Study of MK-4482 for Prevention of Coronavirus Disease 2019 (COVID-19) in Adults (MK-4482-013)

Study Overview
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Brief Summary
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The purpose of the study is to assess if the study medication (molnupiravir, MK-4482) will prevent symptomatic coronavirus disease 2019 (COVID-19) in adults who live with someone with confirmed COVID-19 infection. This is a phase 3, multicenter, randomized, double-blind, placebo-controlled study; half of the study participants will receive molnupiravir twice daily by mouth and the other half will receive a placebo. The primary objectives of the study are to determine if molnupiravir prevents symptomatic COVID-19 disease and to evaluate its safety and tolerability. All participants who develop COVID-19 during the study are still eligible for any COVID-19 treatment recommended by their doctor.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of MK-4482 for the Prevention of COVID-19 (Laboratory-confirmed SARS-CoV-2 Infection With Symptoms) in Adults Residing With a Person With COVID-19

Conditions
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Coronavirus Disease (COVID-19)

Intervention / Treatment
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* Drug: Molnupiravir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lives in a household with an index case where the index case is a person with documented COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms case) and must have 1) a first detectable SARS-CoV-2 test result from a sample collected within ≤5 days prior to randomization of the participant, and 2) at least 1 symptom attributable to COVID-19 (e.g., fever, difficulty breathing) Does not have confirmed or suspected COVID-19 Is willing and able to take oral medication For males, agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving study drug and for ≥3 months after the last dose of study drug Is female and not pregnant/breastfeeding and at least one of the following applies during the study and for ≥4 days after: is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method), or is a WOCBP who is abstinent from heterosexual intercourse Exclusion Criteria: Has a prior history of laboratory-confirmed SARS-CoV-2 infection (with or without symptoms) within 6 months prior to randomization Has either of the following: human immunodeficiency virus (HIV) with a recent viral load >50 copies/mL (regardless of CD4 count) or an acquired immunodeficiency syndrome (AIDS)-defining illness Has a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with any of the following: cirrhosis, end-stage liver disease, hepatocellular carcinoma; aspartate transaminase (AST) and/or (ALT) >3x upper limit of normal at screening 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 with conditions that could limit gastrointestinal absorption of capsule contents Has received, is taking, or is anticipated to require any prohibited therapies Has received a COVID-19 vaccination with the first dose ≥7 days prior to randomization 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 Is living in a household with >10 people

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Molnupiravir<br>Participants take molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5. | Drug: Molnupiravir<br>* Four molnupiravir 200 mg capsules taken by mouth.<br>* Other names: MK-4482;|
| Placebo Comparator: Placebo<br>Participants take placebo Q12H on Days 1 to 5. | Drug: Placebo<br>* Placebo capsule matched to molnupiravir 200 mg capsules taken by mouth.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who have undetectable SARS-CoV-2 in baseline nasopharyngeal (NP) swabs and develop COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 14 | Percentage of participants who have undetectable SARS-CoV-2 in baseline NP swabs and develop COVID-19 (laboratory-confirmed SARS-CoV-2) infection with symptoms) through Day 14. | Up to Day 14 | 
| Percentage of participants with ≥1 adverse event | 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. | Up to 29 days | 
| Percentage of participants discontinuing from study therapy due to AE | 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. | Up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants (regardless of SARS-CoV-2 in baseline NP swabs) who develop COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 14 | Participants who experience targeted symptoms of COVID-19 (e.g., cough, sore throat) will have NP swabs tested for SARS-CoV-2 using reverse-transcription polymerase chain reaction (RT-PCR). | Up to Day 14 | 
| Percentage of participants who have undetectable SARS-CoV-2 in baseline NP swabs and develop COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 29 | Participants who experience targeted symptoms of COVID-19 (e.g., cough, sore throat) will have NP swabs tested for SARS-CoV-2 using RT-PCR. | Up to Day 29 | 
| Percentage of participants who have undetectable SARS-CoV-2 in baseline NP swabs and develop detectable SARS-CoV-2 in NP swabs on or before Day 14 | All participants will have NP swabs collected at screening and through Day 14 to test for SARS-CoV-2 using RT-PCR. | Up to Day 14 | 
| Percentage of participants who have detectable SARS-CoV-2 in baseline NP swabs and develop COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 14 | Participants who experience targeted symptoms of COVID-19 (e.g., cough, sore throat) will have NP swabs tested for SARS-CoV-2 using RT-PCR. | Up to Day 14 |