Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19.

ABSTRACT

BACKGROUND: Molnupiravir is an oral prodrug of ß-D-N4-hydroxycytidine, active against SARS-CoV-2 in vitro and in animal models. We report data from the phase 2 component of MOVe-IN, a clinical trial evaluating molnupiravir in patients hospitalized with Covid-19. METHODS: We conducted a randomized, placebo-controlled, double-blind phase 2/3 trial in patients 18 years old and older requiring in-hospital treatment for laboratory-confirmed Covid-19 with symptom onset 10 or fewer days before randomization. Participants were randomly assigned to placebo or molnupiravir 200 mg, 400 mg, or 800 mg (1111 ratio), twice daily for 5 days. Primary end points were safety and sustained recovery (participant alive and either not hospitalized or medically ready for discharge) through day 29. RESULTS: Of 304 randomly assigned participants, 218 received at least one dose of molnupiravir and 75 of placebo. At baseline, 74.0% had at least one risk factor for severe Covid-19. Adverse events were reported in 121 of 218 (55.5%) molnupiravir-treated and 46 of 75 (61.3%) placebo-treated participants, with no apparent dose effect on adverse event rates and no evidence of hematologic toxicity based on prespecified adverse events. Of 16 confirmed deaths, most were in participants with severe Covid-19 (75.0%), with underlying comorbidities (87.5%), older than 60 years of age (81.3%), and/or symptom duration longer than 5 days (75.0%) at randomization. Median time to sustained recovery was 9 days in all groups, with similar day 29 recovery rates ranging from 81.5% to 85.2%. CONCLUSIONS: In this phase 2 trial of patients hospitalized with Covid-19, a 5-day course of molnupiravir up to 800 mg twice daily was not associated with dose-limiting side effects or adverse events, but did not demonstrate clinical benefit. (Funded by Merck Sharp & Dohme; ClinicalTrials.gov NCT04575584.)