Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002)

Summary

This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the percentage of participants who are hospitalized and/or die through Day 29

Timeline

Start

2020-10-19

Primary completion

2022-05-05

Completion

2022-05-05

Outcome

Met primary endpoint

registry analysis (superiority test); Part 2: Molnupiravir 800 mg vs Part 2: Placebo; p = 0.0012; Difference in Rates % -6.8 (95% CI -11.3 to -2.4); Miettinen & Nurminen NCT04575597 ↗

release “significantly reduced the risk of hospitalization or death at a planned interim analysis of the Phase 3 MOVe-OUT trial” merck.com ↗

release “Data from MOVe-OUT demonstrated that early treatment with molnupiravir significantly reduced the risk of hospitalization or death in high risk, unvaccinated adults with COVID-19.” merck.com ↗

release “Data from MOVe-OUT demonstrated that early treatment with molnupiravir significantly reduced the risk of hospitalization or death in high risk, unvaccinated adults with COVID-19.” msd.com ↗

Publications

• Results Caraco Y, Crofoot GE, Moncada PA, Galustyan AN, Musungaie DB, Payne B, Kovalchuk E, Gonzalez A, Brown ML, Williams-Diaz A, Gao W, Strizki JM, Grobler J, Du J, Assaid CA, Paschke A, Butterton JR, Johnson MG, De Anda C. Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults. NEJM Evid. 2022 Feb;1(2):EVIDoa2100043. doi: 10.1056/EVIDoa2100043. Epub 2021 Dec 16.
• Johnson MG, Strizki JM, Hilbert DW, Zhang Y, Carmelitano P, Brown ML, Wolf DJ, Paschke A, De Anda CS. Impact of baseline humoral immunity on treatment outcomes with molnupiravir in the MOVe-OUT randomized, controlled trial. Virology. 2026 Jan;613:110710. doi: 10.1016/j.virol.2025.110710. Epub 2025 Oct 9.
• Caraco Y, Johnson MG, Chiarappa JA, Maas BM, Stone JA, Rizk ML, Vesnesky M, Strizki JM, Williams-Diaz A, Brown ML, Carmelitano P, Wan H, Pedley A, Chawla A, Wolf DJ, Grobler JA, Paschke A, De Anda C. Impact of differences between interim and post-interim analysis populations on outcomes of a group sequential trial: Example of the MOVe-OUT study. Clin Trials. 2025 Jun;22(3):312-324. doi: 10.1177/17407745251313925. Epub 2025 Mar 2.
• Strizki JM, Grobler JA, Murgolo N, Fridman A, Johnson MG, Du J, Carmelitano P, Brown ML, Paschke A, De Anda C. Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial. Infect Dis Ther. 2023 Dec;12(12):2725-2743. doi: 10.1007/s40121-023-00891-1. Epub 2023 Nov 23.
• Guan Y, Puenpatom A, Johnson MG, Zhang Y, Zhao Y, Surber J, Weinberg A, Brotons C, Kozlov R, Lopez R, Coetzee K, Santiaguel J, Du J, Williams-Diaz A, Brown M, Paschke A, De Anda C, Norquist JM. Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial. Clin Infect Dis. 2023 Nov 30;77(11):1521-1530. doi: 10.1093/cid/ciad409.
• Chawla A, Birger R, Wan H, Cao Y, Maas BM, Paschke A, De Anda C, Rizk ML, Stone JA. Factors Influencing COVID-19 Risk: Insights From Molnupiravir Exposure-Response Modeling of Clinical Outcomes. Clin Pharmacol Ther. 2023 Jun;113(6):1337-1345. doi: 10.1002/cpt.2895. Epub 2023 Apr 27.
• Johnson MG, Strizki JM, Brown ML, Wan H, Shamsuddin HH, Ramgopal M, Florescu DF, Delobel P, Khaertynova I, Flores JF, Fouche LF, Chang SC, Williams-Diaz A, Du J, Grobler JA, Paschke A, De Anda C. Molnupiravir for the treatment of COVID-19 in immunocompromised participants: efficacy, safety, and virology results from the phase 3 randomized, placebo-controlled MOVe-OUT trial. Infection. 2023 Oct;51(5):1273-1284. doi: 10.1007/s15010-022-01959-9. Epub 2023 Jan 17.
• Johnson MG, Puenpatom A, Moncada PA, Burgess L, Duke ER, Ohmagari N, Wolf T, Bassetti M, Bhagani S, Ghosn J, Zhang Y, Wan H, Williams-Diaz A, Brown ML, Paschke A, De Anda C. Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 : A Randomized, Placebo-Controlled Trial. Ann Intern Med. 2022 Aug;175(8):1126-1134. doi: 10.7326/M22-0729. Epub 2022 Jun 7.
• Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, Martin-Quiros A, Caraco Y, Williams-Diaz A, Brown ML, Du J, Pedley A, Assaid C, Strizki J, Grobler JA, Shamsuddin HH, Tipping R, Wan H, Paschke A, Butterton JR, Johnson MG, De Anda C; MOVe-OUT Study Group. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022 Feb 10;386(6):509-520. doi: 10.1056/NEJMoa2116044. Epub 2021 Dec 16.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Molnupiravir	Small molecule	200 mg	Oral
Subject	Molnupiravir	Small molecule	400 mg	Oral
Subject	Molnupiravir	Small molecule	800 mg	Oral

Indications