Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults

作者：Yoseph Caraco, Gordon Crofoot, Pablo Andrés Moncada, A.N. Galustyan, Dany Badibanga Musungaie, Brendan Payne, Evgeniy Kovalchuk, Antonio Gonzalez, Michelle Brown, Angela Williams‐Diaz, Wei Gao, Julie Strizki, Jay A. Grobler, Jiejun Du, Christopher Assaid, Amanda Paschke, Joan R. Butterton, Matthew G. Johnson, Carisa De Anda · 发表于：NEJM Evidence · 年份：2021 · DOI：10.1056/evidoa2100043 · 被引用次数：99 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、SARS-CoV-2 detection and testing

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 hospita...