NCT07393438

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

Acetohydroxamic Acid Combined With a Short-Course Regimen for the Treatment of Multidrug-Resistant Tuberculosis: A Phase II Clinical Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Background: Multidrug-resistant tuberculosis (MDR-TB) remains a significant global health challenge. Current treatment regimens face multiple bottlenecks including serious adverse effects, long treatment duration, and high cost. Acetohydroxamic acid (AHA), a urease inhibitor, represents a novel mechanism of action against tuberculosis. Recent research has revealed that Mycobacterium tuberculosis urease C (UreC) inhibits host DNA repair by interfering with the RUVBL1-RUVBL2-RAD51 complex, promoting bacterial survival. AHA, as a urease inhibitor, may block the pathogenic effect of UreC and restore host DNA repair function. Study Design: This is a parallel dual-study design evaluating AHA combined with two different background regimens: * Study A: AHA + BDLLfxC regimen (6-9 months) * Study B: AHA + BDCZ regimen (6-9 months) Each study randomizes participants in a 1:1:1:1 ratio to low-dose (500mg/day), medium-dose (750mg/day), high-dose (1000mg/day) AHA groups, or placebo group. A double-dummy design is employed to maintain blinding, where all participants receive identical-appearing capsules regardless of treatment assignment. The study includes a 6-9 month treatment period followed by mandatory follow-up visits at 3 and 6 months post-treatment, with optional follow-up every 6 months thereafter.

Conditions

• Multidrug-Resistant Tuberculosis
• Rifampicin-resistant Tuberculosis
• MDR-TB
• RR-TB

Interventions

Type	Name	Description
DRUG	Acetohydroxamic Acid	Acetohydroxamic acid administered according to the protocol-defined dose and schedule, in combination with a short-course anti-tuberculosis regimen.
DRUG	Placebo	Matching placebo identical in appearance, packaging, and administration schedule to acetohydroxamic acid, administered with the same short-course anti-tuberculosis regimen.

Timeline

• Start date: 2026-02-21
• Primary completion: 2027-02-28
• Completion: 2028-11-30
• First posted: 2026-02-06
• Last updated: 2026-02-06

Locations

2 sites across 1 country: China