Journal Article Ppublish 8 citations
PubMed: 40175624 DOI: 10.1007/s41030-025-00289-z
A Phase 2a, Randomized, Placebo-Controlled Human Challenge Trial to Evaluate the Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated with Respiratory Syncytial Virus.
Pulm Ther 11(2):285-304
Authors: Mickie H Cheng, Alex J Mann, Brian M Maas, Tian Zhao, Melissa Bevan, Andrea K Schaeffer, Laura E Liao, Andrew P Catchpole, David W Hilbert, S Aubrey Stoch, Carisa S De Anda
Affiliations
- Merck & Co. Inc. 126 E. Lincoln Ave. Rahway, NJ, 07065, USA.
- hVIVO Services Ltd. London, UK.
- Merck & Co. Inc. 126 E. Lincoln Ave. Rahway, NJ, 07065, USA.
Abstract
INTRODUCTION
Human respiratory syncytial virus (RSV) infections can result in hospitalization and/or death among vulnerable populations. Molnupiravir is a prodrug of ß-D-N4-hydroxycytidine, which has broad-spectrum preclinical activity against RNA viruses. We conducted a pilot trial evaluating molnupiravir for RSV infection.
METHODS
Double-blind, placebo-controlled, phase 2a human challenge study in healthy adults (≥ 18 to ≤ 55 years old). Eligible participants were randomized 1:1:1 to molnupiravir prophylaxis (5 days, 800 mg twice daily; followed by placebo), molnupiravir treatment (5 days, 800 mg twice daily; started on day 5, unless triggered earlier by positive PCR test; preceded and followed by placebo), or placebo. Study intervention was administered for 11 days, from day -1 (evening), prior to inoculation with RSV on day 0 (morning). For 10 days, quarantined participants reported symptoms thrice daily and underwent nasal wash sample collection twice daily. Primary efficacy endpoints (assessed by quantitative viral culture on plaque assay) were peak viral load (PVL) in all participants (for prophylaxis) and area under the viral-load time curve (VL-AUC) in participants with confirmed infection (for treatment). Adverse events were assessed from day 0 to day 28.
RESULTS
Forty participants each were randomized to prophylaxis and placebo and 36 to treatment. Molnupiravir was not statistically significant from placebo in either primary endpoint: with prophylaxis, the difference in mean log 10 PVL was - 0.29 plaque-forming units (PFU)/ml (90% CI - 1.16, 0.58; p = 0.578), and with treatment, the difference in mean log 10 VL-AUC was - 2.69 day*PFU/ml (90% CI - 6.17, 0.79; p = 0.201). Molnupiravir treatment resulted in significantly faster symptom resolution: 6.0 days versus 8.5 days with placebo (hazard ratio: 2.24 [95% CI: 0.99, 5.07]; p = 0.0459). Adverse event rates were comparable between arms.
CONCLUSIONS
Although the primary endpoints were not met, modest, non-significant benefits with molnupiravir treatment were seen across virologic endpoints, along with significantly faster symptom resolution.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov NCT05559905.
MeSH
Respiratory Syncytial Viruses, Safety, Healthy Volunteers, Drug-Related Side Effects And Adverse Reactions, Viruses, Therapeutics, Infections, Respiratory Syncytial Virus Infections