Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants With COVID-19 (MK-4482-001)

NCT ID: NCT04575584

Last Updated: 2023-01-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-19
• Study Completion Date: 2021-08-11

Brief Summary

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.

Detailed Description

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.

Conditions

Coronavirus Disease (COVID-19)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: Molnupiravir 200 mg

200 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)

Group Type: EXPERIMENTAL

Molnupiravir

Intervention Type: DRUG

Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Part 1: Molnupiravir 400 mg

400 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)

Group Type: EXPERIMENTAL

Molnupiravir

Intervention Type: DRUG

Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Part 1: Molnupiravir 800 mg

800 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)

Group Type: EXPERIMENTAL

Molnupiravir

Intervention Type: DRUG

Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Part 1: Placebo

Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Part 2: Molnupiravir

Molnupiravir (dose to be selected) administered orally every 12 hours for 5 days (10 doses total)

Group Type: EXPERIMENTAL

Molnupiravir

Intervention Type: DRUG

Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Part 2: Placebo

Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Interventions

Molnupiravir

Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Intervention Type: DRUG

Placebo

Placebo matching molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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)

Brasília, Federal District, 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, Paraná, Brazil

Hospital Tacchini ( Site 0107)

Bento Gonçalves, Rio Grande do Sul, Brazil

FUNFARME Hospital de Base Centro Integrado de Pesquisa ( Site 0101)

São José do Rio Preto, São Paulo, Brazil

University Health Network - Toronto General Hospital ( Site 0201)

Toronto, Ontario, Canada

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 Clinico Fusat ( Site 0300)

Rancagua, Región del Libertador General Bernardo O’Higgins, Chile

Hospital Pablo Tobon Uribe ( Site 0404)

Medellín, Antioquia, Colombia

Clinica de la Costa Ltda. ( Site 0402)

Barranquilla, Atlántico, Colombia

Hospital Universitario San Ignacio ( Site 0401)

Bogotá, Bogota D.C., Colombia

Oncomedica S.A. ( Site 0406)

Montería, Departamento de Córdoba, Colombia

Fundacion Cardiovascular de Colombia ( Site 0403)

Bucaramanca, Santander Department, Colombia

Fundacion Valle del Lili ( Site 0400)

Cali, Valle del Cauca Department, Colombia

Groupe Hospitalier Pellegrin ( Site 0511)

Bordeaux, Gironde, 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

Pitie Salpetriere University Hospital-Infectious Disease - Tropical Diseases ( Site 0504)

Paris, Île-de-France Region, 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)

Milan, , Italy

Hospital Regional de Alta Especialidad del Bajio ( Site 0807)

León, Guanajuato, Mexico

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800)

Guadalajara, Jalisco, Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0802)

Mexico City, Mexico City, Mexico

Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0803)

Monterrey, Nuevo León, 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

Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 1004)

Lublin, Lublin Voivodeship, Poland

Centrum Medyczne Pratia, Mazowiecki Szpital Specjalistyczny, Oddział Obserwacyjno - Zakaźny ( Site 1

Ostrołęka, Masovian Voivodeship, Poland

Centrum Medyczne w Lancucie Sp.zo.o. ( Site 1000)

Łańcut, Podkarpackie Voivodeship, Poland

Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 1001)

Lodz-Baluty, Łódź Voivodeship, Poland

City Clinical Hospital #40 ( Site 1109)

Moscow, Moscow, Russia

FSBI Central Hospital with Policlinics ( Site 1105)

Moscow, Moscow, Russia

Moscow Clinical Hospital #52 ( Site 1103)

Moscow, Moscow, Russia

Krasnogorsk City Hospital Number 1 ( Site 1119)

Krasnogorsk, Moscow Oblast, Russia

City Hospital #40 ( Site 1113)

Saint Petersburg, Sankt-Peterburg, Russia

City Pokrovskaya hospital ( Site 1116)

Saint Petersburg, Sankt-Peterburg, Russia

City Clinical Hospital #1 ( Site 1112)

Smolensk, Smolensk Oblast, Russia

Republican Clinical Infectious Hospital n.a. A.F. Agafonov ( Site 1100)

Kazan', Tatarstan, Respublika, Russia

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

Chungnam National University Hospital ( Site 2202)

Daejeon, Taejon-Kwangyokshi, South Korea

Inha University Hospital ( Site 2204)

Incheon, , South Korea

The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 2205)

Seoul, , South Korea

Hospital Universitari Vall d Hebron ( Site 1305)

Barcelona, Catalonia, 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-Frankivsk Oblast, Ukraine

CNE Central city clinical hospital of Ivano-Frankivsk city council ( Site 1604)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

MNE Ivano-Frankivsk Regional Phthisiology-Pulmonology Center ( Site 1603)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

CNPE of Kharkiv RC Regional Clinical Infectious Diseases Hospital ( Site 1606)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Сommunal non-com. Institution Oleksandrivska clinical hospital Kyiv ( Site 1600)

Kyiv, Kyivska Oblast, Ukraine

Odesa City Clinical Infectious Hospital ( Site 1611)

Odesa, Odesa Oblast, Ukraine

Communal Non-Commercial Enterprise Central City Hospital ( Site 1615)

Rivne, Rivne Oblast, Ukraine

Volyn Regional Clinical Hospital ( Site 1613)

Lutsk, Volyn 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

Countries

United States; Brazil; Canada; Chile; Colombia; France; Israel; Italy; Mexico; Philippines; Poland; Russia; South Africa; South Korea; Spain; Ukraine; United Kingdom

References

Arribas JR, Bhagani S, Lobo SM, Khaertynova I, Mateu L, Fishchuk R, Park WY, Hussein K, Kim SW, Ghosn J, Brown ML, Zhang Y, Gao W, Assaid C, Grobler JA, Strizki J, Vesnesky M, Paschke A, Butterton JR, De Anda C. Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19. NEJM Evid. 2022 Feb;1(2):EVIDoa2100044. doi: 10.1056/EVIDoa2100044. Epub 2021 Dec 16.

Reference Type: RESULT

PMID: 38319178 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-4482-001

Identifier Type: OTHER

Identifier Source: secondary_id

PHRR201210-003189

Identifier Type: REGISTRY

Identifier Source: secondary_id

jRCT2031200404

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-003367-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

4482-001

Identifier Type: -

Identifier Source: org_study_id