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

• ClinicalTrials.gov Identifier: NCT04575597
• Recruitment Status: Recruiting
• First Posted: October 5, 2020
• Last Update Posted: April 12, 2021
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: September 30, 2020
• First Posted Date: October 5, 2020
• Last Update Posted Date: April 12, 2021
• Actual Study Start Date: October 19, 2020
• Estimated Primary Completion Date: June 23, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 2020)

• Percentage of participants who are hospitalized and/or die [ Time Frame: Up to 29 days ]
  Hospitalization (all cause) is ≥24 hours of acute care in a hospital or similar acute care facility. Death is due to any cause.
• Percentage of participants with an adverse event (AE) [ Time Frame: Up to ~7 months ]
  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.
• Percentage of participants who discontinued study intervention due to an AE [ Time Frame: Up to 6 days ]
  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.

Original Primary Outcome Measures (submitted: October 2, 2020)

• Percentage of participants who are hospitalized and/or die [ Time Frame: Up to 29 days ]
  Hospitalization (all cause) is ≥24 hours of acute care in a hospital or similar acute care facility. Death is due to any cause.
• Percentage of participants with an adverse event (AE) [ Time Frame: Up to 19 days ]
  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.
• Percentage of participants who discontinued study intervention due to an AE [ Time Frame: Up to 6 days ]
  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.

Current Secondary Outcome Measures (submitted: December 22, 2020)

• Time to sustained resolution or improvement of each targeted COVID-19 sign/symptom [ 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.
• Time to progression of each targeted COVID-19 sign/symptom [ 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.
• 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.

Original Secondary Outcome Measures (submitted: October 2, 2020)

• 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 by which the targeted self-reported signs/symptoms improve or resolve.
• 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 by which the targeted self-reported signs/symptoms are newly reported or worsen.
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002)
• Official Title: 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.
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Coronavirus Disease (COVID-19)

Intervention

• Drug: Molnupiravir
  Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)
  Other Name: MK-4482
• Drug: Placebo
  Placebo matching molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 2, 2020): 1450
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 26, 2021
• Estimated Primary Completion Date: June 23, 2021 (Final data collection date for primary outcome measure)

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 ≤7 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 ≤7 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. Participants with mild COVID-19 must have 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 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 (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 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 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.
• 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 study through Day 29 with an investigational compound or device, including those for COVID-19 therapeutics.
• Has a baseline heart rate of < 50 beats per minute at rest
• 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, 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Brazil, Canada, Chile, Colombia, France, Germany, Israel, Italy, Mexico, Philippines, Russian Federation, South Africa, Spain, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04575597
• Other Study ID Numbers: 4482-002; 2020-003368-24 ( EudraCT Number ); MK-4482-002 ( Other Identifier: Merck ); PHRR201209-003186 ( Registry Identifier: PHRR )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Responsible Party: Merck Sharp & Dohme Corp.
• Study Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: April 2021