A Clinical Study of Molnupiravir to Prevent Severe Illness From Coronavirus Disease 2019 (COVID-19) in People Who Are High Risk (MK-4482-023)

Phase 3RecruitingNCT06667700

Merck Sharp & Dohme LLC3,082 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

3,082

Conditions

Coronavirus Disease (COVID-19)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (215)

Cullman Clinical Trials ( Site 3813)

Cullman, Alabama, United States

RECRUITING

Helios Clinical Research ( Site 3826)

Paradise Valley, Arizona, United States

RECRUITING

Absolute Clinical Research ( Site 3709)

Phoenix, Arizona, United States

RECRUITING

Clinica de Salud del Valle de Salinas ( Site 3825)

Castroville, California, United States

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)

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.

Time frame: Up to 29 days

Percentage of Participants Who Experienced an Adverse Event (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. The percentage of participants with at least 1 AE will be presented.

Time frame: Up to approximately 5 months

Percentage of Participants Who Discontinued Study Intervention Due to AE

Time frame: Up to approximately 5 days

Secondary Outcomes

Time to Sustained Alleviation (without relapse) of all selected 8 (5 prespecified and 3 determined by baseline prevalence), self-reported COVID-19 signs/symptoms

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.

Time frame: Up to 29 days

Change from Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA Titer

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.

Time frame: Day 1 (baseline) and up to Day 29

Percentage of Participants with Undetectable SARS-CoV-2 RNA

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.

Time frame: Up to 29 days

Percentage of Participants Who Experienced One or More of Following Through Day 29: All-cause Hospitalization or All-cause Mortality

Time frame: 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

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 frame: Up to 29 days

Time to Sustained Alleviation (without relapse) of all 15 self-reported COVID-19 signs/symptoms through Day 29

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 frame: 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

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.

Time frame: Up to 29 days

A Clinical Study of Molnupiravir to Prevent Severe Illness From Coronavirus Disease 2019 (COVID-19) in People Who Are High Risk (MK-4482-023)

Overview

Conditions

Interventions

Eligibility

Locations (215)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts