Pharmacokinetics, Safety, and Tolerability of Different Maintenance Dose Regimens of Mosnodenvir (JNJ-1802) in Healthy Adult Participants.

Abstract

Dengue virus infection has become a global health concern, and no dengue-specific treatment is available. Mosnodenvir is a pan-serotypic dengue antiviral in clinical development. In this Phase 1, open-label study (NCT05201937), high- and low-dose weekly, and twice weekly maintenance doses (MDs) of mosnodenvir were evaluated following a twice daily loading dose (LD) over 2 days. The utility of a convenient capillary blood sampling device (TASSO-M20) was also explored. Healthy adults were sequentially assigned to receive: 450 mg twice daily LD, 900 mg once weekly MD; 450 mg twice daily LD, 450 mg twice weekly MD; 150 mg twice daily LD, 300 mg once weekly MD; or 150 mg twice daily LD, 150 mg twice weekly MD. Mosnodenvir exposure rapidly increased with LD and was maintained during the MD phase. In general, mosnodenvir increased in a dose-proportional manner with similar areas under the concentration-time curve between once weekly and twice weekly MD. The mean terminal elimination half-life across treatments was 6.7-8.7 days, supporting less frequent dosing. Safety and tolerability were similar across all treatment regimens. TASSO-M20 was preferred over venipuncture by participants. In summary, mosnodenvir administered weekly or biweekly achieved pharmacokinetic exposures that were found to be safe and well tolerated.