Acetohydroxamic Acid Combined With a Short-Course Regimen for MDR-TB (AHA-PLUS)

Summary

This study is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial to evaluate the safety, tolerability, and preliminary efficacy of acetohydroxamic acid (AHA) capsules combined with short-course regimens (BDLLfxC or BDCZ) in patients with multidrug-resistant tuberculosis (MDR-TB). The primary objectives are to assess the safety and tolerability of AHA combined with short-course regimens, and to determine the recommended phase II dose (RP2D) of AHA. The secondary objectives include evaluating the 8-week sputum culture conversion rate, pharmacokinetic parameters, and exploring DNA damage repair biomarkers as potential indicators of treatment response.

Timeline

Start

2026-02-21

Primary completion

2027-02-28

Completion

2028-11-30

Publications

• Background World Health Organization. Global Tuberculosis Report 2024. Geneva: WHO, 2024.
• Background Liu S, Guan L, Peng C, Cheng Y, Cheng H, Wang F, Ma M, Zheng R, Ji Z, Cui P, Ren Y, Li L, Shi C, Wang J, Huang X, Cai X, Qu D, Zhang H, Mao Z, Liu H, Wang P, Sha W, Yang H, Wang L, Ge B. Mycobacterium tuberculosis suppresses host DNA repair to boost its intracellular survival. Cell Host Microbe. 2023 Nov 8;31(11):1820-1836.e10. doi: 10.1016/j.chom.2023.09.010. Epub 2023 Oct 16.
• Background Griffith DP, Gibson JR, Clinton CW, Musher DM. Acetohydroxamic acid: clinical studies of a urease inhibitor in patients with staghorn renal calculi. J Urol. 1978 Jan;119(1):9-15. doi: 10.1016/s0022-5347(17)57366-8.
• Background WHO consolidated guidelines on tuberculosis: Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK588564/

Drugs

Indications