Molnupiravir for intra-household prevention of COVID-19: The MOVe-AHEAD randomized, placebo-controlled trial

Objectives: To evaluate the efficacy and safety of molnupiravir for intra-household post-exposure prophylaxis (PEP) of COVID-19. Methods: MOVe-AHEAD was a randomized, controlled, double-blind, phase 3 trial comparing molnupiravir (800 mg twice daily for 5 days) with placebo. Eligible participants were adult, unvaccinated, asymptomatic household contacts of patients with laboratory-confirmed COVID-19. The primary efficacy endpoint was the incidence of COVID-19 through day 14 in modified intention-to-treat (MITT) participants (those who received >= 1 dose of study intervention) without detectable SARS-CoV-2 at baseline, termed the MITT-VN population. Superiority of molnupiravir was prespecified as a stratified one-sided p-value of < 0.0249 for the treatment difference in this endpoint. Results: The MITT population comprised 763 participants randomized to molnupiravir and 764 to placebo; 83.6% had anti-SARS-CoV-2 antibodies at baseline. In the MITT-VN population, COVID-19 rates through day 14 were 6.5% with molnupiravir and 8.5% with placebo (one-sided p-value: 0.0848). In the molnupiravir arm, 25/35 of confirmed COVID-19 events (71.4%) occurred after completion of treatment (versus 17/49 [34.7%] for placebo). Adverse event rates were low and similar between molnupiravir and placebo. Conclusions: Molnupiravir was well-tolerated but did not meet the prespecified superiority criterion, possibly influenced in part by the high pre-existing immunity in the trial population. <(c)> 2023 Merck Sharp Dohme LLC., a subsidiary of Merck Co., Inc., Rahway, NJ, USA and The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).