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Using Molnupiravir to Prevent Severe COVID-19 in High-Risk Individuals

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

Phase 3 Interventional Merck Sharp & Dohme LLC · NCT06667700

This study is testing if the medication molnupiravir can help prevent severe COVID-19 in high-risk individuals who have recently shown symptoms of the virus.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment3082 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Locations222 sites (Cullman, Alabama and 221 other locations)
Trial IDNCT06667700 on ClinicalTrials.gov

What this trial studies

This clinical study investigates the effectiveness of molnupiravir, a medication designed to inhibit the replication of the COVID-19 virus, in preventing severe illness among individuals at high risk for complications from the disease. Participants must be at least 18 years old and have documented SARS-CoV-2 infection with symptoms that began within the last four days. The study compares the outcomes of those receiving molnupiravir to those receiving a placebo to determine if the treatment can significantly reduce the severity of COVID-19 symptoms. The focus is on individuals with specific health conditions or characteristics that increase their risk of severe illness.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older who have recently tested positive for COVID-19 and exhibit symptoms, particularly those with high-risk factors such as advanced age or immunocompromised status.

Not a fit: Patients who are not at high risk for severe illness from COVID-19 or those who do not have recent symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the incidence of severe COVID-19 illness in high-risk patients.

How similar studies have performed: Other studies have shown promise with antiviral treatments for COVID-19, making this approach both relevant and potentially impactful.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Cullman, Alabama and 221 other locations

+172 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Coronavirus Disease
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.