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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Coronavirus Disease (COVID-19)

Treatments: Drug: Molnupiravir; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04575584

2020-003367-26 (EudraCT Number)

jRCT2031200404 (Registry Identifier)

PHRR201210-003189 (Registry Identifier)

4482-001

MK-4482-001 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 304 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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304 participants in 6 patient groups, including a placebo group

Part 1: Molnupiravir 200 mg

Experimental group

Description:

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

Treatment:

Drug: Molnupiravir

Part 1: Molnupiravir 400 mg

Experimental group

Description:

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

Treatment:

Drug: Molnupiravir

Part 1: Molnupiravir 800 mg

Experimental group

Description:

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

Treatment:

Drug: Molnupiravir

Part 1: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Part 2: Molnupiravir

Experimental group

Description:

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

Treatment:

Drug: Molnupiravir

Part 2: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo