Clinical trial of molnupiravir (MK-4482) in adults who have COVID-19 and are not hospitalized, who are at high risk for serious illness from the infection.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

21 Feb 2025 → ongoing

Decision date (initial)

2025-02-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ridgeback Biotherapeutics, LP/ Ridgeback Pharmaceuticals LLC · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-507227-36-00

WHO UTN

U1111-1295-4678

ClinicalTrials.gov

NCT06667700

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

1. To evaluate the efficacy of MOV compared with placebo as assessed by the percentage of participants in the mITT population who have one or more of the following from randomization through Day 29: hospitalization (all-cause), death (all-cause), or a COVID-19-related MAV.
2. To evaluate the safety and tolerability of MOV compared with the placebo in the APaT population.

Secondary objectives 6

1. To evaluate the efficacy of MOV compared with placebo as assessed by time to sustained alleviation (without relapse) of all 8 selected self-reported COVID-19 signs/symptoms from randomization through Day 29 in the mITT population.
2. To evaluate the antiviral activity of MOV compared with placebo as assessed by the change from baseline in SARS-CoV-2 RNA titer and percentage of participants with undetectable SARS-CoV-2 RNA in NP swabs at Day 3, EOT, Days 10, 14, and 29 in the mITT population.
3. To evaluate the efficacy of MOV compared with placebo as assessed by the percentage of participants in the mITT population who have one or more of the following from randomization through Day 29: hospitalization (all-cause) or death (all-cause).
4. To evaluate the efficacy of MOV compared with placebo as assessed by the percentage of participants with clinically important medical interventions associated with a COVID-19-related MAV and/or a COVID-19-related hospitalization from randomization through Day 29 in mITT participants who have COVID-19-related MAV and/or a COVID-19-related hospitalization.
5. To evaluate the efficacy of MOV compared with placebo as assessed by time to sustained alleviation of all 15 self-reported COVID-19 signs/symptoms without relapse from randomization through Day 29 in the mITT population.
6. To evaluate the efficacy of MOV compared with placebo as assessed by time to sustained resolution without relapse of all 8 selected self-reported COVID-19 signs/symptoms without relapse from randomization through Day 29 in the mITT population.

Conditions and MedDRA coding

SARS-CoV-2 (COVID-19) infection

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Is an individual of any sex/gender, ≥18 years of age
2. Has documentation of SARS-CoV-2 infection with sample collection ≤4 days prior to randomization
3. 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
4. Has ≥1 of the following characteristics or medical conditions associated with the highest risk of severe illness from COVID-19: 1) advanced age of ≥75 years of age, 2) Immunocompromised, 3) Neurocognitive or physical disability or has ≥3 characteristics or medical conditions which increase the risk of severe illness due to COVID-19 (e.g. diabetes, obesity with body mass index (BMI) ≥ 35, chronic lung diseases)
5. Is unable or unwilling to receive treatment with nirmatrelvir/ritonavir (NMV/r) due to 1 or more of the following: 1) Is receiving drug(s) highly dependent on cytochrome P450 (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, 2) Is receiving potent CYP3A inducers where significantly reduces nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance, 3) Has severe hepatic impairment, 4) Has experienced prior adverse reactions or hepatotoxicity to NMV/r that would preclude future use, 5) Has known or suspected NMV/r resistance, 6) Has uncontrolled HIV infection, 7) NMV/r is not approved/authorized in the participant’s country or it is not accessible to participant (e.g. drug shortage), 8) Is unwilling to receive treatment with NMV/r

Exclusion criteria 6

1. Is currently hospitalized or is expected to need hospitalization for COVID-19 imminently
2. 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)
3. Has ≥1 of the following signs/symptoms that are attributable to severe or critical COVID-19: 1) shortness of breath at rest, 2) respiratory rate ≥30 breaths per minute, 3) heart rate ≥125 beats per minute, 4) 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, 5) New or increasing need for supplemental oxygen: Receiving >4 liters/min supplemental oxygen due to COVID-19 OR on supplemental oxygen for a reason other than COVID-19 which has increased due to COVID-19
4. Has received a COVID-19 vaccine within 30 days prior to randomization
5. 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
6. Has known or suspected hypersensitivity to active or inactive ingredients of MOV

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of Participants Who Experienced One or More of following through Day 29: Hospitalization, All-cause Mortality, or COVID-19 Related Medically Attended Visit (MAV)
2. Percentage of Participants Who Experienced an Adverse Event (AE)
3. Percentage of Participants Who Discontinued Study Intervention Due to AE

Secondary endpoints 7

1. Time to Sustained Alleviation (without relapse) of all selected 8 (5 prespecified and 3 determined by baseline prevalence), self-reported COVID-19 signs/symptoms
2. Change From Baseline in SARS-CoV-2 RNA titer
3. Percentage of Participants With Undetectable SARS-CoV-2 RNA
4. Percentage of Participants Who Experienced One or More of following through Day 29: All-cause Hospitalization or All-cause Mortality
5. Percentage of Participants With Clinically Important Medical Interventions Associated with COVID-19 related MAV or COVID-19 related hospitalization through Day 29
6. Time to Sustained Alleviation (without relapse) of all 15 self-reported COVID-19 signs/symptoms through Day 29
7. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Dana Byrne

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Dana Byrne

Third parties 10

Locations

8 EU/EEA countries · 49 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 86 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

18 submissions — initial application plus substantial / non-substantial modifications