinical recovery (TTCR). Time: baseline through day 90
188 Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration
Ranitidine is an over-the-counter and prescription drug, which decreases the amount of acid secreted by the stomach. Some ranitidine medicines contain an impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. The US Food and Drug Administration (FDA) has found levels of NDMA in some ranitidine products similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats. The ranitidine that will be used in this study has been tested twice (months apart) and shown to have stable NDMA levels well below the acceptable daily limit. Of note, the risk of NDMA with ranitidine is only relevant with prolonged chronic administration as at the acceptable limit, there is approximately a 1 in 100,000 chance of cancer after 70 years of exposure to that level. FDA has also conducted tests that simulate the potential formation of NDMA from ranitidine after it has been exposed to acid in the stomach with a normal diet. Results of these tests indicate that NDMA is not formed in typical stomach conditions. Similarly, if ranitidine is exposed to a simulated small intestinal fluid, NDMA is not formed. Other laboratory experiments suggest a combination of nitrites, such as found in processed meats, and an acidic environment may increase NDMA formation, however the levels of nitrites tested were very high. Separately, a previous study in 10 healthy volunteers showed that volunteers who received ranitidine had an increase in urinary NDMA excreted over 24 h. The level of increase was greater than would be expected from laboratory testing. This clinical study is being performed to determine if and how much NDMA is produced from ranitidine in the human body and whether nitrite-containing foods may increase formation of NDMA. The study will use a prescription dose of ranitidine (300 mg) to test whether there is increased urinary NDMA excretion levels over 24-hours after ranitidine administration in comparison to placebo when participants are administered low nitrite/NDMA meals and when subjects are administered high nitrite/NDMA meals. On 4 different days, each participant will receive ranitidine or placebo with high nitrite/NDMA meals and ranitidine or placebo with low nitrite/NDMA meals.
NCT04397445 Ranitidine Adverse Reaction Pharmacokinetics Food-drug Interaction Drug: Ranitidine Other: Low nitrite/NDMA meals Drug: Placebo Other: High nitrite/NDMA meals
Primary Outcomes
Description: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.
Measure: 24-hour Urinary NDMA Excretion Time: 24 hoursOther Outcomes
Description: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.
Measure: Area under the curve from time zero to infinity (AUC(0-inf)) of plasma ranitidine Time: 24 hoursDescription: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.
Measure: AUC(0-inf) of plasma NDMA Time: 24 hoursDescription: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.
Measure: AUC(0-inf) of plasma dimethylamine (DMA) Time: 24 hoursDescription: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.
Measure: Cumulative ranitidine amount excreted in urine over 24 hours after drug administration Time: 24 hoursDescription: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.
Measure: Cumulative DMA amount excreted in urine over 24 hours after drug administration Time: 24 hours189 A Randomized, Double Blind, Placebo-controlled Trial of Mavrilimumab for Acute Respiratory Failure Due to COVID-19 Pneumonia With Hyper-inflammation (the COMBAT-19 Trial)
This study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.
NCT04397497 Covid-19 Acute Respiratory Failure ARDS, Human Sars-CoV2 Viral Pneumonia Drug: Mavrilimumab Drug: Placebo MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult Inflammation
HPO:Pneumonia
Primary Outcomes
Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm
Measure: Reduction in the dependency on oxygen supplementation Time: within day 14 of treatment
Secondary Outcomes
Description: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Proportion of responders (using the WHO 7-point ordinal scale) Time: Day 7, 14, and 28
Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Time to response (using the WHO 7-point ordinal scale) Time: Within day 28 of intervention
Description: Proportion of patients with at least two-point improvement in clinical status
Measure: Proportion of improving patients (using the WHO 7-point ordinal scale) Time: At day 7, 14, and 28
Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner
Measure: Time to resolution of fever Time: Within day 28 of intervention
Description: COVID-19-related death
Measure: Reduction in case fatality Time: Within day 28 of intervention
Description: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)
Measure: Proportion of patient requiring mechanical ventilation/deaths Time: Within day 14 of intervention
Description: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)
Measure: Change in biochemical markers Time: Within day 28 of intervention or discharge -whatever comes first
Description: Median changes of NEWS2 score from baseline
Measure: Median changes in the National Early Warning Score 2 (NEWS2) Time: At day 7, 14, and 28
Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)
Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2) Time: Within day 28 of intervention or discharge -whatever comes first
Description: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.
Measure: Variations in radiological findings Time: Within day 28 of intervention or discharge -whatever comes first
Description: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: By day 84
Other Outcomes
Description: To evaluate the primary and secondary endpoints in different subgroups of patients:
mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg;
moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg
Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity Time: Within day 28 of intervention
Description: Median changes in serum IL-6
Measure: Changes in serum IL-6 (exploratory biomarker) Time: By day 84
Description: Median changes in serum IL-1 receptor antagonist
Measure: Changes in serum IL-1RA (exploratory biomarker) Time: By day 84
Description: Median changes in serum TNF-alpha
Measure: Changes in serum TNF-alpha (exploratory biomarker) Time: By day 84
Description: Median variations in haemoglobin and leucocyte counts
Measure: Changes in CBC + differential (exploratory biomarker) Time: By day 84
Description: Median titres od anti-SARS-CoV2 antibodies
Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker) Time: By day 84
Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR
Measure: Virus eradication (exploratory biomarker) Time: By day 84
Description: Proportion of patients who developed anti-drug antibodies
Measure: Anti-drug antibodies (exploratory biomarker) Time: By day 84
190 A Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptively Designed Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19
Primary Outcomes
Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm
Measure: Reduction in the dependency on oxygen supplementation Time: within day 14 of treatmentSecondary Outcomes
Description: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Proportion of responders (using the WHO 7-point ordinal scale) Time: Day 7, 14, and 28Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Time to response (using the WHO 7-point ordinal scale) Time: Within day 28 of interventionDescription: Proportion of patients with at least two-point improvement in clinical status
Measure: Proportion of improving patients (using the WHO 7-point ordinal scale) Time: At day 7, 14, and 28Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner
Measure: Time to resolution of fever Time: Within day 28 of interventionDescription: COVID-19-related death
Measure: Reduction in case fatality Time: Within day 28 of interventionDescription: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)
Measure: Proportion of patient requiring mechanical ventilation/deaths Time: Within day 14 of interventionDescription: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)
Measure: Change in biochemical markers Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Median changes of NEWS2 score from baseline
Measure: Median changes in the National Early Warning Score 2 (NEWS2) Time: At day 7, 14, and 28Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)
Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2) Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.
Measure: Variations in radiological findings Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: By day 84Other Outcomes
Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg
Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity Time: Within day 28 of interventionDescription: Median changes in serum IL-6
Measure: Changes in serum IL-6 (exploratory biomarker) Time: By day 84Description: Median changes in serum IL-1 receptor antagonist
Measure: Changes in serum IL-1RA (exploratory biomarker) Time: By day 84Description: Median changes in serum TNF-alpha
Measure: Changes in serum TNF-alpha (exploratory biomarker) Time: By day 84Description: Median variations in haemoglobin and leucocyte counts
Measure: Changes in CBC + differential (exploratory biomarker) Time: By day 84Description: Median titres od anti-SARS-CoV2 antibodies
Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker) Time: By day 84Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR
Measure: Virus eradication (exploratory biomarker) Time: By day 84Description: Proportion of patients who developed anti-drug antibodies
Measure: Anti-drug antibodies (exploratory biomarker) Time: By day 84The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.
NCT04397562 COVID-19 Drug: Levilimab Drug: Placebo
Primary Outcomes
Description: The proportion of deaths in each group
Measure: Mortality rate Time: Day 60Secondary Outcomes
Description: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care; 6. Hospitalized, not requiring supplemental oxygen; 7. Not hospitalized / discharged
Measure: 7-point Ordinal Scale Time: Day 60Measure: Duration of hospital stay Time: Day 60
Measure: Rate of subjects required ICU stay Time: Day 60
Measure: Duration of ICU Stay Time: Day 60
Measure: Rate of subjects with COVID-19 progression to critical (respiratory failure required invasive ventilation or septic shock or multiple organ failures Time: Day 60
Measure: Rate of subjects requiring the rescue therapy Time: Day 60
Measure: Duration of oxygen supplementation Time: Day 60
Measure: Rate of subjects requiring the invasive ventilation Time: Day 60
Measure: Duration of invasive ventilation Time: Day 60
191 Phase 1b Randomized, Double-Blind, Placebo-Controlled Study Of The Safety Of Therapeutic Treatment With Immunomodulatory Mesenchymal Stem Cells In Adults With COVID-19 Infection Requiring Mechanical Ventilation
This is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with Coronavirus Disease 2019 (COVID-19). This clinical trial will evaluate the preliminary safety and efficacy of BM-Allo.MSC vs placebo in treating subjects with severe disease requiring ventilator support during COVID 19 infection.
NCT04397796 COVID Biological: BM-Allo.MSC Biological: Placebo MeSH:Infection
Primary Outcomes
Description: Incidence of AEs within 30 days of randomization.
Measure: Incidence of AEs Time: 30 daysDescription: Mortality within 30 days of randomization.
Measure: Mortality Time: 30 daysDescription: Cause of death within 30 days of randomization
Measure: Death Time: 30 daysDescription: Number of ventilator-free days within 60 days of randomization.
Measure: Number of ventilator-free days Time: 60 daysSecondary Outcomes
Description: Time from randomization to an improvement of one category using the ordinal scale. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities
Measure: Improvement of one category Time: 30 daysDescription: Change in the 7-point ordinal scale from baseline. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities
Measure: 7-point ordinal scale Time: 30 daysDescription: Change in NEWS from baseline. The following 7 clinical parameters will be assessed: Respiration rate Oxygen saturation Any supplemental oxygen Temperature Systolic blood pressure Heart rate Level of consciousness Measurements within normal ranges are assigned a 0. If the measurement in each category is substantially above or below the normal range, it is given a +1, +2, or +3. The more far off than normal, the bigger the number (in each category). A higher number indicates worse outcome. Each category can be 0-3, except for supplemental oxygen which is only 0-2. The highest value a patient can get is 20.
Measure: NEWS Time: 30 daysDescription: Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.
Measure: NEWS of ≤ 2 Time: 30 daysDescription: Change from baseline in Sequential Organ Failure Assessment (SOFA) score on days 8, 15, 22, and 29. System Score for each category is 0-4 with 28 is the maximum score for worst outcome. The following categories are: Respiration Coagulation Liver Cardiovascular Central Nervous System Renal
Measure: Sequential Organ Failure Assessment (SOFA) Time: days 8, 15, 22, and 29Description: Number of days requiring oxygen.
Measure: Oxygen Time: 30 daysDescription: Duration of hospitalization from randomization.
Measure: Hospitalization Time: 30 daysDescription: Incidence of SAEs within 30 days of randomization
Measure: Incidence of SAEs Time: 30 days192 A Randomized, Observer-Blind, Dose-escalation Phase I/II Clinical Trial of Ad5-nCoV Vaccine in Healthy Adults From 18 to <85 Years of Age in Canada
This study is a phase I /II adaptive clinical trial to evaluate the safety, tolerability and the Immunogenicity of Ad5-nCoV in healthy adults from 18 to <55 and 65 to <85 years of age，with the randomized, observer-blind, dose-escalation design
NCT04398147 COVID-19 Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Biological: Placebo
Primary Outcomes
Description: The occurrence of Solicited AE in all groups within 0-6 days after each vaccination;
Measure: Incidence of the Solicited AE in all groups Time: 0-6 days after each vaccinationDescription: The occurrence of Unsolicited AE in all groups within 0-28 days after each vaccination.
Measure: Incidence of Unsolicited AE in all groups Time: 0-28 days after each vaccinationDescription: The occurrence of Serious adverse events (SAE) in all groups within 6 months after the final vaccination.
Measure: Incidence of Serious adverse events (SAE) in all groups Time: 6 months after the final vaccinationSecondary Outcomes
Description: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);
Measure: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 (ELISA method); Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: Seroconversion rate (%of subjects with 4-fold or greater increase in antibody level) of the IgG antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method );
Measure: Seroconversion rate of the IgG antibody against SARS-CoV-2(ELISA method ) Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);
Measure: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2(ELISA method); Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)
Measure: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay) Time: Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: Seroconversion rate of the neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group(Pseudo-viral neutralization assay);
Measure: Seroconversion rate of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay) Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)
Measure: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 (Pseudo-viral neutralization assay) Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group;
Measure: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group
Measure: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: The positive rate of IFN-γ stimulated by S protein overlapping peptide library detected by ELISpot
Measure: cellular immune response by ELISpot Time: on Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose groupDescription: The positive rate of IFN-γ, TNF-α, and IL-2 expressed by CD4+ and CD8+ T lymphocytes stimulated by S protein overlapping peptide library detected by Intracellular Cytokine Staining (ICS);
Measure: cellular immune response by ICS Time: Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group193 A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia
The primary objective of this study is determine the safety and efficacy of ACT-20-MSC (allogenic human umbilical derived mesenchymal stem cells) and ACT-20-CM (allogenic human umbilical derived mesenchymal stem cells in conditioned media) in patients with moderate to severe COVID-19 pneumonia.
NCT04398303 COVID-19 Pneumonia Biological: ACT-20-MSC Biological: ACT-20-CM Biological: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Measure: Mortality at day 30 Time: 30 days post treatment
Secondary Outcomes
Description: Number of ventilator-free days
Measure: Ventilated Subjects - Ventilator Free Days Time: 28 days post treatment
Description: Improvement in ventilator settings: Minute ventilation, PEEP, FiO2
Measure: Ventilated Subjects - Improvement in Ventilator Settings Time: 28 days post treatment, or until off of ventilator
Description: Days of step-down O2 therapy as evidenced by: improvement in required volume, change to nasal cannula or face mask delivery or improvement in required concentration.
Measure: High-Flow O2 Support Subjects - Step-Down O2 Therapy Time: 30 days post treatment, or until off of high-flow O2 support
Description: Respiration Rate < 30 for > 24 hours.
Measure: High Flow O2 Support Subjects - Respiration Rate Time: 30 days post treatment, or until off of high-flow O2 support
Description: Number of ICU-free days
Measure: Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days Time: 30 days post treatment, or until off of ventilator or high-flow O2 support
Description: Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation
Measure: Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement Time: 30 days post treatment, or until off of ventilator or high-flow O2 support
Description: Increased Berlin Criteria score > 24 hours
Measure: Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score Time: 30 days post treatment, or until off of ventilator or high-flow O2 support
194 Niclosamide for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)
Primary Outcomes
Measure: Mortality at day 30 Time: 30 days post treatmentSecondary Outcomes
Description: Number of ventilator-free days
Measure: Ventilated Subjects - Ventilator Free Days Time: 28 days post treatmentDescription: Improvement in ventilator settings: Minute ventilation, PEEP, FiO2
Measure: Ventilated Subjects - Improvement in Ventilator Settings Time: 28 days post treatment, or until off of ventilatorDescription: Days of step-down O2 therapy as evidenced by: improvement in required volume, change to nasal cannula or face mask delivery or improvement in required concentration.
Measure: High-Flow O2 Support Subjects - Step-Down O2 Therapy Time: 30 days post treatment, or until off of high-flow O2 supportDescription: Respiration Rate < 30 for > 24 hours.
Measure: High Flow O2 Support Subjects - Respiration Rate Time: 30 days post treatment, or until off of high-flow O2 supportDescription: Number of ICU-free days
Measure: Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days Time: 30 days post treatment, or until off of ventilator or high-flow O2 supportDescription: Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation
Measure: Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement Time: 30 days post treatment, or until off of ventilator or high-flow O2 supportDescription: Increased Berlin Criteria score > 24 hours
Measure: Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score Time: 30 days post treatment, or until off of ventilator or high-flow O2 supportThis study will evaluate the antihelmintic drug, Niclosamide, as a potential treatment for mild to moderate coronavirus disease 2019 (COVID-19).
NCT04399356 COVID (SARS-CoV-2) Drug: Niclosamide Drug: Placebo Other: Telehealth monitoring
Primary Outcomes
Description: Oropharangeal swab
Measure: Change in respiratory viral clearance (by PCR) Time: Day 3 and 10Secondary Outcomes
Description: Fecal swab
Measure: Fecal viral clearance (by PCR) Time: Day 14Description: Oropharngeal swab
Measure: Reduction (change) in viral shedding (by PCR) Time: Days 1,3,7,10,14195 Efficacy and Safety of Octagam 10% Therapy in COVID-19 Patients With Severe Disease Progression
This is a randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to evaluate if high-dose Octagam 10% therapy can stabilize or improve clinical status in patients with severe Coronavirus disease
NCT04400058 Covid-19 Biological: Octagam 10% Other: Placebo MeSH:Disease Progression
Primary Outcomes
Description: Proportion of subjects with stabilized or improved clinical status at Day 7 on at least one category on a 6-point clinical status scale. Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.
Measure: Stabilization or Improvement in Clinical Status Time: 7 daysDescription: Change from Baseline (Day 1) at Day 7 in terms of the 6-point clinical status scale (descriptive analysis). Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.
Measure: Descriptive Clinical Status Analysis Time: 7 daysSecondary Outcomes
Description: Proportion of subjects with maintenance or improvement by at least one category on the 6-point clinical status scale on Day 14. (This endpoint will go into formal hypothesis testing procedure) Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.
Measure: Clinical Status Assessment Time: 14 daysDescription: Time to death
Measure: Time to death Time: Up to 33 daysDescription: Proportion of subjects requiring invasive mechanical ventilation by Day 33.
Measure: Mechanical Ventilation Initiation Time: Up to 33 daysDescription: Duration of invasive mechanical ventilation
Measure: Mechanical Ventilation Duration Time: Up to 33 daysDescription: Results of RT-PCR for SARS-CoV-2 from nares/throat swab and/or sputum and/or lower respiratory tract sample on Day 7.
Measure: SARS-CoV-2 Test Result Time: 7 daysDescription: Incidence of all AEs
Measure: Incidence of all AEs Time: Up to 33 daysDescription: Incidence of AEs considered related to the IMP
Measure: Incidence of AEs considered related to the IMP Time: Up to 33 daysDescription: Incidence of serious adverse events (SAEs)
Measure: Incidence of serious adverse events (SAEs) Time: Up to 33 daysDescription: Radiological findings (chest CT/chest X-ray)
Measure: Radiological findings (chest CT/chest X-ray) Time: Up to 7 daysDescription: Change from baseline in blood glucose
Measure: Blood glucose Time: Up to 33 dayaDescription: Change from baseline in blood calcium
Measure: Blood calcium Time: Up to 33 daysDescription: Change from baseline in sodium
Measure: Sodium Time: Up to 33 daysDescription: Change from baseline in potassium
Measure: Potassium Time: Up to 33 daysDescription: Change from baseline in carbon dioxide
Measure: Carbon dioxide Time: Up to 33 daysDescription: Change from baseline in chloride
Measure: Chloride Time: Up to 33 daysDescription: Change from baseline in albumin
Measure: Albumin Time: Up to 33 daysDescription: Change from baseline in total protein
Measure: Total protein Time: Up to 33 daysDescription: Change from baseline in alkaline phosphatase
Measure: Alkaline phosphatase Time: Up to 33 daysDescription: Change from baseline in alanine transaminase
Measure: Alanine transaminase Time: Up to 33 daysDescription: Change from baseline in aspartate aminotransferase
Measure: Aspartate aminotransferase Time: Up to 33 daysDescription: Change from baseline in bilirubin
Measure: Bilirubin Time: Up to 33 daysDescription: Change from baseline in blood urea nitrogen
Measure: Blood urea nitrogen Time: Up to 33 daysDescription: Change from baseline in D-dimer
Measure: D-dimer Time: Up to 33 daysDescription: Change from baseline in fibrinogen
Measure: Fibrinogen Time: Up to 33 daysDescription: Change from baseline in PT
Measure: PT Time: Up to 33 daysDescription: Change from baseline in PTT
Measure: PTT Time: Up to 33 daysDescription: Change from baseline in INR
Measure: INR Time: Up to 33 daysDescription: Change from baseline in hsCRP
Measure: hsCRP Time: Up to 33 daysDescription: Change from baseline in ferritin
Measure: Ferritin Time: Up to 33 daysDescription: Change from baseline in LDH
Measure: LDH Time: Up to 33 daysDescription: Change from baseline in IgG
Measure: IgG Time: Up to 33 daysDescription: Change from baseline in IgM
Measure: IgM Time: Up to 33 daysDescription: Change from baseline in IgA
Measure: IgA Time: Up to 33 daysDescription: Change from baseline in IFE
Measure: IFE Time: Up to 33 daysDescription: Change from baseline in troponin
Measure: Troponin Time: Up to 33 daysDescription: Change from baseline in red blood cell count
Measure: Red blood cell count Time: Up to 33 daysDescription: Change from baseline in hemoglobjn
Measure: Hemoglobin Time: Up to 33 daysDescription: Change from baseline in hematocrit
Measure: Hematocrit Time: Up to 33 daysDescription: Change from baseline in mean corpuscular volume
Measure: Mean corpuscular volume Time: Up to 33 daysDescription: Change from baseline in mean corpuscular hemoglobin
Measure: Mean corpuscular hemoglobin Time: Up to 33 daysDescription: Change from baseline in mean corpuscular hemoglobin concentration
Measure: Mean corpuscular hemoglobin concentration Time: Up to 33 daysDescription: Change from baseline in red cell distribution width
Measure: Red cell distribution width Time: Up to 33 daysDescription: Change from baseline in white blood cell count
Measure: White blood cell count Time: Up to 33 daysDescription: Change from baseline in white blood cell differential
Measure: White blood cell differential Time: Up to 33 daysDescription: Change from baseline in platelet count
Measure: Platelet count Time: Up to 33 daysDescription: Change from baseline in mean platelet volume
Measure: Mean platelet volume Time: Up to 33 daysDescription: Change from baseline in platelet distribution width
Measure: Platelet distribution width Time: Up to 33 daysDescription: Change from baseline in SpO2
Measure: SpO2 Time: Up to 33 daysDescription: Change from baseline in A-a gradient
Measure: A-a gradient Time: Up to 33 daysDescription: Change from baseline in blood pressure
Measure: Blood Pressure Time: Up to 33 daysDescription: Change from baseline in pulse
Measure: Pulse Time: Up to 33 daysDescription: Change from baseline in respiration rate
Measure: Respiration Rate Time: Up to 33 daysDescription: Change from baseline in body temperature
Measure: Body Temperature Time: Up to 33 days196 Randomized Controlled Trial of Angiotensin 1-7/ TXA127 for the Treatment of Moderate COVID-19
The purpose of this study is to determine if administration of angiotensin-(1-7) / TXA127 prevents acute kidney injury and deterioration into multi-organ failure in patients with moderate to severe COVID-19
NCT04401423 COVID-19 Drug: TXA127 Drug: Placebo
Primary Outcomes
Description: Defined as an increase of serum creatinine by more than 0.3 mg/dL or 50% above baseline (at enrollment)
Measure: Incidence of acute kidney injury Time: Day 1 to Day 7Description: Requiring intubation and ventilatory support
Measure: Incidence of respiratory failure Time: Day 1 to Day 7Secondary Outcomes
Description: death
Measure: Mortality Time: Day 1 to Day 7Description: Requiring dialysis (either continuous or intermittent)
Measure: Renal failure Time: Day 1 to Day 7Description: requiring vasopressors
Measure: Vasoplegic shock Time: Day 1 to Day 7Description: measured via blood work
Measure: Inflammatory markers, specifically IL-6 levels Time: Day 1 to Day 7Description: defined as a reduction in oxygen requirements from start of experimental drug
Measure: Reduction in supplemental oxygen requirements Time: Day 1 to Day 7197 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-2)
ACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.
NCT04401579 COVID-19 Other: Placebo Drug: Remdesivir Drug: Baricitinib
Primary Outcomes
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.
Measure: Time to recovery Time: Day 1 through Day 29Secondary Outcomes
Measure: Change from baseline in alanine transaminase (ALT) Time: Day 1 through Day 29Measure: Change from baseline in aspartate transaminase (AST) Time: Day 1 through Day 29
Measure: Change from baseline in creatinine Time: Day 1 through Day 29
Measure: Change from baseline in glucose Time: Day 1 through Day 29
Measure: Change from baseline in hemoglobin Time: Day 1 through Day 29
Measure: Change from baseline in platelets Time: Day 1 through Day 29
Description: PT reported as international normalized ratio (INR).
Measure: Change from baseline in prothrombin time (PT) Time: Day 1 through Day 29Measure: 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 29Description: 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 29Description: 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 29Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: Measured in days
Measure: Duration of oxygen use Time: Day 1 through Day 29Description: For any reason.
Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Measure: 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 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Participant's clinical status at Day 15 by ordinal scale Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale Time: Days 3, 5, 8, 11, 22, and 29Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 28-day mortality Time: Day 1 through Day 29Description: 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 29Description: 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 29Description: 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 29Measure: Change from baseline in C-reactive protein (CRP) Time: Day 1 through Day 29
Measure: Change from baseline in d-dimer concentration Time: Day 1 through Day 29
198 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19
This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.
NCT04402866 Acute Lung Injury (ALI) Associated With COVID-19 Lung Inflammation Associated With COVID-19 Drug: TD-0903 Drug: Placebo MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Pneumonia Inflammation
HPO:Pneumonia
Primary Outcomes
Description: Change from baseline in SaO2/FiO2 ratio
Measure: Part 2: SaO2/FiO2 ratio Time: Baseline, Day 7
Description: Number of days the subject was not using invasive mechanical ventilation or non-invasive positive pressure ventilation
Measure: Part 2: Ventilator-free Days (VFDs) Time: Baseline through Day 28
Secondary Outcomes
Description: Number of days the subject was not in the ICU
Measure: Part 2: Intensive Care Unit Free Days (ICU-free) Time: Baseline through Day 28
Description: Area under the plasma concentration-time curve (AUC) in SaO2/FiO2 ratio
Measure: Part 2: AUC in SaO2/FiO2 ratio Time: Baseline through Day 7
Description: Change from baseline in SaO2/FiO2 ratio
Measure: Part 2: SaO2/FiO2 ratio Time: Baseline, Day 5
Description: Proportion of subjects with a SaO2/FiO2 ratio > 315
Measure: Part 2: SaO2/FiO2 ratio > 315 Time: Day 5, Day 7
Description: Proportion of subjects discharged
Measure: Part 2: Subjects Discharged Time: Day 7, 14, 21 and 28
Description: Time to hospital discharge
Measure: Part 2: Hospital Discharge Time: Baseline through up to Day 28
Description: The subject mortality rate (all causes)
Measure: Part 2: Mortality Rate Time: Day 28
Description: Change from baseline in the modified Borg Dyspnea Score.
The modified Borg Dyspnea Score is based on a 10-point scale that measures shortness of breath. Scores range from 0 (nothing at all, no shortness of breath) to 10 (maximal shortness of breath).
Measure: Part 2: Modified Borg Dyspnea Score Time: Baseline through Day 7
Description: Proportion of subjects in each category of the Clinical Status scale.
The Clinical Status scale contains 6 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized'), 2 (hospitalized, not requiring supplemental oxygen), 3 (hospitalized, requiring low-flow oxygen supplementation), 4 (hospitalized, on non-invasive positive pressure ventilation or high-flow oxygen supplementation), 5 (hospitalized, on invasive mechanical ventilation, 6 (Death).
Measure: Part 2: Clinical Status Scale Time: Day 7, 14, 21 and 28
Description: Proportion of subjects in each category of Vital Status, where the categories are defined as death, discharge, or hospitalized.
Measure: Part 2: Vital Status Time: Day 7, 14, 21 and 28
199 Pulmozyme to Improve COVID-19 ARDS Outcomes
Primary Outcomes
Description: Change from baseline in SaO2/FiO2 ratio
Measure: Part 2: SaO2/FiO2 ratio Time: Baseline, Day 7Description: Number of days the subject was not using invasive mechanical ventilation or non-invasive positive pressure ventilation
Measure: Part 2: Ventilator-free Days (VFDs) Time: Baseline through Day 28Secondary Outcomes
Description: Number of days the subject was not in the ICU
Measure: Part 2: Intensive Care Unit Free Days (ICU-free) Time: Baseline through Day 28Description: Area under the plasma concentration-time curve (AUC) in SaO2/FiO2 ratio
Measure: Part 2: AUC in SaO2/FiO2 ratio Time: Baseline through Day 7Description: Change from baseline in SaO2/FiO2 ratio
Measure: Part 2: SaO2/FiO2 ratio Time: Baseline, Day 5Description: Proportion of subjects with a SaO2/FiO2 ratio > 315
Measure: Part 2: SaO2/FiO2 ratio > 315 Time: Day 5, Day 7Description: Proportion of subjects discharged
Measure: Part 2: Subjects Discharged Time: Day 7, 14, 21 and 28Description: Time to hospital discharge
Measure: Part 2: Hospital Discharge Time: Baseline through up to Day 28Description: The subject mortality rate (all causes)
Measure: Part 2: Mortality Rate Time: Day 28Description: Change from baseline in the modified Borg Dyspnea Score. The modified Borg Dyspnea Score is based on a 10-point scale that measures shortness of breath. Scores range from 0 (nothing at all, no shortness of breath) to 10 (maximal shortness of breath).
Measure: Part 2: Modified Borg Dyspnea Score Time: Baseline through Day 7Description: Proportion of subjects in each category of the Clinical Status scale. The Clinical Status scale contains 6 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized'), 2 (hospitalized, not requiring supplemental oxygen), 3 (hospitalized, requiring low-flow oxygen supplementation), 4 (hospitalized, on non-invasive positive pressure ventilation or high-flow oxygen supplementation), 5 (hospitalized, on invasive mechanical ventilation, 6 (Death).
Measure: Part 2: Clinical Status Scale Time: Day 7, 14, 21 and 28Description: Proportion of subjects in each category of Vital Status, where the categories are defined as death, discharge, or hospitalized.
Measure: Part 2: Vital Status Time: Day 7, 14, 21 and 28This is a randomized double-blind placebo-controlled Phase II trial of recombinant human deoxyribonuclease I (rhDNase I) - Pulmozyme - in mechanically ventilated patients with COVID-19 pneumonia. Patients admitted to the ICU with severe COVID-19 pneumonia who require mechanical ventilation will be invited to participate in this study. Potential subjects will be identified from medical record review or from direct contact with physicians. Investigators will check medical history and confirm eligibility. Informed consent will be obtained from either the patient or designated healthcare proxy. 60 subjects will be enrolled. After obtaining informed consent, patients will be randomized 2:1 to Pulmozyme 2.5 mg BID for up to 28 days or until they are no longer receiving mechanical ventilation, whichever is sooner plus standard of care vs. placebo normal saline 2.5 ml plus standard of care.
NCT04402944 COVID Drug: Pulmozyme Drug: Placebo
Primary Outcomes
Description: Primary outcome
Measure: Ventilator-free days at 28 days Time: 28 daysSecondary Outcomes
Description: change in airway resistance
Measure: change in airway resistance Time: 28 daysDescription: Change in lung compliance
Measure: change in lung compliance Time: 28 daysDescription: oxygenation
Measure: oxygenation (PaO2/FiO2 ratio) Time: 28 daysDescription: length of stay
Measure: length of stay (ICU and hospital) Time: 28 daysDescription: rate of batotrauma
Measure: rate of barotrauma Time: 28 daysDescription: mortality
Measure: mortality. Time: 28 days200 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)
To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 <10 mL/min/1.73 m2.
NCT04402957 COVID Severe Acute Respiratory Syndrome Sars-CoV2 Acute Kidney Injury Drug: LSALT peptide Drug: Placebo MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Acute Kidney Injury Syndrome Wounds and Injuries
HPO:Acute kidney injury
Primary Outcomes
Description: To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.
Measure: Development of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries Time: 28 days
Secondary Outcomes
Description: High-frequency oscillatory ventilation, with its rapid delivery of low tidal volumes and a respiratory rate in the range of 60 to 900 breaths/minute, has also been utilized in ARDS patients.
Measure: Ventilation-free days Time: 28 days
Description: Oxygen therapy provided as non-invasive therapy for ARDS patients.
Measure: Time on nasal cannula or oxygen masks Time: 28 days
Description: 28 day mortality - all cause and attributable
Measure: 28 day mortality - all cause and attributable Time: 28 days
Description: ICU and hospitalization length of stay (days)
Measure: ICU and hospitalization length of stay (days) Time: 28 days
Description: Swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication → virologic clearance rate
Measure: SARS-CoV2 testing Time: 28 days
Description: Extracorporeal membrane oxygenation (ECMO) is often used for severe ARDS to allow lung healing/repair and reverse respiratory failure.
Measure: Need and duration for extracorporeal membrane oxygenation (ECMO) Time: 28 days
Description: Vasopressor free days
Measure: Vasopressor free days Time: 28 days
Description: Chest X-rays performed at Baseline, Day 3, at clinical improvement, and end-of-treatment (EOT) and study (EOS) to determine presence of bilateral opacities.
Measure: Radiographic pulmonary assessments Time: 28 days
Description: Change in daily mMRC dyspnea and SOFA scores (0 to 4) with 4 being the most severe outcome
Measure: Change in modified Medical Research Council (mMRC) dyspnea and Sequential Organ Failure Assessment (SOFA) scores Time: 28 days
Description: Incidence of other organ (non-lung) disorders
Measure: Incidence of non-lung disorders Time: 28 days
Description: Change in liver function tests (ALT, AST, and total bilirubin levels) from baseline
Measure: Measures of liver dysfunction Time: 28 days
Description: Change in SCr and eGFR from baseline
Measure: Measures of kidney dysfunction Time: 28 days
Description: Change in highly-sensitive troponin (hs-troponin) from baseline
Measure: Measures of cardiac dysfunction Time: 28 days
Description: Change from baseline ACT, aPTT, and/or PT/INR levels
Measure: Measures of coagulopathies Time: 28 days
Description: Change in baseline antiviral immunoglobulins (IgG, IgM) at EOS.
Measure: Changes in immunogenic responses Time: 28 days
Description: Changes in total healthcare costs from admission to discharge between treatment groups.
Measure: Healthcare outcomes Time: 28 days
Description: Change in serum cytokines including IL-1α, IL-1ß, IL-1ra, IL-5, IL-6, IL-8, IL-12, TNFα, CXCL10/IP10, MCP-3, and ferritin drawn at the same time as LSALT peptide levels
Measure: Molecular changes in pro-inflammatory pathways Time: 28 days
Description: Pharmacokinetics of LSALT peptide over the study period.
Measure: Pharmacokinetics of LSALT peptide Time: 28 days
201 Hydroxychloroquine and Lopinavir/ Ritonavir for Hospitalization and Mortality Reduction in Patients With COVID-19 and Mild Disease Symptoms: "The Hope Coalition"
Primary Outcomes
Description: To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.
Measure: Development of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries Time: 28 daysSecondary Outcomes
Description: High-frequency oscillatory ventilation, with its rapid delivery of low tidal volumes and a respiratory rate in the range of 60 to 900 breaths/minute, has also been utilized in ARDS patients.
Measure: Ventilation-free days Time: 28 daysDescription: Oxygen therapy provided as non-invasive therapy for ARDS patients.
Measure: Time on nasal cannula or oxygen masks Time: 28 daysDescription: 28 day mortality - all cause and attributable
Measure: 28 day mortality - all cause and attributable Time: 28 daysDescription: ICU and hospitalization length of stay (days)
Measure: ICU and hospitalization length of stay (days) Time: 28 daysDescription: Swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication → virologic clearance rate
Measure: SARS-CoV2 testing Time: 28 daysDescription: Extracorporeal membrane oxygenation (ECMO) is often used for severe ARDS to allow lung healing/repair and reverse respiratory failure.
Measure: Need and duration for extracorporeal membrane oxygenation (ECMO) Time: 28 daysDescription: Vasopressor free days
Measure: Vasopressor free days Time: 28 daysDescription: Chest X-rays performed at Baseline, Day 3, at clinical improvement, and end-of-treatment (EOT) and study (EOS) to determine presence of bilateral opacities.
Measure: Radiographic pulmonary assessments Time: 28 daysDescription: Change in daily mMRC dyspnea and SOFA scores (0 to 4) with 4 being the most severe outcome
Measure: Change in modified Medical Research Council (mMRC) dyspnea and Sequential Organ Failure Assessment (SOFA) scores Time: 28 daysDescription: Incidence of other organ (non-lung) disorders
Measure: Incidence of non-lung disorders Time: 28 daysDescription: Change in liver function tests (ALT, AST, and total bilirubin levels) from baseline
Measure: Measures of liver dysfunction Time: 28 daysDescription: Change in SCr and eGFR from baseline
Measure: Measures of kidney dysfunction Time: 28 daysDescription: Change in highly-sensitive troponin (hs-troponin) from baseline
Measure: Measures of cardiac dysfunction Time: 28 daysDescription: Change from baseline ACT, aPTT, and/or PT/INR levels
Measure: Measures of coagulopathies Time: 28 daysDescription: Change in baseline antiviral immunoglobulins (IgG, IgM) at EOS.
Measure: Changes in immunogenic responses Time: 28 daysDescription: Changes in total healthcare costs from admission to discharge between treatment groups.
Measure: Healthcare outcomes Time: 28 daysDescription: Change in serum cytokines including IL-1α, IL-1ß, IL-1ra, IL-5, IL-6, IL-8, IL-12, TNFα, CXCL10/IP10, MCP-3, and ferritin drawn at the same time as LSALT peptide levels
Measure: Molecular changes in pro-inflammatory pathways Time: 28 daysDescription: Pharmacokinetics of LSALT peptide over the study period.
Measure: Pharmacokinetics of LSALT peptide Time: 28 daysThe COVID-19 pandemic has been characterized by high morbidity and mortality, especially in certain subgroups of patients. To date, no treatment has been shown to be effective in controlling this disease in hospitalized patients with moderate and / or severe cases of this disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV viral replication in experimental severe acute respiratory symptoms models and have similar activity against SARS-CoV2. Although widely used in studies of critically ill patients, to date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed patients with COVID-19 and mild symptoms.
NCT04403100 COVID-19 Coronavirus Infection Virus Disease Acute Respiratory Infection SARS-CoV Infection Drug: Hydroxychloroquine Sulfate Tablets Drug: Lopinavir/ Ritonavir Oral Tablet Drug: Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets Drug: Placebo MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Virus Diseases
HPO:Respiratory tract infection
Primary Outcomes
Description: Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)
Measure: Proportion of participants who were hospitalized for progression of COVID-19 disease Time: Measuring during 28-day period since randomization (Intention to treat analysis)
Measure: Proportion of participants who died due to COVID-19 progression and/ or complications Time: Measuring during 28-day period since randomization (Intention to treat analysis)
Secondary Outcomes
Description: Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)
Measure: Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization Time: Measuring during 14-day period since randomization
Description: Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.
Measure: Time to clinical improvement Time: Measuring during 28-day period since randomization
Description: Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;
Measure: Time to clinical failure Time: Measuring during 28-day period since randomization
Description: Proportion of participants with hospitalization for any cause
Measure: Hospitalization for any cause Time: Measuring during 28-day period since randomization
Measure: Proportion of participants who died due to pulmonary complications Time: Measuring during 28-day period since randomization
Measure: Proportion of participants who died due to cardiovascular complications Time: Measuring during 28-day period since randomization
Description: Evaluation of adverse events evaluated as associated to any of study arms
Measure: Proportion of participants who presented with adverse events Time: Measuring during 28-day period since randomization
Description: Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.
Measure: Time to improvement on respiratory scale symptoms Time: Measuring during 28-day period since randomization
Measure: proportion of non-adherent participants to any of study drugs Time: Measuring during 10-day period since randomization
202 Randomized Clinical Trial of Açaí Palm Berry Extract as an Intervention in Patients Diagnosed With COVID-19
Primary Outcomes
Description: Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)
Measure: Proportion of participants who were hospitalized for progression of COVID-19 disease Time: Measuring during 28-day period since randomization (Intention to treat analysis)Measure: Proportion of participants who died due to COVID-19 progression and/ or complications Time: Measuring during 28-day period since randomization (Intention to treat analysis)
Secondary Outcomes
Description: Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)
Measure: Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization Time: Measuring during 14-day period since randomizationDescription: Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.
Measure: Time to clinical improvement Time: Measuring during 28-day period since randomizationDescription: Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;
Measure: Time to clinical failure Time: Measuring during 28-day period since randomizationDescription: Proportion of participants with hospitalization for any cause
Measure: Hospitalization for any cause Time: Measuring during 28-day period since randomizationMeasure: Proportion of participants who died due to pulmonary complications Time: Measuring during 28-day period since randomization
Measure: Proportion of participants who died due to cardiovascular complications Time: Measuring during 28-day period since randomization
Description: Evaluation of adverse events evaluated as associated to any of study arms
Measure: Proportion of participants who presented with adverse events Time: Measuring during 28-day period since randomizationDescription: Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.
Measure: Time to improvement on respiratory scale symptoms Time: Measuring during 28-day period since randomizationMeasure: proportion of non-adherent participants to any of study drugs Time: Measuring during 10-day period since randomization
The Açaí trial will be testing if the açaí berry extract, a safe natural product with anti-inflammatory properties, can be used as a treatment option in adult patients with COVID-19 in the community.
NCT04404218 COVID Dietary Supplement: Açaí palm berry extract - natural product Other: Placebo
Primary Outcomes
Description: Symptom comparison between patients from the treatment vs control group, using an ordinal symptom scale based on the WHO scale. Patients who were hospitalized will be classified according to their worst score over 30 days and non-hospitalized patients according to their score at 30 days.
Measure: 7-point ordinal symptom scale Time: 30 daysSecondary Outcomes
Description: First occurrence of all-cause mortality or need for mechanical ventilation
Measure: The composite of all-cause mortality and need for mechanical ventilation Time: 30 daysDescription: First occurrence of all-cause mortality or hospitalization
Measure: The composite of all-cause mortality and hospitalization Time: 30 daysDescription: All-cause mortality
Measure: All-cause mortality Time: 30 daysDescription: Need for mechanical ventilation
Measure: Need for mechanical ventilation Time: 30 daysDescription: Need for hospitalization
Measure: Need for hospitalization Time: 30 days203 A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Pacritinib Plus Standard of Care Versus Placebo and Standard of Care in Hospitalized Patients With Severe COVID-19 With or Without Cancer
This is a Phase 3 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer.
NCT04404361 COVID Drug: Pacritinib Drug: Placebo
Primary Outcomes
Description: The proportion is calculated as the number of patients who progress divided by the total number of patients in the ITT population.
Measure: Proportion of patients who progress to IMV and/or ECMO or death during the 28 days following randomization Time: 28 days204 CACOLAC : Randomized Trial of Citrulline Administration in the Hospital Patient in Intensive Care for COVID-19 Acute Respiratory Distress Syndrome
Respiratory involvement of SARS-CoV2 leads to acute respiratory distress syndrome (ARDS) and significant immunosuppression (lymphopenia) exposing patients to long ventilation duration and late mortality linked to the acquisition of nosocomial infections. Lymphopenia characteristic of severe forms of ARDS secondary to SARS-CoV2 infection may be linked to expansion of MDSCs and arginine depletion of lymphocytes. Severe forms of COVID-19 pneumonitis are marked by persistent ARDS with acquisition of nosocomial infections as well as by prolonged lymphocytic dysfunction associated with the emergence of MDSC. It has been found in intensive care patients hypoargininaemia, associated with the persistence of organ dysfunction (evaluated by the SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, the enteral administration of ARG was not deleterious and increased the synthesis of ornithine, suggesting a preferential use of ARG by the arginase route, without significant increase in argininaemia nor effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, is an interesting alternative to increase the availability of ARG. Recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. The hypothesis is therefore that CIT supplementation is more effective than the administration of ARG to correct hypoargininaemia, decrease lymphocyte dysfunction, correct immunosuppression and organ dysfunction in septic patients admitted to intensive care. The main objective is to show that, in patients hospitalized in intensive care for ARDS secondary to COVID-19 pneumonia, the group of patients receiving L-citrulline for 7 days, compared to the group receiving placebo, has a score of organ failure decreased on D7 (evaluated by the SOFA score) or by the last known SOFA score if the patient has died or been resuscitated.
NCT04404426 ARDS Secondary to COVID-19 Pneumonia Dietary Supplement: L-citrulline Other: Placebo MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
HPO:Pneumonia
Primary Outcomes
Description: SOFA score for organ failures on D7 or last known SOFA score if the patient has died or been resuscitated
Measure: SOFA Time: Day 7
Secondary Outcomes
Description: Number and phenotype of lymphocytes on days 1, 3, 7, 10 and 14
Measure: Number and phenotype of lymphocytes Time: Days 1, 3, 7, 10 and 14
Description: Monocytic expression HLA-DR (Flow cytometry) on days 1, 3, 7, 10 and 14
Measure: HLA-DR Time: Days 1, 3, 7, 10 and 14
Description: Number of Myeloid-derived suppressor cells (Flow cytometry) on days 1, 3, 7, 10 and 14
Measure: Number of Myeloid-derived suppressor cells Time: Days 1, 3, 7, 10 and 14
Description: Plasma cytokines / chemokines (IL-6, IL-8, IL-10, IL-7, CXCL10, G-CSF, TNF-alpha, IFN-β) at days 1, 3, 7, 10 and 14
Measure: Plasma cytokines / chemokines Time: Days 1, 3, 7, 10 and 14
Description: Diversity of the repertoire T at days 1, 3, 7, 10 and 14
Measure: Repertoire T Time: Days 1, 3, 7, 10 and 14
Description: T lymphocyte exhaustion: measurement of lymphocyte apoptosis and lymphocyte proliferation on days 1, 3, 7, 10 and 14
Measure: Lymphocyte T exhaustion Time: Days 1, 3, 7, 10 and 14
Description: Measurement of mitochondrial activity (measurement of the number of mitochondria and their membrane potential, measurement of the expression of Beclin1) on days 1, 3, 7, 10 and 14
Measure: Mitochondrial activity Time: Days 1, 3, 7, 10 and 14
Description: Plasma amino acids (arginine and its metabolites (ornithine, glutamate, glutamine, citrulline, proline) and tryptophan / kynurenine) on days 1, 3, 7, 10 and 14
Measure: Plasma amino acids Time: Days 1, 3, 7, 10 and 14
Description: SOFA score of organ failures on days 3, 7, 10 and 14
Measure: SOFA Time: Days 3, 7, 10 and 14
Description: Duration of hospitalization in intensive care (days), up to day 28 maximum
Measure: Duration of hospitalization in intensive care Time: Day 28
Description: Duration of hospital stay in hospital (days), up to day 28 maximum
Measure: Duration of hospital stay in hospital Time: Day 28
Description: Duration of mechanical ventilation (days), up to day 28 maximum
Measure: Duration of mechanical ventilation Time: Day 28
Description: Mortality in intensive care on day 28
Measure: Mortality in intensive care on day 28 Time: Day 28
Description: Hospital mortality on day 28
Measure: Hospital mortality on day 28 Time: Day 28
Description: Measurement of the presence of SARS-CoV2 in the tracheal aspiration by PCR on days 1, 3, 7, 10 and 14
Measure: Measurement of the presence of SARS-CoV2 Time: Days 1, 3, 7, 10 and 14
Description: Incidence of nosocomial infections during the intensive care unit (maximum D28). The diagnosis of nosocomial infections will be made according to the definitions of nosocomial infections of the CDC. An independent committee of experts will validate or not the infections
Measure: Nosocomial infections Time: D28
Description: Number of days of exposure to each antibiotic per 1000 days of hospitalization (maximum day 28).
Measure: Number of days of exposure to each antibiotic per 1000 days of hospitalization Time: Day 28
205 A Phase 2a, Randomized, Observer-Blind, Placebo Controlled, Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-COV-2 Vaccine in Adults Aged 18 Years and Older
Primary Outcomes
Description: SOFA score for organ failures on D7 or last known SOFA score if the patient has died or been resuscitated
Measure: SOFA Time: Day 7Secondary Outcomes
Description: Number and phenotype of lymphocytes on days 1, 3, 7, 10 and 14
Measure: Number and phenotype of lymphocytes Time: Days 1, 3, 7, 10 and 14Description: Monocytic expression HLA-DR (Flow cytometry) on days 1, 3, 7, 10 and 14
Measure: HLA-DR Time: Days 1, 3, 7, 10 and 14Description: Number of Myeloid-derived suppressor cells (Flow cytometry) on days 1, 3, 7, 10 and 14
Measure: Number of Myeloid-derived suppressor cells Time: Days 1, 3, 7, 10 and 14Description: Plasma cytokines / chemokines (IL-6, IL-8, IL-10, IL-7, CXCL10, G-CSF, TNF-alpha, IFN-β) at days 1, 3, 7, 10 and 14
Measure: Plasma cytokines / chemokines Time: Days 1, 3, 7, 10 and 14Description: Diversity of the repertoire T at days 1, 3, 7, 10 and 14
Measure: Repertoire T Time: Days 1, 3, 7, 10 and 14Description: T lymphocyte exhaustion: measurement of lymphocyte apoptosis and lymphocyte proliferation on days 1, 3, 7, 10 and 14
Measure: Lymphocyte T exhaustion Time: Days 1, 3, 7, 10 and 14Description: Measurement of mitochondrial activity (measurement of the number of mitochondria and their membrane potential, measurement of the expression of Beclin1) on days 1, 3, 7, 10 and 14
Measure: Mitochondrial activity Time: Days 1, 3, 7, 10 and 14Description: Plasma amino acids (arginine and its metabolites (ornithine, glutamate, glutamine, citrulline, proline) and tryptophan / kynurenine) on days 1, 3, 7, 10 and 14
Measure: Plasma amino acids Time: Days 1, 3, 7, 10 and 14Description: SOFA score of organ failures on days 3, 7, 10 and 14
Measure: SOFA Time: Days 3, 7, 10 and 14Description: Duration of hospitalization in intensive care (days), up to day 28 maximum
Measure: Duration of hospitalization in intensive care Time: Day 28Description: Duration of hospital stay in hospital (days), up to day 28 maximum
Measure: Duration of hospital stay in hospital Time: Day 28Description: Duration of mechanical ventilation (days), up to day 28 maximum
Measure: Duration of mechanical ventilation Time: Day 28Description: Mortality in intensive care on day 28
Measure: Mortality in intensive care on day 28 Time: Day 28Description: Hospital mortality on day 28
Measure: Hospital mortality on day 28 Time: Day 28Description: Measurement of the presence of SARS-CoV2 in the tracheal aspiration by PCR on days 1, 3, 7, 10 and 14
Measure: Measurement of the presence of SARS-CoV2 Time: Days 1, 3, 7, 10 and 14Description: Incidence of nosocomial infections during the intensive care unit (maximum D28). The diagnosis of nosocomial infections will be made according to the definitions of nosocomial infections of the CDC. An independent committee of experts will validate or not the infections
Measure: Nosocomial infections Time: D28Description: Number of days of exposure to each antibiotic per 1000 days of hospitalization (maximum day 28).
Measure: Number of days of exposure to each antibiotic per 1000 days of hospitalization Time: Day 28This clinical study will assess the safety, reactogenicity, and immunogenicity of 2 dose levels of mRNA-1273 SARS-COV-2 vaccine in adults 18 years of age or older.
NCT04405076 SARS-CoV-2 Biological: Biological: mRNA-1273: 50 mcg Other: Placebo Biological: Biological: mRNA-1273: 100 mcg
Primary Outcomes
Measure: Solicited local and systemic adverse reactions (ARs) Time: 7 days post-vaccinationMeasure: Unsolicited adverse events (AEs) Time: 28 days post-vaccination
Measure: Medically-attended adverse events (MAAEs) Time: Month 0 through Month 13
Measure: Serious adverse events (SAEs) Time: Month 0 through Month 13
Measure: Change in the measure of clinical safety laboratory values in Cohort 2 from baseline Time: Through 1 month after last vaccination
Measure: The number and percentage of participants with abnormalities in blood pressure, temperature, HR or respiratory rate will be assessed. Time: Through 1 year after last vaccination
Measure: The number and percentage of participants with abnormalities in physical examinations will be assessed Time: Through 1 year after last vaccination
Measure: Evaluate immunogenicity of mRNA-1273 by titer of SARS-CoV-2-specific binding antibody (bAb) measured by enzyme-linked immunosorbent assay (ELISA) Time: Through 1 year after the final dose
Secondary Outcomes
Measure: Titer of SARS-CoV-2-specific neutralizing antibody (nAb) Time: Through 1 year post last vaccinationDescription: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer either from below the limit of detection (LOD) or lower limit of quantification (LLOQ) to equal to or above LOD or LLOQ, or a 4-times higher titer in participants with pre-existing nAb titers.
Measure: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer Time: Through 1 year post last vaccination206 Randomized, Double-blind, Placebo-controlled Trial of TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study)
A randomized parallel double-blinded placebo-controlled clinical trial to evaluate the effect of Emtricitabine/Tenofovir alafenamide (FTC/TAF) compared with placebo on the risk of developing SARS-CoV-2 disease (COVID-19) in healthcare workers with high transmission risk in addition to currently recommended control measures.
NCT04405271 Healthcare Workers COVID-19 SARS-CoV 2 Drug: Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet Drug: Placebo
Primary Outcomes
Description: SARS-CoV-2 disease (COVID-19) with or without symptoms at week 12 of treatment as defined by the presence of specific antibodies against the virus. Positive cases will be confirmed by PCR
Measure: COVID-19 incident cases Time: During treatment (12 weeks)Secondary Outcomes
Description: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology
Measure: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology Time: During treatment (12 weeks)Description: Severity of symptomatic SARS-CoV-2 (Covid-19) infections as defined by the following categories: Mild symptoms: malaise, fever, cough, arthralgia myalgias, Moderate symptoms: same as above plus shortness of breath Severe symptoms: clinical status requiring admission in Intensive care unit
Measure: Severity of symptomatic COVID-19 Time: During treatment (12 weeks)Description: Respiratory symptom duration in days
Measure: Respiratory symptom duration in days Time: During treatment (12 weeks)Description: Relation between treatments and symptoms duration
Measure: Relation between treatments and symptoms duration Time: During treatment (12 weeks)Description: Time course of specific IgM/IgG seroconversion
Measure: Time course of specific IgM/IgG seroconversion Time: During treatment (12 weeks)207 A Phase IIa Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate Infectious Virus Detection in Persons With COVID-19
This is a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 versus placebo as measured by infectious virus detection in symptomatic adult outpatients with COVID-19
NCT04405570 SARS-CoV 2 Drug: 200 mg EIDD-2801 Drug: Placebo MeSH:Communicable Diseases Infection
Primary Outcomes
Description: The distribution of days until first non-detectable SARS-CoV-2 in nasopharyngeal (NP) swabs will be estimated for each randomized arm (drug versus placebo), using Kaplan-Meier methods with a corresponding stratified log-rank test (to account for the "early" versus "late" time from symptom onset randomization strata)
Measure: Virologic Efficacy Time: 28 daysDescription: Measure the safety and tolerability of EIDD-2801 by estimating in the randomization arm the probability of 1) any adverse events (AEs) leading to early discontinuation of blinded treatment (active or placebo), 2) study drug-related discontinuation of treatment, 3) new grade 3 or higher AE (not already present at baseline), and 4) study drug-related new grade 3 or higher AE. The cumulative probability of each safety and each tolerability endpoint (4 endpoints) by using the Kaplan-Meier approach and stratified log-rank test.
Measure: Number of Participants with any Adverse Events (AEs) as Assessed by Kaplan Meier Approach Time: 28 daysSecondary Outcomes
Description: Measure the safety and tolerability of EIDD-2801 by estimating the occurrence of Grade 2 or higher AE and drug related AEs by using the Kaplan-Meier approach and stratified log-rank test.
Measure: Number of Participants With any Adverse Events (AEs), Grade 2 or higher as Assessed by Kaplan Meier Approach Time: 28 days208 Randomized, Placebo Controlled, Double Blind Clinical Trial to Evaluate the Efficacy of Molecule D11AX22 in Adults Patients From Cali, Colombia With Early Stages of SARS COV2 / COVID-19
Double blind, placebo controlled, randomized clinical trial to evaluate the efficacy of ivermectin in preventing progression of disease in adult patients with early stages of COVID-19
NCT04405843 COVID-19 Drug: Ivermectin Oral Product Drug: Placebo
Primary Outcomes
Description: Time until deterioration of 2 or more points in an ordinal 7 points scale.
Measure: Time to event Time: 21 daysSecondary Outcomes
Description: Clinical condition in an ordinal scale of 7 points, on day 2. Higher scores indicate worse outcomes
Measure: Clinical condition on day 2 Time: On day 2 (± 1 day) after randomizationDescription: Clinical condition in an ordinal scale of 7 points, on day 5. Higher scores indicate worse outcomes
Measure: Clinical condition on day 5 Time: On day 5 (± 1 day) after randomizationDescription: Clinical condition in an ordinal scale of 7 points, on day 8. Higher scores indicate worse outcomes
Measure: Clinical condition on day 8 Time: On day 8 (± 1 day) after randomizationDescription: Clinical condition in an ordinal scale of 7 points, on day 11. Higher scores indicate worse outcomes
Measure: Clinical condition on day 11 Time: On day 11 (± 1 day) after randomizationDescription: Clinical condition in an ordinal scale of 7 points, on day 15. Higher scores indicate worse outcomes
Measure: Clinical condition on day 15 Time: On day 15 (± 1 day) after randomizationDescription: Clinical condition in an ordinal scale of 7 points, on day 21. Higher scores indicate worse outcomes
Measure: Clinical condition on day 21 Time: On day 21 (± 1 day) after randomizationDescription: Proportion of subjects who require hospitalization, use of supplementary oxygen for >24 hours or ICU admission
Measure: Proportion of subjects with additional care Time: 21 daysDescription: Proportion of subjects who die
Measure: Proportion of subjects who die Time: From randomization up to 21 daysDescription: Duration of supplementary oxygen, hospitalization, ICU stay
Measure: Duration of additional care Time: 21 daysDescription: Proportion of subjects who develop solicited adverse events
Measure: Adverse events Time: 21 daysDescription: Proportion of subjects who required discontinuation of the trial due to adverse events
Measure: Proportion of subjects who discontinue intervention Time: 21 days209 Ivermectin and Doxycycline in Combination or Ivermectin Alone for the Treatment of Adult Bangladeshi Patients Hospitalized for COVID-19: a Randomised, Double-blind, Placebo-controlled Trial.
Burden: Initial outbreak of corona virus disease 2019 (COVID-19) was reported from Wuhan, China in early December 2019.Presently known to be caused by a novel beta-corona virus, named as Severe acute respiratory syndrome corona virus 2 ( SARS-CoV-2). World Health Organization (WHO) declared a pandemic on March. The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnoea and pneumonia Infected individuals exhibit: 1. Mostly mild illness (80% +) recover without any treatment (~80%) 2. Moderate illness that needs hospitalization and recovers after standard 3. supportive treatment (~14%) 4. Critical illness (~5%) needs ICU support 5. Death (1-2% ) COVID-19 has now spread >210 countries and territories globally. SARS-CoV-2 is a respiratory virus which spreads primarily through droplets generalized when an infected person coughs or sneezes or through droplets of saliva or discharge from the nose. Symptomatic management remains the mainstay of treatment strategy. Mortality appears to be more common in older individuals and those with co-morbidities, such as chronic lung disease, cardiovascular disease and diabetes. Young people with no comorbidities also appear to be at risk for critical illness including multi-organ failure and death. Seen more in Bangladesh between 21-40 yrs of age. Knowledge Gap: There is no specific treatment against this new virus that WHO has officially declared until now.There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. National Guidelines on Clinical Management of Corona virus Disease 2019 (Covid-19): V 5.0 date 9th April 2020) CDC, DGHS, GoB Thus an RCT is urgently needed in Bangladesh: Based on recent literatures on Rx studies in COVID-19 patients from other countries as well as its availability & affordability of those repurposed medicines
NCT04407130 COVID-19 Patients Drug: Ivermectin + Doxycycline + Placebo Drug: Ivermectin + Placebo Drug: Placebo
Primary Outcomes
Description: • Presence of virus will be negative on Day 7 detected by RT PCR
Measure: Virological clearance Time: within 7 days after enrollmentDescription: • Body temperature will be between 36.1 to 37.2 C by day 7 detected by Infrared thermometer
Measure: Remission of fever Time: within 7 days after enrollmentDescription: • Remission of cough: No signs of cough showing respiratory rate within 12-20/ min, on day7
Measure: Remission of cough Time: within 7 days after enrollmentSecondary Outcomes
Description: Detected SPO2 level <94% on Day 7or before by pulse oxymeter
Measure: Patients requiring oxygen Time: within 7 days after enrollmentDescription: Patients who fail to maintain pulse oxymeter detected SpO2 level>88% despite O2 supplementation of 2-6L/min, on Day 7 or before
Measure: Patients failing to maintain SpO2 >88% despite oxygenation Time: within 7 days after enrollmentDescription: Any number of days on oxygen support on Day 7 or before recorded in CRF
Measure: Number of days on oxygen support Time: within 7 days after enrollmentDescription: CXR showing decreases lung opacity or consolidation on day 7 compared with enrollment day
Measure: Chest X-ray improvement Time: within 7 days after enrollmentDescription: Hospital stay ≥7days to ≤14 days as per CRF records
Measure: Duration of hospitalization Time: within 14 days after enrollmentDescription: Death any time during 14 days of study period from any cause recorded in CRF and Hospital death certificate
Measure: All causes of mortality Time: within 14 days after enrollment210 Effects of Nicotinamide Riboside on the Clinical Outcome of Covid-19 in the Elderly. A Randomized Double-blind, Placebo-controlled Trial of Nicotinamide Riboside NR-COVID19
The purpose of this study is to investigate whether nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections in elderly patients. A major event in aging is the loss of the central metabolite nicotinamide adenine dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur during aging. Notably, recent work from our and other groups suggest that aging can be ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside. Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger state even after short term treatment. This vitamin B3- analog is naturally occurring, is readily taken up through oral administration and has been tested in human trials with few side effects. In this randomized double blinded case-control trial, the investigators will treat elderly (>70 year old) COVID19 patients with 1 g of nicotinamide riboside (NR-E) or placebo for 2 weeks and investigate if this affects the clinical course of the disease.
NCT04407390 COVID Dietary Supplement: Nicotinamide riboside Dietary Supplement: Placebo
Primary Outcomes
Description: Hypoxic respiratory failure as defined by need for oxygen therapy
Measure: Hypoxic respiratory failure Time: Day 1Description: Hypoxic respiratory failure as defined by need for oxygen therapy
Measure: Hypoxic respiratory failure Time: Day 7Description: Hypoxic respiratory failure as defined by need for oxygen therapy
Measure: Hypoxic respiratory failure Time: Day 14Description: Hypoxic respiratory failure as defined by need for oxygen therapy
Measure: Hypoxic respiratory failure Time: Day 90Secondary Outcomes
Description: Overall mortality
Measure: Mortality Time: Day 1Description: Overall mortality
Measure: Mortality Time: Day 7Description: Overall mortality
Measure: Mortality Time: Day 14Description: Overall mortality
Measure: Mortality Time: Day 90Description: Sepsis
Measure: Sepsis Time: Day 1Description: Sepsis
Measure: Sepsis Time: Day 7Description: Sepsis
Measure: Sepsis Time: Day 14Description: Sepsis
Measure: Sepsis Time: Day 90Description: Circulatory failure as defined by a need for interventions to support the circulatory system.
Measure: Circulatory failure Time: Day 1Description: Circulatory failure as defined by a need for interventions to support the circulatory system.
Measure: Circulatory failure Time: Day 7Description: Circulatory failure as defined by a need for interventions to support the circulatory system.
Measure: Circulatory failure Time: Day 14Description: Circulatory failure as defined by a need for interventions to support the circulatory system.
Measure: Circulatory failure Time: Day 90Description: Days in hospital
Measure: Days in hospital Time: Day 1Description: Days in hospital
Measure: Days in hospital Time: Day 7Description: Days in hospital
Measure: Days in hospital Time: Day 14Description: Days in hospital
Measure: Days in hospital Time: Day 90Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
Measure: NAD levels Time: Day 1Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
Measure: NAD levels Time: Day 7Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
Measure: NAD levels Time: Day 14Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
Measure: NAD levels Time: Day 90211 Multicenter, Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of Ivermectin in Mild Virus-positive Subjects (SARS-CoV)-2 With or Without Symptoms
This study aims to evaluate the efficacy, safety and tolerability of Ivermectin in patients with mild SARS-CoV-2 infection, in the rate of progression to severe 2019 novel coronavirus disease (COVID-19). The primary efficacy endpoint is the proportion of participants with a disease control status defined as no progression of severe disease Hypothesis (H0): There is no difference between group A (ivermectin + paracetamol) and group B (ivermectin + paracetamol) in terms of the primary endpoint on day 14.
NCT04407507 COVID-19 Drug: Ivermectin Drug: Placebo
Primary Outcomes
Description: The subject is considered to have progressed to severe illness when one or more of the following criteria are present: Breathing difficulty (≥30 breaths per minute); Resting oxygen saturation ≤93%; Severe complications such as: respiratory failure, need for mechanical ventilation, septic shock, non-respiratory organic failure.
Measure: Participants with a disease control status defined as no disease progression to severe. Time: 14 days212 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection in France and Belgium
Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/ kg twice a week for two weeks on immune reconstitution of lymphopenic COVID-19 patients.
NCT04407689 COVID-19 Lymphocytopenia Drug: Interleukin-7 Drug: Placebo MeSH:Lymphopenia
HPO:Lymphopenia
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first Time: 1 month
Secondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: 1 month
Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: 1 month or HD (whichever occurs first)
Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: frequency of secondary infections through day 45 compared tp placebo arm Time: 45 days
Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: length of hospitalization compared to placebo arm Time: 45 days
Description: Number of days in ICU during index hospitalization
Measure: length of stay in ICU compared to placebo arm Time: 45 days
Description: Readmissions to ICU through Day 45
Measure: number of readmissions to ICU compared to placebo arm Time: 45 days
Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Measure: organ support free days compared to placebo arm Time: 45 days
Description: Number of readmissions to the hospital through Day 45
Measure: Frequency of re-hospitalization through day 45 compared to placebo arm Time: 45 days
Description: All-cause mortality through Day 45
Measure: All-cause mortality through day 45 compared to placebo arm Time: 45 days
Description: Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD
Measure: CD4+ and CD8+ T cell counts compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm Time: 30 days
Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Measure: Physiological status through NEWS2 evaluation compared to Placebo arm Time: 30 days
Other Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)
Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events Time: 45 days
213 Efficacy, Safety, and Tolerability of GLS-1200 Topical Nasal Spray in the Prevention of Incident Confirmed, Symptomatic SARS-CoV-2 Infection in Healthcare Personnel
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first Time: 1 monthSecondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: 1 monthDescription: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: 1 month or HD (whichever occurs first)Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: frequency of secondary infections through day 45 compared tp placebo arm Time: 45 daysDescription: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: length of hospitalization compared to placebo arm Time: 45 daysDescription: Number of days in ICU during index hospitalization
Measure: length of stay in ICU compared to placebo arm Time: 45 daysDescription: Readmissions to ICU through Day 45
Measure: number of readmissions to ICU compared to placebo arm Time: 45 daysDescription: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Measure: organ support free days compared to placebo arm Time: 45 daysDescription: Number of readmissions to the hospital through Day 45
Measure: Frequency of re-hospitalization through day 45 compared to placebo arm Time: 45 daysDescription: All-cause mortality through Day 45
Measure: All-cause mortality through day 45 compared to placebo arm Time: 45 daysDescription: Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD
Measure: CD4+ and CD8+ T cell counts compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm Time: 30 daysDescription: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Measure: Physiological status through NEWS2 evaluation compared to Placebo arm Time: 30 daysOther Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)
Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events Time: 45 daysThis clinical trial will evaluate the safety, tolerability and effectiveness of topical GLS-1200 nasal spray to reduce the incidence of confirmed, symptomatic SARS-CoV-2 infection.
NCT04408183 SARS-CoV 2 Infection Drug: GLS-1200 Drug: Placebo MeSH:Infection Communicable Diseases
Primary Outcomes
Measure: Evaluate the number of GLS-1200 topical nasal spray adverse events as assessed by CTCAE v5.0 Time: 4 weeks of treatmentMeasure: Incidence of SARS-CoV-2 infection, confirmed by PCR relative to treatment group Time: 4 weeks of treatment
Secondary Outcomes
Measure: Symptom score of documented SARS-CoV-2 infection relative to treatment group with a higher score being a worse outcome. Time: 4 weeks of treatment214 A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia
This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.
NCT04409262 COVID-19 Pneumonia Drug: Remdesivir Drug: Tocilizumab Drug: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Day 28 Time: Day 28
Secondary Outcomes
Measure: Time to Clinical Improvement (TTCI) Defined as Time from Randomization to National Early Warning Score 2 (NEWS2) Score of Time: Up to Day 28
Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status Time: Up to Day 28
Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Days 7, 14, and 21 Time: Days 7, 14, and 21
Measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline Time: Up to Day 28
Measure: Ventilator-Free Days from Randomization to Day 28 Time: Up to Day 28
Measure: Proportion of Participants Requiring Initiation of Intensive Care Unit (ICU) Care Post-baseline Time: Up to Day 28
Measure: Duration of ICU Stay in Days Time: Up to Day 28
Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.
Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) Time: Up to Day 28
Measure: Mortality Rate on Days 7, 14, 21, 28, and 60 Time: Days 7, 14, 21, 28, and 60
Measure: Time to Recovery, Defined as Time from Randomization to the Time when a Category of 2, Non-ICU Hospital Ward (or "Ready for Hospital Ward") not Requiring Supplemental Oxygen, or Better is Observed Time: Up to Day 28
Measure: Time from Randomization to Hospital Discharge or "Ready for Discharge" (as Evidenced by Normal Body Temperature and Respiratory Rate, and Stable Oxygen Saturation on Ambient Air or Time: Up to Day 28
Measure: Duration of Supplemental Oxygen Use Time: Up to Day 28
Other Outcomes
Measure: Percentage of Participants with Adverse Events (AEs) Time: Up to Day 28
Measure: Proportion of Participants with any Post-Treatment Infection Time: Up to Day 28
Measure: Plasma Concentration of Remdesivir Time: Up to Day 28
215 Randomized Double Blind Placebo-Controlled Study to Determine if Prophylaxis With RTB101 Compared to Placebo Reduces Severity of Lab Confirmed COVID19 in Adults ≥65 Years in a Nursing Home in Which ≥1 Person(s) Have Lab Confirmed COVID19
Primary Outcomes
Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Day 28 Time: Day 28Secondary Outcomes
Measure: Time to Clinical Improvement (TTCI) Defined as Time from Randomization to National Early Warning Score 2 (NEWS2) Score of Time: Up to Day 28Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status Time: Up to Day 28
Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Days 7, 14, and 21 Time: Days 7, 14, and 21
Measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline Time: Up to Day 28
Measure: Ventilator-Free Days from Randomization to Day 28 Time: Up to Day 28
Measure: Proportion of Participants Requiring Initiation of Intensive Care Unit (ICU) Care Post-baseline Time: Up to Day 28
Measure: Duration of ICU Stay in Days Time: Up to Day 28
Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.
Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) Time: Up to Day 28Measure: Mortality Rate on Days 7, 14, 21, 28, and 60 Time: Days 7, 14, 21, 28, and 60
Measure: Time to Recovery, Defined as Time from Randomization to the Time when a Category of 2, Non-ICU Hospital Ward (or "Ready for Hospital Ward") not Requiring Supplemental Oxygen, or Better is Observed Time: Up to Day 28
Measure: Time from Randomization to Hospital Discharge or "Ready for Discharge" (as Evidenced by Normal Body Temperature and Respiratory Rate, and Stable Oxygen Saturation on Ambient Air or Time: Up to Day 28
Measure: Duration of Supplemental Oxygen Use Time: Up to Day 28
Other Outcomes
Measure: Percentage of Participants with Adverse Events (AEs) Time: Up to Day 28Measure: Proportion of Participants with any Post-Treatment Infection Time: Up to Day 28
Measure: Plasma Concentration of Remdesivir Time: Up to Day 28
The purpose of this study is to determine if prophylaxis with RTB101 decreases the severity of laboratory-confirmed COVID-19 among adults ≥ 65 years who reside in a nursing homes in which one or more residents or staff have laboratory-confirmed COVID-19
NCT04409327 COVID19 Drug: RTB101 Drug: Placebo
Primary Outcomes
Measure: The percentage of subjects who develop laboratory-confirmed COVID-19: - with protocol-defined progressive symptoms OR - are hospitalized OR - die Time: Through Week 4Secondary Outcomes
Measure: The percentage of subjects who develop symptomatic laboratory-confirmed COVID-19 infection Time: Through Week 4Measure: Mortality rate in subjects who develop laboratory-confirmed COVID19 Time: Through Week 8
Measure: Percent of subjects who are hospitalized due to having one or more predefined COVID-19 symptoms and laboratory-confirmed SARS-CoV-2 Time: Through Week 4
Measure: Percent of subjects who require mechanical ventilation, noninvasive ventilation, high flow nasal canula oxygen delivery or ICU admission during the hospitalization for COVID19 Time: Through Week 8
Measure: Safety and tolerability will be assessed by report of AE/SAEs Time: Through Week 5 and 8
216 A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)
This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled, parallel group study to assess the safety and efficacy of CSL312 administered intravenously, in combination with standard of care (SOC) treatment, in patients with Coronavirus disease 2019 (COVID 19)
NCT04409509 Coronavirus Disease 2019 (COVID‑19) Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody Drug: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Measure: The incidence of tracheal intubation or death prior to tracheal intubation Time: From randomization to Day 28Secondary Outcomes
Measure: Proportion of subjects with death from all causes Time: From randomization to Day 28Measure: Proportion of subjects intubated Time: From randomization to Day 28
Measure: Number and proportion of subjects with ≥ 2‑point improvement on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal scale Time: From randomization to Day 28
Measure: Number and proportion of subjects within each of the categories of the NIAID Time: From randomization to Day 28
Measure: Proportion of subjects requiring continuous positive airway pressure (CPAP) Time: From randomization to Day 28
Measure: Proportion of subjects requiring bilevel positive airway pressure (BiPAP) Time: From randomization to Day 28
Measure: Proportion of subjects requiring high‑flow nasal cannula (HFNC) Time: From randomization to Day 28
Measure: Proportion of subjects requiring extracorporeal membrane oxygenation (ECMO) Time: From randomization to Day 28
Measure: Maximum change from baseline in Sequential Organ Failure Assessment (SOFA) score Time: From randomization to Day 28
Measure: Change from Baseline in SOFA score and in the individual components of SOFA score Time: From randomization to Day 28
Measure: Length of hospital stay Time: From randomization to Day 28
Measure: Number and proportion of subjects experiencing Adverse Events (AEs) Time: Up to 28 days after CSL312 or placebo administration
Measure: Number and proportion of subjects experiencing serious adverse events (SAEs) Time: Up to 28 days after CSL312 or placebo administration
Measure: Number and proportion of subjects with adverse events of special interest (AESIs) Time: Up to 28 days after CSL312 or placebo administration
Measure: Number and proportion of subjects with CSL312 induced anti‑CSL312 antibodies Time: Up to 28 days after CSL312 or placebo administration
Measure: Maximum plasma concentration (Cmax) of CSL312 Time: Up to 28 days after CSL312 administration
Measure: Time to maximum plasma concentration (Tmax) of CSL312 Time: Up to 28 days after CSL312 administration
Measure: Area under the plasma concentration‑time curve from time zero to the time of the last measurable concentration (AUC0‑last) of CSL312 Time: Up to 28 days after CSL312 administration
Measure: Terminal half-life (T1/2) of CSL312 Time: Up to 28 days after CSL312 administration
217 Study of the P2Et Extract Obtained From Caesalpinia Spinosa in the Symptomatic Treatment of Subjects With COVID-19 at the Hospital Universitario San Ignacio, Colombia.
Antioxidants, and particularly polyphenols, have shown protection in respiratory pathologies, which is related to the decrease in the severity of the clinical picture and suppression of inflammation. This suppression of inflammation may be related to the inhibition of NF-kB polyphenols, where its activation is related to the stimulation of 150 stimuli including cytokines (IL-1β, IL-6, THF-α, GM-CSF, MCP-1), TLRs, among others. There may be other additional mechanisms that can help control virus-induced respiratory pathologies, among which are the regulation of reactive oxygen species (ROS) associated with tissue destruction caused by the virus and a selective antiviral action can be reported. direct. The standardized P2Et extract obtained from C. spinosa, by the Immunobiology Group of the Pontificia Universidad Javeriana, is highly antioxidant, decreases lipid peroxidation and tissue damage and induces complete autophagy in stressed or tumor cells. The induction of a full autophagic flow could inhibit the replication of beta-coronaviruses like SARS-CoV-2. Furthermore, P2Et can decrease the factors involved in tissue damage by reducing IL-6 and decrease ILC2 cells of the lung in animals with lung metastases (unpublished data). These antecedents suggest that the supplementation of patients with COVID-19 with the extract P2Et, could improve their general condition and decrease the inflammatory mediators and the viral load.
NCT04410510 COVID Coronavirus Infection SARS-CoV 2 COVID19 Drug: P2Et (Caesalpinia spinosa extract) Other: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Proportion of patients who reduce the time in the hospital
Measure: Evaluate the efficacy of P2Et in reducing the length of hospital stay of patients with clinical suspicion or confirmed case of COVID-19 Time: 30 daysSecondary Outcomes
Description: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19
Measure: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19 Time: 30 daysDescription: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment
Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment Time: 30 daysDescription: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment
Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment Time: 30 daysDescription: Assess the efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.
Measure: Efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms. Time: 30 daysDescription: Evaluate the efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.
Measure: Efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease. Time: 30 daysDescription: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19
Measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19 Time: 30 days218 Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy
It still unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes, including the timing of maternal viral exposure by gestational age, the effects of parity, age, host immune responses, coexisting medical and obstetrical conditions and the effects of treatment regimens. While further information is gathered, based on the existing evidence from other infections causing pneumonia, pregnant women should be considered to be at high risk for developing severe infection during the current COVID-19 epidemic. Results from clinical trials with HCQ in nonpregnant adults may not be directly extrapolated to pregnant women given the special features of the pregnancy status. Thus, clinical research is urgently needed to improve the care and reduce the risk of poor pregnancy outcomes of women in this and in future epidemics.
NCT04410562 Pregnancy Related COVID Covid-19 Drug: Hydroxychloroquine Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start
Measure: Number of PCR confirmed cases among pregnant women Time: 21 days after interventionSecondary Outcomes
Measure: Incidence of COVID-19 disease during pregnancy Time: through study completion, an average of 1 yearMeasure: Incidence of COVID-19-related admissions Time: through study completion, an average of 1 year
Measure: Incidence of all-cause admissions Time: through study completion, an average of 1 year
Measure: Incidence of all-cause outpatient attendances Time: through study completion, an average of 1 year
Measure: Mean duration of symptoms-signs of COVID-19 Time: through study completion, an average of 1 year
Measure: Frequency and severity of adverse events Time: through study completion, an average of 1 year
Measure: Incidence of preeclampsia Time: through study completion, an average of 1 year
Measure: Incidence of gestational diabetes Time: through study completion, an average of 1 year
Measure: Incidence of SARS-CoV-2 infections during pregnancy Time: through study completion, an average of 1 year
Measure: Prevalence of intrauterine growth restriction Time: through study completion, an average of 1 year
Measure: Maternal mortality rate Time: through study completion, an average of 1 year
Measure: Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate. Time: through study completion, an average of 1 year
Measure: Proportion of neonates with clinical signs/symptoms of COVID-19 Time: through study completion, an average of 1 year
Measure: Prevalence of low birth weight (<10th centile according to local standards) Time: through study completion, an average of 1 year
Measure: Prevalence of preterm birth (<37 weeks of gestational age) Time: through study completion, an average of 1 year
Measure: Prevalence of embryo and foetal losses (miscarriages and stillbirths) Time: through study completion, an average of 1 year
Measure: Frequency of congenital malformations Time: through study completion, an average of 1 year
Measure: Proportion of adverse perinatal outcome Time: through study completion, an average of 1 year
Measure: Neonatal morbidity Time: through study completion, an average of 1 year
Measure: Neonatal mortality rate Time: through study completion, an average of 1 year
219 Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients
The recent inception of the coronavirus SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused thousands of deaths globally. The most frequently reported complications among COVID-19 patients are from respiratory involvement. Vitamin D has immunomodulatory effects that could protect against COVID-19 infection. Indeed, there is good evidence from randomized clinical trials suggesting that high doses of vitamin D administered during cold seasons prevent viral respiratory infections in at risk individual, and more recently, observational studies suggested that the mortality rate from COVID-19 is inversely correlated with levels of serum 25(OH)vitamin D. The hypothesis of the study is that a high dose of vitamin D given orally to patients admitted to the hospital for COVID-19 will prevent the occurrence of respiratory deragement and other adverse clinical events. To evaluate the aforementioned hypothesis, a randomized, controlled, double-blind, clinical trial comparing a 500.000 UI dose of vitamin D versus placebo among COVID-19 patients at moderate risk, requiring hospitalization but without requirements of critical care at admission was designed. The intervention will be one dose of 500.000 UI given orally or matching placebo. The trial has a sequential design with two steps: - The first step, projected to include 200 patients, will assess the effects of the intervention on the respiratory SOFA; and - If there is a detectable effects, the second step, projected to include 1265 patients, will assess the effects on a combined event that includes need of high dose of oxygen or mechanical ventilation. All study outcomes will be measured during the index hospitalization.
NCT04411446 COVID Drug: Vitamin D Drug: Placebo
Primary Outcomes
Description: Is the respiratory component of the sequential organ failure assessment score (SOFA score). It is a 4 points scale, each point indicate a deeper respiratory impairment. The score is based on the relationship between the arterial pressure of oxygen (PaO2) and inspired fraction of oxygen (FiO2), as the ratio of both (PaFi). In the cases were arterial blood gas are not measured, the pulse oximetry will be used instead. The respiratory SOFA is as follows: 1: PaO2/FiO2 >=300; 2: PaO2/FiO2 >=200 and <300; 3: PaO2/FiO2 >=100 and <200; 4: PaO2/FiO2 <300. The minimum respiratory SOFA score will be record on daily basis during first week or to death or discharge, whichever occur first. This outcome is the primary outcome of the first study phase.
Measure: Respiratory SOFA. Time: One weekDescription: The start of oxygen supplementation at FiO2 >40% or the initiation of invasive through orotracheal intubation) or non-invasive ventilation (Continuous positive airway pressure or Bilevel positive airway ventilation). This outcome will be recorded during hospitalization to 30 days, the death or discharge, whichever occur first. This is the primary outcome of the second study phase.
Measure: Need of a high dose of oxygen or mechanical ventilation. Time: 30 daysSecondary Outcomes
Description: Difference between the oxygen saturation at study entry and the lowest oxygen saturation measured during the first week, the death or discharge, whichever occur first. The oxygen saturation will be measured by pulse oximetry using commercially available devices.
Measure: Change in oxygen saturation. Time: One weekDescription: Oxygen saturation equal or less than 90% in any moment during the hospitalization. This outcome will be measured by pulse oximetry using commercially available devices. The outcome will be measured during the first week, the death or hospital discharge, whichever occur first.
Measure: Oxygen desaturation. Time: One weekDescription: The difference between the Quick SOFA score at study entry and the highest value recorded during the hospitalization. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Change in Quick SOFA score. Time: 30 days.Description: Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Myocardial infarction. Time: 30 daysDescription: Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Stroke. Time: 30 daysDescription: Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Acute kidney injury. Time: 30 daysDescription: Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Pulmonary thromboembolism. Time: 30 daysDescription: Combined outcome of the aforementioned events, Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism. Time: 30 daysDescription: Admission to Intensive Care Unit due to clinical deterioration as judged by the treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Admission to ICU. Time: 30 daysDescription: The start of mechanical ventilation invasive during the hospitalization until 30 days, the death or discharge whichever occur first.
Measure: Invasive Mechanical Ventilation. Time: 30 daysDescription: Total duration of initial hospital stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with hospital stays longer than 30 days, it will considered as 30 days.
Measure: Hospital Length of Stay. Time: 30 days.Description: Total duration of initial ICU stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with ICU stays longer than 30 days, it will considered as 30 days.
Measure: ICU length of stay. Time: 30 daysDescription: Death of any cause during the hospitalization until 30 days or discharge whichever occur first.
Measure: Death Time: 30 days.220 A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI
Clinical phase 3 study to investigate the effect of recAP on 28 day mortality in patients admitted to the ICU with acute kidney injury that is caused by sepsis. 1400 patients will be included in the study that is conducted in approx. 100 ICU's in Europe and North America There are two arms in the study, one with active treatment and one with an inactive compound (placebo). Treatment is by 1 hour intravenous infusion, for three days. Patients are followed up for 28 days to see if there is an improvement on mortality, and followed for 90 and 180 days for mortality and other outcomes e.g. long-term kidney function and quality of life.
NCT04411472 Acute Kidney Injury Due to Sepsis Biological: Recombinant human alkaline phosphatase Other: Placebo MeSH:Sepsis Acute Kidney Injury
HPO:Acute kidney injury Sepsis
Primary Outcomes
Description: To demonstrate an effect of recAP on 28 day all cause mortality
Measure: 28-day all-cause mortality Time: 28 days
Secondary Outcomes
Description: MAKE 90: dead or on RRT or ≥25% decline in estimated glomerular filtration rate (eGFR) on Day 90 relative to the known or assumed pre-AKI reference level.
Measure: To investigate the effect of recAP on long-term Major Adverse Kidney Events (MAKE). Time: 90 Days
Description: Days alive and free of organ support through Day 28, i.e., days alive with no MV, RRT, vasopressors or inotropes (with death within 28 days counting as zero days).
Measure: To investigate the effect of recAP on use of organ support, i.e., mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors or inotropes. Time: 28 days
Description: Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).
Measure: To investigate the effect of recAP on length of stay (LOS) in ICU. Time: 28 days
Description: Time to death through Day 90.
Measure: To investigate the effect of recAP on 90-day allcause mortality Time: 90 days
221 A Randomized, Placebo-Controlled, Double-Blind, Sponsor Unblinded, Single Ascending Dose, Phase 1 First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous LY3819253 in Participants Hospitalized for COVID-19
Primary Outcomes
Description: To demonstrate an effect of recAP on 28 day all cause mortality
Measure: 28-day all-cause mortality Time: 28 daysSecondary Outcomes
Description: MAKE 90: dead or on RRT or ≥25% decline in estimated glomerular filtration rate (eGFR) on Day 90 relative to the known or assumed pre-AKI reference level.
Measure: To investigate the effect of recAP on long-term Major Adverse Kidney Events (MAKE). Time: 90 DaysDescription: Days alive and free of organ support through Day 28, i.e., days alive with no MV, RRT, vasopressors or inotropes (with death within 28 days counting as zero days).
Measure: To investigate the effect of recAP on use of organ support, i.e., mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors or inotropes. Time: 28 daysDescription: Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).
Measure: To investigate the effect of recAP on length of stay (LOS) in ICU. Time: 28 daysDescription: Time to death through Day 90.
Measure: To investigate the effect of recAP on 90-day allcause mortality Time: 90 daysThe purpose of this study is to test the safety and tolerability of LY3819253 when it is given by injection into a vein to participants hospitalized with COVID-19. Blood tests will be done to check how much LY3819253 is in the bloodstream and how long the body takes to eliminate it. Participation could last about 8 weeks and may include up to 15 visits in the hospital or the home.
NCT04411628 COVID-19 Drug: LY3819253 Drug: Placebo
Primary Outcomes
Description: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
Measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration Time: Baseline through Day 60Secondary Outcomes
Description: PK: AUC of LY3819253
Measure: Pharmacokinetics (PK): Area Under the Concentration-time Curve (AUC) of LY3819253 Time: Baseline through Day 29Description: PD: Change from Baseline in Viral Load
Measure: Pharmacodynamics (PD): Change from Baseline to Day 29 in Viral Load Time: Baseline, Day 29222 A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-002 in Adults With COVID 19 Pneumonia and Acute Lung Injury
The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT, for the treatment of patients with COVID-19 pneumonia who have mild to moderate ARDS. LIGHT is a cytokine in the TNF super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.
NCT04412057 COVID-19 Pneumonia Acute Lung Injury ARDS Drug: CERC-002 Drug: Placebo MeSH:Pneumonia Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
HPO:Pneumonia
Primary Outcomes
Description: Respiratory failure defined based on resource utilization requiring at least one of the following:
Endotracheal intubation and mechanical ventilation
Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5)
Noninvasive positive pressure ventilation,
Extracorporeal membrane oxygenation
Measure: Proportion of patient alive and free of respiratory failure Time: Baseline to Day 28
Secondary Outcomes
Description: 1-month mortality
Measure: Proportion of subjects who are alive Time: Baseline to Day 28
223 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE SAFETY AND EFFICACY OF TOFACITINIB IN HOSPITALIZED PARTICIPANTS WITH COVID-19 PNEUMONIA WHO ARE RECEIVING STANDARD OF CARE THERAPY
Primary Outcomes
Description: Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation, Extracorporeal membrane oxygenation
Measure: Proportion of patient alive and free of respiratory failure Time: Baseline to Day 28Secondary Outcomes
Description: 1-month mortality
Measure: Proportion of subjects who are alive Time: Baseline to Day 28The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1. Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60. An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.
NCT04412252 COVID-19 Drug: Tofacitinib Other: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using ordinal scale Time: Day 28
Secondary Outcomes
Description: Ordinal scale of disease severity. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using ordinal scale Time: Day 14
Description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Time: Day 14 and Day 28
Description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Status of discharged or not requiring supplemental oxygen Time: Day 28
Description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.
Measure: Mortality Time: Day 60
224 A Randomized Double-blind Placebo-controlled Study to Evaluate the Safety and Efficacy of ATYR1923 In Adult Patients With Severe Pneumonia Related to SARS-CoV-2 Infection (COVID-19)
Primary Outcomes
Description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using ordinal scale Time: Day 28Secondary Outcomes
Description: Ordinal scale of disease severity. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using ordinal scale Time: Day 14Description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Time: Day 14 and Day 28Description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Status of discharged or not requiring supplemental oxygen Time: Day 28Description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.
Measure: Mortality Time: Day 60A Phase 2 study to evaluate the safety and preliminary efficacy of ATYR1923, compared to placebo, in hospitalized patients with SARS-CoV-2 (COVID-19) severe pneumonia not requiring mechanical ventilation
NCT04412668 SARS-CoV-2 (COVID-19) Severe Pneumonia Drug: ATYR1923 1 mg/kg Drug: ATYR1923 3 mg/kg Drug: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Measure: Incidence of treatment-emergent adverse events (TEAEs) Time: Baseline through Day 60
Secondary Outcomes
Measure: Time to normalization of oxygen saturation (SpO2) (>93% on room air sustained for at least 24 hours) Time: Baseline through Day 14 or discharge
Measure: Duration of supplemental oxygen (O2) requirement Time: Baseline through Day 14 or discharge
Measure: Number of days with fever (temperature >100.4ºF [38.0ºC]) Time: Baseline through Day 14 or discharge
Measure: Time to normalization of temperature (≤100.4ºF [38.0ºC]) Time: Baseline through Day 14 or discharge
Measure: Change from baseline in World Health Organization (WHO) Ordinal Scale score on Days 5, 7, 14, 28, and 60 Time: Baseline through Day 60
Measure: Time to improvement from inpatient hospital admission based on at least a 1 point reduction in WHO Ordinal Scale score Time: Baseline through Day 60
225 A Randomized, Controlled Clinical Trial of the Safety and Efficacy of Tocilizumab for the Treatment of Severe COVID-19
Primary Outcomes
Measure: Incidence of treatment-emergent adverse events (TEAEs) Time: Baseline through Day 60Secondary Outcomes
Measure: Time to normalization of oxygen saturation (SpO2) (>93% on room air sustained for at least 24 hours) Time: Baseline through Day 14 or dischargeMeasure: Duration of supplemental oxygen (O2) requirement Time: Baseline through Day 14 or discharge
Measure: Number of days with fever (temperature >100.4ºF [38.0ºC]) Time: Baseline through Day 14 or discharge
Measure: Time to normalization of temperature (≤100.4ºF [38.0ºC]) Time: Baseline through Day 14 or discharge
Measure: Change from baseline in World Health Organization (WHO) Ordinal Scale score on Days 5, 7, 14, 28, and 60 Time: Baseline through Day 60
Measure: Time to improvement from inpatient hospital admission based on at least a 1 point reduction in WHO Ordinal Scale score Time: Baseline through Day 60
The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g. increase in oxygen requirements). Participants will be followed for 28 days.
NCT04412772 COVID-19 Drug: Tocilizumab Drug: Placebo
Primary Outcomes
Description: Clinical Status 7-point ordinal scale: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death
Measure: Clinical status (on a 7-point ordinal scale) at day 28 Time: up to day 28Secondary Outcomes
Description: ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of < 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
Measure: Clinical improvement Time: up to day 28Description: iv. Incidence of mechanical ventilation v. Ventilator-free days
Measure: Mechanical Ventilation Time: up to day 28Description: vi. Duration of time on supplemental oxygen
Measure: Oxygenation Time: up to day 28226 A Randomized Clinical Trial for Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination to Prevent Infections by COVID-19: The ACTIVATE II Trial
Based on findings of the interim analysis of the ACTIVATE study showing 53% decrease of the incidence of all new infections with BCG vaccination, a new trial is designed aiming to validate if BCG can protect against COVID-19 (Corona Virus Disease-19).The aim of the study is to demonstrate in a double-blind, placebo-controlled approach if vaccination of participants susceptible to COVID-19 with BCG vaccine may modulate their disease susceptibility for COVID-19. This will be validated using both clinical and immunological criteria. At the same time, a sub-study will be conducted and the mechanism of benefit from BCG vaccination by assessing its effect on vascular endothelial function and mononuclear blood cells will be studied
NCT04414267 COVID-19 Virus Diseases Corona Virus Infection Coronary Heart Disease Chronic Obstructive Pulmonary Disease Biological: BCG vaccine Biological: Placebo MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Heart Diseases Coronary Disease Virus Diseases
HPO:Chronic pulmonary obstruction Pulmonary obstruction
Primary Outcomes
Description: This is set on visit 3 (90 ± 5 days from the date of visit 1). The two groups of vaccination are compared for the primary endpoints which is composite. Patients who meet any of the following will be considered to meet the primary endpoint:
Positive for the respiratory questionnaire endpoint when at least one of the following combination is met either at visit 2 and/or at visit 3:
One situation definitively related to COVID-19
All four questions of symptoms possibly related to COVID-19
At least two questions of symptoms possibly related to COVID-19 as well as need for admission at the emergency department of any hospital and/or need for intake of antibiotics
At least four questions of symptoms probably related to COVID-19 one of which is "need for admission at the emergency department of any hospital and/or need for intake of antibiotics"
Positive IgG or IgM antibodies against SARS-CoV-2
Measure: Positive for the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 3. Time: Visit 3 (90 +/- 5 days)
Secondary Outcomes
Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint on visit 4
Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 4 Time: Visit 4 (135 +/- 5 days)
Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint (as defined at primary study endpoint) on visit 5
Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 5 Time: Visit 5 (180 +/- 5 days)
Description: Prevalence of IgG/IgM against SARS-CoV-2 will be measured among the patients who failed the eligibility procedure and the patients that were eligible and were enrolled
Measure: Prevalence of IgG/IgM against SARS-CoV-2 Time: Screening Visit and Visit 3 (90 +/- 5 days)
Description: Itemized analysis of each of the components of the respiratory questionnaire on each study visit
Measure: Analysis of each of the components of the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19. Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)
Description: The impact of new cardiovascular events between the two study groups (placebo and BCG) will be analyzed, though the collection of any cardiovascular events occured to the enrolled patients.
Measure: The impact of new cardiovascular events between the two study groups Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)
Description: Differences in repeated measurements of arterial stiffness in visit 3 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.
Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)
Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 3 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.
Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)
Description: Differences in repeated measurements of endothelial function in visit 3 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)
Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 3 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)
Description: Differences in repeated measurements of arterial stiffness in visit 5 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.
Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)
Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 5 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.
Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)
Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 5 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)
Description: Differences in repeated measurements of endothelial function in visit 5 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)
Description: Differences in cardiac ultrasound at visit 5 between the two sub-study groups (placebo or BCG) will be assessed using standard measurements from 2-D and Doppler echocardiography.
Measure: Differences in cardiac ultrasound at visit 5 between the two sub-study groups Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)
Description: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups (placebo or BCG) will be analyzed
Measure: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)
227 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia
Primary Outcomes
Description: This is set on visit 3 (90 ± 5 days from the date of visit 1). The two groups of vaccination are compared for the primary endpoints which is composite. Patients who meet any of the following will be considered to meet the primary endpoint: Positive for the respiratory questionnaire endpoint when at least one of the following combination is met either at visit 2 and/or at visit 3: One situation definitively related to COVID-19 All four questions of symptoms possibly related to COVID-19 At least two questions of symptoms possibly related to COVID-19 as well as need for admission at the emergency department of any hospital and/or need for intake of antibiotics At least four questions of symptoms probably related to COVID-19 one of which is "need for admission at the emergency department of any hospital and/or need for intake of antibiotics" Positive IgG or IgM antibodies against SARS-CoV-2
Measure: Positive for the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 3. Time: Visit 3 (90 +/- 5 days)Secondary Outcomes
Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint on visit 4
Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 4 Time: Visit 4 (135 +/- 5 days)Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint (as defined at primary study endpoint) on visit 5
Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 5 Time: Visit 5 (180 +/- 5 days)Description: Prevalence of IgG/IgM against SARS-CoV-2 will be measured among the patients who failed the eligibility procedure and the patients that were eligible and were enrolled
Measure: Prevalence of IgG/IgM against SARS-CoV-2 Time: Screening Visit and Visit 3 (90 +/- 5 days)Description: Itemized analysis of each of the components of the respiratory questionnaire on each study visit
Measure: Analysis of each of the components of the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19. Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)Description: The impact of new cardiovascular events between the two study groups (placebo and BCG) will be analyzed, though the collection of any cardiovascular events occured to the enrolled patients.
Measure: The impact of new cardiovascular events between the two study groups Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)Description: Differences in repeated measurements of arterial stiffness in visit 3 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.
Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 3 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.
Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)Description: Differences in repeated measurements of endothelial function in visit 3 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 3 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 3 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)Description: Differences in repeated measurements of arterial stiffness in visit 5 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.
Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 5 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.
Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 5 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)Description: Differences in repeated measurements of endothelial function in visit 5 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm
Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 5 Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)Description: Differences in cardiac ultrasound at visit 5 between the two sub-study groups (placebo or BCG) will be assessed using standard measurements from 2-D and Doppler echocardiography.
Measure: Differences in cardiac ultrasound at visit 5 between the two sub-study groups Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)Description: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups (placebo or BCG) will be analyzed
Measure: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)Opaganib, a sphingosine kinase-2 (SphK2) inhibitor, has been broadly tested in Phase I/II studies. Extensive nonclinical data indicates both anti-viral and anti-inflammatory activity via selective SphK2 inhibition which may prove beneficial for treating COVID-19 infection and resulting pneumonia. This proof of concept study will take place in the US and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. Half of the patients, i.e. 20 patients, will receive opaganib in addition to standard of care for 14 days. The other 20 will receive matching placebo (capsules that do not contain the medication) in addition to standard of care. Study drug will be administered every day for 14 days, twice each day, unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.
NCT04414618 Coronavirus Infections Drug: Opaganib Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Measurement of the oxygen requirement
Measure: Evaluation of the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days Time: Every day from day 1 to day 14 of treatment
Secondary Outcomes
Description: Measurement of the oxygen requirement
Measure: Evaluation of the time to 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min Time: Every day from day 1 to day 14 of treatment
Measure: Evaluation of the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment
Description: Measurement of temperature
Measure: Evaluation of the proportion of afebrile patients at Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment
Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2
Measure: Evaluation of the time to negative swabs for SARS-CoV-2 by PCR Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment
Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2
Measure: Evaluation of the proportion of patients with negative swabs for SARS-CoV-2 by PCR at Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment
Measure: The percentage of patients who require intubation and mechanical ventilation by Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment
Measure: Evaluation of the time to mechanical ventilation Time: From screening phase and every day from day 1 to day 14 of treatment
Description: Evaluation the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C[100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14
Measure: Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment
Measure: Evaluation of mortality 30 days post-baseline Time: 30 days after day 1 of treatment
Other Outcomes
Measure: To determine the incidence rate of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) Time: Every day from day 1 to day 14 of treatment and at end of the 4 weeks follow-up after the end of treatment
228 A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Axatilimab for the Treatment of Hospitalized Patients With Respiratory Signs and Symptoms Secondary to Novel Coronavirus Disease (COVID-19)
Primary Outcomes
Description: Measurement of the oxygen requirement
Measure: Evaluation of the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days Time: Every day from day 1 to day 14 of treatmentSecondary Outcomes
Description: Measurement of the oxygen requirement
Measure: Evaluation of the time to 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min Time: Every day from day 1 to day 14 of treatmentMeasure: Evaluation of the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment
Description: Measurement of temperature
Measure: Evaluation of the proportion of afebrile patients at Day 14 Time: From screening phase and every day from day 1 to day 14 of treatmentDescription: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2
Measure: Evaluation of the time to negative swabs for SARS-CoV-2 by PCR Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatmentDescription: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2
Measure: Evaluation of the proportion of patients with negative swabs for SARS-CoV-2 by PCR at Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatmentMeasure: The percentage of patients who require intubation and mechanical ventilation by Day 14 Time: From screening phase and every day from day 1 to day 14 of treatment
Measure: Evaluation of the time to mechanical ventilation Time: From screening phase and every day from day 1 to day 14 of treatment
Description: Evaluation the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C[100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14
Measure: Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14 Time: From screening phase and every day from day 1 to day 14 of treatmentMeasure: Evaluation of mortality 30 days post-baseline Time: 30 days after day 1 of treatment
Other Outcomes
Measure: To determine the incidence rate of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) Time: Every day from day 1 to day 14 of treatment and at end of the 4 weeks follow-up after the end of treatmentThis is a randomized, double-blind, placebo-controlled, 29-day study to assess the efficacy and safety of axatilimab plus standard of care, compared with placebo plus standard of care, in patients with respiratory signs and symptoms secondary to novel coronavirus disease (COVID-19).
NCT04415073 Coronavirus COVID ARDS Cytokine Storm Cytokine Release Syndrome Drug: SNDX-6352 Drug: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Description: Respiratory failure as defined by need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation >6L oxygen/minute, or clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making is driven solely by resource limitation
Measure: Proportion of subjects alive and free of respiratory failure Time: 29 DaysSecondary Outcomes
Description: Proportion of subjects achieving a ≥ 2 category improvement on 7-point ordinal score relative to the baseline on Day 28 as collected on Day 29
Measure: Secondary clinical improvement outcomes Time: 29 DaysDescription: National early warning score (NEWS) of ≤2 maintained for 24 hours
Measure: Time to clinical improvement (TTCI) Time: 29 DaysDescription: Change from baseline to Day 29 or hospital discharge or death, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen (SpO2/FiO2)
Measure: To evaluate improvement in oxygenation in hospitalized adults with respiratory signs and symptoms secondary to COVID 19 treated with axatilimab Time: 29 DaysDescription: Serum concentrations of IL 6 and c-reactive protein (CRP) change from baseline to Day 15 or hospital discharge or death
Measure: To evaluate changes in biomarkers following treatment with axatilimab Time: 15 DaysDescription: Frequency and severity of AEs and SAEs
Measure: To evaluate the safety and tolerability of axatilimab in the same population Time: 29 DaysDescription: Proportion of subjects who require initiation of mechanical ventilation after study entry
Measure: Ventilation outcomes Time: 29 DaysDescription: Proportion of subjects who are SARS CoV-2 virus free by Day 15 or hospital discharge, whichever is sooner
Measure: To evaluate antiviral effect of axatilimab in hospitalized adults with recently diagnosed SARS CoV-2 infection Time: Day 15Description: Serum concentration of axatilimab and presence of anti-drug antibody
Measure: To characterize exposure to axatilimab Time: 29 Day229 Investigation of Tofacitinib to Mitigate the Impact of COVID-19 (I-TOMIC) in Moderate SARS-CoV-2 (MODERATE I-TOMIC)
The purpose of this randomized, double blinded, placebo controlled study is to assess the efficacy and safety of tofacitinib in hospitalized adult (18-65 years old) patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have serologic markers of inflammation but do not need mechanical ventilation.
NCT04415151 COVID-19 Drug: Tofacitinib 10 mg Drug: Placebo
Primary Outcomes
Description: The primary objective of this study is to determine whether tofacitinib improves the clinical outcomes of patients with moderate SARS-CoV-2 infection as determined by the primary outcome measure: Proportion of subjects alive and not needing any form of mechanical ventilation, high flow oxygen, or ECMO by day 14.
Measure: Disease Severity Time: 14 daysSecondary Outcomes
Description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) at day 14. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.
Measure: Clinical improvement Time: 14 daysDescription: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) (days 3 through day 14): The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.
Measure: Clinical improvement Time: Up to 14 daysDescription: Time to recovery [ Time Frame: Day 1 through Day 14] (Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities)
Measure: Time to recovery Time: Up to 14 daysDescription: Time to clinical improvement (defined as a 2-point increase on the NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities). The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.
Measure: Time to clinical improvement Time: 30 daysDescription: Clinical status on the NIAID 8-point ordinal scale at day 30 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.
Measure: Clinical status Time: 30 DaysDescription: Clinical status on the NIAID 8-point ordinal scale at day 60 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.
Measure: Clinical status Time: 60 DaysDescription: Clinical status on the NIAID 8-point ordinal scale at day 90 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.
Measure: Clinical status Time: 90 DaysDescription: Mortality rate at day 30
Measure: Mortality Time: 30 DaysDescription: Mortality rate at day 60
Measure: Mortality Time: 60 DaysDescription: Mortality rate at day 90
Measure: Mortality Time: 90 DaysDescription: Proportion of patients requiring mechanical ventilatory support.
Measure: Mechanical Ventilatory Support Time: Up to 14 DaysDescription: Duration of invasive mechanical ventilation (days).
Measure: Mechanical Ventilatory Support Duration Time: Up to 14 DaysDescription: Invasive mechanical ventilation free days.
Measure: Freedom from mechanical ventilation Time: Up to 14 DaysDescription: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Measure: Adverse events Time: Up to 14 daysDescription: Did the patient receive an intervention with additional immunomodulatory agent (i.e. IL-6 targeting therapy)? (y/n)
Measure: Additional intervention Time: Up to 14 daysDescription: Change in SARS-CoV-2 viral titers during intervention.
Measure: Viral titer Time: Up to 14 days230 Reducing Hospital Admission of Elderly in SARS-CoV-2 Pandemic Via the Induction of Trained Immunity by Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial
Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also been shown to induce protection against various infections with a viral aetiology, leading to significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease severity in elderly people, who are known to be at increased risk of illness and death from SARS-CoV-2 infection. Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).
NCT04417335 COVID-19 Biological: BCG vaccine Biological: Placebo
Primary Outcomes
Measure: SARS-CoV-2 related hospital admission Time: Maximum of 1 yearSecondary Outcomes
Measure: the duration of hospital admission due to documented COVID-19 Time: Maximum of 1 yearMeasure: the cumulative incidence of documented SARS-CoV-2 infection Time: Maximum of 1 year
Measure: the cumulative incidence of self-reported acute respiratory symptoms or fever Time: Maximum of 1 year
Measure: the cumulative incidence of death due to documented SARS-CoV-2 infection Time: 1 year
Measure: the cumulative incidence of hospital admission for any reason Time: Maximum of 1 year
Measure: the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection Time: Maximum of 1 year
231 Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection: A Randomized, Double-blind, Placebo Controlled, Telemedicine Study (SynCov Study)
The investigators hypothesize that the intake of Omni-Biotic® 10 AAD can reduce the duration of diarrhea in Covid-19 disease. The investigators further hypothesize that Omni-Biotic® 10 AAD can reduce stool frequency, improve stool consistency, improve other gastrointestinal symptoms of Covid-19, reduce disease duration and severity, reduce intestinal inflammation and can improve dysbiosis. The investigators aim to perform a randomized, double blind, placebo-controlled study using telemedicine in patients with Covid-19 disease.
NCT04420676 COVID Dietary Supplement: Omnibiotic AAD Dietary Supplement: Placebo MeSH:Infection
Primary Outcomes
Description: Duration of diarrhea (defined as days with 3 or more loose stools)
Measure: Diarrhea Time: 30 daysSecondary Outcomes
Description: stool evacuations per days
Measure: Stool frequency Time: 30 daysDescription: Stool consistency according to Bristol stool scale for each evacuation, score 1-7, a higher score means a lower stool consistancy
Measure: Stool consistency Time: 30 daysDescription: presence of anorexia, nausea, vomiting, abdominal pain, bloating (yes/no)
Measure: Gastrointestinal symptoms Time: 30 daysDescription: days patients feel sick, are not able to work or are on sick leave
Measure: Duration of Covid-19 disease Time: 30 daysDescription: mild/moderate/severe
Measure: Severity of Covid-19 disease Time: 30 daysDescription: measured by ELISA
Measure: Stool Calprotectin Time: 30 daysDescription: measured by ELISA
Measure: Stool Zonulin Time: 30 daysDescription: 16S RNA sequencing
Measure: Microbiome composition Time: 30 days232 A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection
The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.
NCT04421027 COVID-19 Drug: Baricitinib Drug: Placebo
Primary Outcomes
Description: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including ECMO)
Measure: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including extracorporeal membrane oxygenation [ECMO]) Time: Day 1 to Day 28Secondary Outcomes
Description: The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.
Measure: Percentage of Participants with at Least 1-Point Improvement on NIAID-OS or Live Discharge from Hospital Time: Day 10Description: Number of Ventilator-Free Days
Measure: Number of Ventilator-Free Days Time: Day 1 to Day 28Description: Recovery assessed by the NIAID-OS.
Measure: Time to Recovery Time: Day 1 to Day 28Description: Overall Improvement on the NIAID-OS
Measure: Overall Improvement on the NIAID-OS Time: Day 1 to Day 28Description: Duration of Hospitalization
Measure: Duration of Hospitalization Time: Day 1 to Day 28Description: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline
Measure: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline Time: Day 10Description: Mortality
Measure: Mortality Time: Day 1 to Day 28Description: Duration of Stay in the ICU in Days
Measure: Duration of Stay in the Intensive Care Unit (ICU) in Days Time: Day 1 to Day 28Description: Time to Clinical Deterioration (one-category increase on the NIAID-OS)
Measure: Time to Clinical Deterioration (one-category increase on the NIAID-OS) Time: Day 1 to Day 28Description: Time to Resolution of Fever, in Participants with Fever at Baseline
Measure: Time to Resolution of Fever, in Participants with Fever at Baseline Time: Day 1 to Day 28Description: The NEWS is used to detect and report changes in illness severity in participants with acute illness. The score is determined from six physiological parameters readily measured over time in hospitalized participants: Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness
Measure: Mean Change from Baseline on the National Early Warning Score (NEWS) Time: Baseline, Day 1 to Day 28Description: Time to Definitive Extubation
Measure: Time to Definitive Extubation Time: Day 1 to Day 28Description: Time to Independence from Non-Invasive Mechanical Ventilation
Measure: Time to Independence from Non-Invasive Mechanical Ventilation Time: Day 1 to Day 28Description: Time to Independence from Oxygen Therapy in Days
Measure: Time to Independence from Oxygen Therapy in Days Time: Day 1 to Day 28Description: Number of Days with Supplemental Oxygen Use
Measure: Number of Days with Supplemental Oxygen Use Time: Day 1 to Day 28Description: Number of Days of Resting Respiratory Rate <24 Breaths per Minute
Measure: Number of Days of Resting Respiratory Rate <24 Breaths per Minute Time: Day 1 to Day 28233 A Randomized Controlled Adaptive Study Comparing COVID-19 Convalescent Plasma (CCP) to Non-immune Plasma to Limit Coronavirus-associated Complications in Hospitalized Patients
The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset of initial symptoms.
NCT04421404 COVID-19 Sars-CoV2 Biological: COVID-19 Convalescent Plasma (CCP) Biological: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Description: Progression to mechanical ventilation or death within the first 14 days of enrollment.
Measure: Mechanical Ventilation or Death Endpoint Time: Day 14Secondary Outcomes
Description: Progression to mechanical ventilation or death within the first 28 days of enrollment.
Measure: Mechanical Ventilation or Death Endpoint Time: Day 28Description: Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.
Measure: 8-Point Ordinal Scale Endpoint Time: Day 29234 A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Subjects With Mild or Moderate Coronavirus (COVID-19)
A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed inhaled iNO compared to placebo in subjects with COVID-19.
NCT04421508 COVID-19 Coronavirus Coronavirus Infection Combination Product: INOpulse Combination Product: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Measure: The proportion of subjects who died or had respiratory failure Time: Through Day 28Secondary Outcomes
Description: The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale Time: Day 7, 14, 28 and day of dischargeMeasure: Proportion of subject to recover, defined as return to room air or baseline O2, or discharged alive Time: Through Day 28
Measure: Proportion of subjects discharged alive from hospital Time: Through Day 28
Measure: Duration of Hospitalization Time: Through Day 28
Measure: Mortality - all cause and cardiopulmonary Time: Through Day 28
Measure: Proportion of subjects with a negative conversion of reverse transcription polymerase chain reaction (RT-PCR) from a nasopharyngeal swab Time: Through Day 28
Other Outcomes
Measure: Proportion of subjects with adverse events leading to study drug discontinuation Time: Through Day 28235 Coronavirus Smell Therapy for Anosmia Recovery
As the COVID-19 pandemic spread around the world, anosmia and dysgeusia were quickly recognized as two of the key presenting symptoms. The probability of return of smell is related to severity of smell loss at presentation, but it appears that the loss of sense of smell and taste seems to persist in approximately 10% of the affected patients after 6 months. As a result of COVID-19, it is estimated that within the next 12 months > 150,000 Americans will suffer permanent loss of smell. The magnitude of this impairment on the health, safety, and quality of life is truly unprecedented and makes post-COVID olfactory disorder a major public health problem. Thus, there is a pressing need to identify effective treatments. The research questions are to determine the effects of steroid nasal saline lavage and olfactory training among adults with post-COVID olfactory dysfunction and identify confounders and modifiers of any observed effects. To answer the research question, the investigators propose a 2 x 2 factorial design blinded randomized clinical trial whereby 220 subjects with documented COVID-19 with anosmia/hyposmia of 12 weeks duration or longer from Missouri, Illinois, and Indiana will be recruited electronically from COVID patient advocacy sites, social media sites, and other internet sources. Enrolled subjects will be randomized to nasal saline lavage with topical budesonide or placebo to address the presumed role of inflammation in the olfactory cleft and each subject will also be randomized to olfactory training with patient-specific, high- or low-concentration essential oil scent to assess the role of olfactory training. Data will be analyzed in a blinded fashion to allow estimation of observed effect size for both anti-inflammatory and olfactory training. This innovative study will exploit the unique opportunities presented by COVID-19. The study will use a high-tech virtual "contactless" research strategy, including eConsent and digital mHealth techniques to obtain rapid answers to the research questions. The interventions are low-cost, readily available, and results of this study can be directly disseminated to the care of COVID-19 patients with anosmia.
NCT04422275 Anosmia Drug: Budesonide Behavioral: High-Concentration Essential Oil Drug: Placebo Behavioral: Low-Concentration Essential Oil MeSH:Olfaction Disorders
HPO:Anosmia
Primary Outcomes
Description: The University of Pennsylvania Smell Identification Test (UPSIT) (Sensonics, New Jersey)7 is the most widely accepted olfactory identification test in North America. The UPSIT consists of four 10-page booklets, with a total of 40 items. Subjects are asked to scratch each strip with a pencil to release the scents, detect the smell, and identify the smell from the four choice options. The UPSIT comes from a scoring rubric that identifies the normalcy benchmark based on age and gender. Normosmia is defined as ≥34 for males and ≥35 for females, and an increase of 4 points or more from baseline indicates a clinically meaningful improvement. UPSIT has high internal reliability across a wide range of populations.
Measure: University of Pennsylvania Smell Identification Test (UPSIT) Time: The within subject change in UPSIT between baseline and 12- and 24-week assessment time frame.
Secondary Outcomes
Description: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) was adapted from the original 52-item Questionnaire of Olfactory Disorders. This short-modified version is a validated 17-item questionnaire about quality of life and impairments related to olfactory dysfunction. The maximum score is 51, and higher values indicate worse quality of life or higher degree of impairment of normal daily activity. Mean scores in anosmics is 19; hyposmics is 8; and normosmics is 0. Prior studies used a cutoff score of 12.5 to reflect normal vs. abnormal scores.The minimum clinically important difference is 5.2.
Measure: Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). Time: The within subject change in QOD-NS between baseline and assessment time frame.
Description: The Global Rating of Smell is a single-item, global rating that asks:
"Overall, please rate your current sense of smell? Excellent, Very Good, Good, Fair, Poor, Absent."
Measure: Global Rating of Smell. Time: 12 weeks - End of nasal lavage & olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
Description: The Global Rating of Smell Change is a single-item, global rating that asks: "Compared to your sense of smell # weeks ago, how would you rate your change in smell since then? Much better, Somewhat better, Slightly better, Neither better nor worse, Slightly worse, Somewhat worse, or Much worse." The time frame ("#") will be changed to reflect the correct time since enrollment (i.e., 12, or 24 weeks).
Measure: Global Rating of Smell Change. Time: 12 weeks - End of olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
236 Randomized, Single-blind, Double-dummy, 4-fold Cross-over, Placebo- and Active-controlled Study to Investigate the Influence of BAY 1817080 on the QTc Interval in Healthy Male and Female Participants (TQT Study)
Primary Outcomes
Description: The University of Pennsylvania Smell Identification Test (UPSIT) (Sensonics, New Jersey)7 is the most widely accepted olfactory identification test in North America. The UPSIT consists of four 10-page booklets, with a total of 40 items. Subjects are asked to scratch each strip with a pencil to release the scents, detect the smell, and identify the smell from the four choice options. The UPSIT comes from a scoring rubric that identifies the normalcy benchmark based on age and gender. Normosmia is defined as ≥34 for males and ≥35 for females, and an increase of 4 points or more from baseline indicates a clinically meaningful improvement. UPSIT has high internal reliability across a wide range of populations.
Measure: University of Pennsylvania Smell Identification Test (UPSIT) Time: The within subject change in UPSIT between baseline and 12- and 24-week assessment time frame.Secondary Outcomes
Description: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) was adapted from the original 52-item Questionnaire of Olfactory Disorders. This short-modified version is a validated 17-item questionnaire about quality of life and impairments related to olfactory dysfunction. The maximum score is 51, and higher values indicate worse quality of life or higher degree of impairment of normal daily activity. Mean scores in anosmics is 19; hyposmics is 8; and normosmics is 0. Prior studies used a cutoff score of 12.5 to reflect normal vs. abnormal scores.The minimum clinically important difference is 5.2.
Measure: Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). Time: The within subject change in QOD-NS between baseline and assessment time frame.Description: The Global Rating of Smell is a single-item, global rating that asks: "Overall, please rate your current sense of smell? Excellent, Very Good, Good, Fair, Poor, Absent."
Measure: Global Rating of Smell. Time: 12 weeks - End of nasal lavage & olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)Description: The Global Rating of Smell Change is a single-item, global rating that asks: "Compared to your sense of smell # weeks ago, how would you rate your change in smell since then? Much better, Somewhat better, Slightly better, Neither better nor worse, Slightly worse, Somewhat worse, or Much worse." The time frame ("#") will be changed to reflect the correct time since enrollment (i.e., 12, or 24 weeks).
Measure: Global Rating of Smell Change. Time: 12 weeks - End of olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)In this study, researchers want to find whether the study drug BAY1817080 has an effect on the electrocardiogram (ECG). 40 healthy male or female participants with the age of 18 to 65 years will be enrolled into this study. The ECG of the participants will be monitored closely by the researchers to detect any change after intake of the study medication.
NCT04423744 Cough Endometriosis Overactive Bladder Drug: BAY1817080 Drug: Moxifloxacin Drug: Placebo MeSH:Urinary Bladder, Overactive Endometriosis
HPO:Endometriosis
Primary Outcomes
Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 therapeutic dose Time: Baseline and Day 3
Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 supra-therapeutic dose Time: Baseline and Day 3
Secondary Outcomes
Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after a single oral dose of moxifloxacin Time: Baseline and Day 3
Measure: Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose Time: Baseline and Day 3
Measure: Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after a single oral dose of moxifloxacin Time: Baseline and Day 3
Description: Area under the concentration vs. time curve from zero to 24 hours after multiple doses
Measure: AUC(0-24)md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose Time: Predose and up to 24 hours after last dose of BAY1817080 at Day 3
Description: Area under the concentration vs. time curve from zero to infinity after single dose
Measure: AUC after a single oral dose of moxifloxacin Time: Predose and up to 24 hours after single dose of moxifloxacin at Day 3
Description: Maximum observed drug concentration in measured matrix after multiple doses
Measure: Cmax,md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose Time: Up to 24 hours after last dose of BAY1817080 at Day 3
Description: Maximum observed drug concentration in measured matrix after single dose
Measure: Cmax after a single oral dose of moxifloxacin Time: Up to 24 hours after single dose of moxifloxacin at Day 3
Measure: Incidences of treatment-emergent adverse events (TEAEs) after BAY1817080 therapeutic or supra-therapeutic dose Time: From the start of BAY1817080 administration until 7 days after last dose, assessed up to 10 days
237 Proof of Concept, Multicentre, Parallel, Randomized, Double-blind Clinical Trial to Assess the Safety and Efficacy of Nitazoxanide 600 mg Three Times a Day, Compared to Placebo in the Treatment of Hospitalized Patients With COVID-19 in Non-critical Condition
Primary Outcomes
Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 therapeutic dose Time: Baseline and Day 3Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 supra-therapeutic dose Time: Baseline and Day 3
Secondary Outcomes
Measure: Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after a single oral dose of moxifloxacin Time: Baseline and Day 3Measure: Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose Time: Baseline and Day 3
Measure: Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after a single oral dose of moxifloxacin Time: Baseline and Day 3
Description: Area under the concentration vs. time curve from zero to 24 hours after multiple doses
Measure: AUC(0-24)md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose Time: Predose and up to 24 hours after last dose of BAY1817080 at Day 3Description: Area under the concentration vs. time curve from zero to infinity after single dose
Measure: AUC after a single oral dose of moxifloxacin Time: Predose and up to 24 hours after single dose of moxifloxacin at Day 3Description: Maximum observed drug concentration in measured matrix after multiple doses
Measure: Cmax,md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose Time: Up to 24 hours after last dose of BAY1817080 at Day 3Description: Maximum observed drug concentration in measured matrix after single dose
Measure: Cmax after a single oral dose of moxifloxacin Time: Up to 24 hours after single dose of moxifloxacin at Day 3Measure: Incidences of treatment-emergent adverse events (TEAEs) after BAY1817080 therapeutic or supra-therapeutic dose Time: From the start of BAY1817080 administration until 7 days after last dose, assessed up to 10 days
This is a proof of concept study to evaluate the efficacy of nitazoxanide (600 mg TID) to treat hospitalized patients with non-critical COVID-19.
NCT04423861 covid19 Drug: Nitazoxanide 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 21Secondary Outcomes
Description: Time to wean off oxygen supplementation
Measure: Evolution of acute respiratory syndrome Time: 21 daysDescription: 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 daysDescription: Time to be discharged from hospital
Measure: Hospital discharge Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Rate of mortality within 21-days Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Need of mechanical ventilation Time: 21 days238 A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of PRV-015 in Adult Patients With Non-Responsive Celiac Disease as an Adjunct to a Gluten-free Diet
This study will evaluate the efficacy and safety of PRV-015 in adult patients with non-responsive celiac disease (NRCD) who are on a gluten-free diet (GFD).
NCT04424927 Celiac Disease Biological: PRV-015 Other: Placebo MeSH:Celiac Disease
HPO:Celiac disease Gluten intolerance
Primary Outcomes
Description: Celiac Disease Patient-Reported Outcome (CeD PRO)
Measure: Efficacy of PRV-015 in attenuating the symptoms of celiac disease in adult patients with NRCD as measured by the Celiac Disease Patient-Reported Outcome (CeD PRO) questionnaire Time: 24 weeks
Secondary Outcomes
Description: Intraepithelial lymphocyte (IEL) density
Measure: Effect of treatment with PRV-015 on other measures of disease activity Time: 24 weeks
Description: Safety endpoint
Measure: Incidence of treatment-emergent adverse events (TEAEs) Time: 28 weeks
Description: Characterize the pharmacokinetics (PK) of PRV-015
Measure: Serum trough concentrations of PRV-015 at scheduled visits Time: 28 weeks
Description: Immunogenicity endpoint
Measure: Incidence of anti-PRV-015 antibodies Time: 28 weeks
239 A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Adult Patients With COVID-19-Moderate Type
Primary Outcomes
Description: Celiac Disease Patient-Reported Outcome (CeD PRO)
Measure: Efficacy of PRV-015 in attenuating the symptoms of celiac disease in adult patients with NRCD as measured by the Celiac Disease Patient-Reported Outcome (CeD PRO) questionnaire Time: 24 weeksSecondary Outcomes
Description: Intraepithelial lymphocyte (IEL) density
Measure: Effect of treatment with PRV-015 on other measures of disease activity Time: 24 weeksDescription: Safety endpoint
Measure: Incidence of treatment-emergent adverse events (TEAEs) Time: 28 weeksDescription: Characterize the pharmacokinetics (PK) of PRV-015
Measure: Serum trough concentrations of PRV-015 at scheduled visits Time: 28 weeksDescription: Immunogenicity endpoint
Measure: Incidence of anti-PRV-015 antibodies Time: 28 weeksThis is a multi-center, randomized, double-blind, placebo-controlled, phase III clinical study to evaluate the efficacy of Favipiravir combined with supportive care for adult patients with COVID-19-Moderate type.
NCT04425460 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 72h. Criteria for normalization or relief: Pyrexia (body temperature): axillary ≤37℃，or oral≤37.5℃，or rectal or tympanic ≤38℃; Respiratory rate: ≤24/min without oxygen inhalation; SPO2: >94% without oxygen inhalation; Cough: Subject-perceived improvement or resolution of cough.
Measure: Time from randomization to clinical recovery Time: 28 daysSecondary Outcomes
Description: Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;
Measure: Negativity in RT-PCR nucleic acid test Time: 28 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization;
Measure: Rate of auxiliary oxygen therapy or non-invasive ventilation Time: 28 daysDescription: ICU admission rate within 28 days of randomization (except patients already enrolled in ICU which respect eligibility criteria);
Measure: ICU admission rate within 28 days of randomization Time: 28 daysDescription: All-cause mortality within 28 days of randomization.
Measure: All-cause mortality within 28 days of randomization. Time: 28 days240 A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19
The primary objectives are: Phase 1 - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 2 • To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 3 • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo
NCT04425629 COVID-19 Drug: REGN10933+REGN10987 combination therapy Drug: Placebo
Primary Outcomes
Description: Primary: Phase 1 Secondary: Phase 2, Phase 3
Measure: Proportion of patients with treatment-emergent serious adverse events (SAEs) Time: Through Day 29Description: Primary: Phase 1 Secondary: Phase 2, Phase 3
Measure: Proportion of patients with infusion-related reactions Time: Through Day 4Description: Primary: Phase 1 Secondary: Phase 2, Phase 3
Measure: Proportion of patients with hypersensitivity reactions Time: Through Day 29Description: Primary: Phase 1, Phase 2 Secondary: Phase 3
Measure: Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples Time: Baseline up to Day 22Description: Primary: Phase 3 Secondary: Phase 1, Phase 2
Measure: Proportion of patients with at least one COVID-19 related medically attended visit Time: Through Day 29Secondary Outcomes
Description: Phase 1 Only
Measure: Time-weighted average change from baseline in viral shedding measured by RT-qPCR in saliva samples Time: Baseline up to Day 22Description: Phase 1 Only
Measure: Time-weighted average change from baseline in viral shedding measured by RT-qPCR in nasal swab samples Time: Baseline up to Day 22Description: Phase 1 Only
Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples Time: Through Day 29Description: Phase 2, Phase 3
Measure: Time to negative RT-qPCR in NP swabs with no subsequent positive RT-qPCR Time: Through Day 29Measure: Change from baseline in viral shedding as measured by RT-qPCR in NP swabs Time: Baseline up to Day 29
Description: Phase 1 Only
Measure: Change from baseline in viral shedding as measured by RT-qPCR in saliva samples Time: Baseline up to Day 29Description: Phase 1 Only
Measure: Change from baseline in viral shedding as measured by RT-qPCR in nasal swabs Time: Baseline up to Day 29Description: Phase 1 Only
Measure: Correlation of RT-qPCR results over time between different sample types (NP, nasal, and saliva) Time: Up to Day 29Description: Phase 1 Only
Measure: Concordance of RT-qPCR results over time between different sample types (NP, nasal, and saliva) Time: Up to Day 29Measure: Time-weighted average change from baseline in viral shedding Time: Baseline up to Day 29
Measure: Proportion of patients with at least two COVID-19 related medically attended visits Time: Through Day 29
Measure: Total number of COVID-19 related medically-attended visits Time: Through Day 29
Measure: Proportion of patients admitted to a hospital due to COVID-19 Time: Through Day 29
Description: Phase 2, Phase 3
Measure: Proportion of patients admitted to an intensive care unit (ICU) due to COVID-19 Time: Through Day 29Measure: Proportion of patients at least 1 outpatient or telemedicine visit due to COVID-19 Time: Through Day 29
Description: Phase 2, Phase 3
Measure: Proportion of patients requiring mechanical ventilation due to COVID-19 Time: Through Day 29Description: Phase 2, Phase 3
Measure: Number of days of hospitalization due to COVID-19 Time: Through Day 29Description: Phase 2, Phase 3
Measure: Number of deaths due to any cause (All-Cause Mortality) Time: Through Day 29Measure: Serum concentration of REGN10933 over time Time: Through Day 29
Measure: Serum concentration of REGN10987 over time Time: Through Day 29
Description: Phase 1 only
Measure: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 Time: Through Day 29Description: Phase 1 only
Measure: Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 Time: Through Day 29Description: Phase 1 only
Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 Time: Through Day 29Description: Phase 1 only
Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987 Time: Through Day 29Description: Phase 1 only
Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 Time: Through Day 29Description: Phase 1 only
Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 Time: Through Day 29Description: Phase 1 only
Measure: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 Time: Through Day 29Description: Phase 1 only
Measure: Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 Time: Through Day 29Measure: Incidence of anti-drug antibodies (ADA) to REGN10933 Time: Through Day 29
Measure: Incidence of anti-drug antibodies (ADA) to REGN10987 Time: Through Day 29
241 A Study to Assess the Safety, Tolerability, and Pharmacodynamics of Multiple Dose MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia
The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of MK-5475 after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that MK-5475 when administered to participants with COVID-19 pneumonia and hypoxemia improves arterial oxygenation as measured by the ratio of blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio) compared to placebo.
NCT04425733 Coronavirus Disease 2019 (COVID-19) Pneumonia Hypoxemia Drug: MK-5475 Drug: Placebo MeSH:Pneumonia Hypoxia
HPO:Hypoxemia Pneumonia
Primary Outcomes
Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
Measure: Number of Participants Who Experience an Adverse Event (AE) Time: Up to ~Day 21
Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study drug due to an AE will be reported.
Measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) Time: Up to ~Day 7
Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours post-dose on Day 1 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 1 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 1.
Measure: Change From Baseline to Day 1 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 2 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 2 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 2.
Measure: Change From Baseline to Day 2 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 3 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 3 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 3.
Measure: Change From Baseline to Day 3 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 4 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 4 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 4.
Measure: Change From Baseline to Day 4 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 5 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 5 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 5.
Measure: Change From Baseline to Day 5 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 6 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 6 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 6.
Measure: Change From Baseline to Day 6 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 7 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 7 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 7.
Measure: Change From Baseline to Day 7 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
242 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Oncology Cohort
Primary Outcomes
Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
Measure: Number of Participants Who Experience an Adverse Event (AE) Time: Up to ~Day 21Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study drug due to an AE will be reported.
Measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) Time: Up to ~Day 7Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours post-dose on Day 1 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 1 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 1.
Measure: Change From Baseline to Day 1 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 2 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 2 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 2.
Measure: Change From Baseline to Day 2 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 3 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 3 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 3.
Measure: Change From Baseline to Day 3 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 4 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 4 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 4.
Measure: Change From Baseline to Day 4 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 5 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 5 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 5.
Measure: Change From Baseline to Day 5 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 6 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 6 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 6.
Measure: Change From Baseline to Day 6 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 7 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 7 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 7.
Measure: Change From Baseline to Day 7 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Time: Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients
NCT04426201 COVID-19 Lymphocytopenia Drug: CYT107 Drug: Placebo MeSH:Lymphopenia
HPO:Lymphopenia
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or HospitalDischarge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first Time: one month
Secondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: one month
Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: 1 month or HD (whichever occurs first)
Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: frequency of secondary infections through day 45 compared to placebo arm Time: 45 days
Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: length of hospitalization compared to placebo arm Time: 45 days
Description: Number of days in ICU during index hospitalization
Measure: length of stay in ICU compared to placebo arm Time: 45 days
Description: Readmissions to ICU through Day 45
Measure: number of readmissions to ICU compared to placebo arm Time: 45 days
Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Measure: organ support free days compared to placebo arm Time: 45 days
Description: Number of readmissions to the hospital through Day 45
Measure: Frequency of re-hospitalization through day 45 compared to placebo arm Time: 45 days
Description: All-cause mortality through Day 45
Measure: All-cause mortality through day 45 compared to placebo arm Time: 45 days
Description: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA) through Day 30 or HD
Measure: CD4+ and CD8+ T cell counts compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm Time: 30 days
Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Measure: Physiological status through NEWS2 evaluation compared to Placebo arm Time: 30 days
Other Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety
Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events Time: 45 days
243 A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or HospitalDischarge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first Time: one monthSecondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: one monthDescription: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: 1 month or HD (whichever occurs first)Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: frequency of secondary infections through day 45 compared to placebo arm Time: 45 daysDescription: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: length of hospitalization compared to placebo arm Time: 45 daysDescription: Number of days in ICU during index hospitalization
Measure: length of stay in ICU compared to placebo arm Time: 45 daysDescription: Readmissions to ICU through Day 45
Measure: number of readmissions to ICU compared to placebo arm Time: 45 daysDescription: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Measure: organ support free days compared to placebo arm Time: 45 daysDescription: Number of readmissions to the hospital through Day 45
Measure: Frequency of re-hospitalization through day 45 compared to placebo arm Time: 45 daysDescription: All-cause mortality through Day 45
Measure: All-cause mortality through day 45 compared to placebo arm Time: 45 daysDescription: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA) through Day 30 or HD
Measure: CD4+ and CD8+ T cell counts compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm Time: 30 daysDescription: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Measure: Physiological status through NEWS2 evaluation compared to Placebo arm Time: 30 daysOther Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety
Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events Time: 45 daysThe primary objectives are: Phase 1 - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 2 - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 - To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status Phase 3 - To evaluate and confirm the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status
NCT04426695 COVID-19 Drug: REGN10933+REGN10987 combination therapy Drug: Placebo
Primary Outcomes
Description: Primary: Up to Day 169: Phase 1: C1 Secondary: Up to Day 29: Phase 1: C1, Phase 2: C1, C2, C3 Up to Day 57: Phase 2: C1, C2, C3
Measure: Proportion of patients with treatment-emergent Serious Adverse Events (SAEs) Time: Through Day 169Description: Primary: Phase 1:C1 Secondary: Phase 2: C1, C2, C3
Measure: Proportion of patients with infusion-related reactions Time: Through Day 4Description: Primary: Phase 1:C1 Secondary: Phase 2: C1, C2, C3
Measure: Proportion of patients with hypersensitivity reactions Time: Through Day 29Description: Phase 1:C1 Phase 2: C1, C2, C3
Measure: Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples Time: Baseline up to Day 22Description: Primary: Day 8: Phase 2:C1, Phase 3:C1 Day 22: Phase 2:C2, C3, Phase 3:C2, C3 Secondary: Day 8: Phase 1:C1 Day 29: Phase 1:C1, Phase 2:C1, C2, C3 7-point Ordinal Scale: Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized
Measure: Proportion of patients with at least 1-point improvement on a 7-Point Ordinal Scale in clinical status Time: From Day 1 up to Day 29Secondary Outcomes
Description: Phase 1: C1
Measure: Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in saliva samples Time: Baseline up to Day 22Description: Phase 1: C1
Measure: Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in nasal samples Time: Baseline up to Day 22Description: Phase 1: C1
Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples Time: Through Day 29Description: Phase 2: C1, C2, C3
Measure: Time to negative RT-qPCR in NP swabs with no subsequent positive RT-qPCR Time: Through Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Change from baseline in viral shedding as measured by RT-qPCR in NP swabs Time: Baseline up to Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Time-weighted average change in viral shedding Time: Baseline up to Day 29Description: Phase 1: C1
Measure: Change from baseline in viral shedding as measured by RT-qPCR in saliva samples Time: Baseline up to Day 29Description: Phase 1: C1
Measure: Change from baseline in viral shedding as measured by RT-qPCR in nasal swabs Time: Baseline up to Day 29Description: Phase 1: C1
Measure: Correlation of RT-qPCR results over time between different sample types Time: Up to Day 29Description: Phase 1: C1
Measure: Concordance of RT-qPCR results over time between different sample types Time: Up to Day 29Description: Phase 1: C1, Phase 2: C1 Day 8 Phase 2: C2, C3 Day 22 Phase 1: C1, Phase 2: C1, C2, C3 Day 29
Measure: Proportion of patients with at least 2-point improvement on a 7-Point Ordinal Scale in clinical status Time: From Day 1 up to Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Time to no longer requiring oxygen supplementation Time: Through Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Number of days of supplemental oxygen use Time: Through Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Proportion of patients initiating high-intensity oxygen therapy Time: Up to Day 29 or hospital dischargeDescription: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Number of days of high-intensity oxygen therapy Time: Through Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Proportion of patients initiating mechanical ventilation Time: Up to Day 29 or hospital dischargeDescription: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Number of days of mechanical ventilation Time: Through Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Number of Ventilator-free days Time: Through Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Number of days of hospitalization Time: Through Day 29Description: Phase 1: C1: Through Day 169 Phase 2: C1, C2, C3: Through Day 57
Measure: Proportion of patients re-admitted to hospital after discharge through the end of study Time: Through Day 169Description: Phase 1: C1 Through Day 29 and Day 169 Phase 2: C1, C2, C3 Through Day 29 and Day 57
Measure: Number of deaths due to any cause (All-Cause Mortality) Time: Through Day 169Description: Phase 1: C1: Through Day 169 Phase 2: C1, C2, C3: Through Day 57
Measure: Overall Survival Time: Through Day 169Description: Phase 1: C1: Through Day 169 Phase 2: C1, C2, C3: Through Day 29
Measure: Serum concentration of REGN10933 over time Time: Through Day 169Description: Phase 1: C1: Through Day 169 Phase 2: C1, C2, C3: Through Day 29
Measure: Serum concentration of REGN10987 over time Time: Through Day 169Description: Phase 1: C1: Through Day 169 Phase 2: C1, C2, C3: Through Day 29
Measure: Incidence of anti-drug antibodies (ADA) to REGN10933 Time: Through Day 169Description: Phase 1: C1: Through Day 169 Phase 2: C1, C2, C3: Through Day 29
Measure: Incidence of anti-drug antibodies (ADA) to REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 Time: Through day 169Description: Phase 1 only
Measure: Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 Time: Through day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Observed terminal half-life [t1/2] for REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Observed terminal half-life [t1/2] of REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Clearance (CL) for REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Clearance (CL) of REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10987 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Mean residence time (MRT) of REGN10933 Time: Through Day 169Description: Phase 1 only
Measure: Assessment of PK parameter: Mean residence time (MRT) of REGN10987 Time: Through Day 169Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Proportion of patients admitted into an intensive care unit (ICU) Time: Up to Day 29Description: Phase 1: C1 Phase 2: C1, C2, C3
Measure: Days of ICU stay Time: Up to Day 29244 A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of LY3819253 in Participants With Mild to Moderate COVID-19 Illness
The purpose of this study is to measure how well LY3819253 works against the virus that causes COVID-19. LY3819253 will be given to participants with early symptoms of COVID-19, via an injection into a vein. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 weeks and includes one required visit to the study site, with the remainder of assessments performed in the home or by phone.
NCT04427501 COVID-19 Drug: LY3819253 Drug: Placebo
Primary Outcomes
Description: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load
Measure: Change from Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Time: Baseline, Day 11Secondary Outcomes
Description: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization
Measure: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization Time: Baseline, Day 11Description: PK: Mean Concentration of LY3819253
Measure: Pharmacokinetics (PK): Mean Concentration of LY3819253 Time: Day 29Description: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death
Measure: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death Time: Baseline through Day 29245 A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, Tolerability, Biomarkers and Pharmacokinetics of Ibudilast (MN-166) in COVID-19 Subjects at Risk for Developing Acute Respiratory Distress Syndrome
The study aims to evaluate MN-166 (ibudilast) in patients with COVID-19 who are at risk of developing acute respiratory distress syndrome. Subjects will be screened, randomly assigned to MN-166 or placebo groups, receive study drug on Days 1-7, and followed up on Day 14 and Day 28.
NCT04429555 Pneumonia, Viral Drug: Ibudilast Drug: Placebo MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirements (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 7
Measure: Proportion of subjects free from respiratory failure Time: 7 days
Description: Mean change from baseline in clinical status based on the NIAID 8-point scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.
Measure: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 7 Time: 7 days
Description: Percentage of patients with at least a one-point improvement in clinical status using the NIAID 8-point ordinal scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.
Measure: Percentage of patients with improvement in clinical status Time: 7 days
Description: Mean change from baseline (baseline = 1-fold; any value above 1.0 indicates elevation in cytokine levels; any value below 1.0 indicates reduction in cytokine levels) in migration inhibitory factor (MIF), (interleukin 1-beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) at Day 7.
Measure: Change in cytokine levels from baseline Time: 7 days
Secondary Outcomes
Description: Incidence, frequency, and severity of adverse events at Day 7 and Day 14
Measure: Adverse event Incidence, severity, relationship to study drug, and study discontinuations Time: Days 7, 14
Description: Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.
Measure: Changes in laboratory values from baseline Time: 7 days
Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14
Measure: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14 Time: 14 days
Description: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 14 and Day 28
Measure: Mean change from baseline in clinical status Time: Days 14, 28
Description: Proportion of subjects receiving mechanical ventilation or intubation.
Measure: Incidence of mechanical ventilation or intubation Time: Days 7, 14
Description: Proportion of subjects requiring submission to the intensive care unit
Measure: Intensive care unit admission Time: 7 days
Description: Blood sample collection to determine plasma concentrations of ibudilast.
Measure: Plasma concentrations of Ibudilast Time: 7 days
Description: Number of deaths from any cause
Measure: All cause mortality Time: Days 7, 14, 28
246 Safety and Efficacy of Mesenchymal Stem Cells in the Management of Severe COVID-19
Primary Outcomes
Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirements (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 7
Measure: Proportion of subjects free from respiratory failure Time: 7 daysDescription: Mean change from baseline in clinical status based on the NIAID 8-point scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.
Measure: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 7 Time: 7 daysDescription: Percentage of patients with at least a one-point improvement in clinical status using the NIAID 8-point ordinal scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.
Measure: Percentage of patients with improvement in clinical status Time: 7 daysDescription: Mean change from baseline (baseline = 1-fold; any value above 1.0 indicates elevation in cytokine levels; any value below 1.0 indicates reduction in cytokine levels) in migration inhibitory factor (MIF), (interleukin 1-beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) at Day 7.
Measure: Change in cytokine levels from baseline Time: 7 daysSecondary Outcomes
Description: Incidence, frequency, and severity of adverse events at Day 7 and Day 14
Measure: Adverse event Incidence, severity, relationship to study drug, and study discontinuations Time: Days 7, 14Description: Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.
Measure: Changes in laboratory values from baseline Time: 7 daysDescription: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14
Measure: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14 Time: 14 daysDescription: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 14 and Day 28
Measure: Mean change from baseline in clinical status Time: Days 14, 28Description: Proportion of subjects receiving mechanical ventilation or intubation.
Measure: Incidence of mechanical ventilation or intubation Time: Days 7, 14Description: Proportion of subjects requiring submission to the intensive care unit
Measure: Intensive care unit admission Time: 7 daysDescription: Blood sample collection to determine plasma concentrations of ibudilast.
Measure: Plasma concentrations of Ibudilast Time: 7 daysDescription: Number of deaths from any cause
Measure: All cause mortality Time: Days 7, 14, 28The disease caused by the new coronavirus, SARS-CoV-2, called COVID-19, it has considered a worldwide pandemia by the WHO. Suddently, it produces a lot of patients severe ill, in a little geographic area, that could surpase the resourses of the any health system in the world. There is no documentation of an effective alternative for the treatment of the severe ill patients, that can reduce the mortality or the adverse events suffered by these people. It is has suggested the usefulness of the Mesenchymal Stem cells (MSC) for the management of these patients, thanks to their direct and indirect antiviral capacity, and its potency as immunomodulator, that could ameliorate the lung disease and the severity of COVID-19.
NCT04429763 COVID-19 Biological: Umbilical cord derived mesenchymal stem cells Biological: Placebo
Primary Outcomes
Description: Change in two or more degrees in the NEWS scale
Measure: Clinical deterioration or death Time: 4 weeks247 Hydroxychloroquine Use in Hospitalized Patients With COVID-19: Impact on Progression to Severe or Critical Disease
The primary objective is to assess the impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.
NCT04429867 COVID-19 Drug: Hydroxychloroquine Drug: Placebo MeSH:Disease Progression
Primary Outcomes
Description: The impact will be evaluated by comparing rates of a composite primary outcome in patients randomized to hydroxychloroquine versus those randomized to placebo. The composite outcome includes progression to severe/critical disease or death (including withdrawal of care/hospice transfer). Progression to severe/critical disease is defined by requiring oxygen delivery via high flow nasal cannula, non-rebreather mask, bipap, or transfer to intensive care (ICU) or intermediate care units (IMCU) due to COVID-19-related complications.
Measure: Impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease. Time: 30 DaysSecondary Outcomes
Measure: Hospital length of stay Time: 30 DaysMeasure: 30-Day Mortality Time: 30 Days
Description: Resolution of symptoms will be assessed using standard medical interview procedures with the subject and review of the medical records.
Measure: Resolution of Symptoms Time: 14 DaysMeasure: Incidence of QTc >500ms after initiation of therapy Time: 30 Days
Measure: Incidence of discontinuation of therapy Time: 30 Days
248 A Phase I Open Label Followed by a Phase II Randomized, Controlled Study to Assess the Efficacy and Safety of ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic
A Phase I open label followed by a Phase II randomized, controlled study to assess the efficacy and safety of ABTL0812 in combination with FOLFIRINOX for first-line treatment of metastatic pancreatic
NCT04431258 Pancreatic Cancer Drug: ABTL0812 Drug: Folfirinox Drug: Placebo
Primary Outcomes
Description: Recommended Phase II Dose (RP2D) of ABTL0812 in combination with FOLFIRINOX
Measure: RP2D Time: 6 monthsDescription: PFS using RECIST v1.1 by investigator analysis
Measure: PFS Time: 1 yearDescription: Objective response rate (ORR)
Measure: ORR Time: 1 year249 Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Efficacy and Safety of Intravenous Pamrevlumab, a Monoclonal Antibody Against Connective Tissue Growth Factor (CTGF), in Hospitalized Patients With Acute COVID-19 Disease
This is a Phase 2 trial to evaluate the efficacy and safety of intravenous (IV) infusions of pamrevlumab as compared to placebo in hospitalized subjects with acute COVID-19 disease.
NCT04432298 COVID-19 Drug: Pamrevlumab Drug: Placebo
Primary Outcomes
Measure: Proportion of subjects who never received mechanical ventilation and/or ECMO and alive Time: Baseline to Day 28Secondary Outcomes
Measure: Proportion of subjects alive, discharged home, and not on supplemental oxygen Time: Baseline to Day 28Measure: Time to recovery based on a Modified 8-Point Ordinal Scale Time: Baseline to Day 28
Measure: Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) Time: Baseline to Day 28
Measure: Days on mechanical ventilation and/or ECMO Time: Baseline to Day 28
Measure: Time to death from any cause Time: Baseline to Day 28
Measure: Changes in PaO2/FiO2 ratio, both as categorical and continuous variable Time: Baseline to Day 28
Measure: Change in (non-invasive) oxygen supplementation requirements Time: Baseline to Day 28
250 A Randomized Controlled Trial Assessing the Efficacy of Lianhua Qingwen as an Adjuvant Treatment in Patients With Mild Symptoms of COVID-19
COVID-19 virus remains in infected patients for extended periods of time. A great resource burden is placed on the healthcare system and society at large to isolate COVID-19 patients for prolonged periods. Thus, being able to increase the rate of viral clearance, thus reducing the duration of COVID-19 infection, would allow patients to be discharged earlier to free up resources for those who require it. The investigators designed a randomized controlled trial, investigating the use of Lianhua Qingwen, a TCM treatment, in COVID-19 infected patients with mild symptoms. The investigators hypothesize that the use of Lianhua Qingwen will increase the proportion of patients who test negative for COVID-19 after 8 days of TCM treatment when compared to the group of patients provided with standard care and placebo. Patients will be recruited from community isolation facilities, and have onset of symptoms within 5 days prior to admission to the isolation facility. The trial also evaluates the time taken for relief of clinical symptoms associated with COVID-19 and assesses the safety of the TCM treatment given to patients.
NCT04433013 COVID-19 Drug: Lianhua Qingwen Drug: Placebo
Primary Outcomes
Measure: Proportion of participants who test negative for COVID-19 Time: after 8 days of treatmentSecondary Outcomes
Measure: Time taken in days for relief of clinical symptoms Time: during the 8-day course of treatmentMeasure: Proportion of participants with mild symptoms of COVID-19 progressing to moderate or severe illness Time: after 8 days of treatment and at the end of the trial
Measure: Proportion of participants who test positive for COVID-19 with Ct value>30 Time: after 8 days of treatment
251 RepurpoSing Old Drugs TO SuppRess a Modern Threat: The STORM Trial
The primary aim of this study is to test whether Doxycycline can benefit patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by inhibiting the replication of the virus while at the same time blocking the development of cytokine storms or inhibiting cytokine-associated coagulopathy respectively. The investigators hypothesize that Doxycycline will will improve survival and reduce morbidity in SARS-CoV-2 infected patients. A secondary aim is to identify genetic variants that predict either an unusually mild disease or an unusually severe disease - knowledge that can be used to design new and precise medications and to be able to predict patients who might get into early trouble and to therefore hospitalize them.
NCT04433078 Cytokine Storm SARS-CoV-2 Drug: Doxycycline Drug: Placebo
Primary Outcomes
Description: Days Alive and Out of Hospital (Composite Endpoint)
Measure: Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death Time: 21 daysSecondary Outcomes
Description: Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative)
Measure: NP SARS-CoV-2 PCR Time: 21 daysDescription: Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load
Measure: SARS-CoV-2 Serum Quantitative Viral Load Time: 21 daysDescription: Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative)
Measure: SARS-CoV-2 IgM/IgG Antibodies Time: 21 daysDescription: Change From Baseline of White Blood Count (CBC) K/mm3
Measure: White Blood Cell Count (WBC) Time: 21 daysDescription: Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3
Measure: Absolute Lymphocyte Count (ALC) Time: 21 daysDescription: Change From Baseline of C-Reactive Protein (CRP) mg/dL
Measure: C-Reactive Protein (CRP) Time: 21 daysDescription: Change From Baseline of N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) pg/mL
Measure: N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) Time: 21 daysDescription: Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL
Measure: High Sensitivity Troponin I (hsTnT) Time: 21 daysDescription: Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a)
Measure: Tumor Necrosis Factor Alpha (TNF-a) Time: 21 daysDescription: Change From Baseline of IL-1
Measure: IL-1 Time: 21 daysDescription: Change From Baseline of IL-1B
Measure: IL-1B Time: 21 daysDescription: Change From Baseline of IL-6
Measure: IL-6 Time: 21 days252 Efficacy of Pentoxifylline as Add on Therapy in COVID19 Patients
With potential antiviral effects on severe acute respiratory syndrome (SARS) and as a methyl-xanthine derived inhibitor of phosphodiesterase-4, pentoxifylline basically functions as a hemorrheologic agent for a better circulation and oxygenation and exerts unique effects on immune modulation, inflammation and oxidative stress. As the main regulator of cAMP metabolism, posphodiesterase-4 plays a key role in proinflammatory and immune cells. Pentoxifylline plays its anti-inflammatory role by reducing the production of proinflammatory cytokines such as TNF-a, IL-1 and IL-6. Given its unique impacts on immune modulation, homeostasis and fibrinolysis and its supportive effects on oxidative stress and organ failure, pentoxifylline can constitute a multipurpose and generally-safe adjuvant therapy for COVID-19 patients.
NCT04433988 COVID Drug: Pentoxifylline Drug: Placebo
Primary Outcomes
Description: Number of Participants need hospitalization
Measure: Primary Outcome Time: 7 daysSecondary Outcomes
Description: Incidence of any acute respiratory infection
Measure: Respiratory infection Time: 7 daysDescription: Absolute and relative frequencies of Serious Adverse Events
Measure: Serious Adverse Events Time: 7 days253 Prospective, Randomized, Double-blind, Parallel, Placebo Controlled Study to Evaluate the Safety and Efficacy of Nitazoxanide 600 mg Three Times a Day for Post Exposure Prophylaxis of COVID-19 in Subjects From Vulnerable Communities
The primary objective of this study is to evaluate the efficacy of the drug nitazoxanide 600 mg, administered three times a day, in relation to placebo in preventing the development of COVID-19 in subjects from vulnerable communities that had direct contact with patients diagnosed with the disease.
NCT04435314 covid19 Drug: Nitazoxanide Drug: Placebo
Primary Outcomes
Description: PCR will be done to evaluate infection
Measure: The proportion of subjects with laboratory-confirmed COVID-19 identified after start of treatment and before the end of the study Time: 28 daysSecondary Outcomes
Description: Number of participants with treatment-related adverse events
Measure: Incidence of Treatment-Emergent Adverse Events Time: 28 daysDescription: Symptomatic PCR positive subjects
Measure: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the study Time: 28 daysDescription: Asymptomatic PCR will be done to evaluate infection
Measure: The proportion of subjects with asymptomatic laboratory-confirmed COVID identified after the start of treatment and before the end of the study Time: 28 daysDescription: Subject adherence to treatment will be assessed through study diary record
Measure: Treatment adherence Time: 7 daysDescription: Proportion of patients with severe condition
Measure: Disease complication Time: 28 daysDescription: Proportion of patient that needed undergo an unscheduled visit
Measure: Incidence of subjects that underwent unscheduled visit Time: 28 days254 A Phase III, Randomized, Double-blind, Placebo-controlled, Multicentre, Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in the SARS-CoV-2 Pandemic by Modulating the Immune System
The aim of this study is to investigate whether vaccination of elderly with VPM1002 could reduce hospital admissions and/or severe respiratory infectious diseases in the SARS-CoV-2 pandemic . VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the "new corona virus" SARS-CoV 2.
NCT04435379 Infection, Respiratory Tract Biological: VPM1002 Biological: Placebo MeSH:Communicable Diseases Infection Respiratory Tract Infections
HPO:Respiratory tract infection
Primary Outcomes
Measure: Number of days with severe respiratory disease at hospital and/or at home Time: From day 0 to day 240
Secondary Outcomes
Measure: Cumulative incidence of hospital admissions Time: From day 0 to day 240
Measure: Cumulative incidence of documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Number of days with self-reported fever (≥ 38 ºC) Time: From day 0 to day 240
Measure: Number of days with self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of death for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection Time: From day 0 to day 240
255 A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older
Primary Outcomes
Measure: Number of days with severe respiratory disease at hospital and/or at home Time: From day 0 to day 240Secondary Outcomes
Measure: Cumulative incidence of hospital admissions Time: From day 0 to day 240Measure: Cumulative incidence of documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Number of days with self-reported fever (≥ 38 ºC) Time: From day 0 to day 240
Measure: Number of days with self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of self-reported acute respiratory symptoms Time: From day 0 to day 240
Measure: Cumulative incidence of death for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission for any reason Time: From day 0 to day 240
Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection Time: From day 0 to day 240
Measure: Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection Time: From day 0 to day 240
The purpose of the study is to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S at 2 dose levels, administered intramuscularly (IM) as a single-dose or 2-dose schedule, with a single booster vaccination administered in one cohort, in healthy adults aged greater than or equal to 18 to less than or equal to 55 years and in adults aged greater than or equal to 65 years in good health with or without stable underlying conditions.
NCT04436276 Healthy Biological: Ad26.COV2.S Biological: Placebo
Primary Outcomes
Description: Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after first vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after First Vaccination Time: Day 8 (7 Days after first vaccination on Day 1)Description: Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after second vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after Second Vaccination Time: Day 64 (7 Days after second vaccination on Day 57)Description: Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after first vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.
Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after First Vaccination Time: Day 8 (7 Days after first vaccination on Day 1)Description: Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after second vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.
Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after Second Vaccination Time: Day 64 (7 Days after second vaccination on Day 57)Description: Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.
Measure: Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after First Vaccination Time: Day 29 (28 Days after first vaccination on Day1)Description: Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.
Measure: Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after Second Vaccination Time: Day 85 (28 Days after second vaccination)Description: SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.
Measure: Cohort 1 and 3: Number of Participants with Serious Adverse Events (SAEs) from the First Vaccination until 1 Year after the First Vaccination Time: From Day 1 (vaccination 1) up to 1 yearDescription: SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.
Measure: Cohort 2: Number of Participants with SAEs from the First Vaccination until 6 Months after the First Vaccination Time: Day 1 (vaccination 1) up to 6 MonthsSecondary Outcomes
Description: Number of participants with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported.
Measure: Cohorts 1, 2, and 3: Number of Participants With SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA) Time: Up to 38 MonthsDescription: Number of participants with SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.
Measure: Cohorts 1, 2, and 3: Number of Participants with SARS-CoV-2 Binding Antibodies Assessed by ELISA Time: Up to 38 MonthsDescription: Number of participants with Th-1 and Th-2 immune responses will be reported. Th1 and Th2 immune responses will be assessed by flow cytometry after SARS-CoV-2 S protein peptide stimulation of peripheral blood mononuclear cells (PBMCs) and intracellular staining [ICS] including cluster of differentiation (CD)-4+/CD-8+, Interferons (INF)-gamma, interleukin [IL] 2, Tumor Necrosis Factor (TNF)-alpha, IL-4, IL-5, IL-13, and/or other Th-1/Th-2 markers.
Measure: Cohorts 1, 2, and 3: Number of Participants with T-helper (Th)-1 and Th-2 Immune Responses as Assessed by Flow Cytometry Time: Up to 38 MonthsDescription: Number of participants with Th-1 and Th-2 immune responses as assessed by enzyme-linked immunospot (ELISpot) will be reported. Th-1 and Th-2 will be assessed by dual or single IFN-gamma and IL-4 ELISpot assay after stimulation of peripheral blood mononuclear cell (PBMCs) with SARS-CoV-2 S protein peptides.
Measure: Cohorts 1, 2, and 3: Number of Participants With Th-1 and Th-2 Immune Responses as Assessed by ELISpot Time: Up to 38 Months256 Phase 2, Multicentre, Randomized, Double Blind, 2 Arms Placebo-controlled Study in Adults With Moderate COVID-19 With Gastrointestinal Signs and Symptoms
This is a Phase 2, multicentre, randomized, double blind, 2 arm placebo-controlled study in adults with moderate COVID-19 with gastrointestinal signs and symptoms.
NCT04436458 COVID Drug: Niclosamide Oral Tablet Drug: Placebo
Primary Outcomes
Measure: The primary endpoint is the rate of faecal SARS-CoV-2 virus clearance (rectal swab or stool sample) assessed by RT-PCR in the niclosamide group, compared to the placebo group Time: From Day 1 to 42257 Randomized, Double-blind, Multi Centre Phase II, Proof of Concept, Dose Finding Clinical Trial on Ivermectin for the Early Treatment of COVID-19
Prospective, multi-centre, randomized, double-blind trial to assess efficacy and safety of ivermectin for the treatment of initial infection with SARS-CoV2 infection. Study arms: A) placebo B) ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo. C) ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days (I_1200). Patients will be randomized at emergency room of hospitals as well as at outpatient ambulatory care as well as at home, according to routine procedures of recruiting centres. In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C.
NCT04438850 Covid19 Drug: Ivermectin Other: Placebo
Primary Outcomes
Description: Number of serious adverse drug reaction
Measure: SADR Time: 14 daysDescription: Quantitative viral load as measured by quantitative, digital droplet PCR.
Measure: Viral load Time: Assessed at day 7Secondary Outcomes
Description: 1. Trend over time of quantitative viral load at Day 7 and 14 as measured by quantitative, digital droplet PCR.
Measure: Trend viral load Time: Days 7 and 14 from baselineDescription: Time to clinical resolution (for symptomatic patients).
Measure: Clinical resolution Time: Assessed on Day 30Description: Time from diagnosis to documented viral clearance
Measure: Viral clearance Time: assessed on days 14 and 30Description: Proportion of patients with virological clearance
Measure: Virological clearance Time: Assessed at day 14 and 30Description: rate of hospitalization
Measure: hospitalization rate Time: Day 30Description: COVID-19 Severity Score (Coronavirus Diseases 19 Severity Score) - min value 1 ("no limitation of activities), max value 8 ("death"). Higher scores mean worse outcome
Measure: Severity score Time: Assessed at Day 14 and Day 30258 Treatment of COVID-19 Pneumonia With Glucocorticoids. A Randomized Controlled Trial
Around 30% of admitted patients with COVID-19 pneumonia develop a hyper-inflammatory state whose progression to an acute respiratory distress syndrome (ARSD) could be prevented by the early initiation of immune-modulatory agents. The role of glucocorticoids (GC) in this setting remains controversial. This study aims to assess the safety and effectiveness of GC pulses to improve the clinical outcomes of patients with COVID-19 pneumonia with risen inflammatory biomarkers.
NCT04438980 Covid-19 Pneumonia Drug: Methylprednisolone Other: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: • Death
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomization
Description: • Need for admission in an intensive care unit (ICU)
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomization
Description: • Need for mechanical ventilation
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomization
Description: • Decrease in SpO2 <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, associated with radiological impairment
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomization
Secondary Outcomes
Measure: Mortality at day 28 Time: At 28 days after randomization
Measure: Proportion of patients requiring ICU admission Time: At 28 days after randomization
Measure: Proportion of patients requiring rescue-therapy with tocilizumab Time: At 14 days after randomization
Description: Time in days from randomization until the date of hospital discharge.
Measure: Length of hospital stay Time: At 28 days after randomization
Description: Any undesirable experience related to the use of the studied drugs, which causes patient's death, life-threatening risk, hospitalization or extension of a previous hospitalization, disability or permanent damage, requires intervention to prevent permanent impairment or damage, or is considered medically relevant
Measure: Proportion of severe adverse events Time: At 28 days after randomization
Measure: Proportion of bacterial, fungal or opportunistic infections Time: At 28 days after randomization
Description: Change in plasma levels of C-reactive protein (CRP)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomization
Description: Change in plasma levels of ferritin
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomization
Description: Change in plasma levels of interleukin-6 (IL-6)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomization
Description: Change in plasma levels of lactate dehydrogenase (LDH)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomization
Description: Change in plasma levels of D-dimer (DD)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomization
Description: Negativization of RT-PCR for SARS-CoV-2 on nasopharyngeal swab or sputum
Measure: Proportion of SARS-CoV-2 clearance. Time: At 7 days after randomization
259 A Randomized, Double-blind, Placebo-controlled Phase 3 Study: Efficacy and Safety of VPM1002 in Reducing SARS-CoV-2 Infection Rate and COVID-19 Severity
Primary Outcomes
Description: • Death
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomizationDescription: • Need for admission in an intensive care unit (ICU)
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomizationDescription: • Need for mechanical ventilation
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomizationDescription: • Decrease in SpO2 <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, associated with radiological impairment
Measure: Proportion of patients developing treatment failure Time: At 14 days after randomizationSecondary Outcomes
Measure: Mortality at day 28 Time: At 28 days after randomizationMeasure: Proportion of patients requiring ICU admission Time: At 28 days after randomization
Measure: Proportion of patients requiring rescue-therapy with tocilizumab Time: At 14 days after randomization
Description: Time in days from randomization until the date of hospital discharge.
Measure: Length of hospital stay Time: At 28 days after randomizationDescription: Any undesirable experience related to the use of the studied drugs, which causes patient's death, life-threatening risk, hospitalization or extension of a previous hospitalization, disability or permanent damage, requires intervention to prevent permanent impairment or damage, or is considered medically relevant
Measure: Proportion of severe adverse events Time: At 28 days after randomizationMeasure: Proportion of bacterial, fungal or opportunistic infections Time: At 28 days after randomization
Description: Change in plasma levels of C-reactive protein (CRP)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomizationDescription: Change in plasma levels of ferritin
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomizationDescription: Change in plasma levels of interleukin-6 (IL-6)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomizationDescription: Change in plasma levels of lactate dehydrogenase (LDH)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomizationDescription: Change in plasma levels of D-dimer (DD)
Measure: Evolution of inflammatory biomarkers related to COVID-19 Time: At 14 days after randomizationDescription: Negativization of RT-PCR for SARS-CoV-2 on nasopharyngeal swab or sputum
Measure: Proportion of SARS-CoV-2 clearance. Time: At 7 days after randomizationBacille Calmette-Guerin (BCG) is a live attenuated vaccine administered for prevention of tuberculosis. Recently, several groups have hypothesized that BCG may "train" the immune system to respond to a variety of unrelated infections, including viruses and in particular the coronavirus responsible for COVID-19. Trials are currently being conducted in Australia, Netherlands, Germany and the United Kingdom to evaluate its effectiveness. Front line workers includes members of municipal and provincial police services, emergency medical personnel, firefighters, public transport employees, health service workers and food manufacturing employees. They are at high risk of infection from COVID-19, with potentially high infection rate. The investigators propose an interventional trial to evaluate the effectiveness of BCG vaccination to prevent COVID-19 infection and reduce its severity in front-line employees in Ontario.
NCT04439045 SARS-CoV-2 Infection Biological: VPM1002 Other: Placebo MeSH:Infection Communicable Diseases
Primary Outcomes
Description: To compare the self-reported incidence of SARS-CoV-2 infection (confirmed by positive test) following vaccination with either VPM1002 or placebo.
Measure: COVID-19 infection Time: 7 monthsSecondary Outcomes
Description: Compare the incidence of hospitalization in participants with positive COVID-19 test treated with either VPM1002 or placebo
Measure: Incidence of hospitalization for COVID-19 Time: 7 monthsDescription: Compare the incidence of hospitalization requiring intensive care (ICU admission) in participants with positive COVID-19 test treated with either VPM1002 or placebo
Measure: Incidence of ICU admission for COVID-19 Time: 7 monthsDescription: Compare the incidence of acute respiratory distress syndrome (ARDS) in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Measure: Incidence of ARDS Time: 7 monthsDescription: Compare the incidence of the need for mechanical ventilation in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Measure: Mechanical ventilation for COVID-19 Time: 7 monthsDescription: To compare the incidence of secondary infection in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Measure: Secondary infection in COVID-19 Time: 7 monthsDescription: To compare the mortality in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Measure: COVID-19-related Mortality Time: 7 monthsDescription: Compare the incidence of deep vein thrombosis, pulmonary embolism, or stroke in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Measure: Incidence of DVT Time: 7 monthsOther Outcomes
Description: Compare the incidence of COVID-19 in participants who have received BCG vaccination previously.
Measure: Incidence of COVID-19 in Participants with Past BCG Vaccination Time: 7 monthsDescription: To measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin identified as potential biomarkers of COVID-19 infection using blood samples collected prior to the vaccination and at the end of the 7-month follow-up.
Measure: Measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin as biomarkers of COVID-19 Time: 7 monthsDescription: Adverse events following administration of VPM1002 when used for prevention of COVID-19.
Measure: Adverse events following BCG vaccine Time: 7 monthsDescription: To evaluate the ability of the VPM1002 vaccine to prime an innate trained immunity (i.e. inducing Th1 and Th17 responses to unrelated stimuli) compared to participants administered placebo.
Measure: Innate Trained Immunity Time: 7 months260 Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects With COVID-19 (FITE19)
This is a randomized, double-blind, placebo-controlled, multicenter, 28-day study of adult participants hospitalized with COVID-19, with a safety follow-up telephone call at Day 60.
NCT04439071 Pneumonia COVID-19 Coronavirus Drug: PTC299 Other: SOC Drug: Placebo MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Respiratory improvement is defined as sustained peripheral oxygen saturation (SpO2) ≥94% on room air.
Measure: Time from Randomization to Respiratory Improvement Time: up to Day 28
Secondary Outcomes
Measure: Percentage of Participants Requiring Invasive Ventilation Time: up to Day 28
Measure: Percentage of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants who did not Require Supplemental Oxygen at Baseline Time: up to Day 28
Measure: Time from Randomization to Defervescence Time: up to Day 28
Measure: Time from Randomization to Respiratory Rate ≤ 24 Breaths per Minute on Room Air Time: up to Day 28
Measure: Time from Randomization to Cough Reported as Mild or Absent Time: up to Day 28
Measure: Time from Randomization to Dyspnea Reported as Mild or Absent Time: up to Day 28
Measure: Reduction of Immune Responses Time: up to Day 28
Measure: Reduction in Viral Load Time: up to Day 28
Measure: Duration of Hospitalization Time: up to Day 28
Measure: Number of Fatalities Time: up to Day 28
Measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Time: up to Day 28
261 Prospective, Randomized, Double-blind, Parallel, Placebo Controlled Study to Evaluate the Safety and Efficacy of Nitazoxanide 600 mg Three Times a Day to Treat Ambulatory Adult Subjects Diagnosed With COVID-19 With Mild Symptoms Assisted in the Public Health System of the City of Mesquita -RJ
Primary Outcomes
Description: Respiratory improvement is defined as sustained peripheral oxygen saturation (SpO2) ≥94% on room air.
Measure: Time from Randomization to Respiratory Improvement Time: up to Day 28Secondary Outcomes
Measure: Percentage of Participants Requiring Invasive Ventilation Time: up to Day 28Measure: Percentage of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants who did not Require Supplemental Oxygen at Baseline Time: up to Day 28
Measure: Time from Randomization to Defervescence Time: up to Day 28
Measure: Time from Randomization to Respiratory Rate ≤ 24 Breaths per Minute on Room Air Time: up to Day 28
Measure: Time from Randomization to Cough Reported as Mild or Absent Time: up to Day 28
Measure: Time from Randomization to Dyspnea Reported as Mild or Absent Time: up to Day 28
Measure: Reduction of Immune Responses Time: up to Day 28
Measure: Reduction in Viral Load Time: up to Day 28
Measure: Duration of Hospitalization Time: up to Day 28
Measure: Number of Fatalities Time: up to Day 28
Measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Time: up to Day 28
The aim is to demonstrate a decrease in complications among ambulatory patients who are diagnosed with mild COVID-19 by treating them with nitazoxanide for 7 to 14 days on top of standard care compared to patients who receive standard care and placebo only.
NCT04441398 covid19 Drug: Nitazoxanide Drug: Placebo
Primary Outcomes
Description: Symptoms will be assessed using a 5 point scale (1- excellent, 2- good, 3- fair, 4 - poor 5 - very poor).
Measure: Change in signs and symptoms scale Time: 21 daysSecondary Outcomes
Description: Number of participants with treatment-related adverse events
Measure: Incidence of Treatment-Emergent Adverse Events Time: 21 daysDescription: Change in clinical condition - WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)
Measure: The proportion of subjects hospitalized after start of treatment and before the end of the study Time: 21 daysDescription: Change in clinical condition - WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)
Measure: The proportion of subjects that need mechanical ventilation after start of treatment and before the end of the study Time: 21 daysDescription: Time required (days) to full symptom recovery
Measure: Duration of symptoms Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Rate of mortality within 21-days Time: 21 days262 A Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate COPD With Chronic Bronchitis
The purpose of this study is to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in patients with mild to moderate COPD with CB.
NCT04441788 Chronic Bronchitis Chronic Obstructive Pulmonary Disease Drug: ION-827359 Drug: Placebo MeSH:Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Bronchitis Bronchitis, Chronic Acute Disease
HPO:Abnormal lung morphology Bronchitis Chronic bronchitis Chronic pulmonary obstruction Pulmonary obstruction
Primary Outcomes
Measure: Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo Time: From Baseline up to average of Weeks 13 and 14
Secondary Outcomes
Description: The EXACT (E-RS) scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with COPD. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms. The E-RS will be collected on the daily e-diary, which will include all 14 items from the EXACT questionnaire.
Measure: Change From Baseline in the EXACT Respiratory Symptoms (E-RS) Daily Symptom Diary to the Primary Time Point Time: One week prior to first dose through one week after the last dose.
Description: The CAT is an eight-item questionnaire that will be completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. The CAT provides a score of 0-40 to indicate the impact of the disease.
Measure: Change From Baseline in the COPD Assessment Test (CAT) to the Week 14 Time Point Time: From Baseline up to Week 14
Description: The SGRQ is a participant completed, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. Scores of the SGRQ-C range from 0 to 100, with higher scores indicating more limitations.
Measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) to the Week 14 Time Point Time: From Baseline up to Week 14
Measure: Change from Baseline in Post-Bronchodilator FEV1 Time: From Baseline up to average of Weeks 13 and 14
Measure: Cmax: Maximum Observed Plasma Concentration for ION-827359 Time: Up to Week 24
Measure: Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 Time: Up to Week 24
Measure: AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Time Zero to t for ION-827359 Time: Up to Week 24
Measure: Incidence of Participants With at Least One Treatment-Emergent Adverse Event (TEAE), Graded by Severity Time: Up to Week 24
Measure: Number of Participants With Abnormal Laboratory Values Time: Up to Week 24
Measure: Number of Participants With Abnormal Vital Signs Measurements Time: Up to Week 24
263 A Phase 1, Randomized, Placebo-Controlled Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Immunogenicity of LY3832479 Given as a Single Intravenous Dose in Healthy Participants
Primary Outcomes
Measure: Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo Time: From Baseline up to average of Weeks 13 and 14Secondary Outcomes
Description: The EXACT (E-RS) scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with COPD. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms. The E-RS will be collected on the daily e-diary, which will include all 14 items from the EXACT questionnaire.
Measure: Change From Baseline in the EXACT Respiratory Symptoms (E-RS) Daily Symptom Diary to the Primary Time Point Time: One week prior to first dose through one week after the last dose.Description: The CAT is an eight-item questionnaire that will be completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. The CAT provides a score of 0-40 to indicate the impact of the disease.
Measure: Change From Baseline in the COPD Assessment Test (CAT) to the Week 14 Time Point Time: From Baseline up to Week 14Description: The SGRQ is a participant completed, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. Scores of the SGRQ-C range from 0 to 100, with higher scores indicating more limitations.
Measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) to the Week 14 Time Point Time: From Baseline up to Week 14Measure: Change from Baseline in Post-Bronchodilator FEV1 Time: From Baseline up to average of Weeks 13 and 14
Measure: Cmax: Maximum Observed Plasma Concentration for ION-827359 Time: Up to Week 24
Measure: Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 Time: Up to Week 24
Measure: AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Time Zero to t for ION-827359 Time: Up to Week 24
Measure: Incidence of Participants With at Least One Treatment-Emergent Adverse Event (TEAE), Graded by Severity Time: Up to Week 24
Measure: Number of Participants With Abnormal Laboratory Values Time: Up to Week 24
Measure: Number of Participants With Abnormal Vital Signs Measurements Time: Up to Week 24
The main purpose of this study is to learn more about the safety of LY3832479 and any side effects that might be associated with it. Blood tests will be done to measure how much LY3832479 is in the bloodstream and how long it takes the body to eliminate it. Participation could last up to 16 weeks and may include up to 10 visits to the study center.
NCT04441931 Healthy Drug: LY3832479 Drug: Placebo
Primary Outcomes
Description: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
Measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Time: Baseline through Follow-up (Week 12)Secondary Outcomes
Description: PK: AUC of LY3832479
Measure: 2. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3832479 Time: Day 1: Pre-dose through Day 85Description: PK: Cmax of LY3832479
Measure: PK: Maximum Concentration (Cmax) of LY3832479 Time: Day 1: Pre-dose through Day 85264 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Infectious Cohort
Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients
NCT04442178 COVID-19 Lymphocytopenia Drug: CYT107 Drug: Placebo MeSH:Lymphopenia
HPO:Lymphopenia
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first Time: one month
Secondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: one month
Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: one month
Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: frequency of secondary infections through day 45 compared to placebo arm Time: 45 days
Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: length of hospitalization compared to placebo arm Time: 45 days
Description: Number of days in ICU during index hospitalization
Measure: Length of stay in ICU compared to placebo arm Time: 45 days
Description: Readmissions to ICU through Day 45
Measure: number of readmissions to ICU compared to placebo arm Time: 45 days
Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Measure: organ support free days compared to placebo arm Time: 45 days
Description: Number of readmissions to the hospital through Day 45
Measure: Frequency of re-hospitalization through day 45 compared to placebo arm Time: 45 days
Description: All-cause mortality through Day 45
Measure: All-cause mortality through day 45 compared to placebo arm Time: 45 days
Description: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD
Measure: CD4+ and CD8+ T cell counts compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo a Time: 30 days
Description: Level of other known biomarkers of inflammation: CRP compared to placebo arm
Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm Time: 30 days
Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm Time: 30 days
Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Measure: Physiological status through NEWS2 evaluation compared to Placebo arm Time: 30 days
Other Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety
Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events Time: 45 days
265 Infusion of Convalescent Plasma for the Treatment of Patients Infected With Severe Acute Respiratory Syndrome-Coronavirus-2 (COVID-19): A Double-blinded, Placebo-controlled, Proof-of-concept Study
Primary Outcomes
Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first Time: one monthSecondary Outcomes
Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score
Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD. Time: one monthDescription: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD Time: one monthDescription: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Measure: frequency of secondary infections through day 45 compared to placebo arm Time: 45 daysDescription: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Measure: length of hospitalization compared to placebo arm Time: 45 daysDescription: Number of days in ICU during index hospitalization
Measure: Length of stay in ICU compared to placebo arm Time: 45 daysDescription: Readmissions to ICU through Day 45
Measure: number of readmissions to ICU compared to placebo arm Time: 45 daysDescription: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Measure: organ support free days compared to placebo arm Time: 45 daysDescription: Number of readmissions to the hospital through Day 45
Measure: Frequency of re-hospitalization through day 45 compared to placebo arm Time: 45 daysDescription: All-cause mortality through Day 45
Measure: All-cause mortality through day 45 compared to placebo arm Time: 45 daysDescription: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD
Measure: CD4+ and CD8+ T cell counts compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo a Time: 30 daysDescription: Level of other known biomarkers of inflammation: CRP compared to placebo arm
Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm Time: 30 daysDescription: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm Time: 30 daysDescription: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Measure: Physiological status through NEWS2 evaluation compared to Placebo arm Time: 30 daysOther Outcomes
Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety
Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events Time: 45 daysPatients who are ill with COVID-19 may benefit from receiving convalescent plasma infusions containing antibodies from donors who have recovered from the disease and are proven to no longer be infected. Given the current public health emergency due to COVID-19, the FDA has recently fast-tracked the use of convalescent plasma. The purpose for this study is to assess if convalescent plasma collected from donors previously infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can provide clinical benefit to those acutely ill with the virus and to evaluate if such treatment is safe. There will be two arms in the interventional study, where subjects will either be treated with convalescent plasma or fresh frozen plasma in a randomized and blinded manner. As an additional comparison, the clinical course of subjects enrolled during the period of the study who do not receive an alternative treatment for COVID-19 will be assessed.
NCT04442191 COVID-19 Biological: Convalescent plasma Biological: Placebo
Primary Outcomes
Description: The primary endpoint will be clinical response at 8 days, defined as no need for oxygen supplementation for the previous 24 hours.
Measure: Oxygen supplementation Time: 8 daysSecondary Outcomes
Description: Mortality rate during the 28 days of follow-up and during the subjects' initial hospital stays
Measure: 28-day and in-hospital mortality rate Time: 28 daysDescription: Transfer to an ICU bed during the 28 days following study enrollment
Measure: Number of participants transferred to the Intensive Care Unit (ICU) Time: 28 daysDescription: Intubation within the 28 days following study enrollment
Measure: Number of participants intubated Time: 28 daysDescription: Number of days admitted to the hospital during the 28-day follow-up period
Measure: Length of hospital stay in days Time: 28 daysDescription: Type of respiratory support required during the 28-day follow-up period: intubation, high-flow oxygen by nasal canula, nasal canula
Measure: Type of respiratory support Time: 28 daysDescription: Change in CRP following treatment
Measure: C-reactive Protein (CRP) Time: 28 daysDescription: Change in lymphocyte count following treatment
Measure: Lymphocyte count Time: 28 daysDescription: Number of days respiratory support is required
Measure: Length or respiratory support required, in days Time: 28 daysDescription: Change in LDH following treatment
Measure: Lactate dehydrogenase (LDH) Time: 28 daysDescription: Change in Ferritin level following treatment
Measure: Ferritin Time: 28 daysDescription: Change in D-Dimer level following treatment
Measure: D-Dimer Time: 28 daysDescription: Change in WBC count following treatment
Measure: White Blood Cell (WBC) Count Time: 28 daysOther Outcomes
Description: Severe transfusion reaction will be defined as having any of the following occur within 6 hours of the infusion of blood product and not attributable to the underlying disease: 1) an increase of 2 L/minutes or more in supplemental oxygen requirement compared to the baseline requirement before transfusion, 2) oxygen saturations <93% despite oxygen via nasal canula, or 3) need for transfer to the ICU.
Measure: Safety endpoint: Severe transfusion reaction Time: 6 hours following transfusionDescription: Cumulative incidence of adverse events during the study period: transfusion reaction (fever, rash), transfusion related acute lung injury (TRALI), transfusion associated circulatory overload (TACO), transfusion related infection.
Measure: Safety endpoint two: adverse events Time: 24 hours following transfusion266 Phase 2, Double-blind, Randomized, Placebo-controlled Study of NasoVAX in the Prevention of Clinical Worsening in Patients With Early Coronavirus Infectious Disease 2019 (COVID-19)
The purpose of this study is to evaluate the safety and effectiveness of NasoVAX in preventing worsening of symptoms and hospitalization in patients with early COVID-19.
NCT04442230 Coronavirus Infection Biological: NasoVAX Other: Placebo MeSH:Communicable Diseases Infection Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Decrease from baseline in mean resting SpO2
Measure: Proportion of patients with clinical worsening Time: Day 1 to Day 14Secondary Outcomes
Description: Proportion of patients requiring hospitalization
Measure: Maximal severity of COVID-19 after treatment Time: Day 1 to Day 42Measure: All-cause mortality Time: Day 1 to Day 42
267 Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)
Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have carried out/published clinical trials on treatment based on Western medicine, traditional Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small (median sample size 100) and the bulk of potential therapeutic strategies remain in the experimental phase and currently there is no effective specific antiviral with high-level evidence.The aim of this study is assess the efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with moderate/severe COVID-19.
NCT04444271 COVID-19 Drug: Mesenchymal stem cells Other: Placebo
Primary Outcomes
Description: Assessment of Overall survival at 30 days post intervention
Measure: Overall survival Time: 30 days post interventionSecondary Outcomes
Description: days required for oxygen support independence after intervention
Measure: Clinical improvement Time: 30 daysDescription: PCR testing to check PCR negativity
Measure: Time of COVID19 PCR negativity Time: day 1,3,7,10, 14Description: Computed tomography Chest assesment will be done to assess improvment in radiological findings of COVID-19
Measure: Radiological improvement (day 15 and day 30 assessment) Time: day 15 and day30Description: number of days required for discharge from hospital
Measure: days required to discharge from hospital Time: 30 days post admission268 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 1569912 in Healthy Male Subjects (Single-blind, Partially Randomized Within Dose Groups, Placebo-controlled, Parallel-group Design) With an Additional Relative Bioavailability/ Food Effect Part (Open-label, Randomized, Three-way Crossover Design)
SRD-Part: To investigate safety, tolerability, pharmacokinetics and pharmacodynamics following single rising doses (SRD) of BI 1569912 BA/FE-Part: To investigate (a) the relative bioavailability (BA) of BI 1569912 and (b) the influence of food (FE) on the relative bioavailability of BI 1569912
NCT04445090 Healthy Drug: BI 1569912 Drug: Placebo
Primary Outcomes
Measure: SRD-part: % of subjects with drug-related adverse events Time: up to 14 daysMeasure: BA/FE-part: AUC0-tz (area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 to the last quantifiable data point) Time: up to 4 days
Measure: BA/FE-part: Cmax (maximum measured concentration of BI 1569912 in plasma) Time: up to 4 days
Secondary Outcomes
Measure: SRD-Part: AUC0-∞ (area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 extrapolated to infinity) Time: up to 4 daysMeasure: SRD-Part: Cmax (maximum measured concentration of BI 1569912 in plasma) Time: up to 4 days
Measure: BA/FE-Part: AUC0-∞ (area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 extrapolated to infinity) Time: up to 4 days
269 Prasugrel in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients
Inflammatory diseases favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended if concomitant inflammatory disease. In severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pneumonia an inflammation-dependent thrombotic process occurs and platelet activation may promote thrombosis and amplify inflammation, as indicated by previous experimental evidence , and the similarities with atherothrombosis and thrombotic microangiopathies. Antiplatelet agents represent the cornerstone in the prevention and treatment of atherosclerotic arterial thromboembolism, with limited efficacy in the context of venous thromboembolism. The use of purinergic receptor P2Y12 inhibitors in pneumococcal pneumonia may improve inflammation and respiratory function in humans. There are no validated protocols for thrombosis prevention in Covid-19. There is scientific rationale to consider a P2Y12 inhibitor for the prevention of thrombosis in the pulmonary circulation and attenuation of inflammation. This is supported by numerous demonstrations of the anti-inflammatory activity of P2Y12 inhibitors and the evidence of improvement in respiratory function both in human and experimental pathology. Prasugrel could be considered as an ideal candidate drug for Covid-19 patients because of higher efficacy and limited Interactions with drugs used in the treatment of Sars-CoV2. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs through an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients could reduce the incidence of pulmonary thrombosis and respiratory and multi-organ failure improving clinical outcome in patients with SARS-CoV2 pneumonia. The prevention of thrombogenic platelet activity with a P2Y12 inhibitor could be superior to fixed dose enoxaparin alone. The proposed treatment is feasible in all coronavirus disease 2019 (COVID-19) patients, regardless of the treatment regimen (antivirals, anti-inflammatory drugs, antibiotics), except for specific contraindications.
NCT04445623 COVID19 Thrombosis Drug: Prasugrel Hydrochloride 10 MG Oral Tablet Drug: Placebo MeSH:Pneumonia Thrombosis
HPO:Pneumonia
Primary Outcomes
Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected after 7 days of treatment
Measure: P/F ratio at day 7 Time: day 7
Secondary Outcomes
Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected daily for 15 days
Measure: Daily P/F ratio Time: 15 days
Description: daily need for oxygen supply for 15 days
Measure: Daily need for oxygen supply Time: 15 days
Description: Number of patients requiring transfer to the intensive care unit (ICU) by treatment arm
Measure: Need for ICU Time: day 15 and day 30
Description: death by day 15 and day 30 by treatment arm
Measure: Death Time: 15 day and day 30
Description: Multi-organ failure (MOF) by day 15 and day 30 assessed using sequential organ failure assessment score (SOFA) score (Units 0-4 better outcome, over 30 worse outcome) by treatment arm
Measure: MOF Time: day 15 and day 30
Description: Number of patients discharged after improvement by day 15 and day 30 by treatment arm
Measure: Discharge Time: day 15 and day 30
Description: Clinical progression of the disease evaluated by SOFA score (Units 0-6 better outcome, 15-24 worse outcome) by day 15 and day 30
Measure: Clinical progression of the disease SOFA score Time: day 15 and day 30
Description: Clinical progression of the disease evaluated by Acute Physiology And Chronic Health Evaluation (APACHE II) score (Units 1-5 better outcome, over 30 worse outcome) by day 15 and day 30
Measure: Clinical progression of the disease APACHE II Time: day 15 and day 30
Description: Number of patients with venous thrombosis/ pulmonary embolism/thrombosis by day 15 and day 30
Measure: Venous thrombosis/ pulmonary embolism/thrombosis Time: day 15 and day 30
Description: Number of patients requiring computerized tomography (CT) imaging due to worsening of respiratory function by treatment arm
Measure: Need for CT imaging Time: day 15
Description: Body temperature measured twice daily for 15 days, C°
Measure: Daily Temperature Time: 15 days
Description: Blood pressure measured twice daily for 15 days, mmHg
Measure: Daily blood pressure Time: 15 days
Description: Total blood count measured in venous blood for 15 days, Hemoglobin, g/L (cell/mcL
Measure: Daily total blood count Hemoglobin Time: 15 days
Description: Total blood count measured in venous blood for 15 days, Red Blood cells (cell/mcL)
Measure: Daily total blood count Red Blood Cells Time: 15 days
Description: Total blood count measured in venous blood for 15 days, Leukocytes (cell/mcL)
Measure: Daily total blood count Leukocytes Time: 15 days
Description: Total blood count measured in venous blood for 15 days, platelets (cell/mcL)
Measure: Daily total blood count Platelets Time: 15 days
Description: ALT U/L in venous blood
Measure: Daily indices of organ damage Liver Time: 15 days
Description: C-reactive protein microg/L in venous blood
Measure: Indices of inflammation C-reactive protein Time: day 1, 2, 7, 15
Description: PT ratio in venous blood by treatment arm
Measure: Indices of haemostasis PT Time: day 1, 2, 7,15
Description: progression of lung infiltrates as detected by chest-X-ray by treatment arm
Measure: Daily progression at imaging (chest-X-ray) Time: 15 days
Description: Major and/or clinically relevant bleeding according to International Society of Thrombosis and Haemostasis (ISTH) bleeding scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.
Measure: Major bleeding Time: day 1, 2, 7, 15, 30
Description: Total bleeding according to International Society of Thrombosis and Haemostasis (ISTH bleeding) scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.
Measure: Total bleeding Time: day 1, 2, 7, 15, 30
Description: Number of unexpected changes in clinical or laboratory findings not included in the predefined list of outcomes during treatment. .
Measure: Unexpected clinical or laboratory findings Time: day 1, 2, 7, 15
Description: D-dimer microg/L in venous blood
Measure: Indices of inflammation D-dimer Time: day 1, 2, 7, 15
Description: Fibrinogen g/L in venous blood
Measure: Indices of inflammation Fibrinogen Time: day 1, 2, 7, 15
Description: Interleukin (IL)-6 pg/mL in venous blood by treatment arm
Measure: Indices of inflammation IL-6 Time: day 1, 2, 7, 15
Description: Interleukin (IL)-1 pg/mL in venous blood by treatment arm
Measure: Indices of inflammation IL-1 Time: day 1, 2, 7, 15
Description: serum creatinine micromol/L by treatment arm
Measure: Daily indices of organ damage kidney Time: 15 days
Description: troponin t ng/L by treatment arm
Measure: Daily indices of organ damage heart Time: 15 days
Description: aPTT ratio by treatment arm
Measure: Haemostasis aPTT Time: day 1, 2, 7,15
Description: Vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) % by treatment arm
Measure: Haemostasis VASP PRI Time: day 1, 2, 7,15
Description: Platelet-leukocytes aggregates % in peripheral by treatment arm
Measure: Haemostasis platelet-leukocytes aggregates Time: day 1, 2, 7,15
270 A Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Trial to Protect Health Workers Against COVID-19 by Using Previfenon® as Chemoprophylaxis During a SARS-CoV-2 Outbreak. The HERD Study
Primary Outcomes
Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected after 7 days of treatment
Measure: P/F ratio at day 7 Time: day 7Secondary Outcomes
Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected daily for 15 days
Measure: Daily P/F ratio Time: 15 daysDescription: daily need for oxygen supply for 15 days
Measure: Daily need for oxygen supply Time: 15 daysDescription: Number of patients requiring transfer to the intensive care unit (ICU) by treatment arm
Measure: Need for ICU Time: day 15 and day 30Description: death by day 15 and day 30 by treatment arm
Measure: Death Time: 15 day and day 30Description: Multi-organ failure (MOF) by day 15 and day 30 assessed using sequential organ failure assessment score (SOFA) score (Units 0-4 better outcome, over 30 worse outcome) by treatment arm
Measure: MOF Time: day 15 and day 30Description: Number of patients discharged after improvement by day 15 and day 30 by treatment arm
Measure: Discharge Time: day 15 and day 30Description: Clinical progression of the disease evaluated by SOFA score (Units 0-6 better outcome, 15-24 worse outcome) by day 15 and day 30
Measure: Clinical progression of the disease SOFA score Time: day 15 and day 30Description: Clinical progression of the disease evaluated by Acute Physiology And Chronic Health Evaluation (APACHE II) score (Units 1-5 better outcome, over 30 worse outcome) by day 15 and day 30
Measure: Clinical progression of the disease APACHE II Time: day 15 and day 30Description: Number of patients with venous thrombosis/ pulmonary embolism/thrombosis by day 15 and day 30
Measure: Venous thrombosis/ pulmonary embolism/thrombosis Time: day 15 and day 30Description: Number of patients requiring computerized tomography (CT) imaging due to worsening of respiratory function by treatment arm
Measure: Need for CT imaging Time: day 15Description: Body temperature measured twice daily for 15 days, C°
Measure: Daily Temperature Time: 15 daysDescription: Blood pressure measured twice daily for 15 days, mmHg
Measure: Daily blood pressure Time: 15 daysDescription: Total blood count measured in venous blood for 15 days, Hemoglobin, g/L (cell/mcL
Measure: Daily total blood count Hemoglobin Time: 15 daysDescription: Total blood count measured in venous blood for 15 days, Red Blood cells (cell/mcL)
Measure: Daily total blood count Red Blood Cells Time: 15 daysDescription: Total blood count measured in venous blood for 15 days, Leukocytes (cell/mcL)
Measure: Daily total blood count Leukocytes Time: 15 daysDescription: Total blood count measured in venous blood for 15 days, platelets (cell/mcL)
Measure: Daily total blood count Platelets Time: 15 daysDescription: ALT U/L in venous blood
Measure: Daily indices of organ damage Liver Time: 15 daysDescription: C-reactive protein microg/L in venous blood
Measure: Indices of inflammation C-reactive protein Time: day 1, 2, 7, 15Description: PT ratio in venous blood by treatment arm
Measure: Indices of haemostasis PT Time: day 1, 2, 7,15Description: progression of lung infiltrates as detected by chest-X-ray by treatment arm
Measure: Daily progression at imaging (chest-X-ray) Time: 15 daysDescription: Major and/or clinically relevant bleeding according to International Society of Thrombosis and Haemostasis (ISTH) bleeding scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.
Measure: Major bleeding Time: day 1, 2, 7, 15, 30Description: Total bleeding according to International Society of Thrombosis and Haemostasis (ISTH bleeding) scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.
Measure: Total bleeding Time: day 1, 2, 7, 15, 30Description: Number of unexpected changes in clinical or laboratory findings not included in the predefined list of outcomes during treatment. .
Measure: Unexpected clinical or laboratory findings Time: day 1, 2, 7, 15Description: D-dimer microg/L in venous blood
Measure: Indices of inflammation D-dimer Time: day 1, 2, 7, 15Description: Fibrinogen g/L in venous blood
Measure: Indices of inflammation Fibrinogen Time: day 1, 2, 7, 15Description: Interleukin (IL)-6 pg/mL in venous blood by treatment arm
Measure: Indices of inflammation IL-6 Time: day 1, 2, 7, 15Description: Interleukin (IL)-1 pg/mL in venous blood by treatment arm
Measure: Indices of inflammation IL-1 Time: day 1, 2, 7, 15Description: serum creatinine micromol/L by treatment arm
Measure: Daily indices of organ damage kidney Time: 15 daysDescription: troponin t ng/L by treatment arm
Measure: Daily indices of organ damage heart Time: 15 daysDescription: aPTT ratio by treatment arm
Measure: Haemostasis aPTT Time: day 1, 2, 7,15Description: Vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) % by treatment arm
Measure: Haemostasis VASP PRI Time: day 1, 2, 7,15Description: Platelet-leukocytes aggregates % in peripheral by treatment arm
Measure: Haemostasis platelet-leukocytes aggregates Time: day 1, 2, 7,15The purpose of this clinical trial is to determine the efficacy of Previfenon® (EGCG) to prevent COVID-19, enhance systemic immunity, and decrease the frequency and intensity of selected symptoms when used as pre-exposure chemoprophylaxis to SARS-CoV-2.
NCT04446065 COVID-19 SARS-CoV2 Drug: Previfenon® Drug: Placebo
Primary Outcomes
Description: A positive case or event of COVID-19 is defined as a patient with acute respiratory illness presenting fever (37.8º C); at least one of the following symptoms: odynophagia, cough, myalgia, or dyspnea; and a specific positive rtPCR test for SARS-CoV-2.
Measure: Event of clinical acute respiratory disease with a diagnosis of COVID-19 confirmed with rtPCR Time: The date for censoring a case will be defined as that date when the rtPCR test results positive minus 4 days, with the aim to calculate the time free of clinically defined COVID-19 infection over 40 to 70 days of interventionSecondary Outcomes
Description: Rate of positive cases for IgM and IgG anti-SARS-CoV-2 measured by immunochromatographic test in treatment and placebo group at the end of the study
Measure: Rate of positive cases for IgM and IgG anti-SARS-CoV-2 Time: Positive cases in each two-week examination and to the end of the study over 40 to 70 days of interventionDescription: Rate of asymptomatic cases defined as a positive rtPCR for SARS-CoV-2 viral RNA but with no symptoms of COVID-19 in treatment and placebo group at the end of the study, and a composite outcome considering symptomatic and asymptomatic cases (i.e. all cases with positive rtPCR test)
Measure: Composite outcome considering symptomatic and asymptomatic cases with positive rtPCR test Time: Positive cases in each two-weeks examination and to the end of the study over 40 to 70 days of interventionDescription: Rate of hospitalizations due to any acute respiratory infection at the end of the study
Measure: Hospitalization due to any acute respiratory infection Time: Positive cases in each two-week examination visit and to the end of the study over 40 to 70 days of interventionDescription: Global frequency of events of upper and lower airway respiratory infections
Measure: Event of upper and lower airway respiratory infection Time: Positive cases in each two-week examination and to the end of the study over 40 to 70 days of interventionOther Outcomes
Description: Registry of Visual Analogue Scale (VAS) in the log diary of every healthcare worker for the following selected symptoms: cough, muscle pain (myalgia); difficulty breathing (dyspnea); loss of smell (anosmia); loss of taste (ageusia); pain when swallowing (odynophagia, sore throat); and finally headache
Measure: Exploratory outcome: Frequency and intensity of selected symptoms for COVID-19 Time: Different VAS scores calculated each two-week examination visit over 40 to 70 days of interventionDescription: Elevation of liver enzymes over 5 times the normal value
Measure: Primary safety outcome: event of major hepatic harm Time: Cases accounted by liver profile lab test in each two-week examination visit over 40 to 70 days of intervention.Description: Elevation of liver enzymes over 5 times the normal value
Measure: Event of liver enzymes over 3 times the normal value Time: Cases accounted by liver profile lab test in each two-week examination visit over 40 to 70 days of interventionDescription: Any adverse event reported over the intervention period
Measure: Frequency of adverse events Time: Records of self-reported adverse effects on log dairy accounted in each examination visit over 40 to 70 days of intervention271 A Phase II Randomized, Double-Blind, Placebo-Controlled Study of LAM-002A for the Prevention of Progression of COVID-19
This is a clinical trial to evaluate the efficacy of LAM-002A compared to placebo treatment in adults with a confirmed SARS-CoV-2 infection who are receiving standards supportive care in an outpatient setting.
NCT04446377 COVID-19 Disease Drug: Apilimod Dimesylate Capsule Other: Placebo MeSH:Disease Progression
Primary Outcomes
Description: To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 4
Measure: Viral Load Change Time: 4 DaysSecondary Outcomes
Description: To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 6, compared between the LAM-002A arm and the placebo arm.
Measure: Viral Load Change Time: 6 DaysDescription: To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 8, compared between the LAM-002A arm and the placebo arm.
Measure: Viral Load Change Time: 8 DaysDescription: To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 11, compared between the LAM-002A arm and the placebo arm.
Measure: Viral Load Change Time: 11 DaysDescription: To evaluate the antiviral efficacy of LAM-002A in participants with COVID-19 as the change from baseline (Day 1, pre-dose) of SARS-CoV-2 viral load as measured by qRT-PCR from nasopharyngeal samples on day 28, compared between the LAM-002A arm and the placebo arm.
Measure: Viral Load Change Time: 28 DaysDescription: To evaluate the anti-viral efficacy of LAM-002A in participants with COVID-19 as difference in SARS-Cov-2 viral load as measured by qRT-PCR from nasopharyngeal samples based on AUC (days1-28), between LAM-002A arm and placebo arm.
Measure: Viral Load AUC Time: 28 DaysDescription: The proportion of LAM-002A treated patients who develop treatment-emergent adverse events (TEAEs) compared to placebo. TEAEs will be defined as AEs that occur on or after the date and time of study drug administration, or those that first occur pre-dose but worsen in frequency or severity after study drug administration. AEs will be followed up until complete resolution or until the Principal Investigator (PI) or Sub-Investigator deems it safe to discontinue followup.
Measure: Safety and Tolerability measured in proportion of TEAEs Time: 28 DaysOther Outcomes
Description: To evaluate the efficacy of LAM-002A in preventing COVID-19 disease progression in participants who have proven infection with SARS-CoV-2 virus as determined by a molecular test and who have mild manifestations of COVID-19 and less than or equal to 4 days of symptoms; disease progression is defined as occurance of death or hospitalization at day 28.
Measure: Clinical Efficacy in prevention of hospitalization or death Time: 28 DaysDescription: To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.
Measure: Oxygen Saturation Time: 1 DaysDescription: To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.
Measure: Oxygen Saturation Time: 4 DaysDescription: To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.
Measure: Oxygen Saturation Time: 6 DaysDescription: To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.
Measure: Oxygen Saturation Time: 8 DaysDescription: To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo.
Measure: Oxygen saturation Time: 11 DaysDescription: Change in COVID-19 clinical status as defined by the ordinal scale, of participants treated with LAM-002A as compared with placebo at Day 28, in participants who become hospitalized and continue LAM-002A/placebo treatment, based on the following scores: Not in the hospital Hospitalized, requiring low flow supplemental oxygen (such as nasal cannula) Hospitalized, not on invasive ventilation (such as 100% non-rebreather, BIPAP), (pre-ICU) Hospitalized, in the ICU, on invasive ventilation or ECMO Dead For participants (who have the same ordinal score), control versus experimental arms will be compared based on percentage of participants at each score.
Measure: Clinical Status defined by ordinal scale Time: 28 days272 Randomized, Doubled-blind Phase II Trial Evaluating the Use of Ivermectin Plus Losartan for Prophylaxis of Severe Events in Cancer Patients With Recent Diagnosis of COVID-19
Ivermectin plus losartan as prophilaxy to severe events in patients with cancer with recent diagnosis of COVID-19
NCT04447235 Cancer COVID Coronavirus Infection Drug: Placebo Drug: Ivermectin Drug: Losartan MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Incidence of severe complications due COVID-19 infection defined as need for ICU admission, need for mechanical ventilation, or death
Measure: Incidence of severe complications due COVID-19 infection Time: 28 daysSecondary Outcomes
Description: Severe Acute Respiratory Syndrome defined as oxygen saturation less than 93%
Measure: Incidence of Severe Acute Respiratory Syndrome Time: 28 daysDescription: Severe Acute Respiratory Syndrome defined as respiratory rate higher than 24 incursion per minute
Measure: Incidence of Severe Acute Respiratory Syndrome Time: 28 daysDescription: Incidence of hepatic toxicity (elevation of ALT, AST above the upper limit of normal, measured by U/L)
Measure: Adverse events Time: 28 daysDescription: Incidence of hepatic toxicity (elevation of bilirubin above the upper limit of normal, measured by mg/dL)
Measure: Adverse events Time: 28 daysDescription: Incidence of renal toxicity (elevation of serum creatinine levels above the upper limit of normal, measured by mg/dL)
Measure: Adverse events Time: 28 daysDescription: Incidence of symptomatic postural hypotension, diagnosed by clinical assessment of reduction of > 20 mmHG of arterial systolic pressure after measurement in prone position and orthostatic position.
Measure: Adverse events Time: 28 daysDescription: Death of any cause since protocol enrollment
Measure: Overall survival Time: 28 days273 A Randomized, Double-Blind, Placebo Controlled Study to Evaluate Safety and Efficacy of DUR-928 in Subjects Infected With SARS-CoV-2 With Acute Liver or Kidney Injury
Evaluate safety and efficacy of DUR-928 in treatment of acute organ failure in subjects infected with SARS-CoV-2
NCT04447404 SARS-CoV 2 Drug: DUR-928 Drug: Placebo
Primary Outcomes
Description: Free of mechanical ventilation, free of renal replacement therapy and free of acute liver failure
Measure: Composite endpoint of alive and free of organ failure Time: Day 28Measure: Occurrence of serious adverse events following treatment Time: Day 1 to Day 60
Secondary Outcomes
Measure: Alive at days 28 and 60 Time: Days 28 and 60Measure: Alive and out of ICU Time: Day 28
Measure: Alive and out of hospital Time: Day 28 and Day 60
274 A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation
Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).
NCT04447469 COVID Drug: mavrilimumab Other: Placebo MeSH:Pneumonia Inflammation
HPO:Pneumonia
Primary Outcomes
Description: Respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
Measure: Cohort 1: Proportion of Participants Alive and Without Respiratory Failure at Day 15 Time: Day 15
Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 2: Mortality Rate at Day 15 Time: Day 15
Secondary Outcomes
Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (National Institute of Allergy and Infectious Diseases [NIAID] scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Time to Return to Room Air by Day 15 Time: up to Day 15
Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Time to 2-point Clinical Improvement by Day 15 Time: up to Day 15
Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 1: Mortality Rate at Day 29 Time: Day 29
Description: Clinical improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Time to 1-Point Clinical Improvement by Day 15 Time: up to Day 15
Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 2: Mortality Rate at Day 29 Time: Day 29
Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
Measure: Cohort 2: Proportion of Participants Alive and Without Respiratory Failure at Day 15 Time: Day 15
Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
Measure: Cohorts 1 and 2: Proportion of Participants Alive and Without Respiratory Failure At Day 29 Time: Day 29
Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Time to Return to Room Air by Day 29 Time: up to Day 29
Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 2: Time to 2-point Clinical Improvement by Day 15 Time: up to Day 15
Description: Clinical Improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Time to 1-point Clinical Improvement by Day 29 Time: up to Day 29
Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Time to 2-point Clinical Improvement by Day 29 Time: up to Day 29
Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
Measure: Cohort 1: Respiratory Failure-Free Survival by Day 15 Time: up to Day 15
Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
Measure: Cohort 1: Respiratory Failure-Free Survival by Day 29 Time: up to Day 29
Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Proportion of Participants Who Return to Room Air by Day 15 Time: up to Day 15
Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Proportion of Participants Who Return to Room Air by Day 29 Time: up to Day 29
Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 1: Mortality Rate at Day 15 Time: Day 15
Description: Overall survival is defined as time from date of randomization to the date of death.
Measure: Cohorts 1 and 2: Overall Survival by Day 29 Time: up to Day 29
Description: Clinical status, based on the NIAID 8-point ordinal scale. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Clinical Status Over Time Time: Days 4, 8, 15, 22, and 29
Measure: Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90 Time: through Day 90
275 Stop of Proton-pump Inhibitor Treatment in Patients With Liver Cirrhosis - a Double-blind, Placebo-controlled Trial
Primary Outcomes
Description: Respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).
Measure: Cohort 1: Proportion of Participants Alive and Without Respiratory Failure at Day 15 Time: Day 15Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 2: Mortality Rate at Day 15 Time: Day 15Secondary Outcomes
Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (National Institute of Allergy and Infectious Diseases [NIAID] scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Time to Return to Room Air by Day 15 Time: up to Day 15Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Time to 2-point Clinical Improvement by Day 15 Time: up to Day 15Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 1: Mortality Rate at Day 29 Time: Day 29Description: Clinical improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Time to 1-Point Clinical Improvement by Day 15 Time: up to Day 15Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 2: Mortality Rate at Day 29 Time: Day 29Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
Measure: Cohort 2: Proportion of Participants Alive and Without Respiratory Failure at Day 15 Time: Day 15Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
Measure: Cohorts 1 and 2: Proportion of Participants Alive and Without Respiratory Failure At Day 29 Time: Day 29Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Time to Return to Room Air by Day 29 Time: up to Day 29Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 2: Time to 2-point Clinical Improvement by Day 15 Time: up to Day 15Description: Clinical Improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Time to 1-point Clinical Improvement by Day 29 Time: up to Day 29Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Time to 2-point Clinical Improvement by Day 29 Time: up to Day 29Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.
Measure: Cohort 1: Respiratory Failure-Free Survival by Day 15 Time: up to Day 15Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO
Measure: Cohort 1: Respiratory Failure-Free Survival by Day 29 Time: up to Day 29Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohort 1: Proportion of Participants Who Return to Room Air by Day 15 Time: up to Day 15Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Proportion of Participants Who Return to Room Air by Day 29 Time: up to Day 29Description: Mortality rate is defined as the proportion of participants who die.
Measure: Cohort 1: Mortality Rate at Day 15 Time: Day 15Description: Overall survival is defined as time from date of randomization to the date of death.
Measure: Cohorts 1 and 2: Overall Survival by Day 29 Time: up to Day 29Description: Clinical status, based on the NIAID 8-point ordinal scale. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
Measure: Cohorts 1 and 2: Clinical Status Over Time Time: Days 4, 8, 15, 22, and 29Measure: Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90 Time: through Day 90
Proton-pump inhibitors (PPI) are commonly prescribed in an uncritical manner to patients with liver cirrhosis without a clear evidence-based indication. Observational studies suggests that PPI use in cirrhotic patients may be a risk factor for the development of infections, especially spontaneous bacterial peritonitis (SBP). A possible explanation are PPI-associated microbiotic shifts leading to small intestinal bacterial overgrowth with subsequently increased bacterial translocation. Furthermore, PPI therapy in cirrhotic patients may lead to an increased risk for pneumonia and Clostridium difficile-infections. However, the evidence is ambiguous, as other published studies found no evidence for an association of PPI use with an increased risk for SBP or pneumonia. Moreover, an association between episodes of hepatic encephalopathy and PPI use has been reported. Infections and hepatic encephalopathy may often lead to a hospitalization of cirrhotic patients and PPI use at discharge has also been associated to early re-hospitalization. While some studies found an association of PPI and increased mortality in cirrhotic patients, other studies could not observe this association. Thus, some of the current evidence suggests an unfavourable risk profile of PPIs in patients with liver cirrhosis. However, this patient population is considered to be at a high risk of gastrointestinal haemorrhage from peptic ulcers. Importantly, patients with liver cirrhosis have an increased mortality after peptic ulcer bleeding as compared to patients without cirrhosis. Therefore, generous PPI use may also have a yet unproven preventive effect against upper gastrointestinal bleeding. The STOPPIT trial is the first prospective, randomized, controlled, double-blind trial investigating the effect of discontinuation of long-term PPI therapy on hospitalized patients with complicated liver cirrhosis with a pre-existing long-term PPI therapy. Importantly, patients with an evidence-based indication for PPI therapy are excluded from the trial. All study participants (n=476) stop their previous PPI treatment and are then randomized (1:1) to receive either placebo (intervention group) or esomeprazole 20mg/day (control group) for 360 days. The primary hypothesis anticipates a delay of re-hospitalisation and/or death (composite endpoint) in patients who discontinue PPI treatment as compared to patients who continue PPI therapy. Secondary objectives include the assessment of mortality, re-hospitalisation rates, infection rates, rate of acute hepatic decompensation and ACLF, as well as rates of upper and lower gastrointestinal bleeding events in both groups. Impact of prolonged or discontinued PPI therapy on the intestinal microbiota and pharmacoeconomics will be studied as a secondary assessment.
NCT04448028 Liver Cirrhosis Drug: Placebo Drug: Esomeprazole 20mg MeSH:Liver Cirrhosis Fibrosis
HPO:Cirrhosis Hepatic fibrosis
Primary Outcomes
Measure: Timepoint of first unplanned re-hospitalization or death (whichever occurs first) Time: Within 12 months (360 days) after randomization
Secondary Outcomes
Measure: Timepoint of death Time: Within 12 months (360 days) after randomization
Measure: Mortality rate Time: 360 days after randomization
Measure: Timepoint of first unplanned re-hospitalization Time: Within 12 months (360 days) after randomization
Measure: Rate of unplanned re-hospitalizations Time: 360 days after randomization
Measure: Overall infection rate Time: 360 days after randomization
Description: Infection rates by site of infection (SBP, pneumonia, urinary tract infection, blood stream infection, Clostridium difficile-associated enterocolitis, Norovirus-infection, Sars-CoV-2-infection)
Measure: Infection rates differentiated by site Time: 360 days after randomization
Measure: Rate of acute decompensation of liver cirrhosis Time: 360 days after randomization
Measure: Rate of acute-on-chronic liver failure (ACLF) Time: 360 days after randomization
Measure: Rate of upper gastrointestinal bleeding events Time: 360 days after randomization
Measure: Rate of lower gastrointestinal bleeding events Time: 360 days after randomization
Description: The gut microbiota composition will be analyzed by PCR
Measure: Changes of intestinal microbiota between baseline and day 90 Time: 90 days after randomization
Other Outcomes
Measure: Rate of occurence of the safety endpoint (evidence-based indication for open-label re-therapy with PPIs) Time: 360 days after randomization
Measure: Rate of any (serious) adverse events Time: 360 days after randomization
276 A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of M5049 in Hospitalized Participants With COVID-19 Pneumonia
Primary Outcomes
Measure: Timepoint of first unplanned re-hospitalization or death (whichever occurs first) Time: Within 12 months (360 days) after randomizationSecondary Outcomes
Measure: Timepoint of death Time: Within 12 months (360 days) after randomizationMeasure: Mortality rate Time: 360 days after randomization
Measure: Timepoint of first unplanned re-hospitalization Time: Within 12 months (360 days) after randomization
Measure: Rate of unplanned re-hospitalizations Time: 360 days after randomization
Measure: Overall infection rate Time: 360 days after randomization
Description: Infection rates by site of infection (SBP, pneumonia, urinary tract infection, blood stream infection, Clostridium difficile-associated enterocolitis, Norovirus-infection, Sars-CoV-2-infection)
Measure: Infection rates differentiated by site Time: 360 days after randomizationMeasure: Rate of acute decompensation of liver cirrhosis Time: 360 days after randomization
Measure: Rate of acute-on-chronic liver failure (ACLF) Time: 360 days after randomization
Measure: Rate of upper gastrointestinal bleeding events Time: 360 days after randomization
Measure: Rate of lower gastrointestinal bleeding events Time: 360 days after randomization
Description: The gut microbiota composition will be analyzed by PCR
Measure: Changes of intestinal microbiota between baseline and day 90 Time: 90 days after randomizationOther Outcomes
Measure: Rate of occurence of the safety endpoint (evidence-based indication for open-label re-therapy with PPIs) Time: 360 days after randomizationMeasure: Rate of any (serious) adverse events Time: 360 days after randomization
The study will evaluate the safety and efficacy of orally-administered M5049 in COVID-19 pneumonia participants who are hospitalized but not on mechanical ventilation.
NCT04448756 Coronavirus Disease 2019 Drug: M5049 Drug: M5049 Drug: Placebo MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia
Primary Outcomes
Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation Time: Day 14
Measure: Occurrence of Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious AEs (SAEs) Time: Day 1 through Day 60
Measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters and Electrocardiogram Findings Time: Day 1 through Day 28
Secondary Outcomes
Description: A nine point ordinal scale - 0: Uninfected
No limitation of activities
Limitation of activities
Hospitalized, mild disease on, no oxygen therapy
Hospitalized, with oxygen by mask or nasal prongs
Hospitalized, severe disease: noninvasive ventilation or high flow oxygen
Hospitalized, severe disease: intubation and mechanical ventilation
Hospitalized, severe disease: ventilation plus additional organ support - example, vasopressors, Extracorporeal membrane oxygenation (ECMO)
Death.
Measure: Clinical Status of Participants on a 9-Point Ordinal Scale Time: Day 1 through Day 60
Description: Normal oxygen exchange in room air.
Measure: Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours on Room Air Time: Day 1 through Day 28
Description: Percentage of Participants who die for any reason.
Measure: Percentage of Participants With All-Cause Mortality Time: Day 1 through Day 28
Description: Clinical Deterioration
Measure: Clinical Deterioration: Time to Intensive Care Unit (ICU) Admission Time: Day 1 through Day 28
Description: Clinical Deterioration
Measure: Clinical Deterioration: Time to Invasive Mechanical Ventilation Time: Day 1 through Day 28
Description: Clinical Deterioration
Measure: Clinical Deterioration: Time to Non-Invasive Mechanical Ventilation Time: Day 1 through Day 28
Measure: Total Length of Stay in Intensive Care Unit (ICU) Time: Day 1 through Day 60
Measure: Total Length of Hospitalization Stay Time: Day 1 through Day 60
Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation Time: Day 1 through Day 28
Measure: Percentage Change From Baseline in Inflammatory Biomarkers Time: Day 1 through Day 28
Description: Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.
Measure: Percentage of Participants With Relapse Time: Day 5 through Day 60
Description: Percentage or participants who are re-hospitalized for any reason.
Measure: Percentage of Participants who are Re-Hospitalized Time: Day 5 through Day 60
Description: Only the first 15 participants will be evaluated for Pharmacokinetic parameters.
Measure: Maximum Observed Concentration (Cmax) of M5049 Time: Day 1 and Day 7
Measure: Time to Reach the Maximum Observed Concentration (tmax) of M5049 Time: Day 1 and Day 7
Measure: Terminal Rate Constant (Lambda z) of M5049 Time: Day 1 and Day 7
Measure: Apparent Elimination Half-Life (t1/2) of M5049 Time: Day 1 and Day 7
Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t) of M5049 Time: Day 1 and Day 7
Measure: Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h) of M5049 Time: Day 1 and Day 7
Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity) of M5049 Time: Day 1 and Day 7
Measure: Apparent Total Body Clearance (CL/F) of M5049 Time: Day 1 and Day 7
Measure: Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Maximum Observed Concentration (Cmax/Dose) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t/Dose) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity/Dose) of M5049 Time: Day 1 and Day 7
277 A Phase 1, Partially Blind, Placebo-controlled, Dose-escalation, First-in-human, Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity After 1 and 2 Doses of the Investigational SARS-CoV-2 mRNA Vaccine CVnCoV Administered Intramuscularly in Healthy Adults
Primary Outcomes
Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation Time: Day 14Measure: Occurrence of Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious AEs (SAEs) Time: Day 1 through Day 60
Measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters and Electrocardiogram Findings Time: Day 1 through Day 28
Secondary Outcomes
Description: A nine point ordinal scale - 0: Uninfected No limitation of activities Limitation of activities Hospitalized, mild disease on, no oxygen therapy Hospitalized, with oxygen by mask or nasal prongs Hospitalized, severe disease: noninvasive ventilation or high flow oxygen Hospitalized, severe disease: intubation and mechanical ventilation Hospitalized, severe disease: ventilation plus additional organ support - example, vasopressors, Extracorporeal membrane oxygenation (ECMO) Death.
Measure: Clinical Status of Participants on a 9-Point Ordinal Scale Time: Day 1 through Day 60Description: Normal oxygen exchange in room air.
Measure: Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours on Room Air Time: Day 1 through Day 28Description: Percentage of Participants who die for any reason.
Measure: Percentage of Participants With All-Cause Mortality Time: Day 1 through Day 28Description: Clinical Deterioration
Measure: Clinical Deterioration: Time to Intensive Care Unit (ICU) Admission Time: Day 1 through Day 28Description: Clinical Deterioration
Measure: Clinical Deterioration: Time to Invasive Mechanical Ventilation Time: Day 1 through Day 28Description: Clinical Deterioration
Measure: Clinical Deterioration: Time to Non-Invasive Mechanical Ventilation Time: Day 1 through Day 28Measure: Total Length of Stay in Intensive Care Unit (ICU) Time: Day 1 through Day 60
Measure: Total Length of Hospitalization Stay Time: Day 1 through Day 60
Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation Time: Day 1 through Day 28
Measure: Percentage Change From Baseline in Inflammatory Biomarkers Time: Day 1 through Day 28
Description: Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.
Measure: Percentage of Participants With Relapse Time: Day 5 through Day 60Description: Percentage or participants who are re-hospitalized for any reason.
Measure: Percentage of Participants who are Re-Hospitalized Time: Day 5 through Day 60Description: Only the first 15 participants will be evaluated for Pharmacokinetic parameters.
Measure: Maximum Observed Concentration (Cmax) of M5049 Time: Day 1 and Day 7Measure: Time to Reach the Maximum Observed Concentration (tmax) of M5049 Time: Day 1 and Day 7
Measure: Terminal Rate Constant (Lambda z) of M5049 Time: Day 1 and Day 7
Measure: Apparent Elimination Half-Life (t1/2) of M5049 Time: Day 1 and Day 7
Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t) of M5049 Time: Day 1 and Day 7
Measure: Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h) of M5049 Time: Day 1 and Day 7
Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity) of M5049 Time: Day 1 and Day 7
Measure: Apparent Total Body Clearance (CL/F) of M5049 Time: Day 1 and Day 7
Measure: Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Maximum Observed Concentration (Cmax/Dose) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t/Dose) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049 Time: Day 1 and Day 7
Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity/Dose) of M5049 Time: Day 1 and Day 7
This study aims to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of CVnCoV at different dose levels.
NCT04449276 Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2 COVID-19 Biological: CVnCoV Vaccine Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: This data will be collected for decisions on subsequent vaccination of an additional open-label sentinel group with the same dose level.
Measure: Number of Participants With Grade 3 Adverse Reactions or any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 24 Hours After the First Vaccination Time: Up to 24 hours after vaccination on Day 1Description: This data will be collected for decisions on dose escalation as well as continuation of enrollment at the same dose level in the observer-blind placebo-controlled part of the trial.
Measure: Number of Participants With Grade 3 Adverse Reactions or any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 60 Hours After the First Vaccination Time: Up to 60 hours after vaccination on Day 1Measure: Number of Participants with Solicited Local Adverse Events Time: 7 days after vaccination
Measure: Intensity of Solicited Local Adverse Events per the FDA Toxicity Grading Scale Time: 7 days after vaccination
Measure: Duration of Solicited Local Adverse Events Time: 7 days after vaccination
Measure: Number of Participants with Solicited Systemic Adverse Events Time: 7 days after vaccination
Measure: Intensity of Solicited Systemic Adverse Events per the FDA Toxicity Grading Scale Time: 7 days after vaccination
Measure: Duration of Solicited Systemic Adverse Events Time: 7 days after vaccination
Measure: Number of Participants with Solicited Systemic Adverse Events Considered Related to Trial Vaccine Time: 7 days after vaccination
Measure: Number of Participants with Unsolicited Adverse Events Time: 28 days after vaccination
Measure: Intensity of Unsolicited Adverse Events Assessed by the Investigator Time: 28 days after vaccination
Measure: Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine Time: 28 days after vaccination
Measure: Number of Participants with One or More Serious Adverse events (SAEs) Time: Baseline to Day 393
Measure: Number of Participants with One or More Serious Adverse events (SAEs) Considered Related to Trial Vaccine Time: Baseline to Day 393
Measure: Number of Participants with One or More Adverse Events of Special Interest (AESIs) Time: Baseline to Day 393
Measure: Number of Participants with One or More Adverse Events of Special Interest (AESIs) Considered Related to Trial Vaccine Time: Baseline to Day 393
Secondary Outcomes
Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
Measure: Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies Time: Baseline and on Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
Measure: Individual SARS-CoV-2 Spike Protein-Specific Antibody Levels in Serum Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).
Measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393Description: Measured using an activity assay.
Measure: Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies Time: Baseline and on Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393Description: Measured using an activity assay.
Measure: Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393Description: Measured using an activity assay.
Measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393278 Vitamin D Supplementation in Patients With COVID-19: A Randomized, Double-blind, Placebo-controlled Trial
Coronavirus disease 2019 (COVID-19) was declared an emergency public health problem by the World Health Organization (WHO) in March 2020. Since then, several initiatives by the medical and scientific community have sought alternatives to treat infected individuals, as well as identifying risk or protective factors for the contamination and prognosis of patients. In this perspective, vitamin D supplementation can improve some important outcomes in critically ill patients, being considered a potent immunomodulatory agent. Vitamin D deficiency is a common outcome in critically ill patients, thus making it a modifiable risk factor with great potential for reducing hospital stay and intensive care and mortality. The investigators speculate that vitamin D supplementation could have therapeutic effects in patients with COVID-19.
NCT04449718 COVID-19 Dietary Supplement: Vitamin D Dietary Supplement: Placebo
Primary Outcomes
Description: total number of days that patient remained hospitalized
Measure: Length of hospitalization Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 monthSecondary Outcomes
Description: number of patients that died
Measure: Mortality Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 monthDescription: total number of days that patient remained in ICU
Measure: Number of cases admitted to Intensive Care Unit (ICU) Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 monthDescription: total number of days that patient remained in mechanic ventilator
Measure: Length of use of mechanic ventilator Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 monthMeasure: Number and severity of symptoms Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month
Description: C-reactive protein, IL-1alpha (pg/ml), IL-1beta (pg/ml), IL-6 (pg/ml), TNF-alpha (pg/ml), IL-1ra (pg/ml), IL-10 (pg/ml) concentration in the serum
Measure: Inflammatory markers Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)Description: serum concentration
Measure: C-reactive protein Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)Description: serum concentration
Measure: Vitamin D Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)Description: serum concentration
Measure: Creatinine Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)Description: serum concentration
Measure: Calcium Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)Description: Baecke questionnaire (higher scores mean a higher physical activity level)
Measure: Physical activity Time: Baseline279 The Efficacy of Topical Povidone-Iodine Rinses in the Management of the Coronavirus Disease 2019 (COVID-19)
The aim of this study is to determine if Povidone iodine (PVP-I) rinses and throat gargles or a PVP-I gel forming nasal spray compared to a placebo (a treatment that has no physical effect to a person) is an effective treatment for patients diagnosed with COVID-19. These patients have been diagnosed with mild/moderate COVID-19 symptoms and sent home for self-isolation. Patients will be instructed to take either of the two treatments or placebo twice daily for two weeks and have follow up visits 2 and 4 weeks after. The participants will also complete study related procedures such as saliva sample collection, and two questionnaires throughout the study period. The investigators hypothesize that COVID 19 positive participants who use either of the Povidone - Iodine treatment will have a reduction in their viral load, develop a negative oral mucosa sample and improve their clinical symptoms.
NCT04449965 Covid19 Drug: Povidone-iodine Drug: Placebo
Primary Outcomes
Description: A saliva sample will be analyzed to monitor the duration of positivity and when test becomes negative for SARS-CoV-2.
Measure: Change in SARS-CoV-2 positivity in the saliva Time: A saliva sample will be taken every 2 days for 2 weeks, and again at 4 and 6 weeksDescription: Quantify the amount of SAR-CoV-2 viral load present in the saliva.
Measure: Change in the SAR-CoV-2 viral load in the saliva Time: A saliva sample will be taken every 2 days for 2 weeks, and again at 4 and 6 weeksSecondary Outcomes
Description: This is a 44 question, quality of life survey designed to measure different aspects affected by the common cold.
Measure: Change in Wisconsin Upper Respiratory Symptom Survey (WURSS-44) Time: daily for 2 weeks, 4 weeks, and 6 weeksDescription: That includes 22 questions about symptoms and social/emotional consequences of your nasal disorder.
Measure: Change Sino nasal Outcome Test (SNOT-22) Time: baseline, 2 weeks, 4 weeks, 6 weeksDescription: We will record and worsening of clinical condition such as, need for hospitalization/oxygen support.
Measure: Change in clinical condition Time: daily for 2 weeks, 4 weeks, and 6 weeks280 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-CoV-2 Infection in Household Contacts of Individuals Infected With SARS-CoV-2
Primary Objective: - To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing symptomatic SARS-CoV-2 infection (strict-term) confirmed by RT-qPCR - To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing asymptomatic or symptomatic SARS-CoV-2 infection confirmed by RT-qPCR - To evaluate the safety and tolerability of REGN10933+REGN10987 following subcutaneous (SC) administration compared to placebo
NCT04452318 Healthy Participants Drug: REGN10933+REGN10987 Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR (based on central lab test) and signs and symptoms (strict-term) of SARS-CoV-2 infection during the Efficacy assessment period (EAP) Time: Up to 1 monthDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Proportion of participants who have a RT-qPCR confirmed SARS-CoV-2 infection (either symptomatic or asymptomatic) during the EAP Time: Up to 1 monthDescription: Primary: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Secondary: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Incidence and severity of treatment-emergent adverse events (TEAEs) Time: Up to 8 monthsSecondary Outcomes
Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Proportion of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad term) during the EAP Time: Up to 1 monthDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (strict term) during the EAP Time: Up to 1 monthDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (broad term) during the EAP Time: Up to 1 monthDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Number of days of symptomatic SARS-CoV-2 infection (strict-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Number of days of symptomatic SARS-CoV-2 infection (broad-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Time-weighted average of viral shedding (log10 copies/mL) from the first positive SARS CoV-2 RT-qPCR Nasopharyngeal (NP) swab sample (with an onset during the EAP) until the visit within the window including 22 days after the positive test during the EAP Time: Up to 1 monthDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in Nasopharyngeal (NP) swab samples among individuals with ≥1 RT-qPCR positive that has an onset during the EAP Time: Up to 1 monthDescription: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in NP swab samples Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Area under the curve (AUC) in viral shedding (log10 copies/mL) from the first positive SARS-CoV-2 RT-qPCR NP swab sample until the first confirmed negative test, that has an onset during the EAP Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Number of medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Proportion of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset during the EAP Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Number of days of hospital and intensive care unit (ICU) stay in subjects hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP Time: Up to 8 monthsDescription: Daily responsibilities including work (employed adults) or school (matriculating students), or family obligations/responsibilities (childcare or eldercare) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP Time: Up to 8 monthsDescription: Pharmacokinetic (PK) parameters may include, but are not limited to: - Maximum observed plasma concentration (Cmax) - Cmax/Dose - Time of maximum observed plasma concentration (tmax) - Time of Clast (tlast) - Last measurable plasma concentration (Clast) - Area under plasma concentration-time curve from time 0 to infinity (AUCinf) - AUCinf/Dose - Elimination half-life (t1/2) - Concentration in serum 28 days (C28) after dosing) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Concentrations of REGN10933 in serum over time and selected PK parameters Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Concentrations of REGN10987 in serum over time and selected PK parameters Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933 over time Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987 over time Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
Measure: Incidence and severity of TEAEs in baseline seropositive participants (based on central lab test) Time: Up to 8 monthsDescription: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Incidence and severity of symptomatic SARS-CoV-2 infection Time: Up to 8 monthsDescription: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Proportion of participants who subsequently develop signs and symptoms (strict-term) of symptomatic SARS-CoV-2 infection during EAP Time: Within 14 and 28 days of a positive RT-qPCRDescription: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Proportion of participants who subsequently develop signs and symptoms (broad-term) of symptomatic SARS-CoV-2 infection during EAP Time: Within 14 and 28 days of a positive RT-qPCRDescription: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Number of days of symptomatic SARS CoV-2 infection (strict-term) Time: Up to 8 monthsDescription: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Number of days of symptomatic SARS CoV-2 infection (broad-term) Time: Up to 8 monthsDescription: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
Measure: Time-weighted average change from baseline in viral shedding in NP swab samples until the visit within the window including day 23 Time: Until day 23281 A Randomised, Double-blind, Placebo-controlled, Phase 2 Trial Investigating the Safety and Efficacy of C21 in Hospitalised Subjects With COVID-19 Infection Not Requiring Mechanical Ventilation
This is a randomised, double-blind, placebo-controlled phase 2 trial investigating the safety and efficacy of C21 in subjects who are hospitalised with COVID-19 infection, but not in need of mechanical invasive or non-invasive ventilation. In total, approximately 100 subjects will be enrolled and randomised to receive twice daily oral administration of either standard of care (SoC) + placebo (N=50) or SoC + C21 (N=50). Subjects will be treated for 7 days.
NCT04452435 COVID-19 Drug: C21 Drug: Placebo
Primary Outcomes
Description: Primary endpoint
Measure: Change from baseline in C-reactive protein (CRP) after treatment with C21 200 mg daily dose (100 mg b.i.d.) Time: Treatment period of 7 days282 A Multicenter, Randomized, Double-blind, Adaptive, Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab vs. Placebo in Addition to Standard Treatment in Patients With Severe SARS-CoV-2 Infection (COVID-19)
The primary objective of the study is to evaluate the efficacy of a single dose of OKZ (64 mg) vs placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 29.
NCT04452474 COVID-19 Drug: Olokizumab 64 mg Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Difference between OKZ and placebo groups in the percentage of subjects with an improvement of at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category. The points of the scale are: 1. Not hospitalized; 2.Hospitalized, not requiring supplemental oxygen; 3.Hospitalized, supplemental oxygen, spontaneous breathing;4. Hospitalized, mechanical ventilation (invasive/non-invasive) or extracorporeal membrane oxygenation (ECMO); 5. Death
Measure: Percentage of subjects achieving a change in their clinical status defined as improvement for at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category Time: at Day 29Secondary Outcomes
Description: Subjects' clinical status distribution based on 5-point clinical status scale during the study
Measure: Subjects' clinical status distribution based on 5-point clinical status scale during the study Time: from Day 2 tо Day 15, Day 29, Day 60Description: 28-day case fatality rates
Measure: 28-day case fatality rates Time: from Day 1 to Day 29Other Outcomes
Description: Case fatality rates during the intensive care unit (ICU) stay at Days 7, 15, and 60
Measure: Case fatality rates during the intensive care unit (ICU) stay, at Days 7, 15, and 60 Time: from Day 1 to Day 60Description: Duration of oxygen support (if applicable)
Measure: Duration of oxygen support Time: From Day 1 to Day 60Description: The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached
Measure: The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached Time: from Day 2 to Day 60Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable)
Measure: Changes of oxygenation index PaO2/FiO2 from baseline Time: from Day 2 to Day 60Description: Duration of oxygen support (if applicable), in days
Measure: Duration of oxygen support (if applicable) Time: from Day 1 to Day 60Description: Duration of mechanical ventilation and/or ECMO (if applicable), in days
Measure: Duration of mechanical ventilation and/or ECMO (if applicable) Time: from Day 1 to Day 60Description: Duration of ICU stay (if applicable)
Measure: Duration of ICU stay (if applicable) Time: from Day 1 to Day 60Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte counts
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte count Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP) Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides
Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides Time: from Day 2 and until the end of hospitalization, Day 29 as a maximumDescription: The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached
Measure: The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached Time: from Day 1 and until the end of hospitalization, Day 29 as a maximumDescription: The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached
Measure: The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached Time: from Day 1 and until the end of hospitalization, Day 29 as a maximum283 Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial on the Efficacy of BACMUNE (MV130) in the Prevention of Disease Due to SARS-CoV-2 Infection in Healthcare Personnel
The purpose of this trial is to assess the effect of immunotherapy with the bacterial preparation MV130 on the spread and course of SARS-CoV-2 infection in highly exposed subjets, as is the case with healthcare personnel.
NCT04452643 Covid19 Biological: BACMUNE (MV130) Other: Placebo MeSH:Infection
Primary Outcomes
Description: Incidence of subjects with COVID-19, defined by the presence of: Fever Any of the respiratory signs and/or symptoms: cough, dyspnea, respiratory failure, runny nose/nasal obstruction. Positive test for SARS-COV-2 (PCR o serology)
Measure: Incidence of subjects with COVID-19 Time: 60 daysDescription: Incidence of severe COVID-19, defined by CURB > 2 and/or death
Measure: Severity of COVID-19 Time: 60 daysSecondary Outcomes
Description: Rate of subjects with seroconversion to SARS-CoV-2 (negative serology at the beginning of the study and positive at the end of the study
Measure: Seroconversion to SARS-CoV-2 Time: 60 daysDescription: Rate of subjects with any symptoms, whether confirmed, probable or suspected, according to the WHO definition
Measure: Subjects with symptoms Time: 60 daysDescription: The effect of the treatment on the severity of the disease will be measured based on the rate of subjects requiring hospital admission for COVID-19
Measure: Hospital admission due to COVID-19 Time: 60 daysDescription: The effect of the treatment on the severity of the disease will be measured based on the rate of subjects who require admission to an intensive care unit for COVID-19 • Time from confirmation of SARS-CoV-2 infection to the appearance of symptoms.
Measure: Admission to an intensive care unit due to COVID-19 Time: 60 daysDescription: Elapsed time until the first symptoms of COVID-19 appears to hospitalization due to COVID-19.
Measure: Elapsed time until hospitalization Time: 60 daysDescription: Elapsed time until the first symptoms of COVID-19 appears to admission into an intensive care unit pro COVID-19.
Measure: Elapsed time until admission into an care unit for COVID-19 Time: 60 daysDescription: Elapsed time until the first symptoms of COVID-19 appears to death from any cause not related to COVID-19.
Measure: Elapsed time until death not related to COVID-19 Time: 60 days284 Double-blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of the Manremyc® Food Supplement to Prevent SARS-CoV-2 Infection
The purpose of this study is to assess the efficacy of Manremyc® food supplement for reduce the incidence of SARS-CoV-2 infection in a high risk population, as healthcare workers.
NCT04452773 COVID19 Dietary Supplement: Manremyc Dietary Supplement: Placebo MeSH:Infection
Primary Outcomes
Description: % of positive serology at the end of the study or positive PCR test in the course of routine clinical practice
Measure: Documented cumulative incidence of SARS-CoV-2 infection Time: up to 4 monthsSecondary Outcomes
Description: Number of days Documented as sick leave for SARS-CoV-2
Measure: Documented sick leave for SARS-CoV-2 Time: up to 4 months (cumulative)Description: Number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2
Measure: days off work due to the quarantine Time: up to 4 monthsDescription: Number of days in quarantine imposed by close contact outside the center with SARS-CoV-2 positive
Measure: Quarantine imposed by close contact outside the center with SARS-CoV-2 positive Time: up to 4 monthsDescription: Number of days of self-reported fever (≥38 ºC)
Measure: Fever Time: Up to 4 monthsDescription: Cumulative incidence of self-reported acute respiratory symptoms
Measure: Cumulative incidence of self-reported acute respiratory symptoms Time: up to 4 monthsDescription: Number of days of self-reported acute respiratory symptoms
Measure: Number of days of self-reported acute respiratory symptoms Time: up to 4 monthsDescription: Number of participants with pneumonia confirmed by X-ray
Measure: Incidence of pneumonia Time: up to 4 monthsDescription: Cumulative incidence of death from documented SARS-CoV-2 infection
Measure: Cumulative incidence of death from documented SARS-CoV-2 infection Time: Up to 4 monthsDescription: Cumulative incidence of admissions to intensive care unit for documented SARS-CoV-2 infection
Measure: Incidence of admission to ICU Time: Up to 4 monthsDescription: Number of days admitted to the ICU for documented SARS-CoV-2 infection
Measure: Days in IUC Time: Up to 4 monthsDescription: Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection
Measure: Incidence of mechanical ventilation Time: Up to 4 monthsDescription: Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection
Measure: Incidence of hospital admissions Time: Up to 4 monthsDescription: Number of days of hospitalization for documented SARS-CoV-2 infection
Measure: Days of hospitalization Time: Up to 4 monthsDescription: Levels of IgG
Measure: Levels of IgG Time: Up to 4 monthsDescription: Levels of IgM
Measure: Levels of IgM Time: Up to 4 monthsDescription: Levels of SARS-CoV-2 antibodies at the end of the study period
Measure: Levels of SARS-CoV-2 antibodies at the end of the study period Time: Up to 4 monthsOther Outcomes
Description: All adverse events reported by the subjects, both serious and non-serious, will be collected. All events related to a SARS-CoV-2 infection will be exempted from collection, as they will be collected as part of the associated symptoms
Measure: AEs Time: Up to 4 monthsDescription: All thoseAdverse Events that lead to hospitalization of the patient, that endanger his life or cause or may cause death.
Measure: SAEs Time: Up to 4 moths285 A Randomized, Double-blind, Placebo-controlled Phase 2 (2a and 2b) Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia
Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunt an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions1-3. Because a suboptimal endogenous early antibody response with regard to SARS-CoV-2 replication in severe cases is observed, neutralising antibody treatment can be very interesting for patient with COVID-19 induced moderate pneumonia4,5. Convalescent plasma to treat infected patients is therefore an interesting therapeutic option currently under evaluation. However, the difficulties of collecting plasma and its safety aspects are not adapted to many patients. A new polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) is being developed by Xenothera, which can be administered as intravenous treatment. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, inhibiting infection of ACE-2 positive human cells with SARS-CoV-2. Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates and a First In Human study with another fully representative GH-pAb from Xenothera is ongoing in volunteer patients recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objective of this 2-steps phase 2 randomized double-blind, placebo-controlled study is 1) to define the optimal and safety XAV-19 dose to administrate in patients with COVID-19 induced moderate pneumonia ; 2) to show the clinical benefit of selected dose of XAV-19 when administered to patients with COVID-19 induced moderate pneumonia.
NCT04453384 SARS Virus Drug: XAV-19 Drug: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8
Measure: Phase 2a: XAV-19 antibody titers Time: Day 8
Description: Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days
Measure: Phase 2a: Adverse events of XAV-19 Time: Day 29
Description: If patient is still on oxygen at Day 15 or if the patient is weaned but put back on oxygen then the delay will be censored at 15 days.
Measure: Phase 2b: Time to weaning of supplemental oxygen. Time: Day 15
Secondary Outcomes
Description: XAV-19 Antibody titer over the time
Measure: Phase 2a: Pharmacokinetic analysis Time: Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29
Description: b) The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients
Measure: Phase 2a: Antibody titer between the two groups Time: day 15
Description: Duration of supplemental oxygen
Measure: Phase 2a: Supplemental oxygen Time: Day 1 to Day 29
Description: Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen
Measure: Phase 2a: Evaluation of Transfer to intensive care Time: Day 1 to Day 29
Description: Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1
Measure: Phase 2a: Normalization of Fever Time: Day 1 to Day 29
Description: Biomarkers : CRP, Ferritin
Measure: Phase 2a: Biomarkers Time: Day 1 to Day 29
Description: Evaluation of Hospital length of stay
Measure: Phase 2a: Hospital length of stay Time: Day 1 to Day 29
Description: Evaluation of the National Early Warning Score at Day 15 and difference in NEWS between Day1 and Day15. The NEWS is graded from to 23 with an aggregated score between 0-4 being a low clinical risk and an aggregated score >7 being a hich clinical risk
Measure: Phase 2b: National Early Warning Score (NEWS) Time: Day 1 and Day 15
Description: Clinical status using the 7-point ordinal scale assessed
Measure: Phase 2b: clinical status Time: Day 3, Day 5, Day 8, Day 11, Day15, and Day 29
Description: Time to improvement of one category from admission using the 7-point ordinal scale. This scale is rated 0 to 7 with score 0 being the better score (no clinical impact) and 7 being the worst score (death)
Measure: Phase 2b: Time to improvement Time: 29 Days
Description: d) Time to first fever normalization (criteria for normalization: temperature < 36.6°C armpit, < 37.2°C oral, < 37.8°C rectal or tympanic)
Measure: Phase 2b: fever normalization Time: 29 Days
Description: Duration of oxygen therapy
Measure: Phase 2b: Oxygen therapy Time: 29 Days
Description: Comparison of oxygen requirement between the two groups
Measure: Phase 2b: oxygen requirement Time: 29 Days
Description: g) Time to weaning in supplemental oxygen and proportion without O2 requirement at D15, according to baseline (D1) oxygen requirement (≤ 4 L/min or 4 L/min)
Measure: Phase 2b: Time to weaning Time: Day 15
Description: h) Incidence and duration of non-invasive ventilation or high flow oxygen devices, of invasive mechanical ventilation during the study
Measure: Phase 2b: Ventilation Time: 29 Days
Description: Evaluation of hospital length of stay
Measure: Phase 2b: Hospital length of stay Time: 29 Days
Description: All cause mortality
Measure: Phase 2b: mortality Time: 29 Days
Description: Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events
Proportion of participants with treatment emergent adverse events leading to study drug discontinuation
Incidence of major or opportunistic bacterial or fungal infections
Incidence of hypersensitivity reactions and infusion reactions
White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D11, D15 and D29
SARS-CoV-2 viral load over time (D1-D29), as collected by nasopharyngeal swab samples
Time to RT-PCR virus negativity in nasopharyngeal swab samples
Measure: Phase 2b: safety Time: 29 Days
286 Double-blind, Randomized, Placebo-controlled Clinical Trial to Evaluate the Efficacy of the RUTI® Vaccine to Prevent SARS-CoV-2 Infection
Primary Outcomes
Description: The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8
Measure: Phase 2a: XAV-19 antibody titers Time: Day 8Description: Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days
Measure: Phase 2a: Adverse events of XAV-19 Time: Day 29Description: If patient is still on oxygen at Day 15 or if the patient is weaned but put back on oxygen then the delay will be censored at 15 days.
Measure: Phase 2b: Time to weaning of supplemental oxygen. Time: Day 15Secondary Outcomes
Description: XAV-19 Antibody titer over the time
Measure: Phase 2a: Pharmacokinetic analysis Time: Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29Description: b) The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients
Measure: Phase 2a: Antibody titer between the two groups Time: day 15Description: Duration of supplemental oxygen
Measure: Phase 2a: Supplemental oxygen Time: Day 1 to Day 29Description: Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen
Measure: Phase 2a: Evaluation of Transfer to intensive care Time: Day 1 to Day 29Description: Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1
Measure: Phase 2a: Normalization of Fever Time: Day 1 to Day 29Description: Biomarkers : CRP, Ferritin
Measure: Phase 2a: Biomarkers Time: Day 1 to Day 29Description: Evaluation of Hospital length of stay
Measure: Phase 2a: Hospital length of stay Time: Day 1 to Day 29Description: Evaluation of the National Early Warning Score at Day 15 and difference in NEWS between Day1 and Day15. The NEWS is graded from to 23 with an aggregated score between 0-4 being a low clinical risk and an aggregated score >7 being a hich clinical risk
Measure: Phase 2b: National Early Warning Score (NEWS) Time: Day 1 and Day 15Description: Clinical status using the 7-point ordinal scale assessed
Measure: Phase 2b: clinical status Time: Day 3, Day 5, Day 8, Day 11, Day15, and Day 29Description: Time to improvement of one category from admission using the 7-point ordinal scale. This scale is rated 0 to 7 with score 0 being the better score (no clinical impact) and 7 being the worst score (death)
Measure: Phase 2b: Time to improvement Time: 29 DaysDescription: d) Time to first fever normalization (criteria for normalization: temperature < 36.6°C armpit, < 37.2°C oral, < 37.8°C rectal or tympanic)
Measure: Phase 2b: fever normalization Time: 29 DaysDescription: Duration of oxygen therapy
Measure: Phase 2b: Oxygen therapy Time: 29 DaysDescription: Comparison of oxygen requirement between the two groups
Measure: Phase 2b: oxygen requirement Time: 29 DaysDescription: g) Time to weaning in supplemental oxygen and proportion without O2 requirement at D15, according to baseline (D1) oxygen requirement (≤ 4 L/min or 4 L/min)
Measure: Phase 2b: Time to weaning Time: Day 15Description: h) Incidence and duration of non-invasive ventilation or high flow oxygen devices, of invasive mechanical ventilation during the study
Measure: Phase 2b: Ventilation Time: 29 DaysDescription: Evaluation of hospital length of stay
Measure: Phase 2b: Hospital length of stay Time: 29 DaysDescription: All cause mortality
Measure: Phase 2b: mortality Time: 29 DaysDescription: Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events Proportion of participants with treatment emergent adverse events leading to study drug discontinuation Incidence of major or opportunistic bacterial or fungal infections Incidence of hypersensitivity reactions and infusion reactions White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D11, D15 and D29 SARS-CoV-2 viral load over time (D1-D29), as collected by nasopharyngeal swab samples Time to RT-PCR virus negativity in nasopharyngeal swab samples
Measure: Phase 2b: safety Time: 29 DaysThe purpose of this study is to assess the efficacy of RUTI® vaccine preventing SARS-CoV-2 infection (COVID-19) in healthcare workers.
NCT04453488 Covid-19 Sars-CoV2 Biological: RUTI® vaccine Biological: Placebo MeSH:Infection
Primary Outcomes
Description: % positive serology at the end of the study or positive PCR test in the course of routine clinical practice
Measure: Documented cumulative incidence of SARS-CoV-2 infection Time: Up to 4 monthsSecondary Outcomes
Description: Number of days of documented sick leave for SARS-CoV-2
Measure: Sick leave for SARS-CoV-2 Time: Up to 4 monthsDescription: The number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2
Measure: Days off work due to the quarantine Time: Up to 4 monthsDescription: Number of days of quarantine imposed by close contact outside the center with SARS-CoV-2 positive
Measure: Quarantine imposed by close contact outside the center with SARS-CoV-2 positive Time: Up to 4 monthsDescription: Number of MD, nursing, personnel management and services, etc.
Measure: Professional category Time: Up to 4 monthsDescription: Number of days of self-reported fever (≥38 ºC)
Measure: Fever Time: Up to 4 monthsDescription: Cumulative incidence of self-reported acute respiratory symptoms
Measure: Incidence of self-reported acute respiratory symptoms Time: Up to 4 monthsDescription: Number of days of self-reported acute respiratory symptoms
Measure: Days of self-reported acute respiratory symptoms Time: Up to 4 monthsDescription: Number of participants with pneumonia confirmed by X-ray
Measure: Incidence of pneumonia Time: Up to 4 monthsDescription: Cumulative incidence of death from documented SARS-CoV-2 infection
Measure: Incidence of death from SARS-CoV-2 infection Time: Up to 4 monthsDescription: Cumulative incidence of admissions to intensive care unit for documented SARS-CoV-2 infection
Measure: Incidence of admissions to Intensive Care Unit (ICU) Time: Up to 4 monthsDescription: Number of days admitted to the ICU for documented SARS-CoV-2 infection
Measure: Days in ICU Time: Up to 4 monthsDescription: Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection
Measure: Incidence of mechanical ventilation Time: Up to 4 monthsDescription: Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection
Measure: Incidence of hospital admissions Time: Up to 4 monthsDescription: Number of days of hospitalization for documented SARS-CoV-2 infection
Measure: Days of hospitalization Time: Up to 4 monthsDescription: Incidence of SARS-CoV-2 antibodies at the end of the study period
Measure: Incidence of SARS-CoV-2 antibodies Time: Final visitDescription: Frequency and levels of immunoglobulin IgG and immunoglobulin IgM
Measure: Types of antibodies detected Time: Final visitDescription: Levels of SARS-CoV-2 antibodies at the end of the study period
Measure: Levels of SARS-CoV-2 antibodies Time: Final visitOther Outcomes
Description: All adverse events reported by the subjects, both serious and non-serious, will be collected. All events related to a SARS-CoV-2 infection will be exempted from collection as part of the associated symptoms.
Measure: AEs Time: Up to 4 monthsDescription: All those Adverse Events that lead to hospitalization of the patient, that endanger his life or cause or may cause death.
Measure: SAEs Time: Up to 4 months287 A Randomized, Placebo-controlled Study to Evaluate Safety, Pharmacokinetics, Preliminary Efficacy of Three Dose Levels of a Single Dose of STI-1499 (COVI-GUARD), a COVID-19 Targeting Monoclonal Antibody, in COVID-19 Hospitalized Patients
Randomized, placebo-controlled study to evaluate the safety, pharmacokinetics, preliminary efficacy of four dose levels of a single dose of STI-1499 (COVI-GUARD), a COVID-19 targeting monoclonal antibody, in hospitalized patients with COVID-19
NCT04454398 Covid-19 Biological: STI-1499 Other: Standard of Care Drug: Placebo
Primary Outcomes
Description: Types, frequencies, and severities of adverse events and their relationships to STI-1499
Measure: Incidence of treatment-emergent adverse events (safety and tolerability of STI-1499) Time: Randomization through study completion at 28 daysSecondary Outcomes
Description: All-cause mortality at Day 28
Measure: All-cause mortality Time: Randomization through Day 28Description: Change from baseline in clinical status on a 7-point ordinal scale where higher score means better outcome (1=Death, 7=Not hospitalized and no limitations on activities)
Measure: Change in clinical status Time: Randomization to Day 7, 14, 28Description: Change from baseline in SOFA score where lower score means better outcome
Measure: Change in Sequential Organ Failure Assessment (SOFA) score Time: Randomization to Day 7, 14, 28Description: Change from baseline in ratio of partial pressure of arterial oxygen to fraction of inspired oxygen
Measure: Change in PaO2:FiO2 Time: Randomization to Day 7, 14, 28Description: Length of hospitalization of participants (followed up to Day 28)
Measure: Length of hospitalization Time: Randomization up to Day 28Description: Percentage of participants requiring mechanical ventilation at Day 7, 14, and 28
Measure: Percentage of participants requiring mechanical ventilation Time: Randomization to Day 7, 14, 28Description: Change from baseline in viral shedding as assessed by RT-PCR
Measure: Change in viral shedding Time: Randomization to Day 7, 14, 21, 28Description: Incidence of anti-drug antibody (ADA)
Measure: Immunogenicity of STI-1499 Time: Randomization to Day 21, 28288 Pilot Double Blinded Randomized Placebo Controlled Multi Central Clinical Trial on Inflammatory Regulation Effect of NAC on COVID-19
Study times to evaluate the efficacy of N-Acetylcysteine therapy in the management of adult admitted patients with COVID-19.
NCT04455243 COVID-19 Drug: N-Acetyl cysteine Drug: Placebo
Primary Outcomes
Description: Day of recovery is defined as the first day on which of the following three categories from The Ordinal Scale on Covid-19 Clinical Improvement Not-Hospitalized, No limitation on activity. Not Hospitalized, with limitation on activity. Hospitalized, Not requiring supplemental Oxygen
Measure: Time to Recovery Time: 28 days289 Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate Efficacy and Safety in Healthcare Professionals of the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac
This is a phase III clinical trial to assess efficacy and safety of the Adsorbed COVID-19 (inactivated) vaccine manufactured by Sinovac in health care professionals
NCT04456595 COVID-19 Biological: Adsorbed COVID-19 (inactivated) Vaccine Biological: Placebo
Primary Outcomes
Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine
Measure: Incidence of COVID-19 cases after two-doses immunization schedule Time: Two weeks after second dose up to one year after first doseDescription: Frequency of adverse reaction in the seven days following each immunization per age group
Measure: Frequency of adverse events up to seven days after immunization Time: Seven days after each immunizationSecondary Outcomes
Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after first dose of vaccine
Measure: Incidence of COVID-19 cases after 14-days of first immunization Time: Two weeks after first dose up to one year after first doseDescription: Number of virologically-confirmed symptomatic COVID-19 two weeks after last dose of vaccine, regardless the vaccination schedule was completed
Measure: Incidence of COVID-19 cases after 14-days of last immunization Time: Two weeks after last dose uup to one year after first doseDescription: Number of virologically-confirmed and or serologically-confirmed SARS-CoV-2 infections two weeks after first dose of vaccine
Measure: Combined incidence of SARS-CoV-2 infection Time: Two weeks after second dose up to one year after first doseDescription: Frequency of adverse reaction in the 28 days following each immunization per age gropu
Measure: Frequency of adverse events up to 28 days after immunization Time: 28 days after each immunizationDescription: Number of virologically-confirmed severe COVID-19 cases after receiving, at least, one dose of the vaccine
Measure: Incidence of severe COVID-19 cases Time: From first vaccination up to one year after first doseDescription: Number of seroconversion responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants
Measure: Seroconversion rate Time: Two weeks afer each vaccinationDescription: Number of cell-mediated immune response against SARS-CoV-2 in the week two and four after the second vaccination per age group in a subset of participants
Measure: Cell-mediated immune profile Time: Two and four weeks afer each vaccination290 A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study in Healthy Participants and Multiple Dose Study in Participants With Ulcerative Colitis to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-66525433
The purpose of this study is to evaluate safety and tolerability of JNJ 66525433 compared with placebo after administration of: 1) single ascending oral doses of JNJ 66525433 administered to healthy participants (Part 1), 2) multiple, ascending oral doses of JNJ 66525433, administered to healthy participants once daily over 14 consecutive days (Part 2), and 3) multiple oral doses of JNJ 66525433, administered once daily over 14 consecutive and once daily over 42 consecutive days in participants with ulcerative colitis (UC) (Part 3).
NCT04457960 Healthy Colitis, Ulcerative Drug: JNJ-66525433 Drug: Placebo MeSH:Colitis Colitis, Ulcerative Ulcer
HPO:Colitis Ulcerative colitis
Primary Outcomes
Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days will be considered as TEAE.
Measure: Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability Time: Up to 224 Days
Description: Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities Time: Up to 224 Days
Description: Number of participants with physical examination abnormalities will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities Time: Up to 224 Days
Description: Number of participants with clinical laboratory abnormalities (serum chemistry, hematology and urinalysis) will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Clinical Laboratory Abnormalities Time: Up to 224 Days
Description: Number of participants with ECG abnormalities will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities Time: Up to 224 Days
Secondary Outcomes
Description: Plasma concentrations of JNJ-66525433 will be reported.
Measure: Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433 Time: Up to 224 Days
Description: Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.
Measure: Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing Time: Up to Day 14
Description: Mayo scoring system is used for assessment of ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each ranges from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12, where higher score indicates severe disease.
Measure: Part 3: Mayo Score Time: Up to Day 84
Description: Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease.
Measure: Part 3: Partial Mayo Score Time: Up to Day 70
Description: Endoscopy sub-score ranges from 0 to 3 where; 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = severe disease (spontaneous bleeding, ulceration).
Measure: Part 3: Endoscopic Subscore Time: Up to Day 84
Description: IBDQ18 is a validated, 32-item, self-reported questionnaire for participants with inflammatory bowel disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.
Measure: Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score Time: Days 1, 7, 14, 28, 43, 70 and 84
Description: Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.
Measure: Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels Time: Up to 182 Days
Description: Tissue biopsy concentrations of JNJ-66525433 will be reported.
Measure: Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations Time: Up to 182 Days
291 A Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of OP-101 (Dendrimer N-acetyl-cysteine) in Patients With Severe COVID-19
Primary Outcomes
Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days will be considered as TEAE.
Measure: Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability Time: Up to 224 DaysDescription: Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities Time: Up to 224 DaysDescription: Number of participants with physical examination abnormalities will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities Time: Up to 224 DaysDescription: Number of participants with clinical laboratory abnormalities (serum chemistry, hematology and urinalysis) will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Clinical Laboratory Abnormalities Time: Up to 224 DaysDescription: Number of participants with ECG abnormalities will be reported.
Measure: Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities Time: Up to 224 DaysSecondary Outcomes
Description: Plasma concentrations of JNJ-66525433 will be reported.
Measure: Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433 Time: Up to 224 DaysDescription: Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.
Measure: Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing Time: Up to Day 14Description: Mayo scoring system is used for assessment of ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each ranges from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12, where higher score indicates severe disease.
Measure: Part 3: Mayo Score Time: Up to Day 84Description: Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease.
Measure: Part 3: Partial Mayo Score Time: Up to Day 70Description: Endoscopy sub-score ranges from 0 to 3 where; 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = severe disease (spontaneous bleeding, ulceration).
Measure: Part 3: Endoscopic Subscore Time: Up to Day 84Description: IBDQ18 is a validated, 32-item, self-reported questionnaire for participants with inflammatory bowel disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.
Measure: Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score Time: Days 1, 7, 14, 28, 43, 70 and 84Description: Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.
Measure: Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels Time: Up to 182 DaysDescription: Tissue biopsy concentrations of JNJ-66525433 will be reported.
Measure: Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations Time: Up to 182 DaysThe primary purpose is to evaluate the safety and tolerability of OP-101 and secondary purpose is to determine the effect of OP-101 reducing proinflammatory cytokines after a single dose in severe COVID-19 Patients.
NCT04458298 COVID-19 Drug: OP-101 Drug: Placebo
Primary Outcomes
Description: Number of participants with treatment emergent adverse events will be evaluated as a measure of safety and tolerability of OP-101 by monitoring and documenting all adverse events, which include laboratory test variables.
Measure: Number of Participants with Treatment Emergent Adverse Events Graded as Assessed by CTCAE Version 4.0 Time: Up to Day 60Secondary Outcomes
Description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.
Measure: Time to Improvement (2 points) in Clinical Status Assessment Using the World Health Organization 7-Point Ordinal Scale (WHO 7OS) Time: Up to Day 30Measure: Time to Resolution of Fever for at least 48 hours Without Antipyretics for Patients with Documented Fever (>=37.2 degree celsius [oral], or >=37.8 degree celsius [rectal], or >=38.0 degree celsius [tympanic]) Time: Up to Day 30
Description: Improvement in oxygenation is defined by increase in pulse oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) of >=50 compared with nadir SpO2/FiO2.
Measure: Time to Improvement in Oxygenation for at least 48 hours Time: Up to Day 30Description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.
Measure: Change from Baseline in the World Health Organization (WHO)-7 Point Ordinal Scale Time: Baseline up to Day 30Description: NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C).
Measure: Time to Discharge from Clinic or Hospital or to National Early Warning Score 2 (NEWS2) of <=2 and maintained for 24 hours Time: Up to Day 30Measure: Percentage of Patients Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 30 Time: Up to Day 30
Measure: Number of Days of Resting Respiratory Rate of more than 24 breath/min Time: Up to Day 30
Description: Hypoxemia is defined by Saturation of Peripheral Oxygen (SpO2) of less than (<) 95 percent (%) on room air or acute respiratory distress syndrome (ARDS).
Measure: Number of Days with Hypoxemia Time: Up to Day 30Measure: Number of Days of Supplemental Oxygen use Time: Up to Day 30
Measure: Number of Ventilator-free Days Time: Up to Day 28
Measure: Number of Days in Intensive Care Unit (ICU) Time: Up to Day 30
Measure: Number of Days of Hospitalization for Survivors Time: Up to Day 30
Measure: Number of Participants with all cause deaths Time: Up to Day 30
Description: Percent change from baseline in proinflammatory cytokines (C-reactive protein [CRP], ferritin, and interleukin-6 [IL-6]) will be reported.
Measure: Percent change from baseline in Proinflammatory Cytokines Time: Baseline up to Day 30Measure: Incidence of Drug-related Serious Adverse Events (SAEs) Time: Up to Day 60
292 A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 Pneumonia
The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in adults hospitalized with COVID-19 pneumonia.
NCT04460105 COVID-19 Pneumonia Drug: Lanadelumab Other: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.
Measure: Number of Participants with Treatment emergent adverse events (TEAEs) Time: From start of study drug administration to follow-up (up to Day 29)
Secondary Outcomes
Description: Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.
Measure: Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours Post-dose
Description: Percentage change from baseline in pka activity to assess pharmacodynamics (PD) of lanadelumab.
Measure: Percentage Change from Baseline in Plasma Kallikrein Activity (pka) Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-dose
Description: Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.
Measure: Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK) Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-dose
Description: Percentage change from baseline in pre-kallikrein activity to assess PD of lanadelumab.
Measure: Percentage Change from Baseline in Pre-Kallikrein Activity Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-dose
Description: Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.
Measure: Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH) Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-dose
293 PREPARE-IT. Prevention of COVID19 With EPA in Healthcare Providers at Risk - Intervention Trial
Primary Outcomes
Description: Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.
Measure: Number of Participants with Treatment emergent adverse events (TEAEs) Time: From start of study drug administration to follow-up (up to Day 29)Secondary Outcomes
Description: Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.
Measure: Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours Post-doseDescription: Percentage change from baseline in pka activity to assess pharmacodynamics (PD) of lanadelumab.
Measure: Percentage Change from Baseline in Plasma Kallikrein Activity (pka) Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-doseDescription: Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.
Measure: Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK) Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-doseDescription: Percentage change from baseline in pre-kallikrein activity to assess PD of lanadelumab.
Measure: Percentage Change from Baseline in Pre-Kallikrein Activity Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-doseDescription: Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.
Measure: Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH) Time: Single-dose Cohort and Repeat-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours Post-doseThe PREPARE-IT trial is a simple, pragmatic and universally applicable strategy with icosapent ethyl (IPE) at high doses intended to reduce infection rate and subsequent morbidity and mortality among subjects at high risk of infection due to COVID-19.
NCT04460651 COVID19 Drug: Icosapent ethyl (IPE) Drug: Placebo
Primary Outcomes
Description: SARS-CoV-2 positive subjects are defined as subjects with positive tests for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies after developing COVID-19 disease at any stage within the follow-up period (including those subjects with or without symptomatic COVID-19 evaluated before the final visit) or those individuals who test positive for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies at the final visit (day 60).
Measure: Percentage of SARS-CoV-2 positive subjects Time: 60 daysMeasure: Highest mean WHO descriptive score of COVID-19 in the active treatment group compared to the placebo group. Time: 60 days
Secondary Outcomes
Measure: Highest mean WHO score up to day 60 for the active treatment group as compared to placebo among subjects with a positive test received at any moment during the study after the first visit Time: 60 daysDescription: Mean change from baseline will be computed
Measure: Total cholesterol, LDL, HDL, triglycerides (mg/dL) at baseline and at day 60 Time: baseline, 60 daysDescription: Mean change from baseline will be computed
Measure: Ultrasensitive C-reactive Protein (mg/dL) at baseline and at day 60 Time: baseline, 60 daysMeasure: Difference in hospital length of stay between groups Time: 60 days
Measure: Difference in duration of mechanical ventilation in both groups Time: 60 days
Measure: Rate of hospital admissions due to SARS (Severe Acute Respiratory Syndrome) in patients who were negative for SARS CoV-2 upon admission Time: 60 days
Measure: Mean highest WHO descriptive score in active treatment versus placebo groups up to day 60 among hospitalized patients (WHO grades 3 or more) without serum evidence / PCR detecting SARS-CoV-2 infection Time: 60 days
Measure: Rate of total events, non-fatal myocardial infarction or non-fatal stroke or death (initial and subsequent), up to day 60 Time: 60 days
294 A Phase 1 Randomized Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers
This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary objectives are as follows: - To assess the safety and tolerability of AHCQ administered as a single dose by oral inhalation in healthy individuals at escalating doses until either the maximum tolerated dose (MTD) is identified or 1 mL of a 50 mg/mL solution is administered. - To determine the recommended Phase 2a dose (RP2D). Secondary objectives: • To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.
NCT04461353 Severe Acute Respiratory Syndrome Coronavirus 2 Drug: Aerolized Hydroxychloroquine Sulfate Other: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: TEAEs (defined as AEs with onset after study drug administration or existing AEs that worsen in severity after study drug administration)
Measure: Incidences of treatment-emergent adverse events (TEAEs) as assessed by TGSHAAV (September 2007) or CTCAE version 5.0 Time: after treatment (Day 1) through to Day 30Description: Blood sample collected for CBC with differential will be assessed from baseline (at screening)
Measure: Change from baseline in clinical laboratory test results for CBC with differential Time: Screening and Day 8Description: Screening blood sample collected for CBC with differential, counting the number of abnormal clinical tests
Measure: Incidence of abnormal laboratory test results for CBC with differential at Screening Time: ScreeningDescription: Day 8 blood sample collected for CBC with differential
Measure: Incidence of abnormal laboratory test results for CBC with differential - Day 8 Time: Day 8Description: Blood sample collected for blood glucose and measured with a glucometer
Measure: Changes from baseline for blood glucose Time: Screening and Day 1Description: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)
Measure: Incidence of abnormal laboratory test results for chemistry -Screening Time: ScreeningDescription: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)
Measure: Incidence of abnormal laboratory tests results for chemistry - Day 8 Time: Day 8Description: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood
Measure: Incidence of abnormal laboratory tests results for urinalysis - Screening Time: ScreeningDescription: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood
Measure: Incidence of abnormal laboratory tests results for urinalysis- Day 8 Time: Day 8Description: The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (September 2007) (TGSHAAV) will be used as the primary criteria for assessment of clinical abnormalities. Mild (17-20 breaths per minute) to Potentially Life Threatening (intubation)
Measure: Changes in vital signs from baseline (pre-dose) - respiratory rate Time: Screening, Day 1, Day 2 and Day 8Description: Oral temperature
Measure: Changes in vital signs from baseline (pre-dose)- temperature Time: Screening, Day 1, Day 2 and Day 8Description: Systolic and diastolic blood pressure
Measure: Changes in vital signs from baseline (pre-dose) - seated blood pressure Time: Screening, Day 1, Day 2 and Day 8Description: Heart rate measure by radial pulse rate (beats/min)
Measure: Changes in vital signs from baseline (pre-dose) - pulse Time: Screening, Day 1, Day 2 and Day 8Description: O2 saturation (%), measured by pulse oximeter. Graded as per TGSHAAV (September 2007) from Moderate (pulse oximeter <92%) to Potentially Life Threatening (Life-threatening airway compromise; urgent intervention indicated)
Measure: Changes in vital signs from baseline (pre-dose) - O2 saturation Time: Screening, Day 1, Day 2 and Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during Screening- general appearance Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1 - general appearance Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2- general appearance Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8- general appearance Time: Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during Screening- neurological Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1- neurological Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2- neurological Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8- neurological Time: Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during Screening - heart/cardiovascular Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1 - heart/cardiovascular Time: Day 1 (pre-dose, within 3 hours of dose)Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2 - heart/cardiovascular Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8 - heart/cardiovascular Time: Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during Screening - lungs Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1 - lungs Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2 - lungs Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8 - lungs Time: Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during Screening- abdomen Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1 - abdomen Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2- abdomen Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8- abdomen Time: Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during screening- endocrine Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1 - endocrine Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2- endocrine Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8- endocrine Time: Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during Screening- extremities Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1- extremities Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2- extremities Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8- extremities Time: Day 8Description: Physical exam by clinician. A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during Screening- lymphatic Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1- lymphatic Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2 - lymphatic Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8- lymphatic Time: Day 8Description: A directed physical examination will be conducted
Measure: Incidence of abnormal and physical examinations findings during screening - skin Time: ScreeningDescription: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 1 - skin Time: Day 1Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 2 - skin Time: Day 2Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
Measure: Incidence of abnormal and physical examinations findings on Day 8 - skin Time: Day 8Description: Pulmonary function testing and recording of FEV1, both actual and percent predicted
Measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1 Time: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.Description: Pulmonary function testing and recording of FVC, , both actual and percent predicted
Measure: Changes from baseline for pulmonary function tests (PFTs) - FVC Time: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.Description: Pulmonary function testing and recording of FEV1/FVC
Measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1/FVC Time: creening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval (msec) will be the assessment parameter.
Measure: Changes from baseline for ECG readings - QT interval Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QTcB interval (msec) will be the assessment parameter.
Measure: Changes from baseline for ECG readings - QTcB Interval Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QRS duration (msec) will be the assessment parameter.
Measure: Changes from baseline for ECG readings - QRS duration Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG PR interval (msec) will be the assessment parameter.
Measure: Changes from baseline for ECG readings - PR interval Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG heart rate (beats/min) will be the assessment parameter.
Measure: Changes from baseline for ECG readings - heart rate Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.
Measure: Incidence of abnormal ECG - Screening Time: ScreeningDescription: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.
Measure: Incidence of abnormal ECG- Day 1 Time: Day 1 pre-dose (within 3 hours of dose) and +2 and +6 hoursDescription: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.
Measure: Incidence of abnormal ECG - Day 2 Time: Days 2Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.
Measure: Incidence of abnormal ECG - Day 8 Time: Days 8.Secondary Outcomes
Description: Blood samples for PK analysis will be collected via indwelling catheter or via direct venipuncture.
Measure: HCQ concentration in whole blood versus time profiles Time: Day 1 pre-dose (time 0) and +2, +3, +5, and +15 minutes after dose, and also +1, +2, +4 and +6 hours post-dose completion. Day 2 (+24±4 hours post dose) and Day 8.295 Prevention, Efficacy and Safety of BCG Vaccine in COVID-19- Randomized Clinical Trial
In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19.
NCT04461379 BCG COVID-19 SARS-CoV2 Corona Virus Infection Biological: BCG vaccine Other: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Cumulative incidence of infection in 6 months: disease defined as positive SARS-Cov-2 test (serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: Demonstrate COVID- 19 disease incidence among Health care workers: Time: During the 6 months study periodDescription: Cumulative incidence of hospitalization for COVID-19
Measure: Demonstrate cumulative incidence of hospitalization for COVID-19 among Health care workers: Time: During the 6 months study periodDescription: Incidence of specific Antibodies (IgG and IgM) against SARS-CoV-2 will be measured at 3 and 6 months
Measure: Demonstrate the Incidence of specific Antibodies against SARS-CoV-2 at 3 and 6 months in health care workers Time: During the 6 months study periodDescription: Number of participants who needed hospitalization
Measure: Hospitalization of severe disease COVID-19 Time: During the 6 months study periodDescription: Number of participants who Need for oxygen supplementation (nasal cannulas, masks, high flow oxygen) in hospitalized patients
Measure: Oxygen supplementation in severe disease COVID-19 Time: During the 6 months study periodDescription: Number of participants who Need for intubation or non-invasive ventilation in hospitalized patients
Measure: Need for intubation or non-invasive ventilation for the patient. Time: During the 6 months study periodDescription: Number of participants in Critical care admission with SARS-CoV2 in hospitalized patients
Measure: Critical care admission with SARS-CoV2 Time: During the 6 months study periodDescription: Mortality associated to progressive pulmonary disease in hospitalized patients
Measure: Mortality associated to progressive pulmonary disease Time: During the 6 months study periodSecondary Outcomes
Measure: Evaluate the safety of the vaccine by measuring the incidence rates of local and systemic adverse effects that occur after one month its application. Time: 1 month after vaccine/placebo applicationMeasure: Calculate the incidence of COVID-19 complications Time: During the 6 months study period
Measure: Determine the mean days of hospitalization and days in intensive care unit by COIVD-19 Time: During the 6 months study period
Measure: Calculate the cost associated with in-hospital medical care Time: During the 6 months study period
Description: SOFA score: PaO2/FIO2 (mm Hg), SaO2/FIO2, Platelets (×10³/µL), Bilirubin (mg/dL), Hypotension, Glasgow Coma Score and Creatinine (mg/dL) or urine output (mL/d).
Measure: Determine the scores of the Clinical Prediction Rules associated with mortality using Sequential Organ Failure Assessment (SOFA score) at the patient's hospital admission: Time: During the 6 months study periodDescription: APACHE: History of severe organ failure or immunocompromise Heart Failure Class IV, cirrhosis, chronic lung disease, or dialysis-dependent, Age, Temperature (C°), Mean arterial pressure (mmHg), pH, Sodium (mEq/L), Potassium (mEq/L), Creatinine (mg/dL), Hematocrit (%), WBC (x 109/L)
Measure: Determine the scores of the Clinical Prediction Rules associated with mortality using Acute Physiology and Chronic Health disease Classification System (APACHE) at the patient's hospital admission: Time: During the 6 months study periodDescription: CPR, ESR, Ferritin, D-dimer, LDH,Troponins, Procalcitonin, Interleukin-6, Hemoglobin, Hematocrit, Erythrocytes, Leukocytes, MCV, HCM, MCHC, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, Glucose, Urea, Creatinine, BUN, Sodium, Potassium, Chlorine, Calcium, Serum albumin, Direct bilirubin, Indirect bilirubin, Alkaline phosphatase, AST, ALT, bleeding time, Prothrombin Time, Activated partial thromboplastin time, Arterial / Venous Blood Gasometry, pH, pCO2, HCO3, pO2, SaO2%, Lactate.
Measure: Evaluate and determine the alteration profile in laboratory studies at the patient's hospital admission Time: During the 6 months study periodMeasure: Registration of chronic medications Time: During the 6 months study period
Measure: Need for vasopressors Time: During the 6 months study period
296 Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoC-2 Virus Infection (COVID-19). A Pilot, Randomized, Simple Blind, Placebo-controlled, Parallel-group Study
Evaluation of the efficacy and safety of NTX in adult patients (≥18 years and <60 years), with SARS-CoV-2 infection with mild symptoms of COVID-19, compared to a placebo control arm. 135 patients will be randomized to either Nitazoxanide (n=90) or placebo (n=45) (2:1). Simple blind design. Primary endpoint: eradication of virus from patients' respiratory tract secretions by the 7th day of treatment.
NCT04463264 COVID-19 Drug: Nitazoxanide Drug: Placebo MeSH:Infection Virus Diseases
Primary Outcomes
Description: Erradication will be considered a reduction of the viral load on day 7 greater than 35% with respect to placebo. Extraction of genomic material will be performed using a QIAgen mini kit (QIAmp viral RNA) validated by the CDC (United States Center for Disease Control and Prevention (https://www.fda.gov/media/134922/download) (CDC-006-00019) Viral load will be quantified with the following detection kits: Commercial Kit: PCR-EUA-CDC-nCoV-IFU. Commercial KIT SENTINEL - STAT-NAT Covid 19B (Berlín). Rational: In mild cases of COVID-19, 50% of the patients eradicated the virus within a period of 3 weeks, 25% eradicated the virus before the 13th day, 75% during the first month and the rest were " late eradicators." This latter subgroup of patients has been associated with severe cases of COVID-19 disease.
Measure: Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th. Time: 7 daySecondary Outcomes
Description: Consequently, in mild cases, viral eradication will likely occur more frequently during the first to second week of COVID-19 disease; less than 15% could eradicate the virus during the first week of symptom onset. From an epidemiological point of view, increasing the viral eradication rate from less than 15% to more than 35% during the first two weeks of treatment would be clinically relevant.(seven), 14 (fourteen) and 35 (thirty-five) after starting treatment compared to the baseline measurement.
Measure: Comparative decrease of the viral load Time: 3 - 35 daysDescription: Clinical improvement according to the WHO COVID-19 ordinal scale. Minimun 0 (zero), (best), maximum 8 (eight) (worst)
Measure: Clinical improvement Time: 1 - 35 daysDescription: Percentage of pneumonia patients meeting severity criteria.
Measure: Pneumonia patients meeting severity criteria. Time: 1 - 35 daysDescription: Number of days with fever (axillary temperature higher than 37.5°C).
Measure: Number of days with fever Time: 1 - 35 daysOther Outcomes
Description: Percentage of patients requiring mechanical ventilation through orotracheal intubation (OT) and/or ICU hospitalization.
Measure: Patients requiring mechanical ventilation Time: 1 - 35 daysDescription: Mortality rate.
Measure: Mortality rate. Time: 1- 35 daysDescription: Lymphocyte recovery (absolute lymphocyte count > 1000 / mm3).
Measure: Lymphocyte recovery Time: 7 dayDescription: Days of ICU hospitalization.
Measure: ICU hospitalization. Time: 1 - 35 daysDescription: Oxygen saturation (SpO2) > 92% (at ambient FiO2).
Measure: Oxygen saturation Time: 1 - 35 daysDescription: Days of hospitalization
Measure: Days of hospitalization Time: 1 - 35 daysDescription: Respiratory rate per minute (in afebrile state conditions).
Measure: Respiratory rate Time: 1 - 35 days297 Safety and Efficacy of PHR 160 Spray on the Outcomes of Patients With COVID-19 a Multi-center Randomized Blinding Clinical Trial Study
This study is a multi-center randomized, controlled, and blinded clinical trial study that will be performed in four medical-educational centers. In this study, the samples will be selected from among patients with SARS-CoV-2 as easy access and based on entry criteria and will be randomly divided into two groups, including a control group and an intervention group. The study will be conducted in four medical centers. From each center, 56 definitive Corona patients will be selected, who will be randomly divided into two groups of 28, for a total of 224 patients will enter the study. In the intervention group, in addition to receiving the test spray, Patients will also receive standard treatment
NCT04463420 COVID-19 Drug: PHR160 Spray Drug: Placebo Drug: Standard treatment
Primary Outcomes
Description: shortness of breath measured by Visual analog scale (VAS) dyspnea score. The minimum score is zero means shortness of breath and the highest score is 10 means the maximum intensity of shortness of breath.
Measure: Dyspnea Time: up to 14 daysSecondary Outcomes
Description: The length of time the patient is hospitalized after the diagnosis of COVID-19
Measure: long of hospitalization Time: up to 28 daysDescription: CT scans help determine how much the lungs are affected by COVID-19.
Measure: Radiological Treatment Response Time: up to 14 daysDescription: In-hospital mortality
Measure: Mortality Time: Up to 28 daysDescription: There will be known allergic reactions to the drugs.
Measure: Allergic drug Time: up to 14 daysDescription: Normal blood cell count and CRP count (normal laboratory range)
Measure: Laboratory Treatment Response Time: up to 14 daysDescription: Using an oximeter pulse, the amount of oxygen saturation is measured. If the patient is receiving oxygen, first cut off the oxygen for 5 minutes and then measure. If the oxygen drops below 90 degrees, oxygen therapy will be re-established immediately.
Measure: O2 saturation without supplemental oxygen Time: up to 14 daysDescription: Complications in both groups should be evaluated and evaluated during treatment. protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions that measured by Physical examination.
Measure: drug reactions Adverse Time: Up to 14 days298 A Trial of Favipiravir Therapy in Adults With Mild Coronavirus Disease COVID-19
Favipiravir is a selective and potent inhibitor of influenza viral RNA polymerase. It acts as a purine analogue, which selectively inhibits viral RNA-dependent RNA polymerase (RdRps). It has the characteristic of acting on RNA viruses including Ebola and Coronaviruses especially novel coronavirus (2019-nCoV). The purpose of this study is to evaluate the clinical efficacy and safety of Favipiravir in comparison to placebo in the treatment of mild COVID-19 cases. It is a Multicenter, randomized double-blinded, parallel-group trial.
NCT04464408 COVID-19 Drug: Favipiravir Drug: Placebo
Primary Outcomes
Description: Time from randomization to negativity in RT-PCR nucleic acid test for COVID-19 within 15 days of randomization
Measure: PCR negative Time: 15 daysSecondary Outcomes
Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory symptoms, and relief of cough (or other relevant symptoms at enrollment) that is maintained for at least 72 hours.
Measure: Time from randomization to clinical recovery Time: 15 daysMeasure: Symptoms progression based on clinical evaluation using simple scoring system. Time: 28 days
Measure: Rate of daily requirement of using antipyretics, analgesics, or antibiotics. Time: 15 days
Measure: 28 days mortality. Time: 28 days
Measure: Rate of requirement of hospitalization, ICU admission or Mechanical ventilation. Time: 28 days
Description: incidence of GI symptoms secondary to the study drug.
Measure: Incidence of Treatment-related Adverse Events [Safety and Tolerability] Time: 15 days299 A Randomized, Double-Blind, Placebo-Controlled, Multiple Continuous Intravenous Injection, Dose Escalation, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of M201-A in Healthy Japanese Subjects
This Phase I is designed to evaluate the safety, tolerability and pharmacokinetics of multiple ascending doses of M201-A administered by multiple continuous intravenous injection in Healthy Japanese subjects.
NCT04464681 Healthy Volunteers Drug: M201-A Injection Drug: Placebo
Primary Outcomes
Description: Number of participants with adverse events, serious adverse events, physical examinations, vital sign measurements, 12-lead ECGs, Holter ECG, clinical laboratory safety tests (including hematology, chemistry, and urinalysis), recording of concomitant medications and procedures.
Measure: Number of participants with adverse events as a measure of safety and tolerability Time: Throughout the study duration up to day 11300 Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)
This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.
NCT04466098 Acute Respiratory Distress Syndrome ARDS (Moderate or Severe) COVID-19 Pneumonia Biological: Mesenchymal stromal cells Other: Placebo MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acu Acute Lung Injury Syndrome
HPO:Pneumonia
Primary Outcomes
Measure: Incidence of grade 3-5 infusional toxicities and predefined hemodynamic or respiratory adverse events related to the infusion of MSC Time: Within 6 hours of the start of the infusion
Secondary Outcomes
Measure: Incidence of a reduction in one or more biomarkers of inflammation by day 7 Time: Day 7 after first infusion
Measure: Trend changes in PaO2:FiO2 ratio Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Trend changes in Mean Airway Pressure Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Trend changes in peak pressure Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Trend changes in plateau pressure Time: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion
Measure: Trend changes in Positive end-expiratory airway pressure (PEEP) Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Incidence of mortality Time: 28 days after first infusion
Measure: Incidence of mortality Time: 100 days after first infusion
Measure: Number of ICU-free days Time: 28 days after first infusion
Measure: Number of days alive and ventilator free composite score 3 Time: 28 days after first infusion
Description: Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph
Measure: Change in acute lung injury (ALI) score 2 Time: Baseline and Day 28 after first infusion
Measure: Incidence of serious adverse events Time: 28 days after first infusion
Measure: Number of days alive off supplemental oxygen Time: 100 days after first infusion
301 Pragmatic, Double-blind, Placebo-controlled Randomized Clinical Trial, Evaluating Hydroxychloroquine for Prevention of Hospitalization and Respiratory Complications in Non-hospitalized Patients With Confirmed or Probable COVID-19
Primary Outcomes
Measure: Incidence of grade 3-5 infusional toxicities and predefined hemodynamic or respiratory adverse events related to the infusion of MSC Time: Within 6 hours of the start of the infusionSecondary Outcomes
Measure: Incidence of a reduction in one or more biomarkers of inflammation by day 7 Time: Day 7 after first infusionMeasure: Trend changes in PaO2:FiO2 ratio Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Trend changes in Mean Airway Pressure Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Trend changes in peak pressure Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Trend changes in plateau pressure Time: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion
Measure: Trend changes in Positive end-expiratory airway pressure (PEEP) Time: On the day of screening and on days 3, 7 and 14 after first infusion
Measure: Incidence of mortality Time: 28 days after first infusion
Measure: Incidence of mortality Time: 100 days after first infusion
Measure: Number of ICU-free days Time: 28 days after first infusion
Measure: Number of days alive and ventilator free composite score 3 Time: 28 days after first infusion
Description: Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph
Measure: Change in acute lung injury (ALI) score 2 Time: Baseline and Day 28 after first infusionMeasure: Incidence of serious adverse events Time: 28 days after first infusion
Measure: Number of days alive off supplemental oxygen Time: 100 days after first infusion
In December 2019, a group of patients with pneumonia of unknown cause was identified in Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some limited observational trials and also evidence from randomized trials have shown no benefit of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an outpatient setting in non-severe patients can provide important information related to prognosis and safety. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized, double-blind, placebo-controlled trial
NCT04466540 COVID-19 Drug: Hydroxychloroquine Drug: Placebo
Primary Outcomes
Description: To assess if the treatment is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day.
Measure: Hospitalization Time: 30 days from randomizationSecondary Outcomes
Description: Affirmative answer in three or four items of the Global Initiative for Asthma (GINA) questionnaire
Measure: Uncontrolled asthma after ≥ 5 days of starting study medication Time: within 30 days from randomizationDescription: Defined by clinical-radiological criteria - a history of cough and one or more of the following symptoms: sputum, dyspnea, chest pain, sweating or fever (T> 37.8o C) + Chest CT scan showing ground-glass opacity, focal consolidations or mixed opacities (including reverse halo sign), uni or bilateral
Measure: Pneumonia Time: within 30 days from randomizationDescription: Defined by clinical criteria - Fever (T> 37.8o C) and otalgia + bulging of the tympanic membrane
Measure: Otitis media Time: within 30 days from randomizationDescription: Day 0 of fever resolution will be defined as the first afebrile day (T <37.5o C) after inclusion in the study followed by at least two consecutive days. The temperature will be obtained through the participant report in the patient's diary
Measure: Fever resolution time Time: within 30 days from randomizationDescription: Time to improve respiratory symptoms (cough, runny nose)
Measure: Time to improve respiratory symptoms Time: within 30 days from randomizationDescription: Admission to ICU due to clinical reasons related to COVID-19
Measure: Hospitalization in the Intensive Care Unit Time: within 30 days from randomizationDescription: Clinical need for Orotracheal Intubation as assessed by the physician responsible for the case
Measure: Need for Orotracheal Intubation Time: within 30 days from randomizationDescription: Number of days on mechanical ventilation until extubation or death
Measure: Mechanical Ventilation Time Time: within 30 days from randomizationDescription: Death due to any cause that occurred within 30 days after inclusion in the study
Measure: Mortality Time: within 30 days from randomizationOther Outcomes
Description: Change in the frequency of hypoglycemic episodes in diabetic patients using hypoglycemic medication, perceived by clinical signs or symptoms or measured in a capillary or blood glucose device
Measure: Hypoglycemia Time: within 30 days from randomizationDescription: Presence of cardiac arrhythmias in patients without known history of prolongation of the measure between Q wave and T wave in the heart's electrical cycle (QTc) or pre-existing heart disease;
Measure: Palpitations Time: within 30 days from randomizationDescription: Change in visual acuity or new diagnosis of retinal disease not previously documented
Measure: Reduced visual acuity Time: within 30 days from randomizationDescription: Change in bowel habit greater than three (3) diarrheal episodes per day during the use of hydroxychloroquine medication and 3 days after its end
Measure: Diarrhea Time: within 30 days from randomizationDescription: Change in appetite during medication use hydroxychloroquine and 3 days after the end of treatment
Measure: Anorexia Time: within 30 days from randomizationDescription: Perception of change in emotional lability (mood swings) during hydroxychloroquine use and 3 days after the end of treatment
Measure: Emotional lability Time: within 30 days from randomizationDescription: Time from randomization to hospitalization
Measure: Time to hospitalization after randomization Time: within 30 days from randomizationDescription: Clinical and vital signs assessed when admitted to hospital
Measure: Assessment of the patient clinical status at the time of hospitalization Time: within 30 days from randomization302 A Randomized, Double-blind, Placebo-controlled Trial of Anti-SARS-CoV-2 Plasma in Hospitalized Non-ICU Patients With COVID-19
The purpose of this study is to assess the efficacy and safety of the administration of anti-SARS-CoV-2 convalescent plasma in COVID-19 patients who are sick enough to warrant hospitalization, but not yet admitted to the ICU (prior to the onset of overwhelming disease including a systemic inflammatory response, sepsis, and/or ARDS).
NCT04467151 COVID-19 Drug: anti-SARS-CoV-2 plasma Other: Placebo
Primary Outcomes
Description: Disease progression from the state at randomization (with a "3" or "4" on the WHO Ordinal Scale for Clinical Improvement) to requiring invasive mechanical ventilation (which is "6" or greater on the WHO scale) during the study period
Measure: Disease progression measured by WHO scale Time: Day 0 through Day 28 (or hospital discharge)Secondary Outcomes
Description: Comparison of the number of participants reaching a maximum daily WHO score of 5, 7, and 8 during the study period per group
Measure: Comparison of maximum WHO score per group Time: Day 0 through Day 28 (or hospital discharge)Description: Comparison of the median and maximum daily WHO scores during the study period per group
Measure: Comparison of decrease of median and maximum WHO score per group Time: Day 0 through Day 28 (or hospital discharge)Description: Comparison of time to clinical improvement, defined as time between randomization and time to improvement (WHO Ordinal Scale "2" first reached for at least 1 day)
Measure: Comparison of time to clinical improvement per group Time: Day 0 through Day 28 (or hospital discharge)Description: Evaluate the time to reach score of at least 6 within 28 days
Measure: Comparison of time to reach score of "6" or greater on the WHO scale Time: Day 0 through Day 28 (or hospital discharge)Other Outcomes
Description: Evaluate number of days hospitalized
Measure: Comparison of hospital length of stay per group Time: Day 0 through Day 28 (or hospital discharge)Description: Evaluate number of hours in the ICU
Measure: Comparison of ICU length of stay per group Time: Day 0 through Day 28 (or hospital discharge)303 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2/3 Study, in Adult Subjects Hospitalized With Severe SARS-CoV-2 Positive Pneumonia
A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the potential of opaganib to improve and/or stabilize the clinical status of the patient.
NCT04467840 COVID-19 Lung Infection Drug: Opaganib Drug: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: To compare the proportion of patients requiring intubation and mechanical ventilation by Day 14 between subjects taking opaganib and those on placebo.
Measure: Intubation and mechanical ventilation Time: 14 days
Secondary Outcomes
Description: Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.
Measure: WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0 Time: 14 days
Description: To compare the time to intubation and mechanical ventilation between subjects taking opaganib and those on placebo.
Measure: Time to intubation and mechanical ventilation Time: 14 days
Description: To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.
Measure: Time to low oxygen flow via nasal cannula Time: 14 days
Description: To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.
Measure: Supplemental oxygen requirement Time: 14 days
Description: To compare the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days (Day 1 to Day 14) between subjects taking opaganib and those on placebo.
Measure: Total daily oxygen requirement Time: 14 days
Description: To compare the time to two consecutive negative swabs for SARS-CoV-2 by PCR between subjects taking opaganib and those on placebo.
Measure: Time to negative swabs for SARS-CoV-2 Time: 14 days
Description: To compare the proportion of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.
Measure: Negative swabs for SARS-CoV-2 at day 14 Time: 14 days
Description: To compare the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C [100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14 between subjects taking opaganib and those on placebo.
Measure: Fever Time: 14 days
Description: To compare mortality 30 days post-baseline between subjects taking opaganib and those taking placebo
Measure: Mortality Time: 30 days post baseline
Other Outcomes
Description: To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo
Measure: Adverse events Time: Up to 14 days and at the end of the 4 weeks follow-up after the end of treatment
Description: To compare the change in the systemic marker of inflammation, D-dimer, over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - D-dimer Time: 14 days
Description: To compare the change in the systemic marker of inflammation, cardiac troponin, over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - cardiac troponin Time: 14 days
Description: To compare the change in the systemic marker of inflammation, C-reactive protein [CRP], over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - C-reactive protein Time: 14 days
Description: To compare the change in the systemic marker of inflammation lactate dehydrogenase [LDH] over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - lactate dehydrogenase Time: 14 days
Description: To compare the change in the systemic marker of inflammation ferritin over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - ferritin Time: 14 days
304 Phase 1 Double-Blinded, Randomized, Placebo Controlled Safety and Early Efficacy Trial of Cryopreserved Cord Blood Derived T-Regulatory Cell Infusions (CK0802) In The Treatment Of COVID-19 Induced Acute Respiratory Distress Syndrome (ARDS)
Primary Outcomes
Description: To compare the proportion of patients requiring intubation and mechanical ventilation by Day 14 between subjects taking opaganib and those on placebo.
Measure: Intubation and mechanical ventilation Time: 14 daysSecondary Outcomes
Description: Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.
Measure: WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0 Time: 14 daysDescription: To compare the time to intubation and mechanical ventilation between subjects taking opaganib and those on placebo.
Measure: Time to intubation and mechanical ventilation Time: 14 daysDescription: To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.
Measure: Time to low oxygen flow via nasal cannula Time: 14 daysDescription: To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.
Measure: Supplemental oxygen requirement Time: 14 daysDescription: To compare the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days (Day 1 to Day 14) between subjects taking opaganib and those on placebo.
Measure: Total daily oxygen requirement Time: 14 daysDescription: To compare the time to two consecutive negative swabs for SARS-CoV-2 by PCR between subjects taking opaganib and those on placebo.
Measure: Time to negative swabs for SARS-CoV-2 Time: 14 daysDescription: To compare the proportion of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.
Measure: Negative swabs for SARS-CoV-2 at day 14 Time: 14 daysDescription: To compare the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C [100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14 between subjects taking opaganib and those on placebo.
Measure: Fever Time: 14 daysDescription: To compare mortality 30 days post-baseline between subjects taking opaganib and those taking placebo
Measure: Mortality Time: 30 days post baselineOther Outcomes
Description: To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo
Measure: Adverse events Time: Up to 14 days and at the end of the 4 weeks follow-up after the end of treatmentDescription: To compare the change in the systemic marker of inflammation, D-dimer, over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - D-dimer Time: 14 daysDescription: To compare the change in the systemic marker of inflammation, cardiac troponin, over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - cardiac troponin Time: 14 daysDescription: To compare the change in the systemic marker of inflammation, C-reactive protein [CRP], over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - C-reactive protein Time: 14 daysDescription: To compare the change in the systemic marker of inflammation lactate dehydrogenase [LDH] over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - lactate dehydrogenase Time: 14 daysDescription: To compare the change in the systemic marker of inflammation ferritin over the treatment period between subjects taking opaganib and those on placebo.
Measure: Inflammatory markers - ferritin Time: 14 daysTo assess the safety and efficacy of CK0802 in treatment of patients with COVID-19 induced moderate-to-severe PNA-ARDS.
NCT04468971 COVID19 ARDS Biological: CK0802 Drug: Placebo
Primary Outcomes
Description: Regimen related ≥ grade 3 toxicity within 48 hours of first infusion (DLT)
Measure: Regimen related ≥ grade 3 toxicity within 48 hours of first infusion Time: 48 hoursDescription: Alive and not intubated 28 days after the date of first infusion
Measure: 28-day treatment success, defined as S28 Time: 28 daysSecondary Outcomes
Description: Time to extubation
Measure: Time to extubation Time: 28 daysDescription: Oxygenation requirement (PaO2/FiO2) change between day 0 and day +11
Measure: Oxygenation improvement Time: 11 daysDescription: Ventilator free days measured at day 28
Measure: Ventilator free days Time: 28 daysDescription: Organ failure free days measured at day 28
Measure: Organ failure free days Time: 28 daysDescription: ICU free days measured at day 28
Measure: ICU free days Time: 28 daysDescription: All-cause mortality at day 28
Measure: All-cause mortality Time: 28 days305 A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia
Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and acute respiratory distress syndrome (ARDS) in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.
NCT04469114 Covid19 Drug: Tofacitinib 10 mg Drug: Placebo MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: 1, 2 or 3 on the 8-point National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity. The minimum value is 1 (worst outcome) and the maximum value is 8 (best outcome).
Death.
Hospitalized, on invasive mechanical ventilation or ECMO.
Hospitalized, on non-invasive ventilation or high-flow oxygen devices.
Hospitalized, requiring supplemental oxygen.
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise).
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.
Not hospitalized, limitation on activities and/or requiring home oxygen.
Not hospitalized, with no limitations on activities.
Measure: Death or respiratory failure ate Day 28 Time: 28 days
Secondary Outcomes
Description: NIAID ordinal scale of disease severity
Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 Time: 14 days
Description: Categories 3 to 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 and Day 28
Measure: Status of alive and not on mechanical ventilation or ECMO at Day 14 and 28 NIAID ordinal scale of disease severity at Day 14 Time: 14 and 28 days
Description: Categories 1 to 4 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity
Measure: Status of requiring supplemental oxygen at Day 28 Time: 28 days
Description: Categories 7 and 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity
Measure: Status of being alive and not hospitalized at Day 14 and 28 Time: 14 and 28 days
Description: NIAID ordinal scale of disease severity
Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 NIAID ordinal scale of disease severity at Day 28 Time: 28 days
Description: Number of patients with resolution of fever, cough, and need for ventilatory or oxygen support.
Measure: Number of patients with cure Time: 28 days
Description: Number of patients at the ICU or on ventilatory support
Measure: Number of patients at the ICU or on ventilatory support at Day 28 Time: 28 days
Description: Number of days free from mechanical ventilation
Measure: Number of days free from mechanical ventilation at 28 days Time: 28 days
Description: Number of days in hospital
Measure: Number of days in hospital Time: 28 days
Description: Number of days in ICU
Measure: Number of days in ICU Time: 28 days
306 A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Immunomodulatory Effect of the RIPK1 Inhibitor SAR443122 in Hospitalized Patients With Severe COVID-19
Primary Outcomes
Description: 1, 2 or 3 on the 8-point National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity. The minimum value is 1 (worst outcome) and the maximum value is 8 (best outcome). Death. Hospitalized, on invasive mechanical ventilation or ECMO. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. Hospitalized, requiring supplemental oxygen. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise). Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care. Not hospitalized, limitation on activities and/or requiring home oxygen. Not hospitalized, with no limitations on activities.
Measure: Death or respiratory failure ate Day 28 Time: 28 daysSecondary Outcomes
Description: NIAID ordinal scale of disease severity
Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 Time: 14 daysDescription: Categories 3 to 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 and Day 28
Measure: Status of alive and not on mechanical ventilation or ECMO at Day 14 and 28 NIAID ordinal scale of disease severity at Day 14 Time: 14 and 28 daysDescription: Categories 1 to 4 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity
Measure: Status of requiring supplemental oxygen at Day 28 Time: 28 daysDescription: Categories 7 and 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity
Measure: Status of being alive and not hospitalized at Day 14 and 28 Time: 14 and 28 daysDescription: NIAID ordinal scale of disease severity
Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 NIAID ordinal scale of disease severity at Day 28 Time: 28 daysDescription: Number of patients with resolution of fever, cough, and need for ventilatory or oxygen support.
Measure: Number of patients with cure Time: 28 daysDescription: Number of patients at the ICU or on ventilatory support
Measure: Number of patients at the ICU or on ventilatory support at Day 28 Time: 28 daysDescription: Number of days free from mechanical ventilation
Measure: Number of days free from mechanical ventilation at 28 days Time: 28 daysDescription: Number of days in hospital
Measure: Number of days in hospital Time: 28 daysDescription: Number of days in ICU
Measure: Number of days in ICU Time: 28 daysPrimary Objective: To evaluate the effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by C-reactive protein (CRP) levels in adult patients hospitalized with severe COVID-19 Secondary Objectives: - To evaluate the time to onset of effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by CRP levels - To evaluate the time to onset of effect of SAR443122 relative to the control arm on oxygenation status - To evaluate the effect of SAR443122 relative to the control arm on oxygenation status - To evaluate the effect of SAR443122 relative to the control arm on total duration of supplemental oxygen requirement - To evaluate the effect of SAR443122 relative to the control arm on length of ventilator support needed - To evaluate the effect of SAR443122 relative to the control arm on laboratory markers of severe COVID-19 - To evaluate the effect of SAR443122 relative to the control arm on mortality - To evaluate the effect of SAR443122 relative to the control arm on need for thrombolytic therapy - To evaluate the effect of SAR443122 relative to the control arm on need for vasopressor treatment - To evaluate the safety of SAR443122 as compared to the control arm up to End of Study
NCT04469621 Corona Virus Infection Drug: SAR443122 Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Relative change from baseline in CRP level on Day 7
Measure: Relative change from baseline in CRP level Time: Day 7Secondary Outcomes
Description: The time to 50% decrease from baseline in CRP level
Measure: Time to 50% decrease from baseline in CRP level Time: Baseline to Day 28Description: The time to improvement of oxygenation as measured by oxygen saturation >/=92% breathing room air over 48 hrs or until discharge
Measure: Time to improvement of oxygenation Time: Baseline to Day 28Description: Change from baseline in SPO2/FiO2 ratio at Day 7
Measure: Change from baseline in SPO2/FiO2 ratio Time: Day 7Description: Number of Days without need for oxygen support and alive (oxygen saturation >=92% breathing room air) up to Day 28
Measure: Number of Days without need for oxygen support and alive Time: Baseline to Day 28Description: Numbers of Ventilator-free days and alive up to Day 28
Measure: Numbers of Ventilator-free days and alive Time: Baseline to Day 28Description: Change from baseline in white blood cell count and differential blood lymphocytes at Day 7 and End of treatment (EOT)
Measure: Change from baseline in markers of inflammation: white blood cell count and differential blood lymphocytes Time: Day 7 and Day 15Description: Change from baseline in neutrophil to lymphocyte ratio at Day 7 and EOT
Measure: Change from baseline in marker of inflammation: neutrophil to lymphocyte ratio Time: Day 7 and Day 15Description: Change from baseline in IL-6 at Day 7 and EOT
Measure: Change from baseline in marker of inflammation: interleukin 6 (IL-6) Time: Day 7 and Day 15Description: Change from baseline in D-Dimer at Day 7 and EOT
Measure: Change from baseline in D-Dimer Time: Day 7 and Day 15Description: Incidence of Deaths up to Day 28
Measure: Incidence of Deaths Time: Baseline to Day 28Description: Percentage of participants receiving thrombolytic treatment up to Day 28
Measure: Percentage of participants receiving thrombolytic treatment Time: Baseline to Day 28Description: Percentage of participants receiving vasopressor treatment up to Day 28
Measure: Percentage of participants receiving vasopressor treatment Time: Baseline to Day 28Measure: Incidence of serious adverse events (SAEs), adverse events of special interest (AESI) and treatment-emergent adverse events (TEAEs) leading to treatment discontinuation Time: Baseline to Day 28
Measure: Incidence of TEAEs leading to study discontinuation (primary reason) Time: Baseline to Day 28
307 A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older
The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273.
NCT04470427 SARS-CoV-2 Biological: mRNA-1273 Biological: Placebo
Primary Outcomes
Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose of mRNA-1273 Time: Day 29 (second dose) up to Day 759 (2 years after second dose)Measure: Number of Participants with Adverse Events (AEs) or Medically Attended AEs (MAAEs) Leading to Withdrawal Time: Up to Day 759 (2 years after second dose)
Measure: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) Time: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose)
Measure: Number of Participants with Unsolicited AEs Time: Up to Day 57 (28 days after each dose)
Secondary Outcomes
Description: Clinical signs indicative of severe COVID-19 as predefined for the study.
Measure: Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of mRNA-1273 Time: Day 29 (second dose) up to Day 759 (2 years after second dose)Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 Infection as predefined for the study.
Measure: Number of Participants with a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection regardless of symptomatology or Severity Starting 14 Days after Second Dose of mRNA-1273 or Placebo Time: Day 29 (second dose) up to Day 759 (2 years after second dose)]Description: Clinical signs indicative of secondary case definition of COVID-19 as predefined for the study.
Measure: Number of Participants with a Secondary Case Definition of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo Time: Day 29 (second dose) up to Day 759 (2 years after second dose)Description: Clinical signs indicative of COVID-19 as predefined for the study.
Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of mRNA-1273 or Placebo Time: Day 1 (first dose) up to Day 759 (2 years after second dose)Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.
Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo regardless of evidence of prior SARS-CoV-2 Infection Time: Day 29 (second dose) up to Day 759 (2 years after second dose)Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.
Measure: Number of Participants with a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo Time: Day 29 (second dose) up to Day 759 (2 years after second dose)Measure: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759
Measure: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759
Measure: Quantified Levels or GMT of S Protein-Specific Binding Antibody (bAb) Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759
Measure: GMFR of S Protein Specific bAb Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759
308 An Adaptive Phase 1, Followed by Phase 2 Randomized, Double-blind, Multicenter Study to Evaluate the Safety, Reactogenicity, Tolerability, and Immunogenicity of the BBV152 in Healthy Volunteers
The study is designed to evaluate the safety, reactogenicity, tolerability, and immunogenicity of three investigational vaccine groups and one placebo group in healthy volunteers who receive two intramuscular doses of BBV152 vaccine formulations. A total sample size of 1125 healthy volunteers, with 375 and 750 volunteers in phase 1 and 2 studies, respectively.
NCT04471519 Covid19 SARS-CoV Infection Biological: BBV152A Biological: BBV152B Biological: BBV152C Biological: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Safety
Measure: Phase 1: Occurrence of adverse events and Serious Adverse events Time: Through study completion, an average of 6 monthsDescription: Pre- and Post-vaccination immune response
Measure: Phase 2: Evaluation of Neutralizing Antibody Titers Time: Through study completion, an average of 6 monthsSecondary Outcomes
Description: Pre- and Post-vaccination immune response
Measure: Phase 1: Evaluation of Neutralizing Antibody Titers Time: Through study completion, an average of 6 monthsDescription: Safety
Measure: Phase 2: Occurrence of adverse events and Serious Adverse events Time: Through study completion, an average of 6 months309 Phase 2, Randomized, Double-Blind Placebo Controlled Study of Intravenous Abatacept in the Treatment of Hospitalized COVID-19 Participants With Respiratory Compromise
The purpose of this study is to evaluate the efficacy and safety of intravenous abatacept administered to hospitalized COVID-19 participants with respiratory compromise.
NCT04472494 COVID-19 SARS-CoV-2 Biological: Abatacept Other: Placebo
Primary Outcomes
Measure: Proportion of participants with composite end point of mechanical ventilation or death prior to or on Day 28 Time: Up to 28 daysSecondary Outcomes
Measure: Change from baseline in the Ordinal 8-point Outcome Scale on Day 28 Time: Day 28Measure: All-cause mortality on Day 28 Time: Day 28
Measure: Proportion of participants alive and free of respiratory failure on Day 28 Time: Day 28
Measure: Proportion of participants returned to room air by Day 28 Time: Up to 28 days
Measure: Proportion of participants alive and discharged home by Day 28 Time: Up to 28 days
Measure: Proportion of participants with Serious Adverse Events (SAEs) Time: Up to 60 days
Measure: Proportion of participants with serious infections Time: Up to 60 days
310 Sub-cutaneous Ivermectin in Combination With and Without Oral Zinc and Nigella Sativa: a Placebo Randomized Control Trial on Mild to Moderate COVID-19 Patients
To measure the effect of Ivermectin (sub-cutaneous) with or without zinc and Nigella sativa in treating the COVID-19 patients to clear viral load of SARS-CoV-2 along with reduction in severity of symptoms and length of hospitalization of patients with COVID-19.
NCT04472585 Coronavirus Infection COVID Sars-CoV2 Drug: Nigella Sativa / Black Cumin Drug: Ivermectin Injectable Solution Other: Placebo Drug: Zinc MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: time needed to turn positive COVID-19 PCR to negative
Measure: qRT-PCR Time: 14 daysSecondary Outcomes
Description: time needed to make patients clinically better
Measure: Severity of symptoms Time: 14 days311 A Safety, Tolerability, and Pharmacokinetic Study of Single-and Multiple-Ascending Doses of LY3473329 in Healthy Subjects
The main purpose of this study in healthy participants is to learn more about the safety of LY3473329 and any side effects that might be associated with it. Blood tests will be performed to check how much LY3473329 gets into the bloodstream and how long the body takes to eliminate it. This is a two-part study. Participants may only enroll in one part. For each participant: - Part A will last up to about 19 weeks and may include 9 visits. - Part B will last up to about 28 weeks and may include 11 visits.
NCT04472676 Healthy Drug: LY3473329 Drug: Placebo
Primary Outcomes
Description: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
Measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration Time: Baseline up to Day 137Secondary Outcomes
Description: PK: AUC of LY3473329
Measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3473329 Time: Baseline up to Day 137Description: PK: Cmax of LY3473329
Measure: PK: Maximum Observed Drug Concentration (Cmax) of LY3473329 Time: Baseline up to Day 137312 Adaptive Design Phase 2 to 3, Randomized, Double-blind, to Evaluate Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BIO101 in the Prevention of the Respiratory Deterioration in Hospitalized COVID-19 Patients
The COVA clinical study is a global multicentric, double-blind, placebo-controlled, group sequential and adaptive 2 parts phase 2-3 study targeting in patients with SARS-CoV-2 pneumonia. Part 1 is a Phase 2 exploratory Proof of Concept (PoC) study to provide preliminary data on the activity, safety and tolerability of BIO101 in the target population. Part 2 is a phase 3 pivotal randomized study to provide further evidence of safety and efficacy of BIO101 after 28 days of double-blind dosing. BIO101 is the investigational new drug that activates the Mas receptor (MasR) through the protective arm of the Renin Angiotensin System (RAS).
NCT04472728 Covid-19 SARS-CoV2 Drug: BIO101 Drug: Placebo
Primary Outcomes
Description: For interim analysis intended to obtain indication of activity of BIO101. Primary endpoint: • Proportion of subjects with negative events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen
Measure: End-of-Part 1 interim analysis: Proportion of subjects with all cause mortality or with respiratory failure. Time: up to 28 daysDescription: For sample size re-assessment for part 2, time frame - up to 28 days: • Proportion of participants with negative events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring high-flow oxygen
Measure: For part-2 sample size interim analysis: Proportion of subjects with all cause mortality or with respiratory failure. Time: up to 28 daysDescription: • Proportion of participants with of subjects with negative events, of either of the following. All-cause mortality Respiratory failure, defined as any of the following: Mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen
Measure: For the final analysis: Proportion of subjects with all cause mortality or respiratory failure. Time: up to 28 daysSecondary Outcomes
Description: • SpO2/FiO2
Measure: Interim analysis; indication of activity of BIO101: Oxygen saturation by pulse oximetry (SpO2) SpO2 / Fraction of inspired oxygen (FiO2) ratio Time: 28 daysDescription: • Inflammatory markers including: IL 6 TNFα D-dimer
Measure: Interim analysis; indication of activity of BIO101: Inflammatory markers Time: 28 daysDescription: • Renin Angiotensin System biomarkers: Angiotensin 2 Angiotensin-converting enzyme (ACE) levels
Measure: Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers Time: 28 daysDescription: Proportion of participants with events of all-cause mortality Proportion of participants with 'positive' events: o official discharge from hospital care by the department due to improvement in patient condition (self-discharge by patient is not considered a positive event) Proportion of participants with events of respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen
Measure: Key secondary endpoint for final analysis: Proportion of participants with positive or negative events Time: 28 daysDescription: Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2) SpO2/FiO2 Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen)
Measure: Additional secondary endpoints for final analysis: Respiratory function Time: 28 daysDescription: For participants who experienced a positive event: proportion of participants with with sustained positive outcome (to asesss durability of effect after those participants discontinued study medication). Time to event: official discharge from hospital care due to improvement
Measure: Additional secondary endpoints for final analysis:proportion of patients who experienced positive event Time: 28 daysDescription: Time to events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage); Requiring ECMO; Requiring high-flow oxygen • Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen)
Measure: Additional secondary endpoints for final analysis:proportion of patients who experienced negative events Time: 28 daysDescription: National Early Warning Score 2 (NewS2): scores: 0-7
Measure: Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2): Time: 28 daysDescription: Population-Pharmacokinetics study (pop-PK)
Measure: Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK) Time: 28 days313 Efficacy of Iodine Complex in Mild to Moderate COVID-19 Patients
The objective of this study is to measure the effect of Iodine complex in treating the COVID-19 patients to clear viral load of SARS-CoV-2 along with reduction in severity of symptoms and length of hospitalization of patients with COVID-19.
NCT04473261 Covid19 SARS-CoV-2 Corona Virus Infection Drug: Iodine Complex Drug: Iodine Complex Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Time taken for viral load clearance
Measure: qRT-PCR Time: 14 daysSecondary Outcomes
Description: Time taken for symptomatic response in patients
Measure: Severity of Symptoms Time: 14 days314 A Phase I/II, First-in-human, Observer-blinded, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Safety and Immunogenicity of KBP-COVID-19 Vaccine in Healthy Seronegative Adults Aged 18-49 and 50-70
This is an First In Human (FIH), observer-blinded, randomized, placebo-controlled, parallel group study to evaluate the safety and immunogenicity of KBP-COVID-19 vaccine in healthy CoV-2seronegative adult subjects in 2 age groups, Part A (18-49 years) and Part B (50-70 years).
NCT04473690 Covid19 Biological: Low Dose of KBP-COVID-19 Biological: High Dose of KBP-COVID-19 Biological: Placebo
Primary Outcomes
Description: Occurrence of Adverse Events
Measure: Solicited Administration site reactions Time: 7 days after vaccinationDescription: Occurrence of Adverse Events
Measure: Solicited systemic events Time: 7 days after vaccinationSecondary Outcomes
Description: Safety Endpoints
Measure: Unsolicited Adverse Events and medically attended adverse events Time: 43 days after vaccinationDescription: Safety Endpoints
Measure: Serious Adverse Events, Medically Attended Adverse Events and New Onset Chronic Diseae Time: 365 days after vaccinationDescription: Immunogenicity
Measure: Vaccine ELISA and neutralizing antibody titers for each treatment group Time: Baseline, Day 8, 15, 22, 29, 43, 90, 181, 273, 365Description: Immunogenicity
Measure: Seroconversion rates Time: Days 8, 15, 22, 29, 43, 90, 181, 273, 365315 A Multi-center, Randomized, Double-blind, Parallel, Placebo-Controlled, Phase Ⅱ Clinical Trial to Evaluate Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients
This study is a multi-center, randomized, double-blind, parallel, placebo-controlled, phase Ⅱ clinical trial to evaluate efficacy and safety of Pyramax in mild to moderate COVID-19 patients.
NCT04475107 COVID-19 Drug: Pyronaridine-Artesunate Drug: Placebo
Primary Outcomes
Description: * Patients who are rRT-PCR negative for COVID-19
Measure: Proportion (%) of patients with virological clearance of SARS-CoV-2 at day 7 post-dose* Time: Day 7Secondary Outcomes
Measure: Viral load reduction of SARS-CoV-2 at Day 3, 7, 10, and 14 post-dose compared to the baseline Time: Day 3, 7, 10, 14Description: * Patients who are rRT-PCR negative for COVID-19
Measure: Proportion (%) of patients with virological clearance of SARS-CoV-2 at Day 3, 10, and 14 post-dose* Time: Day 3, 10, 14Measure: Change in WHO Ordinal Scale for Clinical Improvement at Day 3, 7, 10, 14, and 28 post-dose from the baseline Time: Day 3, 7, 10, 14, 28
Measure: Change in NEWS score at Day 3, 7, 10, 14, and 28 post-dose from the baseline Time: Day 3, 7, 10, 14, 28
Measure: Time to achieve normalization of body temperature, post-dose Time: Day 3, 7, 10, 14, 28
Measure: Time to achieve normalization of respiratory rate, post-dose Time: Day 3, 7, 10, 14, 28
Measure: Time to achieve normalization of oxygen saturation, post-dose Time: Day 3, 7, 10, 14, 28
316 A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ST-2427 IV Infusion in Healthy Subjects
This randomized, double-blind, placebo controlled, study will be conducted to evaluate the safety, tolerability, and pharmacokinetics of ST-2427. The study will be conducted in 2 parts. In Part A of this study, subjects will be randomized to receive a single dose of ST-2427 or placebo in a Single Ascending Dose (SAD) design. In Part B of this study, subjects will be randomized to receive up to 6 repeat doses of ST-2427 or placebo, administered twice-daily (BID) every 12 hours, in a Multiple Ascending Dose (MAD) design. In Part A and Part B, study drug (ST-2427 or placebo) will be administered intravenously (IV) over 1 hour. A total of 48 subjects will be enrolled. Subjects will be randomized in a 4:2 ratio of ST-2427 to placebo. Study drug will be blinded to all subjects and investigators.
NCT04475198 Acute, Post-operative Pain Drug: ST-2427 Drug: Placebo MeSH:Pain, Postoperative
Primary Outcomes
Description: For purposes of monitoring safety, treatment-emergent adverse events (AEs) will be graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers (FDA 2007) which is appropriate for healthy subjects.
Measure: Incidence and severity of treatment-emergent adverse events Time: Day 1 through Day 8Description: Blood pressure, including orthostatic blood pressure (BP; diastolic blood pressure [DBP], systolic blood pressure [SBP], will be used to analyze for change from baseline.
Measure: Incidence and severity of adverse events assessed by blood pressure Time: Day 1 through Day 8Description: Cardiodynamic evaluation will be performed to evaluate the treatment effects on heart rate-corrected QT interval using the Fridericia (QTcF) corrections, using concentration-QTc analysis, and on other ECG parameters (heart rate, PR and QRS interval and treatment emergent T and U-wave abnormalities).
Measure: Incidence and severity of adverse events assessed by ECG Time: Day 1 through Day 8Description: The Holter recordings will also be analyzed for the presence of arrhythmias and for derivation of heart rate variability (HRV).
Measure: Incidence and severity of adverse events assessed by Continous Holter Monitoring Time: Day 1 through Day 8Description: Descriptive statistics will be used to evaluate the treatment effects on clinical laboratory assessments including clinical chemistry, hematology, and urinalysis.
Measure: Incidence and severity of treatment-emergent events assessed by clinical laboratory assessments Time: Day 1 through Day 8Description: Body weight (kg) will be assessed for changes relative to baseline.
Measure: Incidence and severity of adverse events assessed by body weight Time: Day 1 through Day 8Secondary Outcomes
Description: PK modeling will be performed using compartmental methods. The maximum concentration of ST-2427 in whole blood after the ST-2427 infusion in the SAD, and after the first and fifth infusions of ST-2427 in the MAD will be measured.
Measure: Pharmacokinetics of ST-2427 concentration in whole blood: Cmax Time: Day 1 through Day 5Description: PK modeling will be performed using compartmental methods. The elimination half-life of ST-2427 in whole blood after the ST-2427 infusion in the SAD, and after the first and fifth infusions of ST-2427 in the MAD will be measured.
Measure: Pharmacokinetics of ST-2427 concentration in whole blood: Elimination half-life Time: Day 1 through Day 5Description: PK modeling will be performed using compartmental methods. The AUC (area under the curve) of ST-2427 in whole blood after the ST-2427 infusion in the SAD, and after the first and fifth infusions of ST-2427 in the MAD will be measured.
Measure: Pharmacokinetics of ST-2427 concentration in whole blood: Area under the curve Time: Day 1 through Day 5Description: The ST-2427 concentrations in the urine will be measured in 4 hour increments by cohort for the SAD.
Measure: Pharmacokinetics of ST-2427 concentration in urine Time: Day 1 through Day 5317 A Randomized, Investigator- /Subject-blind, Single- and Multiple-ascending Dose, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 Following Oral Administration in Healthy Male Participants
This study will evaulate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single- and multiple-ascending doses (SAD and MAD) and food effect (FE) of RO6953958 following oral administration in healthy male participants.
NCT04475848 Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Mental Disorders Neurodevelopmental Disorders Drug: RO6953958 Drug: Placebo MeSH:Disease Autism Spectrum Disorder Child Development Disorders, Pervasive Mental Disorders Autistic Disorder Neurodevelopmental Disorders Developmental Disabilities
HPO:Autism Autistic behavior
Primary Outcomes
Measure: Percentage of Participants with Adverse Events in Part 1 Time: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort)
Measure: Percentage of Participants with Adverse Events in Part 2 Time: From randomization up to 8 weeks
Measure: Part 2: Change in suicide risk assessed using the Columbia Suicide Severity Rating Scale (C-SSRS) Time: From randomization up to 8 weeks
Secondary Outcomes
Measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1
Measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1
Measure: Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Terminal Elimination Phase Half-Life (T1/2) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Area Under the Concentration-Time Curve from Time 0 to 12 hours (AUC(0-12h)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Area Under the Concentration-Time Curve from Time Extrapolated to Infinity (AUC (0-inf)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Apparent Clearance (CL/F) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Apparent Volume of Distribution (V/F) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Cumulative Amount of Unchanged Drug Excreted into the Urine (Ae) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Fraction of the Administered Drug Excreted into the Urine (Fe) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Renal Clearance of the Drug from Urine (CLR) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Parts 2: Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 and Day 10
Measure: Parts 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 and Day 10
Measure: Parts 2: Average Plasma Concentration (Cavg) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Tmax of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 and Day 10
Measure: Part 2: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: T1/2 of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: CL/F of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: V/F of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: Ae of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: Fe of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: CLR of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: Trough Plasma Concentration (Ctrough) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Accumulation Ratio based on AUC (Rauc) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Accumulation Ratio based on Ctrough (RCtrough) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
318 Reducing Asymptomatic Infection With Vitamin D in Coronavirus Disease
Primary Outcomes
Measure: Percentage of Participants with Adverse Events in Part 1 Time: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort)Measure: Percentage of Participants with Adverse Events in Part 2 Time: From randomization up to 8 weeks
Measure: Part 2: Change in suicide risk assessed using the Columbia Suicide Severity Rating Scale (C-SSRS) Time: From randomization up to 8 weeks
Secondary Outcomes
Measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1Measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1
Measure: Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Terminal Elimination Phase Half-Life (T1/2) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Area Under the Concentration-Time Curve from Time 0 to 12 hours (AUC(0-12h)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Area Under the Concentration-Time Curve from Time Extrapolated to Infinity (AUC (0-inf)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Apparent Clearance (CL/F) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Apparent Volume of Distribution (V/F) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Cumulative Amount of Unchanged Drug Excreted into the Urine (Ae) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Fraction of the Administered Drug Excreted into the Urine (Fe) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Part 1: Renal Clearance of the Drug from Urine (CLR) of RO6953958 in Fasted and Fed state Time: Day 1 to Day 5
Measure: Parts 2: Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 and Day 10
Measure: Parts 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 and Day 10
Measure: Parts 2: Average Plasma Concentration (Cavg) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Tmax of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 and Day 10
Measure: Part 2: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: T1/2 of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: CL/F of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: V/F of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: Ae of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: Fe of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: CLR of RO6953958 Time: Day 1 to Day 14
Measure: Part 2: Trough Plasma Concentration (Ctrough) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Accumulation Ratio based on AUC (Rauc) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
Measure: Part 2: Accumulation Ratio based on Ctrough (RCtrough) of RO6953958 and its Metabolites RO7021594 and RO7045755 Time: Day 1 to Day 14
This study is intended to address whether oral daily vitamin D supplementation reduces infection with SARS-CoV-2 in healthy young adults. The primary aim of the study is to demonstrate a reduction in 'silent' seroconversion rates, consistent with asymptomatic transmission of SARS-CoV-2, in a young healthy adult population following 24 weeks of taking oral vitamin D supplemented at a dose of 1000 I.U. daily, versus matching placebo. The secondary aims of this study are to explore: 1. Any effect on symptomatic illness. 2. The background 'point' prevalence and subsequent rate of increase in seropositivity for SARS-CoV-2 in healthy young adults. 3. The individual reductions in seropositivity to SARS-CoV-2 over time, and changes in seropositivity in a defined young adult population over time. 4. Where salivary Immunoglobulin A (IgA) may be used to provide an alternative/ complementary serological method 5. The effect (if any) of vitamin D supplementation on seroconversion rates stratified by: i) level of baseline vitamin D 'deficiency/ insufficiency/ sufficiency' status; ii) extent of BMI-defined normal/overweight/obesity cut-offs and iii) gender.
NCT04476680 SARS-CoV Infection Vitamin D D Vitamin D Deficiency Covid19 Acute Respiratory Tract Infection Dietary Supplement: Vitamin D 1000 IU Drug: Placebo MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Vitamin D Deficiency Asymptomatic Infections
HPO:Low levels of vitamin D Respiratory tract infection
Primary Outcomes
Description: asymptomatic seroconversion for SARS-CoV-2
Measure: Seroconversion Time: 24 weeks
Description: asymptomatic seroconversion for SARS-CoV-2
Measure: Interim analysis - seropositivity at 12 weeks Time: 12 weeks
Secondary Outcomes
Description: Sensitivity and specificity of dried blood spot assay compared with venous blood serology
Measure: Dried Blood Spot performance Time: 24 weeks
Description: Sensitivity and specificity of salivary IgA compared with venous blood serology
Measure: Salivary IgA performance Time: 24 weeks
Description: The background 'point' prevalence and subsequent rate of increase in seropositivity for SARS-CoV-2 in healthy young adults.
Measure: Prevalence of SARS-CoV-2 Time: 24 weeks
Description: The individual reductions in seropositivity to SARS-CoV-2 over time, and changes in seropositivity in a defined young adult population over time
Measure: Change in seropositivity Time: 24 weeks
Description: The effect of vitamin D supplementation on seroconversion rates stratified by: i) level of baseline vitamin D 'deficiency/ insufficiency/ sufficiency' status; ii) extent of BMI-defined normal/overweight/obesity cut-offs, iii) gender iv) ethnicity
Measure: Change in seroconversion rate Time: 24 weeks
319 COVID-FISETIN: A Phase 2 Placebo-Controlled Pilot Study in Covid-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Hospitalized Adults
Primary Outcomes
Description: asymptomatic seroconversion for SARS-CoV-2
Measure: Seroconversion Time: 24 weeksDescription: asymptomatic seroconversion for SARS-CoV-2
Measure: Interim analysis - seropositivity at 12 weeks Time: 12 weeksSecondary Outcomes
Description: Sensitivity and specificity of dried blood spot assay compared with venous blood serology
Measure: Dried Blood Spot performance Time: 24 weeksDescription: Sensitivity and specificity of salivary IgA compared with venous blood serology
Measure: Salivary IgA performance Time: 24 weeksDescription: The background 'point' prevalence and subsequent rate of increase in seropositivity for SARS-CoV-2 in healthy young adults.
Measure: Prevalence of SARS-CoV-2 Time: 24 weeksDescription: The individual reductions in seropositivity to SARS-CoV-2 over time, and changes in seropositivity in a defined young adult population over time
Measure: Change in seropositivity Time: 24 weeksDescription: The effect of vitamin D supplementation on seroconversion rates stratified by: i) level of baseline vitamin D 'deficiency/ insufficiency/ sufficiency' status; ii) extent of BMI-defined normal/overweight/obesity cut-offs, iii) gender iv) ethnicity
Measure: Change in seroconversion rate Time: 24 weeksThe purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.
NCT04476953 COVID-19 Drug: Placebo Drug: Fisetin
Primary Outcomes
Description: Number of participants to experience serious adverse events and hypersensitivity reactions.
Measure: Serious Adverse Events Time: 6 monthsDescription: change in oxygenation levels as measured by S/F ratio (SPO2/FiO2)
Measure: Change in oxygenation status Time: baseline, Day 3, 7, 10, 14, 17 and 30; Months 3 and 6Secondary Outcomes
Description: Number of participants to progress to severe or critical classification measure by the WHO/ NIH Baseline Severity Classification criteria descriptions of SARS-CoV-2 infection without symptoms, Mild COVID-19 (CoV), Moderate CoV, Severe CoV and Critical CoV
Measure: COVID-19 Severity Category Time: 6 months320 Randomized, Double-Blind Clinical Trial of Ruxolitinib in Patients With Acute Respiratory Disorder Syndrome Due to SARS-CoV-2 Infection
The COVID-19 pandemic has had a dramatic effect in public health worldwide. In Brazil, there have been more than 2 million confirmed cases and over 75,000 deaths since February 26, 2020. Based on reports of a hyperinflammatory state associated with COVID-19, the use of immunosuppressive drugs may be efficacious in the treatment of this disease. JAK inhibitors have been shown to harness inflammation in a number of different pathologic conditions. The aim of the present study is to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in patients with acute respiratory distress syndrome due to COVID-19.
NCT04477993 Severe Acute Respiratory Syndrome Coronavirus 2 SARS-CoV2 Drug: Janus Kinase Inhibitor (ruxolitinib) Other: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiration Disorders Syndrome Respiratory Tract Diseases
Primary Outcomes
Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 14. Time: 14 daysSecondary Outcomes
Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 28 Time: 28 daysDescription: ICU admission, mechanical ventilation, death or consent withdrawal
Measure: Time to treatment failure Time: 28 daysMeasure: Overall survival at days 14 and 28 Time: 14 and 28 days
Measure: Cumulative incidence of ICU admission rate at days 14 and 28 Time: 14 and 28 days
Measure: Cumulative incidence of mechanical ventilation at days 14 and 28 Time: 14 and 28 days
Measure: Duration of hospital stay Time: 28 days
Measure: Duration of ICU stay Time: 28 days
Measure: Duration of mechanical ventilation Time: 28 days
Measure: Duration of non-invasive ventilation Time: 28 days
Measure: Secondary hemophagocytic syndrome rate Time: 28 days
Measure: Cumulative incidence nosocomial infection rate at days 14 and 28 Time: 14 and 28 days
Measure: Incidence of discontinuation of oxygen supplementation at days 14 and 28 Time: 14 and 28 days
Measure: Rate of grade 1-2 and 3-5 emerging adverse events at day 28 Time: 28 days
Measure: Cumulative dose of methylprednisolone at days 14 and 28 Time: 14 and 28 days
Measure: Change in PaO2/FiO2 ratio from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in d-dimer levels [ng/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in ferritin levels [ng/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in C reactive protein levels [mg/L] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in alanine aminotransferase [U/L] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in creatinine levels [mg/dL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in glucose levels [mg/dL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in hemoglobin levels [g/dL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in prothrombin time ratio from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in partial thromboplastin time ratio from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in bilirubin [mg/dl] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in CPK-MB [ng/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in troponin [ng/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in ADAMTS-13 [%] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in von Willebrand multimeters from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in E-selectin levels [ng/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in P-selectin levels [ng/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in endothelin [fmol/mL] from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in circulating microparticles from baseline to days 14 and 28 Time: 14 and 28 days
Measure: Change in thromboelastography from baseline to days 14 and 28 Time: 14 and 28 days
321 Prevention of Severe Covid-19 in Infected Elderly by Early Administration of Convalescent Plasma With High-titers of Antibody Against SARS-CoV2.
Trial design. Randomized, double-blind, placebo-controlled trial in a catchment population of 2,020,860 age-appropriate subjects in the state of Buenos Aires and 235,000 in the city of Buenos Aires. Institutions. Hospitals San Juan de Dios, Simplemente Evita, Dr. Carlos Bocalandro, Evita Pueblo, Sanatorio Antartida, Hospital Central de San Isidro, Clinica Olivos in the state of Buenos Aires with 38 regional and town hospitals acting as referral centers, and Hospital Militar Central, Sanatorio de Los Arcos, Hospital Universitario CEMIC, Sanatorio Sagrado Corazon, Sanatorio Finochietto, Sanatorio Anchorena, Centro Gallego, and in the city of Buenos Aires in Argentina. Study population. Subjects >= 75 years of age irrespective of presenting comorbidities or between 65-74 years of age with at least one comorbidity (hypertension, diabetes, obesity, chronic renal failure, and COPD) who experience the following signs and symptoms for less than 48 hours at the time of screening for SARS CoV2 by RT-PCR: (a) a temperature >=37.5°C and/or unexplained sweating and/or chills and (b) at least one of the following: dry cough, dyspnea, fatigue, myalgia, anorexia, sore throat, loss of taste and/or smell, rhinorrhea. Subjects consenting to screening will be tested by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for SARS-CoV-2 in a nasopharyngeal and an oropharyngeal swab and invited to participate when RNA for the virus is detected. Intervention. Eligible, consenting patients will be randomized using an electronic system to receive 250 ml of convalescent plasma with an IgG titer against SARS-CoV2 spike (S) protein >1:1,000 (COVIDAR IgG, Insituto Leloir, Argentina) or placebo (normal saline 0.9%) administered in a 1:1 ratio. Both treatment and placebo will be concealed using dark bags and tape to cover the infusion line. Treatment will be administered <72 hours from initiation of symptoms. Subjects will be monitored for 12 hours after treatment for adverse events. Clinical and laboratory monitoring. All participating subjects will be admitted to the hospital upon enrollment. Twenty-four hours after completing the infusion, a sample of venous blood (5 ml) will be obtained from all participants to measure anti-S IgG SARS-CoV2 in serum (COVIDAR IgG, Leloir) and preserved at -20°C until completion of the study. Patient evolution will be assessed daily by study physicians during hospitalization until day 25 and/or at home until day 15, in the event of earlier discharge from the hospital. Study physicians will use predesigned questionnaires to collect clinical information. An Independent Data Safety Monitoring Board (DSMB) will supervise participating subjects during the study. Endpoints. The primary endpoint of the trial is development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93% when breathing room air determined using a predefined protocol. Three other clinical endpoints include (a) life threatening respiratory disease, defined as need for 100% oxygen supplementation and/or non-invasive or invasive ventilation and/or admission to intensive care; (b) critical systemic illness, defined as respiratory failure (PaO2/FiO2 ≤ 200 mm Hg) and/or shock and/or multiorganic distress syndrome; and (c) death. Statistical analysis. The study is designed to have one interim analysis when the outcome results for 50% of the subjects is obtained. The minimally clinically important difference was set at a 40% relative reduction for an expected outcome rate of 50% in the control group reduced to 30% in the intervention group. A total sample size of 210 subjects (105 per trial arm) was estimated to have 80% power at a significance level (alpha) of 0.05 using a two-sided z-test with continuity correction. Ethical considerations. The trial has been approved by the institutional review boards of participating institutions and the Central Ethics Committee of the state of Buenos Aires. The study will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. Written informed consent will be obtained from all patients for screening and enrollment.
NCT04479163 COVID Biological: Convalescent Plasma Other: Placebo
Primary Outcomes
Measure: Development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93% Time: From 12 hours post infusion to day 15 post infusionSecondary Outcomes
Measure: Life threatening respiratory disease Time: From 12 hours post infusion to day 25 post infusionMeasure: Critical systemic illness, defined as respiratory failure Time: From 12 hours post infusion to day 25 post infusion
Measure: Death Time: From 12 hours post infusion to day 25 post infusion
Measure: Combination of secondary outcomes #2 (Life threatening respiratory disease) and/or #3 (Critical systemic illness, defined as respiratory failure) and//or #4 (death) Time: From 12 hours post infusion to day 25 post infusion
Measure: Duration of oxygen support requirement in patients with covid-19 due to saturation in ambient air <93%. Time: From 12 hours post infusion to day 25 post infusion
322 A Phase 1 Randomized, Single-blind, Placebo-controlled, Single Ascending Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Human Monoclonal Antibody, BRII-196 Administered Intravenously to Healthy Adult Volunteers
This is a phase 1 study in which healthy adult volunteers will receive BRII-196 or placebo and will be assessed for safety, tolerability, and pharmacokinetics.
NCT04479631 COVID-19 Drug: BRII-196 Drug: Placebo
Primary Outcomes
Measure: Incidence of adverse events (AEs) by CTCAE v5.0 Time: up to 24 weeksMeasure: Proportion of subjects with SAEs Time: up to 24 weeks
Measure: Proportion of subjects with infusion-related reactions Time: up to 24 weeks
Measure: Proportion of subjects with hypersensitivity reactions Time: up to 24 weeks
Secondary Outcomes
Measure: Serum Concentration of BRII-196 Time: up to 24 weeks323 A Phase 1 Randomized, Single-blind, Placebo-controlled, Single Ascending Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Human Monoclonal Antibody, BRII-198 Administered Intravenously to Healthy Adult Volunteers
This is a phase 1 study in which healthy adult volunteers will receive BRII-198 or placebo and will be assessed for safety, tolerability, and pharmacokinetics.
NCT04479644 COVID-19 Drug: BRII-198 Drug: Placebo
Primary Outcomes
Measure: Incidence of adverse events (AEs) by CTCAE v5.0 Time: up to 24 weeksMeasure: Proportion of subjects with SAEs Time: up to 24 weeks
Measure: Proportion of subjects with infusion-related reactions Time: up to 24 weeks
Measure: Proportion of subjects with hypersensitivity reactions Time: up to 24 weeks
Secondary Outcomes
Measure: Serum Concentration of BRII-198 Time: up to 24 weeks324 A Phase 1/2 Randomised, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Immunogenicity of ARCT-021 in Healthy Adult Subjects
Determine safety and tolerability and immungenicity of investigational vaccine ARCT-021 in healthy adult volunteers.
NCT04480957 SARS-CoV-2 Biological: ARCT-021 Dose 1 Biological: ARCT-021 Dose 2 Biological: ARCT-021 Dose 3 Biological: ARCT-021 Dose Regimen 1 Biological: ARCT-021 Dose Regimen 2 Other: Placebo
Primary Outcomes
Description: Safety and tolerability of ARCT-021 assessed by determining the incidence, severity and dose-relationship of AEs by dose
Measure: Incidence, severity and dose-relationship of AEs Time: 56 daysSecondary Outcomes
Description: SARS-CoV-2-specific serum neutralizing antibody levels, expressed as GMT
Measure: Geometric mean titre for SARS-CoV-2-specific serum neutralizing antibody Time: Up to 56 daysDescription: SARS-CoV-2-specific serum neutralizing antibody levels, expressed as mean titer
Measure: Mean titre for SARS-CoV-2-specific serum neutralizing antibody levels Time: Up to 56 daysDescription: GMFR in titre for SARS-CoV-2-spike protein specific neutralizing antibodies from before vaccination to each subsequent time point
Measure: Geometric mean fold rise in titre for SARS-CoV-2-spike protein specific neutralizing antibody levels Time: Up to 56 daysOther Outcomes
Description: GMFR in SARS-CoV-2--spike protein-specific binding antibody levels from before vaccination to each subsequent time point
Measure: Increase in SARS-CoV-2--spike protein-specific binding antibody levels Time: Up to 56 daysDescription: GMT for SARS-CoV-2--spike protein-specific binding antibody levels
Measure: Geometric mean SARS-CoV-2--spike protein-specific binding antibody titre Time: Up to 56 daysDescription: Mean titer for SARS-CoV-2--spike protein-specific binding antibody levels
Measure: Mean SARS-CoV-2--spike protein-specific binding antibody titre Time: Up to 56 daysDescription: Proportion of participants that are seronegative before vaccination achieving a titer of greater than or equal to 20 for SARS-CoV-2-specific serum neutralizing antibodies
Measure: SARS-CoV-2-specific serum neutralizing antibody seroconversion rate Time: 56 daysDescription: Proportion of participants that are seropositive before vaccination achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific serum neutralizing antibody levels
Measure: SARS-CoV-2-specific serum neutralizing antibody seroconversion rate (seropositive baseline) Time: 56 days325 A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19
COVID-19 morbidity and mortality has been associated with Cytokine Release Syndrome (CRS) and Acute Respiratory Distress Syndrome (ARDS). ATI-450 is an oral small molecule MAPKAPK2 (MK2) inhibitor that potently inhibits multiple inflammatory cytokines. The investigator hypothesizes that MK2 pathway blockade during active COVID-19 infection in hospitalized participants will result in improvement in respiratory-failure free survival.
NCT04481685 Covid19 Drug: ATI-450 Drug: Placebo
Primary Outcomes
Description: Participants medical record
Measure: Respiratory failure-free survival in participants with moderate-severe COVID-19 who are treated with ATI-450 Time: Study day 14Secondary Outcomes
Description: Using World Health Organization (WHO) COVID-19 Ordinal scale measuring: Proportion and time to participants with greater than 2 point improvement on the 7 point categorical scale. This scale measures illness severity over time and has a range of 0-7. 0- Uninfected: No clinical or virological evidence of infection. 1- Ambulatory: No limitation of activities. 2- Ambulatory: Limitation of activities. 3- Hospitalized, mild disease: Hospitalized, no oxygen. 4- Hospitalized, mild disease: Oxygen by mask or nasal prongs. 5- Hospitalized, severe disease: Non- invasive ventilation or high- flow oxygen. 6- Hospitalized, severe disease: Intubation and mechanical ventilation. 7- Hospitalized, severe disease: Ventilation + organ support; pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO).
Measure: Change in 7 point-ordinal scale Time: Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 monthsDescription: Peripheral capillary pulse oximeter to measure: Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) ratio over time, sustainment of normalization in 24 hours, and relative shifts in SpO2/FiO2 categories (<235, between 235 and 315, greater than 315) over time
Measure: Change in oxygen saturation-normalization Time: Baseline and continuous throughout hospitalization up to 14 daysDescription: Derived from medical record
Measure: Need for advanced respiratory care Time: Baseline and continuous throughout hospitalization up to 14 daysDescription: Noted in participant medical record
Measure: All-cause mortality Time: Baseline and through day 60Description: CTCAE v5.0
Measure: Percentage of adverse events (AEs) Time: Baseline through day 14 or at dischargeDescription: CTCAE v5.0
Measure: Percentage of serious adverse events (SAEs) Time: Baseline through day 14 or at dischargeDescription: Standard daily temperature measurement and obtained from participant medical record
Measure: Proportion of participants with normalization of fever for 24 hours Time: Baseline through day 14 or at dischargeDescription: Noted in participant medical record
Measure: Number of participants who develop new bacterial infection Time: Continuous throughout hospitalization up to 14 daysDescription: Noted in participant medical record
Measure: Number of participants who develop new fungal infection Time: Continuous throughout hospitalization up to 14 daysDescription: Noted in participant medical record
Measure: Incidence of Adult Respiratory distress Syndrome (ARDS2) Time: From day 1 though day 14 or at dischargeDescription: Serum collected from blood and assayed on Luminex panel performed by University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core
Measure: Change in serum cytokine Interleukin (IL)-6 Time: Baseline, day 3, day 7 (or dischargeDescription: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
Measure: Change in serum cytokine IL-8 Time: Baseline, day 3, day 7 (or dischargeDescription: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
Measure: Change in serum cytokines IL-1β Time: Baseline, day 3, day 7 (or dischargeDescription: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
Measure: Change in serum cytokine Tumor Necrosis Factor (TNF-α) Time: Baseline, day 3, day 7 (or discharge326 A Phase 2 Study of BIO 300 Oral Suspension in Discharged COVID-19 Patients
Randomized, double-blinded, placebo-controlled, two-arm study to evaluate the effectiveness and safety of BIO 300 Oral Suspension (BIO 300) for the mitigation of impaired pulmonary function in 2019 Coronavirus Disease (COVID-19) patients recently discharged from the hospital. Patients will be randomized 1:1 to receive BIO 300 or placebo. All patients will receive the same background current standard of care.
NCT04482595 Pulmonary Fibrosis Drug: BIO 300 Oral Suspension Drug: Placebo MeSH:Pulmonary Fibrosis
HPO:Pulmonary fibrosis
Primary Outcomes
Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)
Measure: Change in DLCO Time: 12 Weeks
Description: 6 minute walk test (6MWT)
Measure: Change in 6 Minute Walk Test Time: 12 Weeks
Secondary Outcomes
Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)
Measure: Change in DLCO Time: 6 Months and 12 Months
Description: 6 minute walk test (6MWT)
Measure: Change in 6 Minute Walk Test Time: 6 Months and 12 Months
Description: Forced vital capacity (FVC)
Measure: Change in FVC Time: 12 Weeks, 6 Months and 12 Months
Description: Forced expiratory volume in one second (FEV1)
Measure: Change in FEV1 Time: 12 Weeks, 6 Months and 12 Months
Description: Ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)
Measure: Change in FEV1/FVC Ratio Time: 12 Weeks, 6 Months and 12 Months
Description: Oxygen saturation (pulse oximetry) at rest and during the 6 minute walk test (6MWT)
Measure: Change in Pulse Oximetry at Rest and During the 6MWT Time: 12 Weeks, 6 Months and 12 Months
Description: Evidence of pulmonary fibrosis on computerized tomography (CT) scans of the lungs based on a 4-point Likert scale, where 0 is no evidence of fibrosis and 3 is severe fibrosis
Measure: Change in Pulmonary Fibrosis on CT Scan Time: 12 Weeks, 6 Months and 12 Months
Description: Patient reported outcome to measure impact on overall health, daily life, and perceived well-being in patients with impaired pulmonary function. Scores range from 0-100 with higher scores indicating more limitations.
Measure: Change in St. George's Respiratory Questionnaire (SGRQ) Scores Time: 12 Weeks, 6 Months and 12 Months
Description: Monitoring of blood serum levels for alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) (all reported as Units/L)
Measure: Change in Clinical Laboratory Values for Serum Enzymes Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Description: Monitoring of blood serum levels for bilirubin, C-reactive protein (CRP), creatinine, blood urea nitrogen (BUN), cholesterol and triglycerides (all reported as mg/dL)
Measure: Change in Clinical Laboratory Values Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Description: Monitoring of blood serum levels for troponin T, d-dimer and ferritin (all reported as ng/mL)
Measure: Change in Clinical Laboratory Values Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Description: Monitoring of blood serum levels for albumin (g/dL)
Measure: Change in Clinical Laboratory Values for Albumin Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Description: Monitoring of white blood cell, red blood cell and platelet counts
Measure: Change in Complete Blood Counts with Differential Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Description: Mortality at 12 months after initiating treatment
Measure: All-Cause Mortality Time: 12 Months
Description: Incidence of hospitalization after initial discharge and initiating treatment
Measure: Incidence of Re-Hospitalization Time: 12 Months
Description: Evaluate the safety of BIO 300 Oral Suspension treatment
Measure: Adverse Events Related to BIO 300 Oral Suspension Time: 12 Months
Other Outcomes
Description: Duration of supplemental oxygen use
Measure: Change in Duration of Supplemental Oxygen Use Time: 12 Weeks, 6 Months and 12 Months
Description: Prescribed supplemental oxygen flow rate at night, rest and exertion
Measure: Change in Supplemental Oxygen Use Time: 12 Weeks, 6 Months and 12 Months
Description: Expression levels of serum-derived cytokines (IL-1b, IL-6, IL-8, TNFa, and TGFb1)
Measure: Change in Serum Cytokine Expression Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
327 Phase I/Phase II Trial of Off-the-Shelf Allogeneic Hybrid TREG/Th2 Cell (RAPA-501-ALLO) Therapy for Severe, Post-Intubation Stage 3 COVID-19 Disease
Primary Outcomes
Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)
Measure: Change in DLCO Time: 12 WeeksDescription: 6 minute walk test (6MWT)
Measure: Change in 6 Minute Walk Test Time: 12 WeeksSecondary Outcomes
Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)
Measure: Change in DLCO Time: 6 Months and 12 MonthsDescription: 6 minute walk test (6MWT)
Measure: Change in 6 Minute Walk Test Time: 6 Months and 12 MonthsDescription: Forced vital capacity (FVC)
Measure: Change in FVC Time: 12 Weeks, 6 Months and 12 MonthsDescription: Forced expiratory volume in one second (FEV1)
Measure: Change in FEV1 Time: 12 Weeks, 6 Months and 12 MonthsDescription: Ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)
Measure: Change in FEV1/FVC Ratio Time: 12 Weeks, 6 Months and 12 MonthsDescription: Oxygen saturation (pulse oximetry) at rest and during the 6 minute walk test (6MWT)
Measure: Change in Pulse Oximetry at Rest and During the 6MWT Time: 12 Weeks, 6 Months and 12 MonthsDescription: Evidence of pulmonary fibrosis on computerized tomography (CT) scans of the lungs based on a 4-point Likert scale, where 0 is no evidence of fibrosis and 3 is severe fibrosis
Measure: Change in Pulmonary Fibrosis on CT Scan Time: 12 Weeks, 6 Months and 12 MonthsDescription: Patient reported outcome to measure impact on overall health, daily life, and perceived well-being in patients with impaired pulmonary function. Scores range from 0-100 with higher scores indicating more limitations.
Measure: Change in St. George's Respiratory Questionnaire (SGRQ) Scores Time: 12 Weeks, 6 Months and 12 MonthsDescription: Monitoring of blood serum levels for alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) (all reported as Units/L)
Measure: Change in Clinical Laboratory Values for Serum Enzymes Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 MonthsDescription: Monitoring of blood serum levels for bilirubin, C-reactive protein (CRP), creatinine, blood urea nitrogen (BUN), cholesterol and triglycerides (all reported as mg/dL)
Measure: Change in Clinical Laboratory Values Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 MonthsDescription: Monitoring of blood serum levels for troponin T, d-dimer and ferritin (all reported as ng/mL)
Measure: Change in Clinical Laboratory Values Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 MonthsDescription: Monitoring of blood serum levels for albumin (g/dL)
Measure: Change in Clinical Laboratory Values for Albumin Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 MonthsDescription: Monitoring of white blood cell, red blood cell and platelet counts
Measure: Change in Complete Blood Counts with Differential Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 MonthsDescription: Mortality at 12 months after initiating treatment
Measure: All-Cause Mortality Time: 12 MonthsDescription: Incidence of hospitalization after initial discharge and initiating treatment
Measure: Incidence of Re-Hospitalization Time: 12 MonthsDescription: Evaluate the safety of BIO 300 Oral Suspension treatment
Measure: Adverse Events Related to BIO 300 Oral Suspension Time: 12 MonthsOther Outcomes
Description: Duration of supplemental oxygen use
Measure: Change in Duration of Supplemental Oxygen Use Time: 12 Weeks, 6 Months and 12 MonthsDescription: Prescribed supplemental oxygen flow rate at night, rest and exertion
Measure: Change in Supplemental Oxygen Use Time: 12 Weeks, 6 Months and 12 MonthsDescription: Expression levels of serum-derived cytokines (IL-1b, IL-6, IL-8, TNFa, and TGFb1)
Measure: Change in Serum Cytokine Expression Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 MonthsThe first-in-human Phase I study component will evaluate two dose levels of RAPA-501-ALLO off the shelf cells in patients with post-intubation, stage 3 COVID-19 disease, with key endpoints of safety, biologic and potential disease-modifying effects. The randomized, double-blind, placebo-controlled Phase 2 study component will evaluate infusion of RAPA-501 ALLO off the shelf cells or a control infusion, with the primary endpoint assessing whether RAPA-501 cells reduce 30-day mortality. The COVID-19 pandemic is a disaster playing out with progressive morbidity and mortality. As of July 19, 2020, an estimated 14.5 million people have contracted the virus and 605,000 deaths have resulted globally. The United States has the highest totals with an estimated 3.8 million people diagnosed and 141,000 deaths. In stages 1 and 2 of COVID-19, viral propagation within the patient is predominant. As such, therapeutic interventions focus on immune molecules (convalescent serum, monoclonal antibodies) and anti-viral medications (remdesivir). In marked contrast, the most severe and deadly form of COVID-19, stage 3, is driven not by viral propagation, but by an out-of-control immune response (hyperinflammation) caused by increases in immune molecules known as cytokines and chemokines. As such, therapeutic interventions for stage 3 disease focus on anti-inflammatory medications such as anti-cytokine therapy (anti-IL-6 drugs) or corticosteroid therapy. Unfortunately, such interventions do not address the full pathogenesis of stage 3 COVID-19, which includes hyperinflammation due to "cytokine storm" and "chemokine storm," tissue damage, hypercoagulation, and multi-organ failure (including lung, heart, kidney and brain). The pulmonary component of stage 3 disease includes acute respiratory distress syndrome (ARDS), which is a final-common-pathway of patient death due to a myriad of conditions, including pneumonia, sepsis, and trauma. There is a dire need for novel cellular treatments that can deliver both a broad-based immune modulation effect and a tissue regenerative effect. Therefore, off-the-shelf allogeneic hybrid TREG/Th2 Cells (RAPA-501-ALLO) will be evaluated. Stage 3 COVID-19 carries an estimated 30-day mortality of over 50% in spite of ICU utilization, mechanical ventilation, and supportive care therapies to manage ARDS and multiorgan failure. Narrowly acting targeted anti-inflammatory approaches such as anti-IL-6 therapeutics have not been particularly effective in stage 3 COVID-19 and the broad anti-inflammatory pharmaceutical approach of corticosteroid therapy, has only modestly tempered stage 3 disease in some studies. Cell therapy is also being evaluated in stage 3 COVID-19, in particular, mesenchymal stromal cells (MSC) and now, with the current RAPA-501-ALLO protocol, regulatory T (TREG) cells. TREG therapy has a mechanism of action that includes a multi-faceted anti-inflammatory effect, which puts TREG therapy at the forefront of future curative therapy of a wide range of autoimmune and neurodegenerative diseases, plus transplant complications, such as graft-versus-host disease (GVHD) and graft rejection. In addition, TREG therapy can provide a tissue regenerative effect, which places TREG cell therapy at the lead of novel regenerative medicine efforts to repair a myriad of tissue-based diseases, such as diseases of the skin, muscle, lung, liver, intestine, heart (myocardial infarction) and brain (stroke). RAPA-501-ALLO off-the-shelf cell therapy offers the hope of providing this dual threat mechanism of action that incorporates both anti-inflammatory and tissue repair effects for effective treatment of COVID-19 and multiple lethal conditions. RAPA-501-ALLO cells are generated from healthy volunteers, cryopreserved, banked, and are then available for off-the-shelf therapy anytime. During manufacturing, T cells are "reprogrammed" ex vivo using a novel, patented 6-day two-step process that involves T cell de-differentiation and subsequent re-differentiation towards the two key anti-inflammatory programs, the TREG and Th2 pathways, thus creating a "hybrid" product. The hybrid phenotype inhibits inflammatory pathways operational in COVID-19, including modulation of multiple cytokines and chemokines, which attract inflammatory cells into tissue for initiation of multi-organ damage. The hybrid TREG and Th2 phenotype of RAPA-501-ALLO cells cross-regulates Th1 and Th17 populations that initiate hyperinflammation of COVID-19. RAPA-501 immune modulation occurs in a T cell receptor independent manner, thus permitting off-the-shelf cell therapy. Finally, in experimental models of viral pneumonia and ARDS, TREG cells mediate a protective effect on the lung alveolar tissue. Because of this unique mechanism of action that involves both anti-inflammatory and tissue protective effects, the allogeneic RAPA-501 T cell product is particularly suited for evaluation in the setting of post-intubation, Stage 3 COVID-19.
NCT04482699 Severe COVID-19 Disease Biological: RAPA-501-Allo off-the-shelf Therapy of COVID-19 Other: Placebo
Primary Outcomes
Description: On the phase 1 study component, determine the safety of allogeneic RAPA-501 cells when administered at dose level 1 (Cohort 1, 40 x 106 cells) and dose level 2 (Cohort 2, 160 x 106 cells).
Measure: Dose-Limiting Toxicity (DLT) Time: 30 days after the first infusion of allogeneic RAPA-501 cells.Description: On the phase II study component, determine whether allogeneic RAPA-501 cells result in a mortality rate that is reduced relative to the randomized placebo-control cohort.
Measure: Mortality Rate Time: 30 days after the first infusion of allogeneic RAPA-501 cells.Secondary Outcomes
Description: Number of days requiring ventilation support.
Measure: Ventilation Support Time: 90 days after the infusion of allogeneic RAPA-501 cells.Description: Number of days of hospitalization among survivors.
Measure: Days of Hospitalization Time: 90 days after the infusion of allogeneic RAPA-501 cells.Description: Number of deaths due to any cause.
Measure: Number of Deaths Time: 90 days after the infusion of allogeneic RAPA-501 cells.Description: Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection.
Measure: Incidence of Infection Time: 90 days after the infusion of allogeneic RAPA-501 cells.Description: GVHD incidence and severity.
Measure: GVHD Incidence Time: 90 days after the infusion of allogeneic RAPA-501 cells.Other Outcomes
Description: COVID-19 viral load, as determined by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent test on nasopharyngeal and/or endotracheal tube swab samples.
Measure: Viral Load Time: Six months after treatment initiation.Description: Development of potentially protective host immunity to COVID-19, as determined by serologic studies.
Measure: Host Immunity Time: Six months after treatment initiation.Description: Peripheral blood immune counts, including CD4+ and CD8+ T cells, NK cells, and B cells.
Measure: Peripheral Blood Immune Counts Time: Six months after treatment initiation.Description: T cell expression of co-stimulation molecules (including CD28) and checkpoint receptor molecules (including PD-1).
Measure: T Cell Expression Time: Six months after treatment initiation.Description: Peripheral blood micro-chimerism, as determined by PCR amplification of donor and host STR loci.
Measure: Peripheral Blood Micro-chimerism Time: Six months after treatment initiation.328 Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)
This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.
NCT04482712 Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Respiratory Failure Sars-CoV2 Drug: Rapamycin Drug: Placebo MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury Syndrome
Primary Outcomes
Description: The proportion of participants who survive without respiratory failure
Measure: Survival rate Time: 4 weeksSecondary Outcomes
Description: The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8
Measure: Change in Clinical Status assessed by the World Health Organization (WHO) scale Time: Baseline to 4 weeksDescription: An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8)
Measure: Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale Time: Baseline to 4 weeksOther Outcomes
Description: Total number of deaths during the study period
Measure: All cause mortality Time: 4 weeksDescription: Number of days on ECMO
Measure: Duration of ECMO Time: Up to 4 weeksDescription: Number of days participants are on supplemental oxygen
Measure: Duration of supplemental oxygen Time: Up to 4 weeksDescription: Days of hospitalization
Measure: Length of hospital stay Time: Up to 4 weeksDescription: Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)
Measure: Length of time to SARS-CoV2 negativity Time: Up to 4 weeks329 A Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose, Phase I Study to Evaluate the Tolerability, Safety, Pharmacokinetics of SCTA01 in Healthy Subjects
The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics of SCTA01(anti-SARS-CoV-2 monoclonal antibody) in Healthy Chinese Subjects.
NCT04483375 Coronavirus Disease 2019(COVID-19) Biological: SCTA01 Other: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Description: DLT will be assessed by DAIDS v2.1. The measurements include clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs
Measure: Dose-limiting toxicity(DLT) Time: 7 daysDescription: MTD will be assessed by DAIDS v2.1. The measurements include clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs.
Measure: Maximal Tolerable Dose(MTD) Time: 12 weeksSecondary Outcomes
Description: Area under the curve from the time of dosing to the last measurable concentration time t (AUC0-t)
Measure: AUC0-t Time: 12 weeksDescription: Area Under the Concentration Time Curve (AUC) From Time Zero to Infinity (AUC 0-∞)
Measure: AUC0-∞ Time: 12 weeksDescription: Elimination Phase Half-life(t1/2)
Measure: t1/2 Time: 12 weeksDescription: Time to the Maximum Concentration(Tmax)
Measure: Tmax Time: 12 weeksDescription: Positive rate of anti-SCT A01 antibody
Measure: Anti-drug antibody(ADA) Time: 12 weeksDescription: Adverse events as assessed by DAIDS v2.1, including clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs
Measure: Adverse events Time: 12 weeks330 PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams (PROTECT)
In this 16-week randomized control study, health care workers will receive a bolus dose followed by a weekly dose of vitamin D or a placebo bolus and weekly dose. This study will test whether high-dose of vitamin D supplementation decreases the incidence of laboratory-confirmed COVID19 infection (primary outcome), reduces illness severity, duration, as well as work absenteeism among health care workers (HCW) in setting at high-risk of contact with COVID-19 cases in high COVID-19 incidence areas.
NCT04483635 COVID-19 Dietary Supplement: Placebo Dietary Supplement: Vitamin D
Primary Outcomes
Description: self-obtained mid-turbinate nasopharyngeal (NP) swabs analysed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test (NAAT), following standard operating procedures certified by the Quebec Public Health Laboratory of the National Public Health Institute (complemented by NP swabs obtained clinically for screening or diagnostic purposes analyzed using the same technique.
Measure: Change in incidence of laboratory-confirmed COVID-19 infection Time: up to 16 weeksSecondary Outcomes
Description: 5-category ordinal variable [asymptomatic, mild (managed at home); moderate (hospitalisation without supplemental oxygen; severe (oxygen supplementation); critical (mechanical ventilation/death)
Measure: Distribution of disease severity Time: up to 16 weeksDescription: Duration of COVID+ test: that is, between first COVID+ test to first COVID- test
Measure: Duration of COVID-19 positivity Time: up to 16 weeksDescription: SARS-CoV-2 IgG Diasorin on Liaison XL platform
Measure: Number of participants with COVID-19 positive IgG serology Time: up to 16 weeksDescription: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases
Measure: Number of workday absences due to COVID-19 suspected/confirmed infection Time: up to 16 weeksDescription: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases
Measure: Number of workday absences for any reason Time: up to 16 weeksDescription: Number and distribution of adverse health events
Measure: Changes in adverse health events Time: up to 16 weeks331 Sulodexide in the Treatment of Early Stages of COVID-19
Problem: The COVID- 19 pandemic has not only affected our healthcare system, but the impact on the worldwide financial systems and our "normal" way of life is still to be determined. Although the percentage of patients infected with COVID-19 that need hospital care is low, Its high rate of contagiousness makes the total number of patients in need of hospital care cripple any healthcare system, limiting the space available for other patients in need of critical care, who cannot be admitted or even prefer not to attend the hospital in fear of infection. Early investigations report an Increase risk of thromboembolic complications, and a systemic inflammatory response not clearly understood. There is a possible vascular endothelial dysfunction due to chronic comorbidities (Hypertension, diabetes, obesity, chronic kidney disease, lung disease) as a risk factor for a more severe presentation. Justification: Sulodexide is a two-compound drug, each of them with different endothelial action that can be beneficial in COVID-19 patients. Glycosaminoglycans: Can help restore venous and arterial endothelial glycocalyx which can downregulate or limit the response to inflammatory molecules, by maintaining the integrity lost in certain chronic diseases (high blood pressure, diabetes). Heparin compound: It has an antithrombotic effect that could help reduce the incidence of thromboembolic complications, and also add to the anti-inflammatory response due to it anti-thrombin action (similar or a bit less to that of low molecular weight heparin) with less risk of major bleeding. It's a medication that can be used orally with minimal adverse effects and is less expensive than low molecular weight heparin. Hypothesis: We hypothesize that sulodexide instituted early in populations at significant risk and symptomatic patients affected with COVID-19 (shortness of breath, fever, weakness, diarrhoea) and risk factors of diabetes, hypertension, COPD, atherosclerosis, chronic kidney disease, will provide improvement in endothelial integrity, decrease inflammatory responses, and improved clinical outcomes with decreased hospital admission, decrease VTE and arterial complications, morbidity, and mortality. Objective: To use sulodexide in patients that have early onset of COVID-19 symptoms to mitigate the progression of the disease process that can allow them to recover at home, and limit the need of hospital care and a more severe clinical manifestation
NCT04483830 Covid19 Drug: Sulodexide Drug: Placebo
Primary Outcomes
Description: need for hospital care admission
Measure: hospital care Time: 21 days since start of trial participationDescription: number of total days in hospital care
Measure: days of hospital care Time: 21 days since start of trial participationDescription: total days in need of supplemental oxigen via facial mask or nasal
Measure: days of need suplemental oxigen Time: 21 days since the start of trial participationDescription: total value in ng/dl of d-dimmer
Measure: serum level of d-dimmer Time: change betwen basal level and at 14 day follow-upDescription: total value in mg/dl
Measure: serum level of creatinine Time: change between basal level ans at 14 day followupSecondary Outcomes
Description: presence of a tromboembolic event
Measure: thromboembolic event Time: 21 days from start of trialDescription: the need for the use of endotraqueal tube mechanical ventilation
Measure: need for mechanical ventilation Time: 21 days from the start of the trial332 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Severe COVID-19 Patients
The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel SARS-CoV-2 (nCoV2) and severe symptoms of COVID-19 disease.
NCT04483973 Covid19 Coronavirus Coronavirus Infection Corona Virus Infection Drug: Ebselen Drug: Placebo MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respirator Severe Acute Respiratory Syndrome
Primary Outcomes
Measure: Number of participants with treatment-related adverse events Time: 30 daysSecondary Outcomes
Description: Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement
Measure: WHO Ordinal Scale Time: 30 daysDescription: Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)
Measure: Degree of supplemental oxygen Time: 30 daysDescription: Peripheral oxygen saturation measured by pulse oximetry
Measure: Peripheral Oxygen Saturation (SpO2) Time: 30 days333 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Moderate COVID-19 Patients
The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel SARS-CoV-2 (nCoV2) and moderate symptoms of COVID-19 disease.
NCT04484025 Covid19 Corona Virus Infection Coronavirus Coronavirus Infection Drug: Ebselen Drug: Placebo MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Measure: Number of participants with treatment-related adverse events Time: 30 daysSecondary Outcomes
Description: Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement
Measure: WHO Ordinal Scale Time: 30 daysDescription: Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)
Measure: Degree of supplemental oxygen Time: 30 daysDescription: Peripheral oxygen saturation measured by pulse oximetry
Measure: Peripheral Oxygen Saturation (SpO2) Time: 30 days334 Virologic and Immunologic Response to Disulfiram in Early Symptomatic COVID+ Outpatients
Disulfiram a safe, easily dosed, FDA-approved drug for the treatment of alcohol dependence has been identified to be a potential therapeutic target for SARS-CoV-2 infection. Disulfiram may have both antiviral (inhibiting viral replication via blocking the Mpro protease and zinc ejection) and anti-inflammatory effects (via inhibition of NF-kB-induced and NLRP inflammasome-induced cytokine release) on SARS-CoV-2. We will test disulfiram 2000 mg/day for 3 consecutive days (doses shown to be well tolerated and safe in a recent phase 2b trial) in 60 symptomatic COVID PCR+ individuals in a randomized (1:1) clinical trial evaluating the effect on COVID symptoms severity, SARS-CoV-2 viral load, and biomarkers of inflammation over 31 days.
NCT04485130 Covid19 Drug: Disulfiram Drug: Placebo
Primary Outcomes
Description: The safety and tolerability of a 3 day course of disulfiram. The number of adverse events and their grade will be determined for each participant.
Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Time: 31 daysDescription: The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant.
Measure: Change in COVID-19 symptom severity score as assessed by a 5-point adapted somatic symptom severity score (SSS-8) Time: 31 daysSecondary Outcomes
Description: Quantitative SARS-CoV-2 viral load measures will be determined at each visit for each participant.
Measure: Virologic impact of 3 days of disulfiram, as measured by the fold-change in copies of SARS-CoV-2 virus per million cells between Baseline and Day 31. Time: 31 daysDescription: High sensitivity plasma cytokine measures for interleukin 6, interleukin 1-beta, and other pro-inflammatory cytokines will be determined at each visit for each participant.
Measure: Immunologic impact of 3 days of disulfiram, as measured by the fold-change in plasma levels of pro-inflammatory cytokines (e.g, interleukin 6, interleukin 1-beta, etc.). Time: 31 days335 A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Assess the Safety and Efficacy of IGV-001, an Autologous Cell Immunotherapy With Antisense Oligonucleotide (IMV-001) Targeting IGF-1R, in Newly Diagnosed Patients With Glioblastoma Multiforme - the ImmuneSense Study
The purpose of this study is to assess progression-free survival (PFS) in newly diagnosed Glioblastoma Multiforme (GBM) participants treated with IGV-001 as compared with placebo.
NCT04485949 Glioblastoma Multiforme Glioblastoma Biological: IGV-001 Cell Immunotherapy Biological: Placebo Procedure: Standard of Care (SOC): Radiation Therapy Drug: SOC: Temozolomide MeSH:Glioblastoma
HPO:Glioblastoma multiforme
Primary Outcomes
Description: PFS is defined as the time from randomization to event or censoring.
Measure: Progression-free Survival (PFS) Time: Up to 36 months
Secondary Outcomes
Description: OS is defined as the time from randomization to death due to any cause.
Measure: Overall Survival (OS) Time: Up to 48 months
Description: PFS is defined as the time from randomization to event or censoring. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.
Measure: PFS in Participants With O6-methylguanine-DNA Methyltransferase (MGMT) With Methylation [MGMT+] and MGMT Without Methylation [MGMT-] Time: Up to 36 months
Description: OS is defined as the time from randomization to death due to any cause. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.
Measure: OS in Participants With MGMT+ and MGMT- Time: Up to 48 months
Description: EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
Measure: Change From Baseline in Participant-reported Quality of Life (QoL) Questionnaires Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Lif questionnaire (QLQ) -C30 Scores Time: Baseline, Month 36
Description: The QLQ-BN20 is a questionnaire specifically designed as the QLQ-C30 supplement for the evaluation of quality of life in brain tumor participants. It includes 4 multi-item sub-scales: future uncertainty, visual disorder, motor dysfunction, communication deficits, and 7 single-item scales: headaches, seizures, drowsiness, itchy skin, hair loss, weakness of legs, and bladder control. All items are rated on a 4-point Likert-type scale ('1=not at all', '2=a little', '3=quite a bit' and '4=very much'), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
Measure: Change From Baseline in Participant-reported QoL Questionnaires Based on EORTC QLQ Brain Module (EORTC QLQ-BN20) Scores Time: Baseline, Month 36
Description: The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance.
Measure: Change From Baseline in Mini-Mental Status Examination (MMSE) Scores Time: Baseline, Month 36
Description: Time to KPS deterioration was defined as the time from screening to the first date of deterioration of the KPS score. Deterioration of KPS is defined as a stable or increasing steroid dose-dependent stabilization of a KPS score of <70 over 2 consecutive visits no more than 2 months apart. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
Measure: Time to Definitive Deterioration Karnofsky Performance Status (KPS) Score Time: Baseline until KPS deterioration (up to 36 months)
Description: An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 from mild (Grade 1) to death (Grade 5). SAE is an AE or adverse reaction which is considered serious if it results in any of the following outcomes: death, life-threatening AE, require hospitalizations or prolongation of hospitalizations, results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect and is a medically important event.
Measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Time: Up to 12 months or until the last progression visit, whichever comes first
Measure: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities Time: Up to 12 months or until the last progression visit, whichever comes first
Measure: Number of Participants With Clinically Significant Vital Signs Measurements Time: Up to 12 months or until the last progression visit, whichever comes first
Measure: Number of Participants With Clinically Significant Physical Examination Findings Time: Up to 12 months or until the last progression visit, whichever comes first
336 Phase 3, Randomized, Double-Blind, Placebo-Controlled, Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19
Primary Outcomes
Description: PFS is defined as the time from randomization to event or censoring.
Measure: Progression-free Survival (PFS) Time: Up to 36 monthsSecondary Outcomes
Description: OS is defined as the time from randomization to death due to any cause.
Measure: Overall Survival (OS) Time: Up to 48 monthsDescription: PFS is defined as the time from randomization to event or censoring. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.
Measure: PFS in Participants With O6-methylguanine-DNA Methyltransferase (MGMT) With Methylation [MGMT+] and MGMT Without Methylation [MGMT-] Time: Up to 36 monthsDescription: OS is defined as the time from randomization to death due to any cause. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.
Measure: OS in Participants With MGMT+ and MGMT- Time: Up to 48 monthsDescription: EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
Measure: Change From Baseline in Participant-reported Quality of Life (QoL) Questionnaires Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Lif questionnaire (QLQ) -C30 Scores Time: Baseline, Month 36Description: The QLQ-BN20 is a questionnaire specifically designed as the QLQ-C30 supplement for the evaluation of quality of life in brain tumor participants. It includes 4 multi-item sub-scales: future uncertainty, visual disorder, motor dysfunction, communication deficits, and 7 single-item scales: headaches, seizures, drowsiness, itchy skin, hair loss, weakness of legs, and bladder control. All items are rated on a 4-point Likert-type scale ('1=not at all', '2=a little', '3=quite a bit' and '4=very much'), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
Measure: Change From Baseline in Participant-reported QoL Questionnaires Based on EORTC QLQ Brain Module (EORTC QLQ-BN20) Scores Time: Baseline, Month 36Description: The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance.
Measure: Change From Baseline in Mini-Mental Status Examination (MMSE) Scores Time: Baseline, Month 36Description: Time to KPS deterioration was defined as the time from screening to the first date of deterioration of the KPS score. Deterioration of KPS is defined as a stable or increasing steroid dose-dependent stabilization of a KPS score of <70 over 2 consecutive visits no more than 2 months apart. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
Measure: Time to Definitive Deterioration Karnofsky Performance Status (KPS) Score Time: Baseline until KPS deterioration (up to 36 months)Description: An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 from mild (Grade 1) to death (Grade 5). SAE is an AE or adverse reaction which is considered serious if it results in any of the following outcomes: death, life-threatening AE, require hospitalizations or prolongation of hospitalizations, results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect and is a medically important event.
Measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Time: Up to 12 months or until the last progression visit, whichever comes firstMeasure: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities Time: Up to 12 months or until the last progression visit, whichever comes first
Measure: Number of Participants With Clinically Significant Vital Signs Measurements Time: Up to 12 months or until the last progression visit, whichever comes first
Measure: Number of Participants With Clinically Significant Physical Examination Findings Time: Up to 12 months or until the last progression visit, whichever comes first
Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19
NCT04486313 COVID-19 Drug: Nitazoxanide Drug: Placebo Dietary Supplement: Vitamin Super B-Complex
Primary Outcomes
Description: To evaluate the effect of nitazoxanide in reducing the time to sustained response compared to placebo in subjects with mild or moderate COVID-19
Measure: Reducing the Time to Sustained Response Time: Up to 21 daysSecondary Outcomes
Description: To evaluate the effect of nitazoxanide in reducing the rate of progression to severe COVID-19 illness compared to placebo
Measure: Reducing the Rate of Progression Time: Up to 21 days337 A Multicenter, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of XC221, Tablets, 100 mg in Patients With COVID-19
The innovative drug XC221 100 mg tablet is designed for the treatment of COVID-19 (SARS-CoV-2 infection). A multicenter, adaptive, randomized, double-blind, placebo-controlled Phase III clinical study is aimed to assess the efficacy and safety of XC221 100 mg tablet, in COVID-19 patients during a 14-day treatment. The primary objective of the study is to demonstrate the efficacy of XC221 100 mg tablet (200 mg daily dose) in achieving clinical improvement of COVID-19 symptoms. The secondary objective of the study is to evaluate the safety of XC221 100 mg tablet (200 mg daily dose) in COVID-19 patients.
NCT04487574 SARS-CoV-2 Infection Drug: XC221 Drug: Placebo
Primary Outcomes
Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
Measure: Patient rate with a transition to category 3 or lower according to the WHO scale by Day 14 after the beginning of drug administration. Time: Day 1 - Day 14Secondary Outcomes
Description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; RR ≤ 22 / min without oxygen therapy; SpO2 ≥ 95% without oxygen therapy.
Measure: Time till clinical improvement, which is described by presence of all of the following factors during 48 hours in a row. Time: Day 1 - Day 28Description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; RR ≤ 22 / min without oxygen therapy; SpO2 ≥ 95% without oxygen therapy.
Measure: Patient rate with clinical improvement by day 2-28. Presence of all of the following factors during 48 hours in a row. Time: Day 1 - Day 28Measure: Patient rate with a negative test result for SARS-CoV-2 by Day 7±1, 15±1, 21 ±1 and 28 ± 1. Time: Day 1 - Day 28
Measure: Duration of hospitalization. Time: Day 1 - Day 28
Measure: Patient rate transferred to the intensive care unit (ICU) during hospitalization. Time: Day 1 - Day 28
Measure: Duration of ICU stay. Time: Day 1 - Day 28
Measure: Patient rate with ARDS during hospitalization. Time: Day 1 - Day 28
Measure: Presence of a fatal outcome. Time: Day 1 - Day 28
Measure: Patient rate requiring oxygen therapy by Day 2-28. Time: Day 1 - Day 28
Measure: Patient rate requiring high-flow oxygen therapy by Day 2-28. Time: Day 1 - Day 28
Measure: Patient rate requiring non-invasive ventilation by Day 2-28. Time: Day 1 - Day 28
Measure: Patient rate requiring invasive ventilation by Day 2-28. Time: Day 1 - Day 28
Measure: Patient rate requiring extracorporeal membrane oxygenation (EMO) by Day 2-28. Time: Day 1 - Day 28
Measure: The total duration of oxygen therapy by the last day of hospitalization. Time: Day 1 - Day 28
Measure: The total duration of high-flow oxygen therapy by the last day of hospitalization. Time: Day 1 - Day 28
Measure: The total duration of non-invasive ventilation by the last day of hospitalization. Time: Day 1 - Day 28
Measure: The total duration of invasive ventilation of lungs by the last day of hospitalization. Time: Day 1 - Day 28
Measure: The total duration of EMO by the last day of hospitalization. Time: Day 1 - Day 28
Measure: Patient rate with Sp02 > 95% by Day 2-28. Time: Day 1 - Day 28
Measure: Average alteration of Sp02 by Day 2-28 from baseline. Time: Day 1 - Day 28
Measure: Average time to reach SpO2 ≥ 95%. Time: Day 1 - Day 28
Measure: Patient rate with RR < 22 / min by Day 2-28. Time: Day 1 - Day 28
Measure: Average alteration in RR by Day 2-28 from baseline. Time: Day 1 - Day 28
Measure: Average time to reach RR ≤ 22 / min. Time: Day 1 - Day 28
Measure: Patient rate with body temperature < 37.5°C by Day 2-28. Time: Day 1 - Day 28
Measure: Average alteration in body temperature by Day 2-28 from baseline. Time: Day 1 - Day 28
Measure: Average time until the patient reaches a body temperature of ≤37.5°C. Time: Day 1 - Day 28
Measure: Patient rate with CT-1 according to CT data by Day 2-28. Time: Day 1 - Day 28
Measure: Average alteration in CT data by 1 point in terms of severity (CT-1, CT-2, CT-3, CT-4) by Day 7, 10, 15, 18, 21 and 28 compared to the baseline value. Time: Day 1 - Day 28
Measure: Average time to reach CT-1 according to CT data. Time: Day 1 - Day 28
Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).
Measure: Patient rate with a score < 2 according to the Daytime and Nighttime Cough Scale by Day 2-28. Time: Day 1 - Day 28Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).
Measure: Mean change in Daytime and Nighttime Cough scores by Day 2-28 from baseline. Time: Day 1 - Day 28Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).
Measure: Average time to reach < 2 points when assessed according to the Daytime and Nighttime Cough Scale. Time: Day 1 - Day 28Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.
Measure: Patient rate with a score < 1 for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28. Time: Day 1 - Day 28Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.
Measure: Average change in score for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28 from baseline. Time: Day 1 - Day 28Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.
Measure: Average time to reach a score of < 1 for each symptom (general fatigue, feeling of congestion in the chest, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale. Time: Day 1 - Day 28Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
Measure: Patient rate with a transition decrease to category 3 or lower according to the WHO scale by Day 2-13 and Day 15-28. Time: Day 1 - Day 28Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
Measure: Mean WHO grade change by Day 2-28 from baseline. Time: Day 1 - Day 28Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).
Measure: Average time to reach the 3rd category or below according to the WHO scale. Time: Day 1 - Day 28Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.
Measure: Patient rate with a NEWS score < 2 by Day 2-28. Time: Day 1 - Day 28Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.
Measure: Average change in NEWS score by Day 2-28 from baseline. Time: Day 1 - Day 28Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.
Measure: Average time to reach a NEWS score ≤ 2. Time: Day 1 - Day 28Other Outcomes
Description: (Search Outcome)
Measure: Concentration of IL-6 on Days 3 ± 1, 7 ± 1, 15 ± 1. Time: Day 1 - Day 15338 Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection
In this study, a total of 80 patients with severe coronavirus disease 2019 (COVID-19) infection will be randomized to receive Duvelisib or a placebo. Participants will be enrolled at Emory University Hospital and at the University of Pennsylvania and will be identified and recruited by their treating physician and research team.
NCT04487886 COVID-19 Drug: Duvelisib Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.
Measure: Number of Participants Requiring Mechanical Ventilation or Dying Time: Up to Day 29
Secondary Outcomes
Description: Time to recovery (in days) is defined as a score of greater than 5 from the following eight categories from the NIAID ordinal scale. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities.
Measure: Days to Recovery Time: Up to Day 29
Description: The number of days spent hospitalized will be compared between study arms.
Measure: Duration of Hospitalization Time: Up to Day 29
Description: The incidence of death within 29 days of randomization will be compared between study arms.
Measure: Incidence of Death Time: Up to Day 29
Description: Comparing the proportion of subjects in each group requiring ICU transfer within 29 days of randomization
Measure: Proportion of Participants Transferred to ICU Time: Up to Day 29
Description: The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active and 5 = dead. Median ECOG performance will be compared between study arms.
Measure: Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score Time: Day 15, Day 29
Description: The incidence of grade III-V adverse events or Serious Adverse Events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, will be compared between study arms.
Measure: Incidence of Grade III-V Adverse Events Time: Up to Day 29
Description: The incidence of documented secondary bacterial or viral infections among participants will be compared between study arms.
Measure: Incidence of Secondary Bacterial or Viral Infections Time: Up to Day 29
Description: The mean frequency of Th1 T cells in blood mononuclear cells will be compared between study arms.
Measure: Change in Th1 T Cell Frequency Time: Weeks 1, 2, and 4
Description: The mean frequency of Th17 T cells in blood mononuclear cells will be compared between study arms.
Measure: Change in Th17 T Cell Frequency Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker IL-2 will be compared between study arms.
Measure: Change in Interleukin-2 (IL-2) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker IL-2R will be compared between study arms.
Measure: Change in Interleukin-2 receptor (IL-2R) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker IL-6 will be compared between study arms.
Measure: Change in Interleukin-6 (IL-6) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker IL-7 will be compared between study arms.
Measure: Change in Interleukin-7 (IL-7) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker IL-8 will be compared between study arms.
Measure: Change in Interleukin-8 (IL-8) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker IL-10 will be compared between study arms.
Measure: Change in Interleukin-10 (IL-10) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker IP-10 will be compared between study arms.
Measure: Change in Interferon gamma-induced Protein 10 (IP-10) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker MIP-1a will be compared between study arms.
Measure: Change in Macrophage Inflammatory Protein 1alpha (MIP-1a) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker MCP-1 will be compared between study arms.
Measure: Change in Monocyte Chemoattractant Protein-1 (MCP-1) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker G-CSF will be compared between study arms.
Measure: Change in Granulocyte Colony-stimulating Factor (G-CSF) Time: Weeks 1, 2, and 4
Description: Mean levels of the inflammatory serum biomarker TNF-alpha will be compared between study arms.
Measure: Change in Tumor Necrosis Factor (TNF)-alpha Time: Weeks 1, 2, and 4
Description: VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.
Measure: Change in Vasoactive Intestinal Peptide (VIP) Time: Weeks 1, 2, and 4
Description: Mean levels of the Tregs will be compared between study arms.
Measure: Change in Gene Expression Profile of Regulatory T Cells (Tregs) Time: Weeks 1, 2, and 4
Description: Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.
Measure: Change in Gene Expression Profile of cluster of differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage colony-stimulating factor (GM-CSF)+ Time: Weeks 1, 2, and 4
Description: Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.
Measure: Change in Gene Expression Profile of CD8+ T cell immunoglobulin and mucin domain-containing protein 3 (Tim3)+ Programmed cell death protein 1 (PD-1)+ Time: Weeks 1, 2, and 4
Description: Mean levels of CD14+CD16+ monocytes will be compared between study arms.
Measure: Change in Gene Expression Profile of cluster of differentiation 14 (CD14)+ cluster of differentiation (CD16)+ monocytes Time: Weeks 1, 2, and 4
Description: Mean levels of SARS-CoV-2 viremia in respiratory specimens will be compared between study arms.
Measure: Change in SARS-CoV-2 Viremia Time: Weeks 1, 2, and 4
Description: Median titers of IgG antibodies to SARS-CoV-2 will be compared between study arms.
Measure: Change in Immunoglobulin G (IgG) Antibodies Time: Weeks 1, 2, and 4
Description: Median titers of IgM antibodies to SARS-CoV-2 will be compared between study arms.
Measure: Change in Immunoglobulin M (IgM) Antibodies Time: Weeks 1, 2, and 4
Description: Overall survival is defined as days from randomization to death and censored at last follow up.
Measure: Overall Survival Time: Up to Day 29
339 A Phase 2 Double-blind Placebo-controlled Study Investigating the Safety and Efficacy of EDP1815 in the Treatment of Patients Hospitalized With SARS-CoV-2 Infection
Primary Outcomes
Description: This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.
Measure: Number of Participants Requiring Mechanical Ventilation or Dying Time: Up to Day 29Secondary Outcomes
Description: Time to recovery (in days) is defined as a score of greater than 5 from the following eight categories from the NIAID ordinal scale. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities.
Measure: Days to Recovery Time: Up to Day 29Description: The number of days spent hospitalized will be compared between study arms.
Measure: Duration of Hospitalization Time: Up to Day 29Description: The incidence of death within 29 days of randomization will be compared between study arms.
Measure: Incidence of Death Time: Up to Day 29Description: Comparing the proportion of subjects in each group requiring ICU transfer within 29 days of randomization
Measure: Proportion of Participants Transferred to ICU Time: Up to Day 29Description: The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active and 5 = dead. Median ECOG performance will be compared between study arms.
Measure: Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score Time: Day 15, Day 29Description: The incidence of grade III-V adverse events or Serious Adverse Events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, will be compared between study arms.
Measure: Incidence of Grade III-V Adverse Events Time: Up to Day 29Description: The incidence of documented secondary bacterial or viral infections among participants will be compared between study arms.
Measure: Incidence of Secondary Bacterial or Viral Infections Time: Up to Day 29Description: The mean frequency of Th1 T cells in blood mononuclear cells will be compared between study arms.
Measure: Change in Th1 T Cell Frequency Time: Weeks 1, 2, and 4Description: The mean frequency of Th17 T cells in blood mononuclear cells will be compared between study arms.
Measure: Change in Th17 T Cell Frequency Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker IL-2 will be compared between study arms.
Measure: Change in Interleukin-2 (IL-2) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker IL-2R will be compared between study arms.
Measure: Change in Interleukin-2 receptor (IL-2R) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker IL-6 will be compared between study arms.
Measure: Change in Interleukin-6 (IL-6) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker IL-7 will be compared between study arms.
Measure: Change in Interleukin-7 (IL-7) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker IL-8 will be compared between study arms.
Measure: Change in Interleukin-8 (IL-8) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker IL-10 will be compared between study arms.
Measure: Change in Interleukin-10 (IL-10) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker IP-10 will be compared between study arms.
Measure: Change in Interferon gamma-induced Protein 10 (IP-10) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker MIP-1a will be compared between study arms.
Measure: Change in Macrophage Inflammatory Protein 1alpha (MIP-1a) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker MCP-1 will be compared between study arms.
Measure: Change in Monocyte Chemoattractant Protein-1 (MCP-1) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker G-CSF will be compared between study arms.
Measure: Change in Granulocyte Colony-stimulating Factor (G-CSF) Time: Weeks 1, 2, and 4Description: Mean levels of the inflammatory serum biomarker TNF-alpha will be compared between study arms.
Measure: Change in Tumor Necrosis Factor (TNF)-alpha Time: Weeks 1, 2, and 4Description: VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.
Measure: Change in Vasoactive Intestinal Peptide (VIP) Time: Weeks 1, 2, and 4Description: Mean levels of the Tregs will be compared between study arms.
Measure: Change in Gene Expression Profile of Regulatory T Cells (Tregs) Time: Weeks 1, 2, and 4Description: Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.
Measure: Change in Gene Expression Profile of cluster of differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage colony-stimulating factor (GM-CSF)+ Time: Weeks 1, 2, and 4Description: Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.
Measure: Change in Gene Expression Profile of CD8+ T cell immunoglobulin and mucin domain-containing protein 3 (Tim3)+ Programmed cell death protein 1 (PD-1)+ Time: Weeks 1, 2, and 4Description: Mean levels of CD14+CD16+ monocytes will be compared between study arms.
Measure: Change in Gene Expression Profile of cluster of differentiation 14 (CD14)+ cluster of differentiation (CD16)+ monocytes Time: Weeks 1, 2, and 4Description: Mean levels of SARS-CoV-2 viremia in respiratory specimens will be compared between study arms.
Measure: Change in SARS-CoV-2 Viremia Time: Weeks 1, 2, and 4Description: Median titers of IgG antibodies to SARS-CoV-2 will be compared between study arms.
Measure: Change in Immunoglobulin G (IgG) Antibodies Time: Weeks 1, 2, and 4Description: Median titers of IgM antibodies to SARS-CoV-2 will be compared between study arms.
Measure: Change in Immunoglobulin M (IgM) Antibodies Time: Weeks 1, 2, and 4Description: Overall survival is defined as days from randomization to death and censored at last follow up.
Measure: Overall Survival Time: Up to Day 29Evelo will investigate the safety and efficacy of EDP1815 in the treatment of patients hospitalized with SARS-CoV-2 Infection
NCT04488575 Covid19 Drug: EDP1815 Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Pulmonary function as measured by the change in Oxygen Saturation (SpO2) / Fraction of Inspired Oxygen (FiO2) [S/F ratio]
Measure: Change from baseline to the lowest S/F oxygen ratio Time: 14 daysSecondary Outcomes
Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using change in S/F ratio at days 4, 7, 10 and 14/discharge day.
Measure: Change in S/F Ratio Time: 14 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage change in S/F ratio at days 4, 7, 10 and 14/discharge day.
Measure: Percentage change in S/F Ratio Time: 14 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants at each level on the WHO OSCI score at days 4, 7, 14, 21 and 42
Measure: Percentage of participants at each level on the WHO OSCI score Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants with shifts from each level of the WHO OSCI score at baseline at days 4, 7, 14, 21 and 42
Measure: Percentage of participants with shifts from each level of the WHO OSCI score at baseline Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants remaining at their baseline score on the WHO OSCI (or lower) at days 4, 7, 14, 21 and 42
Measure: Percentage of participants remaining at their baseline score on the WHO OSCI (or lower) Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants reporting each level of the WHO OSCI score at their worst post-baseline day
Measure: Percentage of participants reporting each level of the WHO OSCI score at their worst post-baseline day Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the time in days spent at each participant's worst reported WHO OSCI score (excluding death).
Measure: The time in days spent at each participant's worst reported WHO OSCI score (excluding death). Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the intubation and mechanical-ventilation free survival, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 6 or more.
Measure: Intubation and mechanical-ventilation free survival Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using overall survival, defined as the time in days from start of treatment to death by any cause
Measure: Overall survival Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days requiring oxygen therapy
Measure: Number of days requiring oxygen therapy Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days with pyrexia ≥ 38C
Measure: Number of days with pyrexia Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using maximum daily temperature
Measure: Maximum daily temperature Time: 42 daysDescription: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using minimum and maximum SpO2 levels
Measure: SpO2 level Time: 42 daysDescription: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to discharge, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 2 or less.
Measure: Time to discharge Time: 42 daysDescription: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to oxygen saturation (SpO2) ≥94% on room air without further requirement for oxygen therapy.
Measure: Time to oxygen saturation (SpO2) ≥94% Time: 42 daysDescription: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to recovery, defined as the time in days from symptom onset to alleviation of all COVID-19 symptoms.
Measure: Time to recovery Time: 42 daysDescription: The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing AEs by seriousness and relationship to treatment
Measure: Number of participants experiencing AEs by seriousness and relationship to treatment Time: 42 daysDescription: The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing clinically significant abnormal changes in safety lab parameters
Measure: Incidence of clinically significant abnormal lab parameters Time: 42 days340 A Double-Blind Randomized, Placebo-Controlled, Single and Repeated Oral Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics (Including Food Effect) of GSK3882347 in Healthy Participants
This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, first time in human (FTIH) study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetics (PK) of GSK3882347 in healthy adult men and Woman of Non Childbearing Potential (WONCBP). Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each participant in the SAD cohort will receive a single dose of GSK3882347 or placebo (PBO) in 3:1 ratio and in Part 2 (MAD), participants will be randomized in a 4:1 ratio to receive active treatment and placebo. Part 1 will consist of two cohorts with a maximum of four-period for each cohort, the food effect evaluation will be conducted in last period (Period 4) in only one of the cohorts based on the observed human pharmacokinetics (PK). Part 2 will consist of maximum of four cohorts for each of the MAD dose or placebo.
NCT04488770 Urinary Tract Infections Drug: GSK3882347 Drug: Placebo MeSH:Urinary Tract Infections
Primary Outcomes
Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Measure: Part 1: Number of participants with Adverse events (AEs) Time: Up to Week 15Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Measure: Part 2: Number of participants with AEs Time: Up to Week 4Description: Treatment related AE is any untoward medical occurrence in a clinical study participant, having causal relation with the use of a study intervention.
Measure: Part 1: Number of participants with treatment related AEs Time: Up to Week 15Description: Treatment related AE is any untoward medical occurrence in a clinical study participant, having causal relation with the use of a study intervention.
Measure: Part 2: Number of participants with treatment related AEs Time: Up to Week 4Description: Number of participants with clinically significant abnormal findings in hematology parameters will be assessed.
Measure: Part 1: Number of participants with clinically significant abnormal findings in hematology parameters Time: Up to Week 15Description: Number of participants with clinically significant abnormal findings in hematology parameters will be assessed.
Measure: Part 2: Number of participants with clinically significant abnormal findings in hematology parameters Time: Up to Week 4Description: Number of participants with clinically significant abnormal findings in clinical chemistry parameters will be assessed.
Measure: Part 1: Number of participants with clinically significant abnormal findings in clinical chemistry parameters Time: Up to Week 15Description: Number of participants with clinically significant abnormal findings in clinical chemistry parameters will be assessed.
Measure: Part 2: Number of participants with clinically significant abnormal findings in clinical chemistry parameters Time: Up to Week 4Description: Number of participants with abnormal urinalysis parameters will be assessed.
Measure: Part 1: Number of participants with abnormal urinalysis results Time: Up to Week 15Description: Number of participants with abnormal urinalysis parameters will be assessed.
Measure: Part 2: Number of participants with abnormal urinalysis results Time: Up to Week 4Description: Number of participants with clinically significant abnormal vital signs will be assessed.
Measure: Part 1: Number of participants with clinically significant abnormal vital signs Time: Up to Week 15Description: Number of participants with clinically significant abnormal vital signs will be assessed.
Measure: Part 2: Number of participants with clinically significant abnormal vital signs Time: Up to Week 4Description: Number of participants with abnormal ECG parameters will be assessed.
Measure: Part 1: Number of participants with clinically significant abnormal Electrocardiogram (ECG) findings Time: Up to Week 15Description: Number of participants with abnormal ECG parameters will be assessed.
Measure: Part 2: Number of participants with clinically significant abnormal ECG findings Time: Up to Week 4Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Area under the concentration-time curve from time zero to 24 hours after dosing (AUC [0-24]) of GSK3882347 single dose Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hour post dose in each treatment period]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of GSK3882347 single dose Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: AUC extrapolated from time zero to infinity (AUC[0-inf]) of GSK3882347 single dose Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Maximum plasma concentration (Cmax) of GSK3882347 single dose (nanograms per milliliter) Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Plasma concentrations at 24 hours after dosing (C24h) of GSK3882347 single dose Time: Day 1: 24 hour post dose in each treatment periodDescription: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Time to Cmax (Tmax) of GSK3882347 single dose Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Lag time for absorption (tlag) of GSK3882347 single dose Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Terminal elimination half-life (T1/2) of GSK3882347 single dose Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 2: AUC over the dosing interval tau (AUC[0-tau]) of GSK3882347 repeat dose Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 2: Cmax of GSK3882347 repeat dose Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 2: Tmax of GSK3882347 repeat dose Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]Description: Plasma samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 2: Plasma concentrations over the dosing interval (Ctau) of GSK3882347 repeat dose Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24 hour post dose]Description: Urine samples will be collected at indicated time points for the assessment of urinary concentration.
Measure: Part 1: Urine concentration at 22-24 hours collection time point Time: Day 1 [22-24 hours post dose in each treatment period]Description: Urine samples will be collected at indicated time points for the assessment of urinary concentration.
Measure: Part 2: Urine concentration at 22-24 hours collection time point Time: Days 1 and 7 [22-24 hours post dose]Description: Urine samples will be collected at indicated time intervals for the assessment of amount excreted in urine of unchanged GSK3882347.
Measure: Part 1: Amount excreted in urine (Ae) of unchanged GSK3882347 Time: Day 1 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48- 60, 60-72, 72-84, and 84-96 hour post dose in each treatment period]Description: Urine samples will be collected at indicated time intervals for the assessment of amount excreted in urine of unchanged GSK3882347.
Measure: Part 2: Amount excreted in urine (Ae) of unchanged GSK3882347 Time: Days 1 and 7 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 hour post dose]Description: Urine samples will be collected at indicated time points for the assessment of fraction of the dose excreted in urine GSK3882347.
Measure: Part 1 Fraction of the dose excreted in urine (fe) following single dose GSK3882347 Time: Day 1 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48- 60, 60-72, 72-84, and 84-96 hours post dose in each treatment period]Description: Urine samples will be collected at indicated time points for the assessment of fraction of the dose excreted in urine GSK3882347.
Measure: Part 2: Fraction of the dose excreted in urine (fe) following single dose GSK3882347 Time: Days 1 and 7 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 post dose in each of the 4 cohorts]Description: Urine samples will be collected at indicated time points for the assessment renal clearance of GSK3882347.
Measure: Part 1: Renal clearance (CLr) following single dose GSK3882347 Time: Day 1 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24, 24-26, 26-32, 32-38, 38-48, 48- 60, 60-72, 72-84, and 84-96 hours post dose]Description: Urine samples will be collected at indicated time points for the assessment renal clearance of GSK3882347.
Measure: Part 2: Renal clearance (CLr) following single dose GSK3882347 Time: Days 1 and 7 [0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-22, 22-24 post dose]Secondary Outcomes
Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: AUC from time zero to 12 hours after dosing (AUC[0-12]) following single dose of GSK3882347 Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hour post dose in each treatment period]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Plasma concentrations at 12 hours (C12) following single dose of GSK3882347 Time: Day 1 [12 hour post dose in each treatment period]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Apparent oral clearance (CL/F) following single dose of GSK3882347 Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Apparent volume of distribution after non-intravenous administration (Vd/F) following single dose of GSK3882347 Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 1: Mean residence time (MRT) following single dose of GSK3882347 Time: Day 1 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 32, 48, 72, and 96 hour post dose in each treatment period]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 2: AUC[0-12] following repeat dose of GSK3882347 Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, and 12, hour post dose]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 2: C12 following repeat dose of GSK3882347 Time: Days 1 and Day 7 [12 hour post dose]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347.
Measure: Part 2: Observed accumulation ratio (Ro) using AUC(0-tau) following repeat dose of GSK3882347 Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24, hour post dose]Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3882347. The time invariance will be estimated by calculating the ratio of AUC(0-tau) on Day 7 to AUC(0-inf) on Day 1.
Measure: Part 2: Time invariance of GSK3882347 using AUC(0-tau) (repeat dose) and AUC(0-inf) (single dose) Time: Days 1 and 7 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, and 24, hour post dose]Description: Blood samples will be collected at indicated time points to confirm achievement of steady-state of GSK3882347 after repeated dosings.
Measure: Part 2: Plasma concentrations over the dosing interval (Ctau) of GSK3882347 after repeat doses Time: Pre-dose on Days 3 through 7341 Sildenafil for Treating Patients With COVID-19 and Perfusion Mismatch: A Pilot Randomised Trial
This randomised trial aims to assess the role of sildenafil in improving oxygenation amongst hospitalised patients with COVID19.
NCT04489446 Covid19 SARS-COV2 Infection Drug: Sildenafil Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.
Measure: Arterial Oxygenation Time: One hour after sildenafil administrationDescription: Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.
Measure: Arterial Oxygenation Time: Daily until the end of follow-up (up to 15 days after randomisation)Description: Mean difference in the alveolo-arterial gradient between study groups.
Measure: Alveolo-arterial gradient Time: One hour after sildenafil administrationDescription: Mean difference in the alveolo-arterial gradient between study groups.
Measure: Alveolo-arterial gradient Time: Daily until the end of follow-up (up to 15 days after randomisation)Secondary Outcomes
Description: Proportion of patients requiring admission to an intensive care unit in each study group
Measure: Intensive care unit admission Time: Up to two weeks after randomisationDescription: Proportion of patients requiring noninvasive mechanical ventilation o high-flow nasal cannula unit in each study group
Measure: Noninvasive Mechanical Ventilation or Requirement of High-Flow Nasal Cannula Time: Up to two weeks after randomisationDescription: Proportion of patients requiring invasive mechanical ventilation in each study group
Measure: Invasive mechanical ventilation Time: Up to two weeks after randomisationDescription: Proportion of patients that survived COVID19 in each study group
Measure: Survival Time: Up to two weeks after randomisationOther Outcomes
Description: Adverse events attributable to sildenafil use.
Measure: Adverse events Time: Up to two weeks after randomisation342 Phase I, Randomized, Double Blinded, Placebo Control Study to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Placebo to Treat Acute Pulmonary Inflammation Due to COVID-19 With Moderate to Severe Symptoms
The purpose of this study is to demonstrate the safety of Umbilical Cord Tissue Derived Mesenchymal Stem Cells (UCMSCs) administered intravenously in patients with acute pulmonary inflammation due to COVID-19 with moderately severe symptoms
NCT04490486 COVID-19 Acute Respiratory Distress Syndrome Corona Virus Infection Biological: UCMSCs Other: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Pneumonia Inflammation
HPO:Pneumonia
Primary Outcomes
Description: Safety of UCMSCs will be reported as the percentage of participants in each treatment group that experienced a treatment related SAEs.
Measure: Percent of participants with treatment related Serious Adverse Events (SAE) Time: 12 months
Secondary Outcomes
Description: Change in serum inflammatory marker levels including Interleukin (IL) IL-6, IL-2, Tumor Necrosis Factor Alpha (TNF-a) and procalcitonin will be evaluated in ng/L.
Measure: Change in inflammatory marker levels Time: Baseline, Day 30
Description: Change in serum systemic inflammatory marker levels including D-dimer, high sensitivity C-reactive protein (hsCRP) and ferritin will be evaluated in mg/L.
Measure: Change in systemic inflammatory marker levels Time: Baseline, Day 30
Description: Assessed using blood samples or nose/throat swabs.
Measure: COVID-19 Viral Load Time: Up to 30 Days
Description: Sequential Organ Failure Assessment (SOFA) will be used to assess organ failure including the cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs. SOFA score ranges from 0-24 with the higher score indicating worse outcomes.
Measure: Change in SOFA score Time: Baseline, Up to 30 Days
Description: Sodium, Potassium, Chloride and Carbon Dioxide (CO2) will be evaluated in mmol/L. Changes from baseline to Day 30 will be compared between groups.
Measure: Change in electrolytes levels Time: Baseline, Up to 30 Days
Description: Serum Lactate Dehydrogenase (LDH) levels assessed in U/L. Changes in LDH from baseline to Day 30 will be compared between groups.
Measure: Change in LDH levels Time: Baseline, Up to 30 Days
Description: ICU monitoring status will be reported as the number of subjects discharged from the ICU within 7 days.
Measure: Number of subjects discharged from the ICU Time: Up to 7 Days
Description: Percentage of participants requiring less use of vasoactive agents will be reported.
Measure: Percentage of participants with less requirement for vasoactive agents Time: Up to 30 Days
Description: Percentage of participant deaths throughout the study period.
Measure: Rate of Mortality Time: Up to 30 Days
Description: The percentage of participants with changes in serum immune marker levels including Cluster of Differentiation (CD) CD 4+ and CD 8+, as evaluated by treating physician will be reported.
Measure: Percentage of participants with changes in immune marker expression Time: Up to 30 Days
Description: Percentage of participants with changes in their chest imaging such as ground-glass opacity, local patch shadowing, bilateral patch shadowing and interstitial abnormalities will be reported. Imaging will be assessed by treating physician using chest radiography or chest Computed Tomography (CT).
Measure: Percentage of participants with changes in radiologic findings Time: Up to 30 Days
Description: Percentage of participants showing less pneumonia symptoms will be reported as evaluated by treating physician using chest radiography or chest CT.
Measure: Percentage of participants with less pneumonia symptoms Time: Up to 30 Days
343 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-3)
Primary Outcomes
Description: Safety of UCMSCs will be reported as the percentage of participants in each treatment group that experienced a treatment related SAEs.
Measure: Percent of participants with treatment related Serious Adverse Events (SAE) Time: 12 monthsSecondary Outcomes
Description: Change in serum inflammatory marker levels including Interleukin (IL) IL-6, IL-2, Tumor Necrosis Factor Alpha (TNF-a) and procalcitonin will be evaluated in ng/L.
Measure: Change in inflammatory marker levels Time: Baseline, Day 30Description: Change in serum systemic inflammatory marker levels including D-dimer, high sensitivity C-reactive protein (hsCRP) and ferritin will be evaluated in mg/L.
Measure: Change in systemic inflammatory marker levels Time: Baseline, Day 30Description: Assessed using blood samples or nose/throat swabs.
Measure: COVID-19 Viral Load Time: Up to 30 DaysDescription: Sequential Organ Failure Assessment (SOFA) will be used to assess organ failure including the cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs. SOFA score ranges from 0-24 with the higher score indicating worse outcomes.
Measure: Change in SOFA score Time: Baseline, Up to 30 DaysDescription: Sodium, Potassium, Chloride and Carbon Dioxide (CO2) will be evaluated in mmol/L. Changes from baseline to Day 30 will be compared between groups.
Measure: Change in electrolytes levels Time: Baseline, Up to 30 DaysDescription: Serum Lactate Dehydrogenase (LDH) levels assessed in U/L. Changes in LDH from baseline to Day 30 will be compared between groups.
Measure: Change in LDH levels Time: Baseline, Up to 30 DaysDescription: ICU monitoring status will be reported as the number of subjects discharged from the ICU within 7 days.
Measure: Number of subjects discharged from the ICU Time: Up to 7 DaysDescription: Percentage of participants requiring less use of vasoactive agents will be reported.
Measure: Percentage of participants with less requirement for vasoactive agents Time: Up to 30 DaysDescription: Percentage of participant deaths throughout the study period.
Measure: Rate of Mortality Time: Up to 30 DaysDescription: The percentage of participants with changes in serum immune marker levels including Cluster of Differentiation (CD) CD 4+ and CD 8+, as evaluated by treating physician will be reported.
Measure: Percentage of participants with changes in immune marker expression Time: Up to 30 DaysDescription: Percentage of participants with changes in their chest imaging such as ground-glass opacity, local patch shadowing, bilateral patch shadowing and interstitial abnormalities will be reported. Imaging will be assessed by treating physician using chest radiography or chest Computed Tomography (CT).
Measure: Percentage of participants with changes in radiologic findings Time: Up to 30 DaysDescription: Percentage of participants showing less pneumonia symptoms will be reported as evaluated by treating physician using chest radiography or chest CT.
Measure: Percentage of participants with less pneumonia symptoms Time: Up to 30 DaysACTT-3 will evaluate the combination of interferon beta-1a and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.
NCT04492475 COVID-19 Drug: Interferon beta-1a 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 and no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to recovery Time: Day 1 through Day 29Secondary Outcomes
Measure: Change from baseline in alanine aminotransferase (ALT) Time: Day 1 through Day 29Measure: Change from baseline in aspartate aminotransferase (AST) Time: Day 1 through Day 29
Measure: Change from baseline in C-reactive protein (CRP) Time: Day 1 through Day 29
Measure: Change from baseline in creatinine Time: Day 1 through Day 29
Measure: Change from baseline in d-dimer concentration Time: Day 1 through Day 29
Measure: Change from baseline in hemoglobin Time: Day 1 through Day 29
Measure: Change from baseline in international normalized ratio (INR) Time: Day 1 through Day 29
Measure: Change from baseline in platelets Time: Day 1 through Day 29
Measure: Change from baseline in total bilirubin Time: Day 1 through Day 29
Measure: Change from baseline in white blood cell count (WBC) with differential Time: Day 1 through Day 29
Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Change in National Early Warning Score (NEWS) from baseline Time: Day 1 through Day 29Description: 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 29Description: 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 29Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of invasive mechanical ventilation Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of non invasive ventilation/high flow oxygen use Time: Day 1 through Day 29Description: Measured in days
Measure: Duration of oxygen use Time: Day 1 through Day 29Description: For any reason.
Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Measure: 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 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Participant's clinical status at Day 15 by ordinal scale Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale Time: Days 3, 5, 8, 11, 22, and 29Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 28-day mortality Time: Day 1 through Day 29Description: 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 29Description: 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 29Description: 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 29Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to recovery for participants not on mechanical ventilation (baseline ordinal score of 4, 5, or 6) Time: Day 1 through Day 29344 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation
The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
NCT04492514 COVID 19 SARS-CoV 2 Pneumonia Drug: Mavrilimumab Drug: Placebo MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia
Primary Outcomes
Description: Proportion of subjects alive and off oxygen at day14
Measure: Primary Outcome Measure: Time: Day 14
Secondary Outcomes
Description: Proportion of subjects alive and without respiratory failure at 28 days
Measure: Secondary Outcome Measures: Time: 28 days
345 A Phase 2b Randomised, Double-Blind, Placebo-Controlled, Multi-Centre, Dose-Ranging Study of AZD5718 in Participants With Proteinuric Chronic Kidney Disease
Primary Outcomes
Description: Proportion of subjects alive and off oxygen at day14
Measure: Primary Outcome Measure: Time: Day 14Secondary Outcomes
Description: Proportion of subjects alive and without respiratory failure at 28 days
Measure: Secondary Outcome Measures: Time: 28 daysThe purpose of the study is to evaluate the dose-response efficacy, safety, and pharmacokinetics (PK) of AZD5718 in participants with proteinuric chronic kidney disease.
NCT04492722 Chronic Kidney Disease Drug: AZD5718 Drug: Dapagliflozin 10 mg Drug: Placebo MeSH:Kidney Diseases Renal Insufficiency, Chronic
HPO:Abnormality of the kidney Chronic kidney disease Nephropathy
Primary Outcomes
Description: To evaluate the dose-response effect of AZD5718 on urine ACR at 20 weeks
Measure: Change from baseline in urine albumin to creatinine ratio (ACR) to Week 20 Time: Week 1 to Week 20
Secondary Outcomes
Description: To evaluate the dose-response effect of AZD5718 on urine ACR at 12 weeks
Measure: Change from baseline in urine ACR to Week 12 Time: Week 1 to Week 12
Description: To assess the safety and tolerability profile of AZD5718 treatment
Measure: Number of participants with adverse events and serious adverse events Time: Screening to Week 24
Description: To evaluate the effect of AZD5718 on ambulatory blood pressure
Measure: Change from baseline in 24-hours mean systolic blood pressure to Week 12 Time: Week 1 to Week 12
Description: To assess the PK of AZD5718 after repeated oral dosing for 20 weeks
Measure: Plasma concentrations of AZD5718 Time: Week 2 to Week 20
Description: To assess the effect of AZD5718 on renal function
Measure: Change from baseline in estimated glomerular filtration rate (eGFR) to Week 12 Time: Week 1 to Week 12
346 A Phase IIb, Randomized, Partially Blind, Active Controlled, Dose-range Finding Study of GSK3640254 Compared to a Reference Arm of Dolutegravir, Each in Combination With Nucleoside Reverse Transcriptase Inhibitors, in HIV-1 Infected Antiretroviral Treatment-naive Adults
Primary Outcomes
Description: To evaluate the dose-response effect of AZD5718 on urine ACR at 20 weeks
Measure: Change from baseline in urine albumin to creatinine ratio (ACR) to Week 20 Time: Week 1 to Week 20Secondary Outcomes
Description: To evaluate the dose-response effect of AZD5718 on urine ACR at 12 weeks
Measure: Change from baseline in urine ACR to Week 12 Time: Week 1 to Week 12Description: To assess the safety and tolerability profile of AZD5718 treatment
Measure: Number of participants with adverse events and serious adverse events Time: Screening to Week 24Description: To evaluate the effect of AZD5718 on ambulatory blood pressure
Measure: Change from baseline in 24-hours mean systolic blood pressure to Week 12 Time: Week 1 to Week 12Description: To assess the PK of AZD5718 after repeated oral dosing for 20 weeks
Measure: Plasma concentrations of AZD5718 Time: Week 2 to Week 20Description: To assess the effect of AZD5718 on renal function
Measure: Change from baseline in estimated glomerular filtration rate (eGFR) to Week 12 Time: Week 1 to Week 12Infection with HIV-1 continues to be a serious health threat throughout the world, with more than 40 million individuals infected worldwide. The current standard of care treatment for HIV-1 is combination anti-retroviral therapy (cART) with recommendations to start regardless of cluster of differentiation 4 (CD4) plus (+) T-cell count, committing people living with HIV to lifelong, lifesaving therapy. However, the chronic exposure to cART has identified anti-retroviral (ARV)-associated long-term toxicities (central nervous system [CNS] or cardiovascular [CV]/metabolic effects, renal disease), creating a need to address and prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 maturation inhibitor (MI) and has completed a short-term, monotherapy, proof of concept (POC) Phase 2a study. This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses [100, 150 and 200 milligrams {mg}]), active controlled clinical trial. It will aim to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine [ABC/3TC] or emtricitabine/tenofovir alafenamide [FTC/TAF]), in approximately 240 treatment-naïve HIV-1 infected adults. The total study duration will be approximately 7 years.
NCT04493216 HIV Infections Drug: GSK3640254 Drug: ABC/3TC Drug: FTC/TAF Drug: Dolutegravir Drug: Placebo MeSH:HIV Infections
Primary Outcomes
Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Week 24.
Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 24 Time: At Week 24Secondary Outcomes
Description: Proportion of participants with plasma HIV-1 RNA <50 c/mL will be assessed at Weeks 48 and 96.
Measure: Proportion of participants with plasma HIV-1 RNA <50 c/mL at Weeks 48 and 96 Time: At Weeks 48 and 96Description: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.
Measure: Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Change from Baseline in level of plasma HIV-1 RNA at Weeks 24, 48 and 96 will be assessed.
Measure: Change from Baseline in plasma HIV-1 RNA at Weeks 24, 48 and 96 (c/mL) Time: Baseline and Weeks 24, 48 and 96Description: Absolute values of CD4+ cells at Weeks 24, 48, and 96 will be assessed.
Measure: Absolute values of CD4+ T-cell counts at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Change from Baseline in CD4+ cells at Weeks 24, 48 and 96 will be assessed.
Measure: Change from Baseline in CD4+ T-cell counts at Weeks 24, 48 and 96 Time: Baseline and Weeks 24, 48 and 96Description: An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose; results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability or incapacity or is a congenital anomaly or birth defect or any other situation that require medical or scientific judgment. Number of participants with SAEs, death and AEs leading to treatment discontinuation will be assessed at Weeks 24, 48 and 96.
Measure: Number of participants with serious adverse events (SAEs), Deaths and adverse events (AEs) leading to treatment discontinuation at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants with AEs will be assessed at Weeks 24, 48 and 98.
Measure: Number of participants with AEs at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Severity of AEs will be assessed at Weeks 24, 48 and 96.
Measure: Severity of AEs at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Number of participants with AEs in GI, Psych/CNS will be assessed at Weeks 24, 48 and 96.
Measure: Number of participants with AEs in Gastrointestinal (GI), Psychological (Psych)/Central nervous system (CNS) at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Plasma samples will be collected for analyzing phenotypic resistance at Weeks 24, 48 and 96 using PhenoSense genotype testing (GT) for reverse transcriptase (RT) (NRTI and non-nucleoside reverse transcriptase inhibitors [NNRTI]) and Protease inhibitor (PI), PhenoSense Integrase, PhenoSense Gag assays for GSK3640254.
Measure: Number of participants who develop phenotypic resistance at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Plasma samples will be collected for analyzing genotypic resistance at Weeks 24, 48 and 96 using PhenoSense GT for RT and Protease genotype, GeneSeq Integrase, and Gag genotype (using a Next Generation Sequencing platform).
Measure: Number of participants who develop genotypic resistance at Weeks 24, 48 and 96 Time: At Weeks 24, 48 and 96Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: Maximum observed concentration (Cmax) of GSK3640254 at steady state at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: Cmax of GSK3640254 at steady state at Week 48 Time: At Week 48Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: AUC over the dosing interval (AUC [0-tau]) of GSK3640254 at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: AUC (0-tau) of GSK3640254 at steady state at Week 48 Time: At Week 48Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 24.
Measure: Plasma concentration at the end of the dosing (Ctau) of GSK3640254 at steady state at Week 24 Time: At Week 24Description: Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK3640254 at Week 48.
Measure: Ctau of GSK3640254 at steady state at Week 48 Time: At Week 48347 A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3739937 in Healthy Participants
Human immunodeficiency virus 1 (HIV-1) infections continues to be a serious health threat throughout the world and development of medicines with new mechanism of action have an important role to play. The purpose of this study is to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937. The information collected in this study will help in further clinical development of GSK3739937, including a Phase IIA Proof of Concept (PoC) study in HIV-infected participants as well as a FTIH study of long acting formulation of GSK3739937 administered parenterally (subcutaneously or intramuscularly). This randomized, placebo controlled, single and repeat-dose escalation study of GSK3739937 in healthy participants and will be executed in two-part. In Part 1 single ascending dose (SAD), approximately 18 participants will be randomized with approximately 9 participants within each of Cohort 1 and Cohort 2. In Part 2 multiple ascending dose (MAD), approximately 30 participants will be randomized with approximately 10 participants within each of Cohorts 3 to 5. Approximately 48 participants will be enrolled in the study and all doses will be administered after a moderate fat meal. Maximum duration of study participation will be approximately 22 weeks in Part 1 and approximately 18 weeks in Part 2.
NCT04493684 HIV Infections Drug: GSK3739937 Drug: Placebo MeSH:HIV Infections
Primary Outcomes
Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure: Part 1: Cohort 1-2: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Time: Up to Day 44Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets (Giga cells per liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameters: RBC count.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) count (Trillion cells per liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be e collected to analyze the hematology parameters: MCV.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameters: Mean Corpuscular Volume (MCV) (Femtoliter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: MCH.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) (Picogram) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: percent of reticulocytes.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage of reticulocyte) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the hematology parameter: Hb.
Measure: Part 1: Cohort 1-2: Change From Baseline in Hematology Parameter: Hemoglobin (Hb) (Grams per deciliter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: ALT, AST, and ALP.
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphate (ALP) (International units per Liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.
Measure: Part 1:Cohort 1-2:Change from Baseline in bicarbonate,calcium,glucose,chloride,magnesium,phosphate,potassium,sodium,blood urea nitrogen (BUN),cholesterol,high density lipoprotein (HDL),low density lipoprotein (LDL),triglycerides (Millimole per Liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (units per liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, direct bilirubin and creatinine.
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) Time: Baseline (Day -1) and up to Day 44Description: Blood samples will be collected to analyze the chemistry parameter: total protein.
Measure: Part 1: Cohort 1-2: Change From Baseline in Clinical Chemistry Parameter: total protein (Gram per Liter) Time: Baseline (Day -1) and up to Day 44Description: Urine samples will be collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measure: Part 1: Cohort 1-2: Number of Participants With Abnormal Urinalysis Time: Baseline (Day -1) and up to Day 44Description: SBP and DBP will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeters of mercury) Time: Baseline (Day -1) and up to Day 44Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute) Time: Baseline (Day -1) and up to Day 44Description: Temperature was will be in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Signs: Temperature (Degrees Celsius) Time: Baseline (Day -1) and up to Day 44Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 1: Cohort 1-2: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute) Time: Baseline (Day -1) and up to Day 44Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.
Measure: Part 1: Cohort 1-2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings Time: Baseline (Day 1, Pre-dose) and up to Day 44Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure: Part 2: Cohort 3-4: Number of Participants With AEs and SAEs Time: Up to Day 28Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measure: Part 2: Cohort 3-4:Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets (Giga cells per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameters: RBC count.
Measure: Part 2: Cohort 3-4:Change From Baseline in Hematology Parameters: RBC count (Trillion cells per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameters: MCV.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameters: MCV (Femtoliter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: MCH.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: MCH (Picogram) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: Percent of reticulocytes
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage reticulocyte) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the hematology parameter: Hb.
Measure: Part 2: Cohort 3-4: Change From Baseline in Hematology Parameter: Hb (Grams per deciliter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be e collected to analyze the chemistry parameter: ALT, AST and ALP.
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: ALT, AST and ALP (International units per Liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (units per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL and triglycerides.
Measure: Part 2: Cohort 3-4: Change From Baseline in bicarbonate, glucose, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL and triglycerides (Millimoles per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, creatinine and direct bilirubin
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinin and Direct Bilirubin (Micromoles per liter) Time: Baseline (Day -1) and up to Day 28Description: Blood samples will be collected to analyze the chemistry parameter: total protein.
Measure: Part 2: Cohort 3-4: Change From Baseline in Clinical Chemistry Parameter: Total protein (Grams per liter) Time: Baseline (Day -1) and up to Day 28Description: Urine samples collected at given time points to analyze the abnormal findings for pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measure: Part 2: Cohort 3-4: Number of Participants With Abnormal Urinalysis Time: Baseline (Day -1) and up to Day 28Description: SBP and DBP measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: DBP and SBP (Millimeters of mercury) Time: Baseline (Day -1) and up to Day 28Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute) Time: Baseline (Day -1) and up to Day 28Description: Temperature will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Signs: Temperature (Degrees Celsius) Time: Baseline (Day -1) and up to Day 28Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 3-4: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute) Time: Baseline (Day -1) and up to Day 28Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.
Measure: Part 2: Cohort 3-4: Number of Participants With Abnormal ECG Findings Time: Baseline (Day -1) and up to Day 28Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure: Part 2: Cohort 5: Number of Participants With AEs and SAEs Time: Up to Day 42Description: Blood samples will be collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measure: Part 2: Cohort 5:Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets (Giga cells per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameters: RBC count
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameters: RBC count (Trillion cells per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameters: MCV.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameters: MCV (Femtoliter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: MCH.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: MCH (Picogram) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: hematocrit.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: Percent of reticulocytes
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Percent of reticulocytes (Percentage reticulocyte) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the hematology parameter: Hb.
Measure: Part 2: Cohort 5: Change From Baseline in Hematology Parameter: Hb (Grams per deciliter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be e collected to analyze the chemistry parameter: ALT, AST, and ALP.
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: ALT, AST, ALP (International units per Liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: amylase and lipase
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameters : amylase and lipase (Units per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, BUN, cholesterol, HDL, LDL, and triglycerides.
Measure: Part 2: Cohort 5:Change From Baseline in Bicarbonate, glucose (non-fasting), Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL Cholesterol, LDL Cholesterol and Triglycerides (Millimoles per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: bilirubin, creatinine and direct bilirubin
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine and Direct Bilirubin (Micromoles per liter) Time: Baseline (Day -1) and up to Day 42Description: Blood samples will be collected to analyze the chemistry parameter: total protein.
Measure: Part 2: Cohort 5: Change From Baseline in Clinical Chemistry Parameter: Total protein (Grams per liter) Time: Baseline (Day -1) and up to Day 42Description: Urine samples collected at given time points to analyze the abnormal findings for pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measure: Part 2: Cohort 5: Number of Participants With Abnormal Urinalysis Time: Baseline (Day -1) and up to Day 42Description: SBP and DBP measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: DBP and SBP (Millimeters of mercury) Time: Baseline (Day -1) and up to Day 42Description: Pulse rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: Pulse Rate (Beats per minute) Time: Baseline (Day -1) and up to Day 42Description: Temperature will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Signs: Temperature (Degrees Celsius) Time: Baseline (Day -1) and up to Day 42Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest for the participants at indicated time points.
Measure: Part 2: Cohort 5: Change From Baseline in Vital Sign: Respiratory Rate (Breaths per minute) Time: Baseline (Day -1) and up to Day 42Description: 12-lead ECGs will be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.
Measure: Part 2: Cohort 5: Number of Participants With Abnormal ECG Findings Time: Baseline (Day -1) and up to Day 42Secondary Outcomes
Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-24) of GSK3739937.
Measure: Part 1: Cohort 1-2:Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 hours (AUC[0-24]) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-doseDescription: Blood samples will be collected at indicated time points for the PK analysis of AUC(0-t) of GSK3739937.
Measure: Part 1: Cohort 1-2: AUC From zero (pre-dose) to t (AUC [0-t]) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of AUC(0-inf) of GSK3739937.
Measure: Part 1: Cohort 1-2: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.
Measure: Part 1: Cohort 1-2: Apparent Terminal Phase Half-life (T1/2) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.
Measure: Part 1: Cohort 1-2: Apparent Oral Clearance (CL/F) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 1: Cohort 1-2: Maximum Observed Concentration (Cmax) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of C24 of GSK3739937.
Measure: Part 1: Cohort 1-2: Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937 Time: At 24 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Clast of GSK3739937.
Measure: Part 1: Cohort 1-2: Last Quantifiable Concentration (Clast) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 1: Cohort 1-2: Time of Occurrence of Cmax (Tmax) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Tlag of GSK3739937.
Measure: Part 1: Cohort 1-2: Lag Time (Tlag) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Tlast of GSK3739937.
Measure: Part 1: Cohort 1-2: Time to Reach Clast (Tlast) of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of AUC(0-24) of GSK3739937.
Measure: Part 2: Cohort 3-4: AUC (0-24) of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Cmax of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of C24 of GSK3739937.
Measure: Part 2: Cohort 3-4: C24 of GSK3739937 on Day 1 Time: At 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Tmax of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Tlag of GSK3739937.
Measure: Part 2: Cohort 3-4: Tlag of GSK3739937 on Day 1 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 1 (pre-dose on Day 2)Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Tmax of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 2: Cohort 3-4: Cmax of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) of GSK3739937.
Measure: Part 2: Cohort 3-4: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Ctau of GSK3739937.
Measure: Part 2: Cohort 3-4: Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14 Time: At 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.
Measure: Part 2: Cohort 3-4: T1/2 of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours on Day 14Description: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.
Measure: Part 2: Cohort 3-4: CL/F of GSK3739937 on Day 14 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Tmax of GSK3739937.
Measure: Part 2: Cohort 5: Tmax of GSK3739937 on Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Cmax of GSK3739937.
Measure: Part 2: Cohort 5: Cmax of GSK3739937 on Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) of GSK3739937.
Measure: Part 2: Cohort 5: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Ctau of GSK3739937.
Measure: Part 2: Cohort 5: Plasma Trough Concentration (Ctau) of GSK3739937: Day 28 Time: At 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of T1/2 of GSK3739937.
Measure: Part 2: Cohort 5:T1/2 of GSK3739937: Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of CL/F of GSK3739937.
Measure: Part 2: Cohort 5: CL/F of GSK3739937: Day 28 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-inf) Following Single Dose of GSK3739937.
Measure: Part 1: Cohort 1-2: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of Cmax Following Single Dose of GSK3739937.
Measure: Part 1: Cohort 1-2: Dose Proportionality for Cmax Following Single Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 3-4: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of AUC(0-tau) Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 5: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Ctrough Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 3-4: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3739937 Time: At 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Ctrough Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 5: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3739937 Time: At 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Cmax Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 3-4: Dose Proportionality (Cmax) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 14Description: Blood samples will be collected at indicated time points for the analysis of Cmax Following Repeated Dose of GSK3739937.
Measure: Part 2: Cohort 5: Dose Proportionality (Cmax) Following Repeated Dose of GSK3739937 Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, and 24 hours post-dose on Day 28Description: Blood samples will be collected at indicated time points for the analysis of Predicted accumulation ratio Rp based on AUC.
Measure: Part 1: Cohort 1-2: Predicted accumulation ratio Rp based on AUC Time: Pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post-doseDescription: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]).
Measure: Part 2: Cohort 3-4: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 14Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]).
Measure: Part 2: Cohort 5: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 28Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of Cmax (R [CMAX]).
Measure: Part 2: Cohort 3-4: Accumulation Ratio of Cmax (R [CMAX]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 14Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of Cmax (R [CMAX]).
Measure: Part 2: Cohort 5: Accumulation Ratio of Cmax (R [CMAX]) Time: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,12 and 24 hours post-dose on Day 1 and Day 28Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of C(Tau) (R[CTAU]).
Measure: Part 2: Cohort 3-4: Accumulation Ratio of C(Tau) (R[CTAU]) Time: At 24 hours post-dose on Day 1 and Day 14Description: Blood samples will be collected at indicated time points for the analysis of accumulation Ratio of C(Tau) (R[CTAU]).
Measure: Part 2: Cohort 5: Accumulation Ratio of C(Tau) (R[CTAU]) Time: At 24 hours post-dose on Day 1 and Day 28Description: Blood samples will be collected at indicated time points for the analysis of pre-dose Concentration of GSK3739937.
Measure: Part 2: Cohort 3-4: Pre-dose Concentration of GSK3739937 from Day 2 to Day 14 Time: Pre-dose from Day 2 to Day 14Description: Blood samples will be collected at indicated time points for the analysis of Pre-dose Concentration of GSK3739937.
Measure: Part 2: Cohort 5: Pre-dose Concentration of GSK3739937 from Day 2 to Day 28 Time: Pre-dose from Day 2 to Day 28348 BARCONA: A Phase II/III, Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19)
This multi-center, double-blind, placebo-controlled, randomized Phase 2/3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in approximately 400-440 patients hospitalized with confirmed COVID-19. The Phase 2 portion of the trial will include approximately 40 patients and is designed to provide an early interim analysis of safety. The Phase 3 portion of the trial will include approximately 360-400 additional patients, and is designed to determine whether bardoxolone methyl increases the probability of recovery at Day 29 when compared with matching placebo. Patients will be randomized using permuted block randomization in a 1:1 fashion to either once-daily administration of bardoxolone methyl (20 mg) or matching placebo and treatment will be administered for the duration of hospitalization (until recovery), with a maximum treatment duration of 29 days.
NCT04494646 Covid19 Drug: Bardoxolone methyl Drug: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Measure: Incidence of Serious Adverse Events in Phase 2 Time: Day 29Description: Recovery is defined as alive, free of respiratory failure (e.g., need for noninvasive, or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of renal replacement therapy (RRT).
Measure: Proportion of participants who have recovered in Phase 3 Time: Day 29Secondary Outcomes
Measure: Average number of renal replacement therapy (RRT)-free days Time: Day 29Measure: Average number of mechanical ventilation-free days Time: Day 29
Measure: Incidence of All-Cause Mortality Time: Day 29
Description: Deterioration is defined by a 1-point worsening scale: 0- Uninfected; no viral RNA detected, 1- Asymptomatic; viral RNA detected, 2- Symptomatic; Independent, 3- Symptomatic; assistance needed, 4- Hospitalized; no oxygen therapy, 5- Hospitalized; oxygen by mask or nasal prongs, 6- Hospitalized; oxygen by NIV or High flow, 7- Intubation & Mechanical ventilation; pO2/FIO2 >/= 150 or SpO2/FIO2 >/=200, 8- Mechanical ventilation pO2/FIO2 < 150 (SpO2/FIO2 <200) or vasopressors, 9- Mechanical ventilation pO2/FIO2 < 150 and vasopressors, dialysis or ECMO, 10- Death
Measure: Proportion of participants who experienced deterioration from baseline Time: Day 29349 A Phase 2 Trial to Evaluate the Safety and Tolerability of Clazakizumab® [Anti-Interleukin (IL)-6 Monoclonal] Compared to Placebo for the Treatment of COVID-19 Infection
The purpose of this study is to investigate the effectiveness and safety of treatment with clazakizumab compared to a placebo (inactive substance). We are proposing to try this drug to treat coronavirus disease 2019 (COVID-19) infection. Patients with COVID-19 infection have been shown to have increases in certain inflammatory processes. Clazakizumab is an antibody (immune system protein) that blocks certain inflammatory processes. The treatment plan is to attempt to inhibit or block these inflammatory processes in order to try to limit the damage COVID-19 causes to the lungs.
NCT04494724 COVID-19 Infection Drug: Clazakizumab Drug: Placebo MeSH:Infection Communicable Diseases
Primary Outcomes
Description: Proportion of participants who experience treatment-related adverse events (TEAE) ≥ Grade 3 (CTCAE v5.0) during the first 24 hours after infusion of clazakizumab or placebo
Measure: Primary Endpoint Time: 24 hoursSecondary Outcomes
Description: Proportion of participants who need mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) after the first dose of clazakizumab or placebo
Measure: Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) Time: 14 daysDescription: Proportion of participants who experience infusion-related reactions during the first 24 hours after infusion of clazakizumab or placebo
Measure: Infusion-related reactions during 24 hours from the time of infusion Time: 24 hoursDescription: Proportion of participants alive at day 28 after the first dose of clazakizumab or placebo
Measure: Patient survival at 28 days Time: 28 daysDescription: Proportion of participants alive at day 60 after the first dose of clazakizumab or placebo
Measure: Patient survival at 60 days Time: 60 daysDescription: Proportion of participants who require an open-label dose of clazakizumab
Measure: Requirement for open-label clazakizumab Time: 14 daysDescription: Number of days in the ICU following the first dose of clazakizumab or placebo
Measure: Time in the intensive care unit (ICU) Time: 60 daysDescription: Number of days in the hospital following the first dose of clazakizumab or placebo
Measure: Time in the hospital Time: 60 daysDescription: Number of days from first dose of clazakizumab or placebo to requiring mechanical ventilation
Measure: Time to mechanical ventilation Time: 60 daysDescription: Difference in WHO Clinical Progression Scale between clazakizumab and placebo
Measure: Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14 Time: 14 daysDescription: Difference in WHO Clinical Progression Scale between clazakizumab and placebo
Measure: Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28 Time: 28 daysDescription: Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 14 from baseline between clazakizumab or placebo
Measure: Change in Radiologic Assessment of Lung Edema (RALE) at day 14 Time: 14 daysDescription: Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 28 from baseline between clazakizumab or placebo
Measure: Change in Radiologic Assessment of Lung Edema (RALE) at day 28 Time: 28 days350 A Stage 2/3, Adaptive, Randomized, Controlled, Double-blind Study to Investigate the Pharmacokinetics, Efficacy and Safety of the Hyperimmune Equine Serum (INM005) in Adult Patients With Moderate to Severe Confirmed SARS-CoV2 Disease.
This study aims to analyze the efficacy and safety of passive immunotherapy by administering an equine hyperimmune serum (INM005) against the SARS-CoV2 RBD to Covid19 patients. Improvement of the clinical course 28 days after the start of treatment will be evaluated.
NCT04494984 Covid19 Drug: INM005 Drug: Placebo
Primary Outcomes
Description: The primary endpoint will be the proportion of patients who show a change in symptoms 28 days after the administration of the first dose. A responding subject is defined as a subject with improvement in at least 2 categories on the 8-point World Health Organization (WHO) ordinal scale of clinical status or a subject who is discharged.
Measure: Clinical changes in COVID-19 symptoms Time: 4 weeksSecondary Outcomes
Description: INM005 product concentration in serum at different time points after dosing
Measure: Pharmacokinetics evaluation of INM005 Time: 1 weekDescription: Time to achieve a change in at least 2 categories on the 8-point WHO ordinal scale of clinical status. Time to discharge (days). Time to intensive care unit (ICU) discharge (days).
Measure: Time to progression of disease Time: 4 weeksDescription: Proportion of patients who present change in at least 2 categories on the 8-point WHO ordinal scale of clinical status at 7 and 14 days after the start of the treatment.
Measure: Disease progression Time: up to 2 weeksDescription: Proportion of patients discharged at 28 days
Measure: Discharge Time: up to 4 weeksDescription: Proportion of patients who require ICU hospitalization
Measure: Intensive care unit (ICU) hospitalization Time: up to 4 weeksDescription: Proportion of patients who require MVA
Measure: Mechanical ventilation assistance (MVA) Time: up to 4 weeksDescription: Proportion of patients who die due to complications from COVID19
Measure: Mortality Time: up to 4 weeksDescription: Change in viral load from baseline to 7 and 21 days after the start of the treatment.
Measure: Changes in viral load Time: up to 3 weeksOther Outcomes
Description: Measurement of anti SARS-CoV2 antibodies titer levels. IgG (0, 21 days)
Measure: Anti SARS-CoV2 antibodies levels Time: 3 weeksDescription: Changes in Troponin T levels will be evaluated at 7 and 21 days as a measurement of disease progression
Measure: Changes in Troponin T levels Time: 3 weeksDescription: Changes in D-dimer levels will be evaluated at 7 and 21 days as a measurement of disease progression
Measure: Changes in D-dimer levels Time: 3 weeksDescription: Changes in Ferritin levels will be evaluated at 7 and 21 days as a measurement of disease progression
Measure: Changes in Ferritin levels Time: 3 weeksDescription: Changes in LDH levels will be evaluated at 7 and 21 days as a measurement of disease progression
Measure: Changes in LDH levels Time: 3 weeksDescription: Changes in C-reactive protein levels will be evaluated at 7 and 21 days as a measurement of disease progression
Measure: Changes in C-reactive protein levels Time: 3 weeksDescription: Measurement of anti-INM005 antibodies: baseline and 21 days
Measure: Immunogenicity Time: 3 weeks351 A Phase 1, Randomised, Double-Blind, Placebo-Controlled, Dosage-Escalation, Single Centre Study to Evaluate the Safety and Immunogenicity of an Adjuvanted SARS-CoV-2 Sclamp Protein Subunit Vaccine in Healthy Adults Aged 18 to 55 Years Old.
This study is being conducted to look at the safety and immune response (how the immune system of the human body reacts) to a vaccine for SARS-CoV-2 (the virus responsible for COVID-19 infection) when administered as an intramuscular injection (an injection directly into the muscle) to the upper arm of healthy participants, on two occasions at least 28 days apart.
NCT04495933 SARS-CoV2 Covid19 Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg Other: Placebo
Primary Outcomes
Description: - the frequency of solicited local reactogenicity adverse events (AEs)
Measure: Frequency of Solicited local reactogenicity adverse events (AEs) Time: 7 days following each vaccination (at Days 1 and 29)Description: - the frequency of solicited systemic reactogenicity AEs
Measure: Frequency of Solicited systemic reactogenicity adverse events (AEs) Time: 7 days following each vaccination (at Days 1 and 29)Description: - the grading of solicited local reactogenicity adverse events (AEs)
Measure: Grading of Solicited local reactogenicity adverse events (AEs) Time: 7 days following each vaccination (at Days 1 and 29)Description: - the grading of solicited systemic reactogenicity AEs
Measure: Grading of Solicited systemic reactogenicity adverse events (AEs) Time: 7 days following each vaccination (at Days 1 and 29)Description: - the frequency, duration, intensity and relationship to vaccination of unsolicited local adverse events (AEs)
Measure: Unsolicited adverse events (AEs) Time: 28 days following each vaccination (at Days 1 and 29)Description: - the frequency, duration, intensity and relationship to vaccination of Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study (including decision by the Principal Investigator [PI] not to proceed with the second dose) at any time during the study
Measure: Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study Time: through study completion (394 days)Description: - Geometric mean titre (GMT) of the serum antibody response compared to placebo
Measure: Geometric Mean Titer (GMT) of the serum antibody response Time: 28 days following each vaccination (Days 29 and 57)Description: GMT of the serum NAb titres to SARS-CoV-2 virus compared to placebo
Measure: Geometric Mean Titer (GMT) of the serum neutralizing antibody (NAb) response to SARS-CoV-2 virus Time: 28 days following each vaccination (Days 29 and 57)Secondary Outcomes
Description: GMT of the serum antibody response compared to placebo
Measure: Total serum antibody immune responses Time: through study completion (394 days)Description: proportion of participants with greater than or equal to 4 fold increase in titre above baseline compared to placebo.
Measure: proportion of participants with ≥ 4 fold increase in titer above baseline Time: through study completion (394 days)Description: GMT of the serum neutralizing antibody (NAb) immune responses compared to placebo
Measure: GMT of the serum neutralizing antibody (NAb) titres Time: through study completion (394 days)352 A Prospective, Double-Blind, Placebo-controlled Study of Suramin in Subjects With Furosemide-Resistant Acute Kidney Injury (AKI): Efficacy in Preventing Dialysis Dependent AKI
This is a prospective, double-blind, randomized, placebo-controlled study to assess the effects of suramin as a potential treatment option to prevent subjects with AKI from progressing to Kidney Disease Improving Global Outcomes (KDIGO) Stage III or dialysis dependent AKI.
NCT04496596 Acute Kidney Injury Drug: Suramin Drug: Placebo MeSH:Acute Kidney Injury
HPO:Acute kidney injury
Primary Outcomes
Description: The difference between the effect of a 3.0 mg/kg infusion of suramin versus placebo will be based on meeting 2 or more of the composite event endpoints of: peak serum creatinine (Cr) of 6 mg/dL or above from investigational product (IP) infusion through Day or progression to KDIGO Stage III within 72 hours (hr) from IP infusion or death or dialysis from IP infusion through Day 7.
Measure: To evaluate and compare the efficacy of a single 3.0 mg/kg infusion of suramin versus placebo in subjects with diuretic unresponsive AKI Time: 7 days
353 A Randomized, Placebo-controlled Trial, to Evaluate the Safety and Immunogenicity of the COVID-19 Vaccine, a Measles Vector-based Vaccine Candidate Against COVID-19 in Healthy Volunteers Consisting of an Unblinded Dose Escalation and a Blinded Treatment Phase
Primary Outcomes
Description: The difference between the effect of a 3.0 mg/kg infusion of suramin versus placebo will be based on meeting 2 or more of the composite event endpoints of: peak serum creatinine (Cr) of 6 mg/dL or above from investigational product (IP) infusion through Day or progression to KDIGO Stage III within 72 hours (hr) from IP infusion or death or dialysis from IP infusion through Day 7.
Measure: To evaluate and compare the efficacy of a single 3.0 mg/kg infusion of suramin versus placebo in subjects with diuretic unresponsive AKI Time: 7 daysThis is a randomized, placebo-controlled, two center, Phase I trial in healthy adult volunteer participants consisting of two phases, an unblinded dose escalation and a double blind treatment phase to investigate the safety, tolerability and immunogenicity of a novel measles-vector based vaccine candidate against SARS-CoV-2 infection (TMV-083).
NCT04497298 COVID-19 Biological: Two COVID-19 vaccine candidate (TMV-083) administrations - Low dose Biological: Two COVID-19 vaccine candidate (TMV-083) administrations - High dose Biological: One COVID-19 vaccine candidate (TMV-083) administration - High dose Other: Placebo
Primary Outcomes
Description: Rate of solicited Adverse Event up to 14 days after each injection. Rate of unsolicited AE up to 28 days after the last injection. Rate of serious adverse events (SAEs) and adverse events of special interest (AESI) all along the study period.
Measure: To assess the safety and tolerability of the COVID-19 vaccine following one or two consecutive intramuscular injections in healthy volunteers Time: Day 390Secondary Outcomes
Description: SARS-CoV-2 specific antibodies up to study day 390 as measured by spike protein-specific ELISA
Measure: To assess induction of SARS-CoV-2 spike protein-binding antibodies upon one or two administrations of the COVID-19 vaccine by means of ELISA up to study day 390 Time: Day 390Description: SARS-CoV-2 specific antibodies up to study day 390 for each cohort as measured by neutralization assay
Measure: To assess induction of SARS-CoV-2 neutralizing antibodies upon one or two administrations of the COVID-19 vaccine by means of serum neutralization assay up to study day 390 Time: Day 390Description: SARS-CoV-2 spike protein-specific cell-mediated immune response up to study day 390 induced by one or two doses as measured by intracellular staining
Measure: To assess SARS-CoV-2 spike protein-specific, cell-mediated immune responses induced by one or two doses of vaccine, by means of intracellular staining Time: up to Day 390Description: SARS-CoV-2 spike protein-specific cell-mediated immune response up to study day 390 induced by one or two doses as measured by flow cytometry
Measure: To assess SARS-CoV-2 spike protein-specific, cell-mediated immune responses induced by one or two doses of vaccine, by means of flow cytometry Time: up to Day 390Description: Occurrence of measles virus shedding as evidenced by a positive RT-PCR for saliva, nasal swab, urine, or blood sample in sentinel groups.
Measure: To assess potential measles virus shedding by means of RT-qPCR of saliva, nasal swab, urine, or blood samples in sentinel groups on day 0 and up to day 42 Time: up to Day 42Other Outcomes
Description: Measles virus antibody levels as assessed by standard ELISA assays on day 0 and day 28.
Measure: To assess the anti-measles antibody levels at baseline and on day 28 by ELISA Time: up to Day 28Description: SARS-CoV-2 N protein specific antibody up to study day 390 as measured by ELISA to differentiate the response to the COVID-19 vaccine from infection
Measure: To assess the natural exposure of the subjects to SARS-CoV-2 during the duration of the trial by means of N protein-specific ELISA Time: Day 390Description: Occurrence of confirmed COVID-19 (i.e. asymptomatic, paucisymptomatic or symptomatic) cases in the study participant all along the study period
Measure: To assess the occurrence of COVID-19 cases in study participants all along the duration of the study Time: Day 390354 A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of LY3819253 in Preventing SARS-CoV-2 Infection and COVID-19 in Skilled Nursing and Assisted Living Facility Residents and Staff; a NIAID and Lilly Collaborative Study
The purpose of this study is to evaluate whether LY3819253 prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease - 2019 (COVID-19) in facility staff and residents in contracted skilled nursing and assisted living facility networks with a high risk of SARS-CoV-2 exposure. Participants with a high risk of SARS-CoV-2 exposure will receive LY3819253 or placebo via an injection into a vein. Samples will be taken from the nose. Blood samples will be drawn. Participation could last up to 25 weeks and may include up to 19 visits.
NCT04497987 COVID-19 SARS-CoV2 Drug: LY3819253 Drug: Placebo MeSH:Infection
Primary Outcomes
Description: Percentage of Participants with SARS-CoV-2 Infection
Measure: Percentage of Participants with SARS-CoV-2 Infection Time: Week 4Secondary Outcomes
Description: Percentage of Participants with Moderate or Worse Severity COVID-19
Measure: Percentage of Participants with Moderate or Worse Severity COVID-19 Time: Week 8Description: Percentage of Participants with Mild or Worse Severity COVID-19
Measure: Percentage of Participants with Mild or Worse Severity COVID-19 Time: Week 8Description: Percentage of Participants Who are Hospitalized due to COVID-19
Measure: Percentage of Participants Who are Hospitalized due to COVID-19 Time: Week 8Description: Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death
Measure: Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death Time: Week 8Description: Percentage of Participants Who Die Due to COVID-19
Measure: Percentage of Participants Who Die Due to COVID-19 Time: Week 8355 A Phase 1/Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Safety, Tolerability and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Younger and Older Participants
The primary objective of this early Phase 1 study is to identify the V591 dose that achieves the target immune response in humans based on preclinical or early clinical data.
NCT04498247 Coronavirus Disease (COVID-19) Biological: V591 Other: Placebo MeSH:Coronavirus Infections
Primary Outcomes
Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measure: Percentage of Participants with at Least 1 Solicited Injection Site Adverse Event Time: Up to ~5 days after vaccinationDescription: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measure: Percentage of Participants with at Least 1 Solicited Systemic Adverse Event Time: Up to ~14 days after vaccinationDescription: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measure: Percentage of Participants with at Least 1 Unsolicited Adverse Event Time: Up to ~28 days after vaccinationDescription: A serious adverse event is "life threatening," requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect.
Measure: Percentage of Participants with at Least 1 Serious Adverse Event Time: Up to ~365 days (±14 days) after vaccinationDescription: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measure: Percentage of Participants who Discontinued Study Treatment due to an Adverse Event Time: Up to ~365 days (±7 days) after vaccinationSecondary Outcomes
Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.
Measure: Geometric Mean Titers for Serum Neutralizing Antibodies (nAb) as Measured by Plaque Reduction Neutralization Test (PRNT): All Panels Time: Day 29Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.
Measure: Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA): All Panels Time: Day 29Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.
Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by Plaque Reduction Neutralization Test (PRNT): Panels A,B, I and J Time: Day 85Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.
Measure: Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA): Panels A,B, I and J Time: Day 85Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.
Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by Plaque Reduction Neutralization Test (PRNT): Panels K and L Time: Day 197Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.
Measure: Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA): Panels K and L Time: Day 197Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.
Measure: Geometric Mean Titers for Serum Neutralizing Antibodies (nAb) as Measured by Plaque Reduction Neutralization Test (PRNT) Time: Panels C-H: Days 1, 15, 29, 57, 85, 115, 211, and 365; Panels A,B, I and J: Days 1, 15, 29, 57, 71, 85, 115, 211, and 422; Panels K and L: Days 1, 15, 29, 85, 169, 197, 365 and 534Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.
Measure: Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) Time: Panels C-H: Days 1, 15, 29, 57, 85, 115, 211, and 365; Panels A,B, I and J: Days 1, 15, 29, 57, 71, 85, 115, 211, and 422; Panels K and L: Days 1, 15, 29, 85, 169, 197, 365 and 534356 COVID-19 Outpatient Thrombosis Prevention Trial: A Multi-center Adaptive Randomized Placebo-controlled Platform Trial Evaluating the Efficacy and Safety of Anti-thrombotic Strategies in COVID-19 Adults Not Requiring Hospitalization at Time of Diagnosis
A multi-center adaptive randomized placebo-controlled platform trial evaluating the efficacy and safety of anti-thrombotic strategies in COVID-19 adults not requiring hospitalization at time of diagnosis
NCT04498273 COVID-19 Drug: Apixaban 2.5 MG Drug: Apixaban 5MG Drug: Aspirin Drug: Placebo MeSH:Thrombosis
Primary Outcomes
Description: The primary outcome will be a composite endpoint of need for hospitalization for cardiovascular/pulmonary events, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality for up to 45 days after initiation of assigned treatment.
Measure: Primary Time: 45 days357 A Phase I and Pilot Study Evaluating the Effect of NT-I7, a Long Acting Interleukin-7, to Increase Lymphocyte Counts and Enhance Immune Clearance of SARS-CoV-2
Lymphopenia is common in patients with COVID-19 and is associated with worse clinical outcomes. NT-I7 is a long-acting human interleukin-7 (IL-7) that has been shown to increase absolute lymphocyte count (ALC) and CD4+ and CD8+ T cell counts with a well-tolerated safety profile in humans. In this study, patients who have tested positive for SARS-CoV-2 by PCR testing without severe disease and with ALC <1500 cells/mm3 will be enrolled.
NCT04498325 COVID-19 SARS-CoV-2 Drug: NT-I7 Drug: Placebo Procedure: Blood for research purposes Procedure: Blood for pharmacokinetic samples Procedure: Nasopharyngeal, oropharyngeal, or saliva swab Procedure: Blood for anti-drug antibody (ADA)
Primary Outcomes
Description: The safe tolerated dose is defined as the dose level immediately below the dose level at which 1 patient of a cohort of 3 patients experiences dose-limiting toxicity within 14 days after administration of NT-I7 Dose limiting toxicities (DLT) are defined as: A serious adverse event that is at least possibly related to NT-I7 A grade 3 or higher adverse event that is at least possibly related to NT-I7 (excluding injection site swelling, irritation or discomfort) A clinically significant lab abnormality that is at least possibly related to NT-I7
Measure: Safe and tolerable dose of NT-I7 (Phase I only) Time: Completion of DLT assessment window of Phase I portion of study (estimated to be 8 months)Measure: Percent change in absolute lymphocyte count (ALC) Time: From baseline to Day 14
Secondary Outcomes
Measure: Percent change in absolute lymphocyte count (ALC) Time: From baseline through Day 21Description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva
Measure: Change in SARS-CoV-2 viral load Time: From baseline to Day 7Description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva
Measure: Change in SARS-CoV-2 viral load Time: From baseline to Day 14Measure: COVID-19 Symptom severity as measured by WHO Ordinal Scale for clinical improvement Time: From baseline, day 7, day 14, and day 21
Measure: Time to resolution of COVID-19 symptoms Time: From baseline through Day 21
Description: -A treatment emergent adverse event (TEAE) is defined as any event that begins or worsens on or after date of first dose of study treatment.
Measure: Incidence of treatment-emergent adverse events Time: From baseline through Day 21Description: -If quantitative PCR is not available
Measure: Number of participants by PCR result status (positive or negative) Time: -From baseline to Day 7Description: -If quantitative PCR is not available
Measure: Number of participants by PCR result status (positive or negative) Time: From baseline to Day 14358 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Multicenter Study to Evaluate the Efficacy and Safety of F-652 (IL-22:IgG2 Fusion Protein) in Patients With Moderate to Severe COVID-19
This is an interventional, multicenter, 2-arm, parallel-group, randomized, double-blind, placebo controlled, dose-escalation, safety and efficacy study of F-652 treatment versus placebo in patients aged 18 years or older with a COVID-19 diagnosis confirmed by PCR. Eligible patients will have moderate to severe COVID-19 symptoms within 5 days post hospitalization and a positive COVID-19 testing.
NCT04498377 Covid19 Biological: F-652 Biological: Placebo
Primary Outcomes
Description: The proportion of patients with a greater or equal 2-point change in the NIAID 8-point ordinal scale from baseline to Day 29
Measure: NIAID 8-point ordinal scale Time: Study day 1 before dose to day 29359 Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients
The aim of this study is to test Cenicriviroc (CVC) as a means to reduce the severity of the lung disease COVID-19 caused by an infection with SARS-CoV-2. The safety of CVC, when administered to COVID-19 patients, will also be assessed. Furthermore, the clinical trial aims to answer the question of whether patients with pre-existing conditions, who have an increased risk of severe COVID-19 progression, benefit more and particularly from CVC. CVC is an orally available dual inhibitor of the chemokine receptors CCR2 and CCR5, which is expected to reduce (hyper-) inflammation in COVID-19. The main goal of the study is to determine whether CVC helps increase the number of patients who are symptom-free and not hospitalized after 14 days compared to a placebo. Approximately 66.7% of the patients enrolled in the study will receive CVC and 33.3% will get an optically identical pill (placebo). Subjects will be assessed daily while hospitalized. Discharged patients will be asked to attend study visits at Days 8, 15, 22, and 29 and 85. All subjects will undergo a series of clinical, safety, and laboratory assessments. Blood samples and oropharyngeal (OP) swabs will be obtained on Day 1; 3, 5 (while hospitalized); and Day 8, 15 and 29 (if able to return to clinic or still hospitalized). The presence of anti-SARS-CoV-2 antibodies will be determined on Days 29 and 85.
NCT04500418 Covid19 Drug: Cenicriviroc (CVC) Drug: Placebo
Primary Outcomes
Description: The Primary Endpoint will be the subject's responder status defined by achieving a score of "1" or "2" (discharged from hospital e.g.) on Day 15 on the following 7-point scale: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high-flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO (Extracorporeal membrane oxygenation); Death.
Measure: Subject´s Responder status (score on the 7-point ordinal scale on Day 15) Time: 14 days after enrollment (Day 15)Secondary Outcomes
Description: 7-point ordinal scale to be assessed on Day 15 (and Day 1 for baseline comparison), analyses of ordinal change of 2 or more, compared with baseline ordinal change of 1 or more, compared with baseline
Measure: Evaluation of change in clinical condition based on the 7-point ordinal scale Time: day of enrollment and 15 days after enrollmentDescription: 7-point ordinal scale assessed on: Days 8, 22, 29 (and Day 1 for baseline comparison), analyses of: Responder status (achieving a score of a "1" or a "2") ordinal change of 2 or more, compared with baseline ordinal change of 1 or more, compared with baseline
Measure: Evaluation of change in clinical condition based on the 7-point ordinal scale and Responder Status Time: day of enrollment, 8 days, 22 days and 29 days after enrollmentDescription: Analysis of: Length of time spent in the ICU (days) Length of time spent in the hospital (days) Days alive and out of hospital through Day 29 Days free of endotracheal tube-based ventilation through Day 29
Measure: Hospital resource utilization comparison Time: 29 days after enrollment, 85 days after enrollment360 A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19
This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.
NCT04501978 Covid19 Drug: LY3819253 Drug: Placebo Drug: Remdesivir
Primary Outcomes
Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary ordinal outcome (Stage 1) Time: Day 5Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary+ ordinal outcome (Stage 1) Time: Day 5Description: Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
Measure: Time from randomization to sustained recovery (Stage 2) Time: Up to Day 90Secondary Outcomes
Measure: All-cause mortality Time: Thru Day 90Measure: Composite of time to sustained recovery and mortality Time: Thru Day 90
Measure: Days alive outside short-term acute care hospital Time: Up to Day 90
Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary ordinal outcome Time: Days 1-7, 14 and 28Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary+ ordinal outcome Time: Days 1-7Description: Total of: Respiratory rate (breaths per minute) scored from 0 to +3; Oxygen saturation (%) scored from 0 to +3; Any supplemental oxygen scored from 0 to +2; Temperature scored from 0 to +3; Systolic BP scored from 0 to +3; Heart rate (beats per minute) scored from 0 to +3.; and AVPU (alert, voice, pain, unresponsive) scored from 0 to +3. A higher score denotes a worse outcome.
Measure: Change in New Early Warning (NEW) Score Time: Baseline to Day 5Measure: Incidence of clinical organ failure Time: Thru Day 28
Measure: Composite of death or serious clinical COVID-19 related events Time: Thru Day 90
Measure: Composite of cardiovascular events and thromboembolic events Time: Thru Day 90
Measure: Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death Time: Thru Days 5 and 28
Measure: Incidence of infusion reactions Time: Thru Day 0
Measure: Composite of SAEs or death Time: Thru Day 90
Measure: Change in SARS-CoV-2 neutralizing antibody levels Time: Baseline to Days 1, 3, 5, 28 and 90
Measure: Change in overall titers of antibodies Time: Baseline to Days 1, 3, 5, 28 and 90
Measure: Change in neutralizing antibody levels Time: Baseline to Days 1, 3, 5, 28 and 90
361 A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19
The purpose of this study is to assess safety and clinical efficacy of rivaroxaban in people with mild Coronavirus Disease 2019 who are at increased risk of disease progression.
NCT04504032 COVID-19 Drug: Rivaroxaban Drug: Placebo
Primary Outcomes
Measure: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) Time: Up to approximately 35 daysMeasure: Number of Participants With AEs Leading to Study Discontinuation Time: Up to approximately 35 days
Measure: Number of Participants With Serious Adverse Events (SAEs) Time: Up to approximately 35 days
Description: Disease progression is defined as the proportion of participants who progress to moderate or severe disease category or higher (Gates Medical Research Institute ordinal scale ≥3). The assessments will be performed using Gates Medical Research Institute ordinal scale.
Measure: Proportion of Participants With Disease Progression Time: Up to Day 28Secondary Outcomes
Description: Time to disease resolution is defined as symptoms resolution (new onset Coronavirus Disease 2019 [COVID-19] symptoms resolved, and pre-existing symptoms returned to baseline) with viral clearance (two consecutive negative diagnostic tests) through Day 28. Baseline refers to health status prior to contracting new onset COVID-19 symptoms.
Measure: Median Time to Disease Resolution Time: Up to Day 28Description: Time to disease resolution is defined as symptoms resolution only (new onset COVID-19 symptoms resolved, and preexisting symptoms returned to baseline) through Day 28. Baseline refers to health status prior to contracting new onset COVID-19 symptoms.
Measure: Median Time to Disease Resolution Time: Up to Day 28Measure: Proportion of Participants With Disease Progression Time: Days 8, 14, and 21
Measure: Proportion of Participants Who Achieve Disease Resolution Time: Days 8, 14, 21, and 28
Measure: Mean Gates Medical Research Institute Ordinal Scale Score Time: Days 8, 14, 21, and 28
Measure: Change From Baseline in Gates Medical Research Institute Ordinal Scale Score Time: Days 8, 14, 21, and 28
Measure: Mean World Health Organization Ordinal Scale Score Time: Days 8, 14, 21, and 28
Measure: Change From Baseline in World Health Organization Ordinal Scale Score Time: Days 8, 14, 21, and 28
Measure: Incidence of Hospitalization Time: Days 8, 14, 21, and 28
Measure: Number of Days of Hospitalization Time: Days 8, 14, 21, and 28
362 A Randomized, Double-blind, Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) Doses of GSK3494245 in Healthy Participants
This is a Phase 1, double-blind, randomized, placebo-controlled, first time in human (FTIH) study to assess the safety, tolerability and PK of a single dose of GSK3494245. The study will consist of 3 cohorts, conducted in a sequential manner. Cohorts 1 and 2 will consist of a single ascending dose (SAD), crossover design where each participant will receive a maximum of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. At each dose level, GSK3494245 and placebo will be administered in a 3:1 ratio, within each period, according to the randomization schedule in a blinded manner. Cohort 3 will comprise of a 2-way crossover which includes 1 dosing regimen under fasted then fed conditions and 1 regimen under fed then fasted conditions in a 1:1 ratio. The fed conditions will investigate the effect of safety, tolerability and PK of a single dose of GSK3494245 following food administration.
NCT04504435 Leishmaniasis Drug: GSK3494245 Drug: Placebo MeSH:Leishmaniasis
Primary Outcomes
Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Time: Up to 14 days post last dose in each treatment periodDescription: Treatment emergent AE and SAE are any untoward medical occurrences in a clinical study participant, having causal relation with the use of a study intervention.
Measure: Number of participants with treatment emergent AEs and SAEs Time: Up to 14 days post last dose in each treatment periodDescription: Blood samples will be collected for the assessment of hematology parameters.
Measure: Number of participants with clinically significant abnormal findings in hematology parameters Time: Up to 14 days post last dose in each treatment periodDescription: Blood samples will be collected for the assessment of chemistry parameters
Measure: Number of participants with clinically significant abnormal findings in clinical chemistry parameters Time: Up to 14 days post last dose in each treatment periodDescription: Urine samples will be collected for the assessment of urinalysis parameters.
Measure: Number of participants with urinalysis findings Time: Up to 14 days post last dose in each treatment periodDescription: Number of participants with abnormal vital signs will be assessed.
Measure: Number of participants with clinically significant abnormal findings in vital signs Time: Up to 14 days post last dose in each treatment periodDescription: Triplicate 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS interval, QT interval, Corrected QT (QTc) interval.
Measure: Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters Time: Up to 14 days post last dose in each treatment periodDescription: Telemetry is the continuous monitoring of a participants heart rate and rhythm from a remote location. Continuous cardiac telemetry will start in a supine position after at least 5 minutes rest.
Measure: Number of participants with abnormal cardiac telemetry findings Time: Up to 24 hours post dose on Day 1Secondary Outcomes
Description: Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fasting condition.
Measure: Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration under fasting condition Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 minutes [min], 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fed condition.
Measure: AUC (0-t) of GSK3494245 following single dose administration under fed condition Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate AUC (0-inf) of GSK3494245 under fasting condition.
Measure: AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245 under fed condition.
Measure: AUC (0-inf) of GSK3494245 following single dose administration under fed condition Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fasting condition.
Measure: Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting condition Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fed condition.
Measure: Cmax of GSK3494245 following single dose administration under fed condition Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fasting condition.
Measure: Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting condition Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fed condition.
Measure: Tmax of GSK3494245 following single dose administration under fed condition Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
Measure: Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting condition Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
Measure: t1/2 of GSK3494245 following single dose administration under fed condition Time: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Urine samples will be collected at the indicated time points to evaluate Ae0-24h of GSK3494245.
Measure: Amount of GSK3494245 excreted in urine over 24 hours (Ae0-24h) following single dose administration Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Urine samples will be collected at the indicated time points to evaluate fe% of GSK3494245
Measure: Fraction of dose excreted in urine over 24 hours (fe%) of GSK3494245 following single dose administration Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Urine samples will be collected at the indicated time points to evaluate CLr of GSK3494245.
Measure: Renal Clearance (CLr) of GSK3494245 following single dose administration Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245.
Measure: Dose-proportionality assessment using AUC(0-inf) following single dose of GSK3494245 Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)Description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245.
Measure: Dose-proportionality assessment using Cmax following single dose of GSK3494245 Time: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)363 Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients With Mild-Moderate COVID-19
This is a Phase 3, multi-center, randomized, double blind, placebo controlled, clinical study of bucillamine (2 dosage levels) in patients with mild-moderate COVID-19. Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine 200 mg TID or placebo TID for up to 14 days. After the first interim analysis when a single dose is selected, patients will then be randomized 2:1 to the selected bucillamine dose or placebo The study will be overseen by an independent Data and Safety Monitoring Board (DSMB). Up to 10 centers in the United States will conduct this study. Up to 1000 patients will be enrolled in this study. Patients will participate in the study approximately 45 days.
NCT04504734 Covid19 Drug: Bucillamine Drug: Placebo Drug: Bucillamine
Primary Outcomes
Description: Proportion of patients meeting a composite endpoint of hospitalization or death
Measure: Efficacy: Frequency of hospitalization or death Time: From time of first dose through Day 28 following randomizationSecondary Outcomes
Description: Number of adverse events
Measure: Safety: Changes in adverse events from baseline to end of study Time: From time of first dose through Day 28 following randomization364 Tenecteplase With Concomitant Anticoagulation for Severe Acute Respiratory Failure in Patients With COVID-19
This is a placebo-controlled, double blind, randomized, Phase II dose escalation study intended to evaluate the potential safety and efficacy of tenecteplase for the treatment of COVID-19 associated respiratory failure. The hypothesis is that administration of the drug, in conjunction with heparin anticoagulation, will improve patients' clinical outcomes.
NCT04505592 COVID-19 Respiratory Failure ARDS Drug: Tenecteplase Drug: Placebo MeSH:Respiratory Insufficiency
Primary Outcomes
Description: The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days
Measure: Number of participants free of respiratory failure Time: 28 DaysDescription: Safety as assessed by number of occurrences of intracranial bleeding or major bleeding
Measure: Number of occurrences of bleeding Time: 28 daysSecondary Outcomes
Measure: Number of participants with in-hospital deaths at 14 days Time: 14 daysMeasure: Number of participants with death at 28 days Time: 28 days
Measure: Number of ventilator-free days Time: 28 days
Description: Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation
Measure: Number of respiratory failure-free days Time: 28 daysMeasure: Number of vasopressor-free days Time: 28 days
Measure: Vasopressor doses at 24 hours Time: 24 hours
Measure: Vasopressor doses at 72 hours Time: 72 hours
Description: The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).
Measure: P/F ratio at 24 hours Time: 24 hoursDescription: The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).
Measure: P/F ratio at 72 hours Time: 72 hoursMeasure: Number of ICU-free days Time: 28 days
Measure: Hospital length of stay Time: 28 days
Measure: Number of participants with new-onset renal failure Time: 28 days
Measure: Number of participants with need for renal replacement therapy Time: 28 days
365 A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older
The purpose of the study is to demonstrate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical COVID-19, as compared to placebo, in SARS-CoV-2 adult participants.
NCT04505722 Healthy Biological: Ad26.COV2.S Other: Placebo
Primary Outcomes
Description: Moderate defined as one sign and one symptom from a list of signs, such as respiratory rate >90 and symptoms such as shortness of breath or cough or 2 symptoms from a list of symptoms or Severe COVID-19 defined in FDA guidance.
Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status Time: Up to 2.1 yearsSecondary Outcomes
Description: Moderate defined as one sign and one symptom from a list of signs, such as respiratory rate >90 and symptoms such as shortness of breath or cough or 2 symptoms from a list of symptoms or Severe COVID-19 defined in FDA guidance.
Measure: Number of Participants with First Occurrence of Molecularly confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus Time: Up to 2.1 yearsDescription: Moderate defined as one sign and one symptom from a list of signs, such as respiratory rate >90 and symptoms such as shortness of breath or cough or 2 symptoms from a list of symptoms or Severe COVID-19 defined in FDA guidance.
Measure: Number of Participants with First Occurrence of Molecularly confirmed Moderate to Severe/Critical Coronavirus Disease COVID-19 with Seronegative Status Time: Day 2 (1 day post-vaccination)Description: Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), linked to objective measures such as decreased oxygenation, X-ray or CT findings) or linked to any molecularly confirmed, COVID-19 at least 28 days post vaccination will be reported.
Measure: Number of Participants with First Occurrence of COVID-19 Requiring Medical Intervention Time: Day 29 (28 days post- vaccination)Description: The viral load of SARS-CoV-2 will be assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs will be used to detect and/or quantify SARS-CoV-2.
Measure: SARS-CoV-2 Viral Load as Assessed by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) in Participants with Molecularly Confirmed, Moderate to Severe/Critical COVID-19 Time: Day 29 (28 days post vaccination)Description: Molecularly confirmed mild COVID-19 is defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Mild COVID-19 includes: Fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, or chills, without shortness of breath or dyspnea.
Measure: Number of Participants with First Occurrence of Molecularly confirmed Mild COVID-19 Time: Day 29 (28 days post vaccination)Description: Molecularly confirmed moderate and severe/critical COVID-19 defined as a positive SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case Definition at the time of finalization of this protocol: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.
Measure: Number of Participants with First Occurrence of Molecularly confirmed COVID-19 Defined by the US Food and Drug Administration (FDA) Harmonized case Definition Time: Day 29 (28 days post vaccination)Description: Number of participants with first occurrence of molecularly confirmed COVID-19 with any severity (Moderate, Mild, severe/Critical) will be reported.
Measure: Number of Participants with First Occurrence of Molecularly Confirmed COVID-19 with any Severity (Moderate, Mild, Severe/Critical) Time: Day 29 (28 days post vaccination)Description: Serologic conversion between baseline and 1 year post-vaccination using an ELISA and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein will be reported.
Measure: Serologic Conversion Between Baseline and 1- year Post-vaccination using an Enzyme-linked Immunosorbent Assay (ELISA) Time: Between baseline and 1-year post-vaccination (up to 52 weeks)Description: SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
Measure: Number of Participants with Serious Adverse Events (SAEs) Time: Up to 104 weeksDescription: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.
Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs) Time: Up to 6 monthsDescription: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs.
Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs) Leading to Study Discontinuation Time: Up to 104 weeksDescription: Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post-vaccination (day of vaccination and the subsequent 7 days).
Measure: Number of Participants with Solicited Local Adverse Events (AEs) During 7 Days after Vaccination Time: Up to Day 8 (7 Days after first vaccination on Day 1)Description: Participants will be instructed on how to record daily temperature using a thermometer provided for home use. Participants should record the temperature in the e-Diary in the evening of the day of vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement is made on any given day, the highest temperature of that day will be recorded in the e-Diary. Fever is defined as endogenous elevation of body temperature >= 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily basis for 7 days post-vaccination (day of vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.
Measure: Number of Participants with Solicited Systemic AEs During 7 Days After Vaccination Time: Up to Day 8 (7 Days after first vaccination on Day 1)Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.
Measure: Number of Participants with Unsolicited Local Adverse Events (AEs) During 28 Days Post-vaccination Time: Up to Day 29 (28 days after first vaccination on Day 1)Description: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported
Measure: SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA) Time: Up to 104 weeksDescription: SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.
Measure: SARS-CoV-2 Binding Antibodies Assessed by ELISA Time: Up to 104 weeks366 A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD7442 in Healthy Adults
In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs). The study is intended to enable future studies of AZD7442's efficacy in preventing and treating COVID-19.
NCT04507256 COVID-19 Combination Product: AZD7442 Other: Placebo
Primary Outcomes
Description: Safety and tolerability will be evaluated in terms of number of participants with AEs/SAEs, abnormal values of vital signs, safety laboratory parameters, 12 lead safety electrocardiogram, injection site reactions, and physical examination.
Measure: Number of participants with adverse events (AEs) and serious AEs Time: From Day 1 to up to last follow-up day (Day 361)Secondary Outcomes
Description: Cmax will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Observed maximum concentration (Cmax) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: Tmax will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Time to reach maximum concentration (Tmax) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: t½λz will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Terminal elimination half life, estimated as (ln2)/λz (t½λz) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: AUClast will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Area under the concentration curve from time zero to the time of last quantifiable concentration (AUClast) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: AUCinf will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Area under the concentration time curve from time zero extrapolated to infinity (AUCinf) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: Vss will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Volume of distribution at steady state (Vss) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: Vz will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Volume of distribution at terminal phase (Vz) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: CL will be assessed after IV infusion of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Systemic clearance (CL) (IV infusion) Time: From Day 1 to up to last follow-up day (Day 361)Description: Cmax will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Cmax (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: Tmax will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Tmax (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: t½λz will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: t½λz (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: AUClast will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: AUClast (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: AUCinf will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: AUCinf (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: CL/F will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Extravascular systemic clearance (CL/F) (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: F will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Bioavailability (F) (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: Vz/F will be assessed after IM injection of AZD7442 using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.
Measure: Extravascular terminal-phase volume of distribution (Vz/F) (IM injection) Time: From Day 1 to up to last follow-up day (Day 361)Description: The incidence of ADAs to AZD7442 in serum will be summarised by number and percentage of participants who are ADA positive. The ADA titer will be listed by participant at different time points.
Measure: Number and percentage of participants who are ADA positive Time: From Day 1 to up to last follow-up day (Day 361)367 A Multicenter, Randomized, Placebo-Controlled, Pragmatic Phase 3 Study Investigating the Efficacy and Safety of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19 Infection
The purpose of this study is to evaluate whether rivaroxaban reduces the risk of a composite endpoint of major venous and arterial thrombotic events, all-cause hospitalization, and all-cause mortality compared with placebo in outpatients with acute, symptomatic Coronavirus Disease 2019 (COVID-19) Infection.
NCT04508023 Coronavirus Disease 2019 (COVID-19) Drug: Rivaroxaban Other: Placebo Other: Standard of Care (SOC) MeSH:Coronavirus Infections
Primary Outcomes
Description: Time to first occurrence of a composite endpoint of symptomatic venous thromboembolism (VTE), myocardial infarction (MI), ischemic stroke, acute limb ischemia, noncentral nervous system (non-CNS) systemic embolization, all-cause hospitalization, and all-cause mortality will be assessed.
Measure: Time to First Occurrence of a Composite Endpoint of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, All-cause Hospitalization and All-cause Mortality Time: Up to Day 35Secondary Outcomes
Description: Time to first occurrence of a composite endpoint of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-CNS systemic embolization, and all-cause mortality will be assessed.
Measure: Time to First Occurrence of a Composite Endpoint of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, and All-cause Mortality Time: Up to Day 35Description: Time to first occurrence of all-cause hospitalization will be assessed.
Measure: Time to First Occurrence of All-cause Hospitalization Time: Up to Day 35Description: Time to first occurrence of symptomatic VTE which includes DVT or pulmonary embolism (PE) will be assessed.
Measure: Time to First Occurrence of Symptomatic VTE Time: Up to Day 35Description: Time to first occurrence of an ER visit will be assessed.
Measure: Time to First Occurrence of an Emergency Room (ER) Visit Time: Up to Day 35Description: Time to first occurrence of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-CNS systemic embolization, and all-cause hospitalization will be assessed.
Measure: Time to First Occurrence of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, and All-cause Hospitalization Time: Up to Day 35Description: Percentage of participants who are hospitalized or dead from any cause at Day 35 will be assessed.
Measure: Percentage of Participants who are Hospitalized or Dead From Any Cause Time: Day 35Description: Time to all-cause mortality up to Day 35 will be assessed.
Measure: Time to All-cause Mortality up to Day 35 Time: Up to Day 35Description: Time to first occurrence of ISTH critical site and fatal bleeding will be assessed.
Measure: Time to First Occurrence of International Society on Thrombosis and Hemostasis (ISTH) Critical Site and Fatal Bleeding Time: Up to 37 Days (last dose on Day 35 plus 2 Days)Description: Time to first occurrence of ISTH major bleeding will be assessed. Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome.
Measure: Time to First Occurrence of ISTH Major Bleeding Events Time: Up to 37 Days (last dose on Day 35 plus 2 Days)Description: Time to first occurrence of clinically relevant non-major bleeding will be assessed. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, or unscheduled contact with a physician, or temporary cessation of study treatment, or discomfort such as pain, or impairment of activities of daily life.
Measure: Time to First Occurrence of Clinically Relevant Non-major Bleeding Time: Up to 37 Days (last dose on Day 35 plus 2 Days)368 A Phase III, Observer-blind, Randomized, Placebo-controlled Study of the Efficacy, Safety and Immunogenicity of SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 Years in Indonesia
This phase III trial aims to assess the efficacy, safety and immunogenicity of SARS-CoV-2 Vaccine (inactivated) and lot-to-lot consistency evaluation
NCT04508075 SARS-CoV2 Infection Biological: SARS-CoV-2 vaccine (inactivated) Biological: Placebo MeSH:Infection
Primary Outcomes
Description: Percentage of laboratory-confirmed COVID-19 cases
Measure: Incidence of laboratory-confirmed COVID-19 after the second dose Time: 14 days to 6 months after the second doseSecondary Outcomes
Description: Percentage of suspected COVID-19 cases
Measure: Incidence of suspected COVID-19 cases Time: within 14 days to 6 months after the second dose.Description: Percentage of laboratory-confirmed cases (severe, critical, death)
Measure: Incidence of laboratory-confirmed cases (severe, critical and death) Time: within 14 days to 6 months after the second doseDescription: Percentage of subjects with four-fold increasing anti-S antibody IgG titer (ELISA) compare to baseline and between batches
Measure: Seroconversion rate anti-S antibody IgG titer (ELISA) Time: 14 days after two doses of vaccinationDescription: Percentage of subjects with four-fold increasing anti-S antibody IgG titer (ELISA) compare to baseline and between batches
Measure: Seroconversion rate anti-S antibody IgG titer (ELISA) Time: 6 months after two doses of vaccinationDescription: Percentage of subjects with four-fold increasing serum neutralizing antibody compared to baseline and between batches
Measure: Seropositive rate of neutralizing antibodies Time: 14 days after two doses of vaccinationDescription: Percentage of subjects with four-fold increasing serum neutralizing antibody compared to baseline and between batches
Measure: Seropositive rate of neutralizing antibodies Time: 6 months after two doses of vaccinationOther Outcomes
Description: Number of Local reactions and systemic events
Measure: Local reaction and systemic events Time: 30 minutes to 14 days after each vaccinationDescription: Number of Local reactions and systemic events
Measure: Local reaction and systemic events occurring after the last vaccination Time: 14 days to 28 days following last vaccinationDescription: Number of any SAE occur
Measure: Serious adverse events during study Time: 6 months after the last dose369 A Randomized, Double-blind, Placebo-controlled Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.COV2.S in Adults
The purpose of this study is to assess the safety and reactogenicity of Ad26.COV2.S administered intramuscularly (IM) at 2-dose levels, as 2-dose schedule in healthy participants aged greater than or equal to 20 years in good health with or without stable underlying conditions.
NCT04509947 Healthy Biological: Ad26.COV2.S Biological: Placebo
Primary Outcomes
Description: Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically questioned and which are noted by participants in their diary for 7 days post first vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling and induration at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
Measure: Number of Participants with Solicited Local Adverse Events (AEs) for 7 days after First Vaccination Time: Day 8 (7 days after first vaccination on Day 1)Description: Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically questioned and which are noted by participants in their diary for 7 days post second vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling and induration at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
Measure: Number of Participants with Solicited Local AEs for 7 days after Second Vaccination Time: Day 64 (7 days after second vaccination on Day 57)Description: Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia.
Measure: Number of Participants with Solicited Systemic AEs for 7 days after First Vaccination Time: Day 8 (7 days after first vaccination on Day 1)Description: Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia.
Measure: Number of Participants with Solicited Systemic AEs for 7 days after Second Vaccination Time: Day 64 (7 days after second vaccination on Day 57)Description: Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.
Measure: Number of Participants with Unsolicited AEs for 28 days after First Vaccination Time: Day 29 (28 days after first vaccination on Day 1)Description: Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.
Measure: Number of Participants with Unsolicited AEs for 28 days after Second Vaccination Time: Day 85 (28 days after second vaccination on Day 57)Description: SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.
Measure: Number of Participants with Serious Adverse Events (SAEs) Time: Up to 12 monthsSecondary Outcomes
Description: SARS-CoV‑2 neutralization will be measured by VNA to analyse the neutralizing antibodies to the wild-type virus and/or pseudovirion expressing S protein.
Measure: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Neutralization as measured by Virus Neutralization Assay (VNA) Time: Up to 12 monthsDescription: SARS-CoV-2 binding antibodies will be measured by ELISA to analyse the antibodies binding to the SARS-CoV-2 S protein.
Measure: SARS-CoV-2‑Binding Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) Time: Up to 12 months370 Randomized Trial of Bicalutamide to Block TMPRSS2 in Males With COVID-19 Infection
COVID-19 outcomes are worse in male patients. Androgen signaling, therefore, is a target for clinical exploration. TMPRSS2 is a membrane protease required for COVID pathogenesis that is regulated by androgens. Blocking TMPRSS2 with bicalutamide may reduce viral replication and improve the clinical outcome. Therefore, the study proposes to test bicalutamide at 150 mg oral daily dosing in a double-blind placebo-controlled randomized trial in male patients with early symptomatic COVID-19 disease.
NCT04509999 COVID-19 Drug: Bicalutamide 150 Mg Oral Tablet Drug: Placebo MeSH:Infection
Primary Outcomes
Description: COVID-19 symptom relief at day 28, and % of COVID-19 symptom relief and its 95% confidence interval (CI) will be calculated using the exact binomial distribution and compared using Fisher's exact test.
Measure: Proportion x 100 = percent of patients with improved COVID-19 symptoms Time: Day 28371 MET-Covid Trial - METformin for Prevention and Outpatient Treatment of COVID-19
The purpose of this trial is to: 1. Determine whether metformin can reduce the severity of COVID-19 disease; 2. Determine whether metformin can prevent symptomatic COVID-19 disease; 3. Determine whether metformin can prevent SARS-CoV-2 infection (seroconversion of SARS-CoV2 antibody tests or PCR positivity)
NCT04510194 Covid19 SARS-CoV Infection Drug: Metformin Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
Description: Outcome reported as the percent of participants in each arm who expire due to COVID-19 within 14 days of the initiation of treatment.
Measure: Rate of Death due to COVID-19 Time: 14 daysDescription: Outcome reported as the percent of participants in each arm who are admitted to hospital due to COVID-19 within 14 days of the initiation of treatment.
Measure: Rate of Hospitalization due to COVID-19 Time: 14 daysDescription: Outcome reported as the percent of participants in each arm who utilize emergency department services due to COVID-19 within 14 days of the initiation of treatment.
Measure: Rate of Emergency Department Utilization Time: 14 daysDescription: Outcome reported as the percent of participants in each arm who utilize urgent care services due to COVID-19 within 14 days of the initiation of treatment.
Measure: Rate of Urgent Care Utilization Time: 14 daysSecondary Outcomes
Description: Outcome measured using a visual analog Scale of COVID-19 symptom maximum severity at days 14 and 28 among those who develop PCR or antibody positivity. Scale ranges from 1-10 with higher scores indicating great symptom severity.
Measure: Incidence of Possible COVID-19 Symptoms Time: 14 days, 28 daysDescription: Outcome reported as the percent of participants in each arm who discontinue use of the study drug due to any reason.
Measure: Incidence of all-cause study medicine discontinuation Time: 28 daysDescription: Outcome reported as the percent of participants who fall into each of 8 ordinal categories on days 7, 14, and 28 of study treatment. Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Time: 7, 14, and 28 daysDescription: 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. 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: Dyspnea Assessment (PROMIS survey) Time: 28 daysDescription: The PROMIS Gobal-10 is a 10-item short-form survey measuring symptoms, functioning, and healthcare-related quality of life for a wide variety of chronic diseases and conditions. Nine items are rated on a 5-point scale. Item 7 is rated on an 11-point scale and then transformed to a 5-point scale. Items 3, 6, 7, and 8 are scored in reverse. Item scores are summed to calculate a total raw score. Raw scores are then matched with a t-score using a scoring table. Outcome will be reported as t-score. T-scores range from 16.2 to 67.7 with higher scores indicating greater global health.
Measure: Global Health Survey (PROMIS survey) Time: 28 daysDescription: Outcome reported as the percent of participants in the treatment and placebo groups who contract SARS-CoV-2 during participation in the prevention arm of the study.
Measure: Seroconversion of SARS-Cov2 Antibodies OR SARS-Cov2 PCR Positivity (Prevention Cohort Only) Time: up to 3 months372 Multicenter, Randomized, Double Blind, Parallel Placebo Controlled, Phase III Clinical Trial to Evaluate the Protective Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above
This is a multicenter, randomized, double blind, parallel placebo controlled, phase 3 clinical trial to evaluate the protective efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy population 18 years old and above.
NCT04510207 COVID-19 Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Biological: Placebo
Primary Outcomes
Measure: The incidence of COVID-19 cases after two-doses of vaccination Time: From14 days after the second dose to 6 month after the second doseSecondary Outcomes
Measure: The incidence of severe cases of SARS-CoV-2 pneumonia and deaths accompanied by COVID-19 after two-doses of vaccination Time: From14 day after the second dose to 6 month after the second doseMeasure: The incidence of any adverse reactions/events Time: 28 days after each immunization
Measure: The incidence of serious adverse events (SAE) Time: From the beginning of the first dose to 12 months after the second immunization
Measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody Time: 14 days after full course of immunization
Measure: The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody Time: 14 days after full course of immunization
Measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody Time: 14 days after full course of immunization
Measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
Measure: The 4-fold increase rate of anti-SARS-CoV-2 neutralizing antibody Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
Measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
Other Outcomes
Measure: the anti-SARS-CoV-2 neutralizing antibody protective level against COVID-19 Time: 14 days after 2 doses of vaccinationMeasure: The occurrence of ADE Time: From the beginning of the first dose to 12 months after the second immunization
373 Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial
The purpose of this study is to evaluate whether Canakinumab has beneficial effects on patients with Type 2 diabetes mellitus and coronavirus disease 19 (COVID19).
NCT04510493 Coronavirus Infection Diabetes Mellitus, Type 2 Drug: Canakinumab Drug: Placebo MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Diabetes Mellitus Diabetes Mellitus, Type 2
HPO:Diabetes mellitus Type II diabetes mellitus
Primary Outcomes
Description: unmatched win ratio determined by the ordered components:
longer survival time
longer ventilation-free time
longer ICU-free time
shorter hospitalization time
Measure: unmatched win ratio after treatment with canakinumab compared to placebo Time: within 4 weeks after treatment with canakinumab or placebo
Secondary Outcomes
Description: Time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever comes first. "The seven-category ordinal scale consists of the following categories:
not hospitalized with resumption of normal activities;
not hospitalized, but unable to resume normal activities;
hospitalized, not requiring supplemental oxygen;
hospitalized, requiring supplemental oxygen;
hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both;
hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and
death"
Measure: Time to clinical improvement Time: From randomization up to 4 weeks
Description: Death rate during the 4-week period after study treatment
Measure: Death rate Time: 4 weeks
Description: Admission to the intensive care unit from the medical ward during the 4-week period after study treatment
Measure: Admission to intensive care unit (ICU) Time: 4 weeks
Description: Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)
Measure: Secondary worsening of disease Time: 4 weeks
Description: Prolonged hospital stay > 3 weeks
Measure: Prolonged hospital stay Time: >3 weeks
Description: Ratio to baseline in the glycated hemoglobin
Measure: Change in ratio to baseline in the glycated hemoglobin Time: Baseline, Day 29 and Day 90
Description: Ratio to baseline in the fasting glucose
Measure: Change in ratio to baseline in the fasting glucose Time: Baseline, Day 29
Description: Ratio to baseline in the fasting insulin
Measure: Change in ratio to baseline in the fasting insulin Time: Baseline, Day 29
Description: Ratio to baseline in the fasting c-peptide
Measure: Change in ratio to baseline in the fasting c-peptide Time: Baseline, Day 29
Description: Ratio to baseline in the C-reactive protein (CRP)
Measure: Ratio to baseline in the C-reactive protein (CRP) Time: Baseline, Day 29 and Day 90
Description: Ratio to baseline in the D-dimer
Measure: Change in ratio to baseline in the D-dimer Time: Baseline, Day 29
Description: Ratio to baseline in the Natriuretic peptide (NTproBNP)
Measure: Change in ratio to baseline in the Natriuretic peptide (NTproBNP) Time: Baseline, Day 29 and Day 90
Description: Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)
Measure: Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR) Time: Baseline, Day 29 and Day 90
Description: Type of antidiabetic treatment at Day 29
Measure: Type of antidiabetic treatment at Day 29 Time: Day 29
Description: Number of antidiabetic treatment at Day 29
Measure: Number of antidiabetic treatment at Day 29 Time: Day 29
Description: Type of antidiabetic treatment at three months
Measure: Type of antidiabetic treatment at three months Time: Month 3
Description: Number of antidiabetic treatment at three months
Measure: Number of antidiabetic treatment at three months Time: Month 3
374 Pilot Study to Evaluate Safety and Efficacy of Anti-SARS-CoV-2 Equine Immunoglobulin F(ab')2 Fragments (INOSARS) in Hospitalized Patients With COVID-19
Primary Outcomes
Description: unmatched win ratio determined by the ordered components: longer survival time longer ventilation-free time longer ICU-free time shorter hospitalization time
Measure: unmatched win ratio after treatment with canakinumab compared to placebo Time: within 4 weeks after treatment with canakinumab or placeboSecondary Outcomes
Description: Time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever comes first. "The seven-category ordinal scale consists of the following categories: not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalized, not requiring supplemental oxygen; hospitalized, requiring supplemental oxygen; hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and death"
Measure: Time to clinical improvement Time: From randomization up to 4 weeksDescription: Death rate during the 4-week period after study treatment
Measure: Death rate Time: 4 weeksDescription: Admission to the intensive care unit from the medical ward during the 4-week period after study treatment
Measure: Admission to intensive care unit (ICU) Time: 4 weeksDescription: Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)
Measure: Secondary worsening of disease Time: 4 weeksDescription: Prolonged hospital stay > 3 weeks
Measure: Prolonged hospital stay Time: >3 weeksDescription: Ratio to baseline in the glycated hemoglobin
Measure: Change in ratio to baseline in the glycated hemoglobin Time: Baseline, Day 29 and Day 90Description: Ratio to baseline in the fasting glucose
Measure: Change in ratio to baseline in the fasting glucose Time: Baseline, Day 29Description: Ratio to baseline in the fasting insulin
Measure: Change in ratio to baseline in the fasting insulin Time: Baseline, Day 29Description: Ratio to baseline in the fasting c-peptide
Measure: Change in ratio to baseline in the fasting c-peptide Time: Baseline, Day 29Description: Ratio to baseline in the C-reactive protein (CRP)
Measure: Ratio to baseline in the C-reactive protein (CRP) Time: Baseline, Day 29 and Day 90Description: Ratio to baseline in the D-dimer
Measure: Change in ratio to baseline in the D-dimer Time: Baseline, Day 29Description: Ratio to baseline in the Natriuretic peptide (NTproBNP)
Measure: Change in ratio to baseline in the Natriuretic peptide (NTproBNP) Time: Baseline, Day 29 and Day 90Description: Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)
Measure: Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR) Time: Baseline, Day 29 and Day 90Description: Type of antidiabetic treatment at Day 29
Measure: Type of antidiabetic treatment at Day 29 Time: Day 29Description: Number of antidiabetic treatment at Day 29
Measure: Number of antidiabetic treatment at Day 29 Time: Day 29Description: Type of antidiabetic treatment at three months
Measure: Type of antidiabetic treatment at three months Time: Month 3Description: Number of antidiabetic treatment at three months
Measure: Number of antidiabetic treatment at three months Time: Month 3This is a two-center, randomized, placebo-controlled pilot study of anti-SARS-CoV-2 equine immunoglobulin fragments F(ab')2 (INOSARS) to evaluate safety and preliminary efficacy in the treatment of hospitalized COVID-19 patients. Clinical improvement at 28 days from the start of treatment will be evaluated.
NCT04514302 COVID-19 Drug: Placebo Drug: Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS)
Primary Outcomes
Description: The primary endpoint is the proportion of patients with clinical improvement at 28 days after treatment. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale. Scale categories as follows: 1 = not hospitalized; 2 = not hospitalized with limitation of activities and/or oxygen requirement; 3 = hospitalized not requiring supplemental oxygen and not requiring active medical care, 4 = hospitalized requiring active medical care without requiring oxygen supplementation; 5 = hospitalized requiring oxygen supplementation; 6 = hospitalized requiring high-flow oxygen or non-invasive mechanical ventilation; 7 = hospitalized requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8 = death.
Measure: Proportion of patients with improvement in clinical status Time: 28 daysSecondary Outcomes
Description: Time from the day of treatment until the first day with clinical improvement, defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale.
Measure: Time to clinical improvement Time: 28 daysDescription: Proportion of participant death or non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation requirement.
Measure: Proportion of patients that reach a score of 6, 7 or 8 in the NIAID 8-point ordinal scale Time: 28 daysDescription: Measured in days
Measure: Duration of hospitalization Time: 28 daysDescription: Proportion of patients that have a negative polymerase chain reaction assay for SARS-CoV-2 at 72 hrs from start of treatment.
Measure: SARS-CoV-2 PCR negativization rate Time: 3 daysDescription: Proportion of patients with clinical improvement at day 7. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale
Measure: Proportion of patients with clinical improvement at day 7 Time: 7 daysDescription: Proportion of patients that present within 24 hours of treatment with immediate adverse events defined as: skin rash and/or respiratory findings (dyspnea, wheezing, bronchospasm, hypoxia) and/or circulatory compromise (reduction of blood pressure or associated symptoms, i.e. syncope).
Measure: Proportion of patients with immediate adverse events (< 24 hours) Time: 24 hoursDescription: Proportion of patients that present events associated with serum sickness (type 3 hypersensitivity), vasculitis, glomerulonephritis, arthritis.
Measure: Proportion of patients with late adverse events (1 - 28 days) Time: 28 days