Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults
et al., NEJM Evidence, doi:10.1056/EVIDoa2100043, MOVe-OUT Phase 2, NCT04575597, Jan 2022
Phase 2 RCT of 302 nonhospitalized adults showing possible benefit with molnupiravir (200, 400, or 800 mg twice daily for 5 days) for treatment of mild-to-moderate COVID-19.
Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-15. Multiple analyses have identified variants potentially created by molnupiravir16-20. Studies show significantly increased risk of acute kidney injury21, cardiovascular toxocity22, and neurological symptoms21. Treatment may increase viral rebound23,24.
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risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 74 (0.0%), control 1 of 74 (1.4%), NNT 74, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), 800mg, day 29.
|
|
risk of hospitalization, 25.0% lower, RR 0.75, p = 1.00, treatment 3 of 74 (4.1%), control 4 of 74 (5.4%), NNT 74, 800mg, day 29.
|
|
risk of no recovery, 22.0% higher, OR 1.22, p = 0.63, treatment 74, control 74, inverted to make OR<1 favor treatment, 800mg, day 29, Table S7, RR approximated with OR.
|
|
risk of no recovery, 49.3% higher, OR 1.49, p = 0.25, treatment 74, control 74, inverted to make OR<1 favor treatment, 800mg, day 15, Table S7, RR approximated with OR.
|
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risk of no recovery, 17.6% higher, OR 1.18, p = 0.79, treatment 74, control 74, inverted to make OR<1 favor treatment, 800mg, day 5, Table S7, RR approximated with OR.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
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Caraco et al., 25 Jan 2022, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, peer-reviewed, mean age 49.2, 19 authors, trial NCT04575597 (history) (MOVe-OUT Phase 2).
Contact: matthew.johnson1@merck.com.
Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults
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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