Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002)

PHRR201209-003186

MK-4482-002; CT.gov NCT04575597

2020-CT0569

A Phase 2/3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MK-4482 in Non-Hospitalized Adults With COVID-19

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 percentage of participants who are hospitalized and/or die through Day 29

Completed

Coronavirus Disease (COVID-19)

1. Time to improvement or resolution of targeted COVID-19 signs/symptoms [ Time Frame: Up to 29 days ]
The number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement of each sign/symptom will be assessed.

2. Time to progression of targeted COVID-19 signs/symptoms [ Time Frame: Up to 29 days ]
The number of days from randomization to the first day on or before study Day 29 for each targeted self-reported sign/symptom will be assessed.

3.WHO 11-point outcomes score on a scale [ Time Frame: Up to 29 days ]
The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 to 10 with higher score indicating clinical progression.

Completed

• Brazil
• Canada
• Chile
• Colombia
• France
• Germany
• Israel
• Italy
• Mexico
• Philippines
• Russia
• South Africa
• Spain
• Sweden
• Ukraine
• United Kingdom
• United States

Clinical Trial

20201001071746

2020-11-04

0000-00-00

35

27

N/A

2021-05-27

Key Inclusion Criteria:

-Has documentation of  laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with sample collection ≤5 days prior to the day of randomization. PCR is the preferred method; however with evolving approaches to laboratory confirmation of SARS-CoV-2 infection, other molecular or antigen tests that detect viral ribonucleic acid (RNA) or protein are allowed if authorized for use in the country. Serological tests that detect host antibodies generated in response to recent or prior infection are not allowed.

-Has initial onset of signs/symptoms attributable to COVID-19 for ≤ 5 days prior to randomization and at least 1 of the following sign/symptom attributable to COVID-19 on the day of randomization

-Has mild or moderate COVID-19. 

-Has at least 1 characteristic or underlying medical condition associated with an increased risk of severe illness from COVID-19.

-Males agree to the following during the intervention period and for at least 4 days after the last dose of study intervention: 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 at least 4 days after the last dose of study intervention; for at least 4 days after the last dose of study intervention; a WOCBP must have a negative highly sensitive pregnancy test (urine or serum test is required) within 24 hours before the first dose of study intervention.

Key Exclusion Criteria:

 -Is currently hospitalized or is expected to need hospitalization for COVID-19 within 48 hours of randomization.

-Is on dialysis or has reduced estimated glomerular filtration rate (eGFR) 

-Has any of the following conditions: human immunodeficiency virus (HIV) with a recent viral load >50 copies/mL (regardless of CD4 count) or an AIDS-defining illness in the past 6 months, participants with HIV may only be enrolled if on a stable antiretroviral therapy regimen; a neutrophilic granulocyte absolute count <500/mm^3.

-Has a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) with cirrhosis, end-stage liver disease, hepatocellular carcinoma, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3X upper limit of normal at screening.

- Has a platelet count <100,000/μL or received a platelet transfusion in the 5 days prior to randomization.

-Is taking or is anticipated to require any prohibited therapies.

-Is unwilling to abstain from participating in another interventional clinical study through Day 29 with an investigational compound or device, including those for COVID-19 therapeutics.

-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 with a recent history of mechanical ventilation not associated with COVID-19, or participants with conditions that could limit gastrointestinal absorption of capsule contents.

Interventional

Molnupiravir and Placebo

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)

Randomized

Double Blind

Double: (Participant, Investigator)

Parallel

The trial is currently ongoing; therefore results are not currently available.

Phase II/III