A Phase 3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adults With COVID-19 at High Risk for Disease Progression
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 3,082
- Locations
- 226
- Primary Endpoint
- Percentage of Participants Who Experienced One or More of Following Through Day 29: All-cause Hospitalization, All-cause Mortality, or Covid-19-related Medically-attended Visit (MAV)
Study Overview
Brief Summary
Researchers are looking for other ways to prevent severe illness from COVID-19. COVID-19 is a virus that most often causes mild flu or cold-like symptoms. However, people with certain health conditions or other factors have a high risk (chance) of getting severely ill from COVID-19, which can require a hospital stay or lead to death. Some people who are high risk for severe illness may be unable to take certain treatments for COVID-19 because they are not available to them, or they take other medicines that may react with a treatment and cause an unwanted effect.
Molnupiravir (MK-4482) is a study medicine designed to stop the COVID-19 virus from copying itself in the body (multiplying). The goal of this study is to learn if molnupiravir prevents severe illness from COVID-19 more than placebo in people who are high risk.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The main inclusion criteria include but are not limited to the following:
- •Is an individual of any sex/gender, ≥18 years of age
- •Has documentation of SARS-CoV-2 infection with sample collection ≤4 days prior to randomization
- •Has initial onset of signs/symptoms attributable to COVID-19 for ≤4 days prior to the day of randomization and ≥2 of the following signs/symptoms attributable to COVID-19 on the day of randomization: cough, sore throat, nasal congestion, shortness of breath or difficulty breathing with exertion, muscle or body aches, fatigue, fever >38.0°C or chills, nausea or vomiting or diarrhea, change in sense of smell or change in sense of taste, or headache
- •Has ≥1 of the following characteristics or medical conditions associated with the highest risk of severe illness from COVID-19:
- •Advanced age of ≥75 years of age
- •Immunocompromised
- •Neurocognitive or physical disability
- •Has ≥3 characteristics or medical conditions which increase the risk of severe illness due to COVID-19 (e.g., chronic lung disease, obesity with body mass index (BMI) ≥35, diabetes)
- •Is unable or unwilling to receive treatment with nirmatrelvir/ritonavir (NMV/r) due to 1 or more of the following:
- •Is receiving drug(s) highly dependent on cytochrome P450 3A (CYP3A) for clearance and for which elevated concentrations are associated with serious and/or life-threatening consequences or drug(s) with a clinically significant drug-drug interaction for which co-administration is not possible
- •Is receiving potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance
- •Has severe hepatic impairment
- •Has experienced prior adverse reactions or hepatotoxicity to NMV/r that would preclude future use
- •Has known or suspected NMV/r resistance
- •Has uncontrolled HIV infection
- •NMV/r is not approved/authorized in the participant's country or it is not accessible to participant (e.g., drug shortage)
- •Is unwilling to receive treatment with NMV/r
- •Inclusion note: Participants may receive remdesivir as standard of care in addition to molnupiravir or placebo. If remdesivir is available and clinically appropriate per local clinical practice, investigators will aim to ensure that those who are most vulnerable to severe COVID-19 receive timely access to remdesivir as standard of care on this study.
Exclusion Criteria
- •The main exclusion criteria include but are not limited to the following:
- •Is currently hospitalized or is expected to need hospitalization for COVID-19 imminently
- •Has received or plans to receive SARS-CoV-2 directed oral antivirals or monoclonal antibodies for current episode of COVID-19 (other than study intervention and, if applicable, remdesivir as standard of care)
- •Has ≥1 of the following signs/symptoms that are attributable to severe or critical COVID-19:
- •Shortness of breath at rest
- •Respiratory rate ≥30 breaths per minute
- •Heart rate ≥125 beats per minute
- •Peripheral oxygen saturation (SpO2) ≤93% on room air or on supplemental oxygen for a reason other than COVID-19 which has not increased since onset of COVID-19 signs/symptoms
- •New or increasing need for supplemental oxygen: receiving >4 liters/minute supplemental oxygen due to COVID-19 OR on supplemental oxygen for a reason other than COVID-19 which has increased due to COVID-19
- •Has received a COVID-19 vaccine within 30 days prior to randomization
- •Has a history of confirmed influenza, respiratory syncytial virus (RSV), or SARS-CoV-2 infection (with or without symptoms; excluding current infection) within 30 days prior to randomization
- •Has known or suspected hypersensitivity to active or inactive ingredients of molnupiravir
Arms & Interventions
Molnupiravir
Participants will receive 800 mg molnupiravir orally every 12 hours for 5 days (a total of 10 consecutive doses)
Intervention: Molnupiravir (Drug)
Placebo
Participants will receive molnupiravir-matching placebo orally every 12 hours for 5 days (a total of 10 consecutive doses)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Who Experienced One or More of Following Through Day 29: All-cause Hospitalization, All-cause Mortality, or Covid-19-related Medically-attended Visit (MAV)
Time Frame: Up to 29 days
Hospitalization is defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms or facilities created to address hospitalization needs specifically for COVID-19. Hospitalization and death may be due to any cause. An MAV is defined as any unscheduled, nonroutine healthcare visit where the participant is evaluated by a licensed (according to local/national guidelines) healthcare provider. As prespecified by the protocol, the percentage of participants who experience ONE OR MORE of these 3 events (hospitalization, death, or COVID-19-related MAV) occurring from randomization through Day 29 will be presented.
Percentage of Participants Who Experienced One or More of Following Through Day 29: All-cause Hospitalization, All-cause Mortality, or Covid-19-related Medically-attended Visit (MAV)
Time Frame: Up to 29 days
Hospitalization is defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms or facilities created to address hospitalization needs specifically for COVID-19. Hospitalization and death may be due to any cause. An MAV is defined as any unscheduled, nonroutine healthcare visit where the participant is evaluated by a licensed (according to local/national guidelines) healthcare provider. As prespecified by the protocol, the percentage of participants who experience ONE OR MORE of these 3 events (hospitalization, death, or COVID-19-related MAV) occurring from randomization through Day 29 will be presented.
Percentage of Participants Who Experienced an Adverse Event (AE)
Time Frame: Up to approximately 5 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. The percentage of participants with at least 1 AE will be presented.
Percentage of Participants Who Discontinued Study Intervention Due to AE
Time Frame: Up to approximately 5 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. The percentage of participants who discontinue study intervention due to an AE will be presented.
Secondary Outcomes
- Percentage of Participants Who Experienced One or More of Following Through Day 29: All-cause Hospitalization or All-cause Mortality(Up to 29 days)
- Percentage of Participants With Clinically Important Medical Interventions (CIMI) Associated with COVID-19-related MAV or COVID-19-related Hospitalization Through Day 29(Up to 29 days)
- Time to Sustained Alleviation (without relapse) of all selected 8 (5 prespecified and 3 determined by baseline prevalence), self-reported COVID-19 signs/symptoms(Up to 29 days)
- Change from Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA Titer(Day 1 (baseline) and up to Day 29)
- Percentage of Participants with Undetectable SARS-CoV-2 RNA(Up to 29 days)
- Percentage of Participants Who Experienced One or More of Following Through Day 29: All-cause Hospitalization or All-cause Mortality(Up to 29 days)
- Percentage of Participants With Clinically Important Medical Interventions (CIMI) Associated with COVID-19-related MAV or COVID-19-related Hospitalization Through Day 29(Up to 29 days)
- Time to Sustained Alleviation (without relapse) of all 15 self-reported COVID-19 signs/symptoms through Day 29(Up to 29 days)
- Time to Sustained Resolution Without Relapse of all 8 (5 prespecified and 3 determined by baseline prevalence) self-reported COVID-19 signs/symptoms through Day 29(Up to 29 days)