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Not yet recruiting NCT07393438

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

Phase II Interventional Multidrug-Resistant Tuberculosis Rifampicin-resistant Tuberculosis MDR-TB RR-TB

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Acetohydroxamic Acid, Placebo.
Who it may be relevant to
Registry conditions: Multidrug-Resistant Tuberculosis, Rifampicin-resistant Tuberculosis, MDR-TB, RR-TB. Basic parameters: 18 years — 65 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

  • 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.

Primary outcome measures

  • Change in Mycobacterium tuberculosis sputum bacterial load [Time frame: Baseline to Day 14]
Secondary outcome measures (1)
  • Time to sputum culture conversion [Time frame: Baseline to Week 8]

Eligibility criteria

Inclusion criteria

  • Age 14 to < 65 years, male or female
  • Confirmed rifampicin-resistant TB (RR-TB) or multidrug-resistant TB (MDR-TB) by molecular testing (e.g., Xpert MTB/RIF) or drug susceptibility testing
  • Positive sputum culture for Mycobacterium tuberculosis or positive molecular test
  • Chest imaging consistent with active pulmonary TB, or histologically confirmed extrapulmonary TB (excluding CNS, osteoarticular, and disseminated TB)
  • Body weight ≥ 40 kg
  • Karnofsky Performance Status ≥ 50
  • Adequate laboratory parameters:
  • Hemoglobin ≥ 8.0 g/dL
  • ANC ≥ 1000/mm³
  • Platelets ≥ 75,000/mm³
  • ALT/AST ≤ 3 × ULN
  • Total bilirubin ≤ 2 × ULN
  • Creatinine clearance ≥ 30 mL/min
  • QTcF interval < 450 ms (male) or < 470 ms (female)
  • HIV-negative, confirmed by approved testing
  • No prior exposure to bedaquiline, delamanid, or linezolid for more than 1 month
  • Female participants of childbearing potential must agree to use effective contraception and have a negative pregnancy test
  • Signed informed consent

Exclusion criteria

  • Central nervous system TB (e.g., TB meningitis), osteoarticular TB, or disseminated/miliary TB
  • Known allergy or serious adverse reaction to any study drug or background regimen component
  • Known resistance to bedaquiline, delamanid, or linezolid
  • Use of anti-TB drugs within the past 30 days that may interfere with study assessments, except in documented treatment failure cases
  • Severe comorbidities, including:
  • NYHA Class III-IV heart failure
  • History or risk factors for Torsades de Pointes
  • Child-Pugh B or C cirrhosis
  • Uncontrolled diabetes (HbA1c > 10%)
  • Active malignancy
  • Current use of QT-prolonging medications that cannot be substituted
  • Current use of MAO inhibitors or serotonergic drugs
  • BMI < 17 kg/m² with severe malnutrition
  • Grade 3-4 peripheral neuropathy at baseline
  • Pregnant or breastfeeding women
  • Any condition that, in the investigator's judgment, may interfere with study completion or data interpretation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

China · 2 centers
  • Anhui Chest Hospital — Hefei
  • Shanghai Pulmonary Hospital — Shanghai

Publications

  • World Health Organization. Global Tuberculosis Report 2024. Geneva: WHO, 2024.
  • 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. PMID 37848028
  • 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. PMID 23442
  • 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/ PMID 36630546

Identifiers

NCT: NCT07393438 · AHA-PLUS-MDRTB-2026 · 2025ZD1802404

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗