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

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ClinicalTrials.gov Identifier: NCT04575584
Recruitment Status : Recruiting
First Posted : October 5, 2020
Last Update Posted : April 22, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Coronavirus Disease (COVID-19) Drug: Molnupiravir Drug: Placebo Phase 2 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MK-4482 in Hospitalized Adults With COVID-19
Actual Study Start Date : October 19, 2020
Estimated Primary Completion Date : June 27, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: Molnupiravir 200 mg
200 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
 Drug: Molnupiravir
Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)
Experimental: Part 1: Molnupiravir 400 mg
400 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
 Drug: Molnupiravir
Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)
Experimental: Part 1: Molnupiravir 800 mg
800 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total)
 Drug: Molnupiravir
Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)
Placebo Comparator: Part 1: Placebo
Placebo matching molnupiravir administered orally 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)
Experimental: Part 2: Molnupiravir
Molnupiravir (dose to be selected) administered orally every 12 hours for 5 days (10 doses total)
 Drug: Molnupiravir
Molnupiravir administered orally in capsule form every 12 hours for 5 days (10 doses total)
Placebo Comparator: Part 2: Placebo
Placebo matching molnupiravir administered orally 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)


Outcome Measures
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Primary Outcome Measures :
  1. Time-to-sustained recovery [ Time Frame: Up to 29 days ]
    Sustained recovery is defined as: the participant is alive and not hospitalized; or the participant is alive and medically ready for discharge as determined by the investigator.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. Percentage of participants with all-cause mortality [ Time Frame: Up to 29 days ]
    All-cause mortality is death due to any cause

  2. Pulmonary score on a scale [ Time Frame: Up to 29 days ]
    Pulmonary score is a score on an ordinal scale which focuses on respiratory sequalae based on oxygen requirements using 7 mutually exclusive categories. The score ranges from 1 to 7 with a higher score indicating more severe respiratory sequalae.

  3. Pulmonary+ score on a scale [ Time Frame: Up to 29 days ]
    Pulmonary+ score is a score on an ordinal scale which is a 7-category assessment that captures the range of disease severity, including coagulation-related complications and respiratory dysfunction. The score ranges from 1 to 7 with a higher score indicating more severe sequalae.

  4. National Early Warning Score on a scale [ Time Frame: End of Treatment (EOT) (Up to 6 days) ]
    The National Early Warning Score assesses a participant's degree of illness as assessed by clinical risk prediction categories for poor clinical outcomes including mortality within 24 hours of a set of vital sign measurements. There are 7 physiological parameters, of which 6 are assigned a point value ranging from 0 to 3, and 1 is assigned a point value ranging from 0 to 2. The total aggregate score may range from 0 to 20 with an increasing aggregate score indicating increasing clinical risk.

  5. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04575584


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

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04575584    
Other Study ID Numbers: 4482-001
2020-003367-26 ( EudraCT Number )
MK-4482-001 ( Other Identifier: Merck )
PHRR201210-003189 ( Registry Identifier: PHRR )
jRCT2031200404 ( Registry Identifier: jRCT )
First Posted: October 5, 2020    Key Record Dates
Last Update Posted: April 22, 2021
Last Verified: April 2021
Individual Participant Data (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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases