Coronavirus Disease (COVID-19)
Conditions
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.
Interventions
DRUGMolnupiravir
Molnupiravir administered orally as two 400 mg film-coated tablets every 12 hours for 5 days (a total of 10 consecutive doses)
DRUGPlacebo
Molnupiravir-matching placebo administered orally as two film-coated tablets every 12 hours for 5 days (a total of 10 consecutive doses)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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) | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Time to sustained alleviation without relapse is defined as the number of days from randomization to the first of 2 consecutive days when alleviation (lessening of symptoms) is demonstrated, collectively, for all 8 selected COVID-19-related sign/symptoms. Participants who experience sustained alleviation for 2 consecutive days must not relapse in any of the 8 signs/symptoms before Day 29. The time to sustained alleviation without relapse of all 8 selected COVID-19-related signs/symptoms from randomization through Day 29 will be presented. |
| Change from Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA Titer | Day 1 (baseline) and up to Day 29 | SARS-CoV-2 RNA titer (viral load) will be measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) of samples from nasopharyngeal (NP) swabs, and the mean change from baseline will be presented. |
| Percentage of Participants with Undetectable SARS-CoV-2 RNA | Up to 29 days | SARS-CoV-2 RNA (viral load) will be measured by quantitative RT-PCR of samples from NP swabs, and the percentage of participants with undetectable (i.e., below the lower limit of quantification) SARS-CoV-2 RNA (viral load) will be presented. |
| Percentage of Participants Who Experienced One or More of Following Through Day 29: All-cause Hospitalization or All-cause Mortality | 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. As prespecified by the protocol, the percentage of participants who experience hospitalization AND/OR death occurring from randomization through Day 29 will be presented. |
| 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 | CIMIs were prespecified by the protocol and include, but are not limited to, supplemental oxygen therapy, IV fluid administration, and nebulizer treatment. 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. 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. The percentage of participants with CIMIs associated with a COVID-19-related MAV AND/OR a COVID-19-related hospitalization through Day 29 will be reported. |
| 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 alleviation without relapse is defined as the number of days from randomization to the first of 2 consecutive days when alleviation (lessening of symptoms) is demonstrated, collectively, for all 15 COVID-19-related sign/symptoms. Participants who experience sustained alleviation after 2 consecutive days must not relapse in any of the 15 signs/symptoms before Day 29. The time to sustained alleviation without relapse of all 15 COVID-19-related signs/symptoms from randomization through Day 29 will be presented. |
| 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 | Time to sustained resolution without relapse is defined as the number of days from randomization to the first of 2 consecutive days when resolution (having no symptoms or only mild symptoms) is demonstrated, collectively, for all 8 selected COVID-19-related sign/symptoms. Participants who experience sustained resolution after 2 consecutive days must not relapse in any of the 8 signs/symptoms before Day 29. The time to sustained resolution without relapse of all 8 selected COVID-19-related signs/symptoms from randomization through Day 29 will be presented. |
Countries
Argentina, Brazil, Bulgaria, Colombia, Finland, France, Georgia, Germany, Italy, Japan, Mexico, New Zealand, Peru, Philippines, Poland, Puerto Rico, Romania, South Korea, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed