Daily Mosnodenvir as Dengue Prophylaxis in a Controlled Human Infection Model
Anna P. Durbin, Liesbeth Van Wesenbeeck, Kristen K. Pierce, Guillermo Herrera‐Taracena, Laura Ebone, Annemie Buelens, Patricia Lutton, Beulah P. Sabundayo, Veerle Van Eygen, Kim De Clerck, Isabel Fetter, Natalia V. Voge, Xi Fang, Nele Goeyvaerts, Yannick Vandendijck, Jeffrey Mayfield, Oliver Lenz, Sandra De Meyer, Thomas N. Kakuda, Haiyin He, Emérito Amaro-Carambot, Ruxandra Draghia‐Akli, Marya P. Carmolli, Tine De Marez, Stephen S. Whitehead, Marnix Van Loock, Freya Rasschaert
Abstract
BACKGROUND: Approximately half the worldwide population is at risk for dengue. No antiviral prophylaxis or treatment options are available. METHODS: ). The high-dose and placebo groups were compared in the primary end-point analysis. Safety, pharmacokinetic features, and virologic and serologic features were evaluated through day 85. RESULTS: , than placebo (two-sided P<0.001 by tobit analysis of variance). In this small trial, mosnodenvir did not result in any serious adverse events. Plasma concentrations of mosnodenvir increased from day -5 to day 1 and were maintained through day 21. Among participants with available NS4B sequencing data, emerging amino acid variations in the NS4B region of the rDEN3Δ30 genome were detected in 14 of 14 mosnodenvir recipients and none of 7 placebo recipients. CONCLUSIONS: In 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.).