Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants With COVID-19 (MK-4482-001)
Coronavirus Disease (COVID-19)
About this trial
This is an interventional treatment trial for Coronavirus Disease (COVID-19)
Eligibility Criteria
Inclusion Criteria:
- Has documentation of polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with sample collection ≤ 10 days prior to the day of randomization. PCR is the preferred method; however other diagnostic methods are allowed if authorized by use in the country
- Had initial onset of signs/symptoms attributable to COVID-19 for ≤10 days prior to the day of randomization and ≥1 sign/symptom attributable to COVID-19 present at randomization
- Requires medical care in the hospital for ongoing clinical manifestations of COVID-19 (not just for public health or quarantine purposes)
- Has mild, moderate, or severe COVID-19
- Is willing and able to take oral medication
- Males agree to the following during the intervention period and for at least 90 days after the last dose of study intervention: Refrain from donating sperm; and either abstain from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception
- Females are not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of child bearing potential (WOCBP); or is a WOCBP and using a contraceptive method that is highly effective (a low user dependency method OR a user dependent method in combination with barrier method), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) for 28 days from the start of study intervention; a WOCBP must have a negative highly sensitive pregnancy test (serum test is required) within 24 hours before the first dose of study intervention
Exclusion Criteria:
- Has critical COVID-19 with any of the following: respiratory failure (including endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (flow rates >20L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO))
- Is on dialysis or has reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 by the Modification of Diet in Renal Disease (MDRD) equation
- Has any of the following conditions: human immunodeficiency virus (HIV) with a recent viral load >50 copies/mL or cluster of differentiation 4 (CD4) <200 cell/mm^3; chemotherapy required within 6 weeks before randomization; a neutrophilic granulocyte absolute count <500/mm^3; autologous or allogeneic hematopoietic stem cell transplant recipient
- Has history of Hepatitis B or Hepatitis C infection with any of the following: 1) cirrhosis 2) end-stage liver disease 3) hepatocellular carcinoma 4) aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit of normal at screening
- Has a history of acute pancreatitis within 3 months prior to randomization or a history of chronic pancreatitis
- Is taking or is anticipated to require any prohibited therapies
- Is unwilling to abstain from participating in another interventional clinical trial through Day 29 with an investigational compound or device, including those for COVID-19 therapeutics
- Is anticipated to require transfer to a non-study hospital within 72 hours
- Has a baseline heart rate of < 50 beats per minute at rest
- Has a platelet count <100,000/μL or received a platelet transfusion in the 5 days prior to randomization
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments including but not limited to: participants who are not expected to survive longer than 48 hours after randomization or participants who are expected to require mechanical ventilation within 48 hours after randomization or participants with a recent history of mechanical ventilation or participants with conditions that could limit gastrointestinal absorption of capsule contents
Sites / Locations
- Kaiser Foundation Hospital - South Bay ( Site 1832)
- Cedars-Sinai Medical Center ( Site 1822)
- University of California Davis Health ( Site 1809)
- University Of Florida ( Site 1810)
- Wellstar Kennestone Hospital ( Site 1801)
- Loretto Hospital ( Site 1838)
- LSU-HSC Shreveport ( Site 1824)
- Henry Ford Health System ( Site 1821)
- University of Mississippi Medical Center ( Site 1846)
- University of Nebraska Medical Center ( Site 1835)
- University of New Mexico, Health Sciences Center ( Site 1806)
- Carolinas Medical Center ( Site 1850)
- ECU Adult Specialty Care ( Site 1865)
- Sanford Health ( Site 1851)
- Temple University ( Site 1836)
- CHRISTUS Institute for Innovation & Advanced Clinical Care ( Site 1864)
- Houston Methodist Hospital ( Site 1863)
- Swedish Medical Center ( Site 1812)
- Valley Medical Center ( Site 1815)
- Swedish Medical Center ( Site 1861)
- Chronos Pesquisa Clínica ( Site 0105)
- Santa Casa de Misericordia de Belo Horizonte ( Site 0100)
- Hospital de Clinicas da Universidade Federal do Parana ( Site 0104)
- Hospital Tacchini ( Site 0107)
- FUNFARME Hospital de Base Centro Integrado de Pesquisa ( Site 0101)
- University Health Network - Toronto General Hospital ( Site 0201)
- Hospital Clinico Fusat ( Site 0300)
- Clinica Universidad de los Andes ( Site 0301)
- Hospital Sotero del Rio [Santiago, Chile] ( Site 0304)
- Complejo Hospitalario San Jose ( Site 0306)
- Servicio de Salud Sur Hospital Lucio Cordova ( Site 0305)
- Hospital Pablo Tobon Uribe ( Site 0404)
- Clinica de la Costa Ltda. ( Site 0402)
- Oncomedica S.A. ( Site 0406)
- Hospital Universitario San Ignacio ( Site 0401)
- Fundacion Cardiovascular de Colombia ( Site 0403)
- Fundacion Valle del Lili ( Site 0400)
- Groupe Hospitalier Pellegrin ( Site 0511)
- Pitie Salpetriere University Hospital-Infectious Disease - Tropical Diseases ( Site 0504)
- C.H.U. de Toulouse. Hopital de Purpan ( Site 0501)
- Centre Hospitalier de Tourcoing ( Site 0502)
- CHU Hopital Saint Antoine ( Site 0505)
- Hopital Bichat - Claude Bernard ( Site 0503)
- Rambam Medical Center ( Site 2102)
- Hadassah Medical Center. Ein Kerem ( Site 2103)
- Chaim Sheba Medical Center ( Site 2100)
- ASST Fatebenefratelli-Ospedale Sacco ( Site 0601)
- Chungnam National University Hospital ( Site 2202)
- Inha University Hospital ( Site 2204)
- The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 2205)
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0802)
- Hospital Regional de Alta Especialidad del Bajio ( Site 0807)
- Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800)
- Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0803)
- University of the Philippines-Philippine General Hospital ( Site 0900)
- Lung Center of the Philippines ( Site 0902)
- Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 1001)
- Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 1004)
- Centrum Medyczne Pratia, Mazowiecki Szpital Specjalistyczny, Oddział Obserwacyjno - Zakaźny ( Site 1
- Centrum Medyczne w Lancucie Sp.zo.o. ( Site 1000)
- Krasnogorsk City Hospital Number 1 ( Site 1119)
- City Clinical Hospital #40 ( Site 1109)
- FSBI Central Hospital with Policlinics ( Site 1105)
- Moscow Clinical Hospital #52 ( Site 1103)
- City Hospital #40 ( Site 1113)
- City Pokrovskaya hospital ( Site 1116)
- City Clinical Hospital #1 ( Site 1112)
- Republican Clinical Infectious Hospital n.a. A.F. Agafonov ( Site 1100)
- IATROS International ( Site 1202)
- Wits Baragwanath Clinical Trial Site ( Site 1204)
- TREAD Research ( Site 1201)
- Clinical Projects Research Centre ( Site 1205)
- Hospital Universitari Vall d Hebron ( Site 1305)
- Hospital Clinic ( Site 1304)
- Hospital Universitari Germans Trias i Pujol ( Site 1303)
- Hospital Universitario Gregorio Maranon ( Site 1302)
- Hospital Universitario Ramon y Cajal ( Site 1301)
- Hospital Universitario La Paz ( Site 1300)
- Ivano-Frankivsk Regional Clinical Infectious Diseases Hospital ( Site 1605)
- CNE Central city clinical hospital of Ivano-Frankivsk city council ( Site 1604)
- MNE Ivano-Frankivsk Regional Phthisiology-Pulmonology Center ( Site 1603)
- CNPE of Kharkiv RC Regional Clinical Infectious Diseases Hospital ( Site 1606)
- Сommunal non-com. Institution Oleksandrivska clinical hospital Kyiv ( Site 1600)
- Odesa City Clinical Infectious Hospital ( Site 1611)
- Communal Non-Commercial Enterprise Central City Hospital ( Site 1615)
- Volyn Regional Clinical Hospital ( Site 1613)
- Royal Free London NHS Foundation Trust ( Site 1700)
- King's College Hospital ( Site 1705)
- North Manchester General Hospital ( Site 1701)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Part 1: Molnupiravir 200 mg
Part 1: Molnupiravir 400 mg
Part 1: Molnupiravir 800 mg
Part 1: Placebo
Part 2: Molnupiravir
Part 2: Placebo
200 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
400 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
800 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)
Molnupiravir (dose to be selected) administered orally every 12 hours for 5 days (10 doses total)
Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)