Daily Mosnodenvir as Dengue Prophylaxis in a Controlled Human Infection Model.

backgroundApproximately half the worldwide population is at risk for dengue. No antiviral prophylaxis or treatment options are available.

methodsIn a phase 2a, double-blind, randomized trial, we assigned healthy adults to receive oral mosnodenvir once daily as a low dose (40-mg loading dose followed by 10-mg maintenance dose), medium dose (200 mg followed by 50 mg), or high dose (600 mg followed by 200 mg) or matched placebo. Loading doses were given for 5 days and maintenance doses for 21 days. In a controlled human infection model, participants received subcutaneous inoculation of an underattenuated dengue virus serotype 3 (DENV-3) strain (rDEN3Δ30) on the day of the first maintenance dose (day 1). The primary efficacy end point was the DENV-3 RNA load, assessed as the log

resultsThe percentage of participants without signs of DENV-3 infection was 0% (0 of 6 participants) with the low dose of mosnodenvir, 17% (1 of 6) with the medium dose, and 60% (6 of 10) with the high dose, as compared with 0% (0 of 7) with placebo. High-dose mosnodenvir led to a significantly lower DENV-3 RNA load, assessed as the log

conclusionsIn a controlled human infection model, a high daily dose of oral mosnodenvir led to a significantly lower DENV-3 RNA load than placebo. Mosnodenvir did not result in any serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and Johnson & Johnson; ClinicalTrials.gov number, NCT05048875.).