Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults
M.D Yoseph Caraco, M.D Gordon E Crofoot, M.D Pablo Andres Moncada, M.D Anna Nikolaevna Galustyan, M.D Dany Badibanga Musungaie, M.D Brendan Payne, M.D Evgeniy Kovalchuk, M.D Antonio Gonzalez, Michelle L Brown, Angela Williams-Diaz, Ph.D Wei Gao, Ph.D Julie M Strizki, Ph.D Jay Grobler, Ph.D Jiejun Du, Ph.D Christopher A Assaid, M.D Amanda Paschke, M.D Joan R Butterton, M.D Matthew G Johnson, Pharm.D Carisa De Anda
NEJM Evidence, doi:10.1056/evidoa2100043
BACKGROUND Safe and effective oral treatments are needed to improve clinical outcomes for nonhospitalized patients with Covid-19. Molnupiravir is an orally administered, small-molecule ribonucleoside prodrug shown to inhibit replication of severe acute respiratory syndrome coronavirus 2 in vitro and in animal models. METHODS MOVe-OUT is an ongoing, phase 2/3, randomized, placebo-controlled, double-blind study evaluating the safety, efficacy, and pharmacokinetics of molnupiravir in nonhospitalized adults. In the phase 2 component, participants had mild or moderate, laboratory-confirmed Covid-19 with sign/symptom onset up to (and including) 7 days before randomization. Participants were randomly assigned 1:1:1:1 to receive 200, 400, or 800 mg of molnupiravir or placebo twice daily for 5 days, stratified by time since sign/ symptom onset and by being at increased risk for severe illness from Covid-19. The primary efficacy end point was the proportion of participants who were hospitalized and/or died through day 29.
RESULTS The phase 2 component randomly assigned 302 participants to treatment; baseline characteristics were comparable across treatment groups. Molnupiravir had no apparent dose-related effect on adverse events, and no clinically meaningful abnormalities in laboratory test results were observed in relation to dose or treatment. Eleven participants were hospitalized or died through day 29. Of 225 participants in the combined molnupiravir group, 7 (3.1%) were hospitalized or died, compared with 4 of 74 participants (5.4%) in the placebo group. Subgroup analyses suggested lower incidences of hospitalization and/or death in the molnupiravir versus placebo groups in participants older than 60 years of age, those with increased risk for severe illness, those with symptom onset up to (and including) 5 days before randomization, and those with both symptom onset up to (and including) 5 days before randomization and increased risk for severe illness.
Author Affiliations
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