This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the rate of sustained recovery through Day 29.
This study was intended to include two parts: Part 1 was a dose-ranging phase 2 study, and
Part 2 was a phase 3 study to evaluate the dose selected in Part 1. However, this study was
terminated due to business reasons prior to conducting Part 2. Participants in Part 1 were
followed until Month 7.
Drug: Molnupiravir
Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)
Drug: Placebo
Placebo matching molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)
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
Kaiser Foundation Hospital - South Bay ( Site 1832)
Harbor City, California, United States
Cedars-Sinai Medical Center ( Site 1822)
Los Angeles, California, United States
University of California Davis Health ( Site 1809)
Sacramento, California, United States
University Of Florida ( Site 1810)
Gainesville, Florida, United States
Wellstar Kennestone Hospital ( Site 1801)
Marietta, Georgia, United States
Loretto Hospital ( Site 1838)
Chicago, Illinois, United States
LSU-HSC Shreveport ( Site 1824)
Shreveport, Louisiana, United States
Henry Ford Health System ( Site 1821)
Detroit, Michigan, United States
University of Mississippi Medical Center ( Site 1846)
Jackson, Mississippi, United States
University of Nebraska Medical Center ( Site 1835)
Omaha, Nebraska, United States
University of New Mexico, Health Sciences Center ( Site 1806)
Albuquerque, New Mexico, United States
Carolinas Medical Center ( Site 1850)
Charlotte, North Carolina, United States
ECU Adult Specialty Care ( Site 1865)
Greenville, North Carolina, United States
Sanford Health ( Site 1851)
Fargo, North Dakota, United States
Temple University ( Site 1836)
Philadelphia, Pennsylvania, United States
CHRISTUS Institute for Innovation & Advanced Clinical Care ( Site 1864)
Corpus Christi, Texas, United States
Houston Methodist Hospital ( Site 1863)
Houston, Texas, United States
Swedish Medical Center ( Site 1812)
Edmonds, Washington, United States
Valley Medical Center ( Site 1815)
Renton, Washington, United States
Swedish Medical Center ( Site 1861)
Seattle, Washington, United States
Chronos Pesquisa Clínica ( Site 0105)
Brasilia, Distrito Federal, Brazil
Santa Casa de Misericordia de Belo Horizonte ( Site 0100)
Belo Horizonte, Minas Gerais, Brazil
Hospital de Clinicas da Universidade Federal do Parana ( Site 0104)
Curitiba, Parana, Brazil
Hospital Tacchini ( Site 0107)
Bento Goncalves, Rio Grande Do Sul, Brazil
FUNFARME Hospital de Base Centro Integrado de Pesquisa ( Site 0101)
Sao Jose do Rio Preto, Sao Paulo, Brazil
University Health Network - Toronto General Hospital ( Site 0201)
Toronto, Ontario, Canada
Hospital Clinico Fusat ( Site 0300)
Rancagua, Libertador General Bernardo O Higgins, Chile
Clinica Universidad de los Andes ( Site 0301)
Santiago, Region M. De Santiago, Chile
Hospital Sotero del Rio [Santiago, Chile] ( Site 0304)
Santiago, Region M. De Santiago, Chile
Complejo Hospitalario San Jose ( Site 0306)
Santiago, Region M. De Santiago, Chile
Servicio de Salud Sur Hospital Lucio Cordova ( Site 0305)
Santiago, Region M. De Santiago, Chile
Hospital Pablo Tobon Uribe ( Site 0404)
Medellin, Antioquia, Colombia
Clinica de la Costa Ltda. ( Site 0402)
Barranquilla, Atlantico, Colombia
Oncomedica S.A. ( Site 0406)
Monteria, Cordoba, Colombia
Hospital Universitario San Ignacio ( Site 0401)
Bogota, Distrito Capital De Bogota, Colombia
Fundacion Cardiovascular de Colombia ( Site 0403)
Bucaramanca, Santander, Colombia
Fundacion Valle del Lili ( Site 0400)
Cali, Valle Del Cauca, Colombia
Groupe Hospitalier Pellegrin ( Site 0511)
Bordeaux, Gironde, France
Pitie Salpetriere University Hospital-Infectious Disease - Tropical Diseases ( Site 0504)
Paris, Ile-de-France, France
C.H.U. de Toulouse. Hopital de Purpan ( Site 0501)
Toulouse, Midi-Pyrenees, France
Centre Hospitalier de Tourcoing ( Site 0502)
Tourcoing, Nord, France
CHU Hopital Saint Antoine ( Site 0505)
Paris, France
Hopital Bichat - Claude Bernard ( Site 0503)
Paris, France
Rambam Medical Center ( Site 2102)
Haifa, Israel
Hadassah Medical Center. Ein Kerem ( Site 2103)
Jerusalem, Israel
Chaim Sheba Medical Center ( Site 2100)
Ramat Gan, Israel
ASST Fatebenefratelli-Ospedale Sacco ( Site 0601)
Milano, Italy
Chungnam National University Hospital ( Site 2202)
Daejeon, Taejon-Kwangyokshi, Korea, Republic of
Inha University Hospital ( Site 2204)
Incheon, Korea, Republic of
The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 2205)
Seoul, Korea, Republic of
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0802)
Ciudad de mexico, Distrito Federal, Mexico
Hospital Regional de Alta Especialidad del Bajio ( Site 0807)
Leon, Guanajuato, Mexico
Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800)
Guadalajara, Jalisco, Mexico
Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0803)
Monterrey, Nuevo Leon, Mexico
University of the Philippines-Philippine General Hospital ( Site 0900)
Manila, National Capital Region, Philippines
Lung Center of the Philippines ( Site 0902)
Quezon City, National Capital Region, Philippines
Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 1001)
Lodz-Baluty, Lodzkie, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 1004)
Lublin, Lubelskie, Poland
Centrum Medyczne Pratia, Mazowiecki Szpital Specjalistyczny, Oddział Obserwacyjno - Zakaźny ( Site 1
Ostroleka, Mazowieckie, Poland
Centrum Medyczne w Lancucie Sp.zo.o. ( Site 1000)
Lancut, Podkarpackie, Poland
Krasnogorsk City Hospital Number 1 ( Site 1119)
Krasnogorsk, Moskovskaya Oblast, Russian Federation
City Clinical Hospital #40 ( Site 1109)
Moscow, Moskva, Russian Federation
FSBI Central Hospital with Policlinics ( Site 1105)
Moscow, Moskva, Russian Federation
Moscow Clinical Hospital #52 ( Site 1103)
Moscow, Moskva, Russian Federation
City Hospital #40 ( Site 1113)
Saint Petersburg, Sankt-Peterburg, Russian Federation
City Pokrovskaya hospital ( Site 1116)
Saint-Petersburg, Sankt-Peterburg, Russian Federation
City Clinical Hospital #1 ( Site 1112)
Smolensk, Smolenskaya Oblast, Russian Federation
Republican Clinical Infectious Hospital n.a. A.F. Agafonov ( Site 1100)
Kazan, Tatarstan, Respublika, Russian Federation
IATROS International ( Site 1202)
Bloemfontein, Free State, South Africa
Wits Baragwanath Clinical Trial Site ( Site 1204)
Soweto, Gauteng, South Africa
TREAD Research ( Site 1201)
Cape Town, Western Cape, South Africa
Clinical Projects Research Centre ( Site 1205)
Worcester, Western Cape, South Africa
Hospital Universitari Vall d Hebron ( Site 1305)
Barcelona, Cataluna, Spain
Hospital Clinic ( Site 1304)
Barcelona, Spain
Hospital Universitari Germans Trias i Pujol ( Site 1303)
Barcelona, Spain
Hospital Universitario Gregorio Maranon ( Site 1302)
Madrid, Spain
Hospital Universitario Ramon y Cajal ( Site 1301)
Madrid, Spain
Hospital Universitario La Paz ( Site 1300)
Madrid, Spain
Ivano-Frankivsk Regional Clinical Infectious Diseases Hospital ( Site 1605)
Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
CNE Central city clinical hospital of Ivano-Frankivsk city council ( Site 1604)
Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
MNE Ivano-Frankivsk Regional Phthisiology-Pulmonology Center ( Site 1603)
Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
CNPE of Kharkiv RC Regional Clinical Infectious Diseases Hospital ( Site 1606)
Kharkiv, Kharkivska Oblast, Ukraine
Сommunal non-com. Institution Oleksandrivska clinical hospital Kyiv ( Site 1600)
Kyiv, Kyivska Oblast, Ukraine
Odesa City Clinical Infectious Hospital ( Site 1611)
Odesa, Odeska Oblast, Ukraine
Communal Non-Commercial Enterprise Central City Hospital ( Site 1615)
Rivne, Rivnenska Oblast, Ukraine
Volyn Regional Clinical Hospital ( Site 1613)
Lutsk, Volynska Oblast, Ukraine
Royal Free London NHS Foundation Trust ( Site 1700)
London, London, City Of, United Kingdom
King's College Hospital ( Site 1705)
London, London, City Of, United Kingdom
North Manchester General Hospital ( Site 1701)
Manchester, United Kingdom
Medical Director, Study Director
Merck Sharp & Dohme LLC