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

Phase 2

Completed

Conditions: Coronavirus Disease (COVID-19)

Interventions: Drug: Placebo
Drug: Molnupiravir

Registration Number: NCT04575597

Lead Sponsor: Merck Sharp & Dohme LLC

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1735

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.
Had initial onset of signs/symptoms attributable to COVID-19 for ≤5 days prior to the day of 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; 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.

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) <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 (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, or participants with conditions that could limit gastrointestinal absorption of capsule contents.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1: Placebo	Placebo	Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)
Part 2: Placebo	Placebo	Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total)
Part 1: Molnupiravir 200 mg	Molnupiravir	200 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
Part 1: Molnupiravir 400 mg	Molnupiravir	400 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
Part 1: Molnupiravir 800 mg	Molnupiravir	800 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
Part 2: Molnupiravir 800 mg	Molnupiravir	800 mg Molnupiravir (dose to be selected) administered orally every 12 hours for 5 days (10 doses total)

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Were Hospitalized and/or Died Through Day 29 (Primary Pre-specified Analysis)	Up to 29 days	The percentage of participants who were hospitalized and/or died through Day 29 is presented. Hospitalization (all cause) is defined as at least 24 hours of acute care in a hospital or similar acute care facility. Death was due to any cause. Any participants with an unknown survival status at Day 29 were treated as failure. The analysis in Part 2 was based on all participants enrolled by the pre-specified futility/early efficacy analysis and was used for demonstration of superiority to placebo for the primary efficacy outcome measure.
Number of Participants With an Adverse Event (AE)	Up to 318 days	The number of participants with at least 1 AE is presented. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Discontinued Study Intervention Due to an AE	Up to 5 days	The number of participants who discontinued study intervention due to an AE is presented. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Secondary Outcome Measures

Name	Time	Method
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Vomiting	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Sore Throat	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Chills	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Headache	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Nasal Congestion	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Rhinorrhea	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Fatigue	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Diarrhea	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Cough	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Nasal Congestion	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Muscles or Body Aches	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Rhinorrhea	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Shortness of Breath or Difficulty Breathing	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Feeling Hot or Feverish	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Nausea	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Loss of Smell	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Chills	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Headache	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Number of Participants With Responses on WHO 11-point Ordinal Outcomes Score on a Scale on Day 29	Day 29	The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 ("uninfected") to 10 ("dead") with higher score indicating clinical progression. The number of participants at each score category is presented.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Shortness of Breath or Difficulty Breathing	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Loss of Taste	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Number of Participants With Responses on WHO 11-point Ordinal Outcomes Score on a Scale on End of Treatment (EOT [Day 5])	EOT (Day 5)	The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 ("uninfected") to 10 ("dead") with higher score indicating clinical progression. The number of participants at each score category is presented.
Time to Sustained Resolution or Improvement of Each Targeted COVID-19 Sign/Symptom - Loss of Taste	Up to 29 days	Time to sustained resolution or improvement of the targeted sign/symptom was defined as the number of days from randomization to the first of three consecutive days when resolution or improvement of the targeted sign/symptom was demonstrated and did not worsen by Day 29. The median number of days from randomization to the first day on or before study Day 29 for sustained resolution or improvement is presented. Per protocol, participants without the targeted sign/symptom reported at randomization were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Sore Throat	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Fatigue	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Feeling Hot or Feverish	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Nausea	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Loss of Smell	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Number of Participants With Responses on WHO 11-point Ordinal Outcomes Score on a Scale on Day 3	Day 3	The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 ("uninfected") to 10 ("dead") with higher score indicating clinical progression. The number of participants at each score category is presented.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Cough	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Muscle or Body Aches	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Vomiting	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Time to Progression of Each Targeted COVID-19 Sign/Symptom - Diarrhea	Up to 29 days	Time to progression of the targeted sign/symptom was defined as the number of days from randomization to the first of two consecutive days when the targeted sign/symptom was worsened. The median number of days from randomization to the first day on or before study Day 29 for progression/worsening is presented. Per protocol, participants with symptoms reported at randomization as severe for the targeted sign/symptom were not included in the analysis.
Number of Participants With Responses on WHO 11-point Ordinal Outcomes Score on a Scale on Day 15	Day 15	The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 ("uninfected") to 10 ("dead") with higher score indicating clinical progression. The number of participants at each score category is presented.
Number of Participants With Responses on WHO 11-point Ordinal Outcomes Score on a Scale on Day 10	Day 10	The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 ("uninfected") to 10 ("dead") with higher score indicating clinical progression. The number of participants at each score category is presented.

Trial Locations

Locations (173): Phoenix Medical Group ( Site 1822)
🇺🇸
Peoria, Arizona, United States
Ruane Clinical Research Group, Inc. ( Site 2406)
🇺🇸
Los Angeles, California, United States
Men's Health Foundation ( Site 1820)
🇺🇸
Los Angeles, California, United States
Carbon Health Technologies Inc ( Site 2505)
🇺🇸
North Hollywood, California, United States
UC Davis Medical Center ( Site 1833)
🇺🇸
Sacramento, California, United States
Emerson Clinical Research Institute ( Site 1828)
🇺🇸
Washington, District of Columbia, United States
JEM Research Institute ( Site 2508)
🇺🇸
Atlantis, Florida, United States
Midway Immunology and Research Center ( Site 1837)
🇺🇸
Fort Pierce, Florida, United States
Indago Research & Health Center, Inc ( Site 1809)
🇺🇸
Hialeah, Florida, United States
Advanced Research For Health Improvement LLC ( Site 1816)
🇺🇸
Immokalee, Florida, United States
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Phoenix Medical Group ( Site 1822)
🇺🇸Peoria, Arizona, United States