Dosing and Safety of Once-Weekly Rifapentine and Isoniazid for 12 Weeks for Tuberculosis Preventive Therapy in Children With and Without HIV: Protocol for a Phase I/II Open-Label, Exposure-Controlled, Dose-Finding, and Safety Study (Tuberculosis Trials Consortium Study 35).

Background: Young children with exposure to or infection with Objective: This protocol describes Tuberculosis Trials Consortium (TBTC) Study 35, which aims to establish practical age- and weight-banded rifapentine doses for 3HP in children aged 0 to 12 years, including children younger than 2 years, and children living with HIV, while assessing safety, tolerability, palatability, and acceptability. Methods: TBTC Study 35 was a phase I/II, open-label, multisite, single-arm, exposure-controlled dose-finding and safety study of 3HP in children aged 0 to 12 years, including children living with HIV. Novel water-dispersible rifapentine and isoniazid formulations were used. Building on TBTC Study 26 data, initial rifapentine doses were selected, and nonlinear mixed-effects modeling was used to analyze the pharmacokinetic data and evaluate subsequent rifapentine doses. Safety was monitored throughout the 12-week treatment period and 12-week posttreatment follow-up. Results: Data collection began with the first recruitment in November 2019. The last participant was enrolled in December 2023, and participant follow-up and data collection were completed in May 2024. As of now, 69 participants were enrolled. The trial was funded throughout this time period. Data analysis is ongoing, and trial results are expected to be disseminated in 2026. Conclusions: TBTC Study 35 is expected to provide pharmacokinetic and safety data to inform practical pediatric 3HP dosing recommendations, including for children younger than 2 years and children living with HIV.