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

NCT07393438 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: AHA-PLUS-MDRTB-20262025ZD1802404
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

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

Keywords

Acetohydroxamic Acid; Short-Course Regimen; BDLLfxC; BDCZ; DNA Repair; RP2D; Phase II

Outcome Measures

Primary Outcomes (1)

• Change in Mycobacterium tuberculosis sputum bacterial load

  Change in quantitative Mycobacterium tuberculosis colony-forming units (CFU) in sputum, expressed as log10 CFU/mL/day, measured using standardized microbiological culture methods.

  Baseline to Day 14

Secondary Outcomes (1)

• Time to sputum culture conversion

  Baseline to Week 8

Other Outcomes (6)

• Peak Plasma Concentration (Cmax)

  Baseline to Day 14

• Changes in inflammatory biomarkers

  Baseline to Day 14

• Radiographic Severity Score on Chest X-ray or CT

  Baseline to Week 8

Study Arms (2)

AHA plus Short-Course Regimen

EXPERIMENTAL

Participants in this arm receive acetohydroxamic acid (AHA) in combination with a short-course anti-tuberculosis regimen. AHA is administered at the protocol-defined dose and schedule. All background treatments are identical to those in the control arm.

Drug: Acetohydroxamic Acid

Placebo plus Short-Course Regimen

PLACEBO COMPARATOR

Participants in this arm receive a matching placebo in combination with the same short-course anti-tuberculosis regimen used in the experimental arm. The placebo is identical in appearance, packaging, and administration schedule to maintain blinding.

Drug: Placebo

Interventions

Acetohydroxamic Acid DRUG

Acetohydroxamic acid administered according to the protocol-defined dose and schedule, in combination with a short-course anti-tuberculosis regimen.

AHA plus Short-Course Regimen

Placebo DRUG

Matching placebo identical in appearance, packaging, and administration schedule to acetohydroxamic acid, administered with the same short-course anti-tuberculosis regimen.

Placebo plus Short-Course Regimen

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (2)

Anhui Chest Hospital

Hefei, Anhui, 230000, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Related Publications (4)

• 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.

  PMID: 37848028 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.

  PMID: 23442 BACKGROUND

• World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment of drug-resistant tuberculosis. 2024 update. Geneva: WHO; 2024.

  BACKGROUND

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

acetohydroxamic acid

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• liu yidian

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

liu yidian, MD

CONTACT

021-65115006; liuyidian115@139.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, care providers, investigators, and outcomes assessors are blinded to treatment allocation. The study drug and placebo are identical in appearance, packaging, and administration schedule.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants are randomly assigned in a 1:1 ratio to receive either acetohydroxamic acid plus a short-course regimen or placebo plus the same regimen, with no crossover between groups.

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: February 6, 2026
• Study Start: February 21, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): November 30, 2028
• Last Updated: February 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)