Viral Dynamic Model-Informed Dose Selection of Mosnodenvir Prophylaxis against DENV-3 in a Controlled Human Infection Model.
Nele Goeyvaerts, Xavier Woot de Trixhe, Martine Neyens et al.
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In 30 seconds
This Phase IIa controlled human infection model study evaluated mosnodenvir prophylaxis against DENV-3 and used combined population pharmacokinetic and viral dynamic modelling to inform dose selection. The models incorporated pharmacokinetic data from three Phase I studies and the first Phase IIa cohort, then simulated regimens for further assessment. Using the complete Phase IIa data, the estimated basic reproductive number for DENV-3 in this model was 21.7; the typical steady-state average concentration estimated to achieve complete virus eradication was 1,410 ng/mL. The modelling characterized the exposure–antiviral activity relationship and supported further regimen evaluation.
Key findings
- The estimated basic reproductive number for DENV-3 in the controlled human infection model was 21.7.
- The typical steady-state average mosnodenvir concentration estimated to achieve complete virus eradication was 1,410 ng/mL.
- Simulations supported daily and weekly dosing regimens for further pharmacokinetic/pharmacodynamic characterization in the second cohort.
Why it matters
A combined pharmacokinetic and viral dynamic model can connect drug exposure with antiviral activity and help select regimens for evaluation in a controlled infection setting. The estimated concentration associated with complete viral eradication provides a quantitative model-based target, while the study’s findings remain specific to DENV-3 infection in this human challenge model.
What to keep in mind
The findings are model-based and arise from a controlled human infection model focused on DENV-3; the abstract does not establish effectiveness in naturally acquired dengue infection.