Multidrug-Resistant TuberculosisPhase 2AHA-PLUSNCT07393438
Acetohydroxamic Acid Combined With a Short-Course Regimen for MDR-TB (AHA-PLUS)
A Phase 2 study testing Acetohydroxamic Acid in people with Multidrug-Resistant Tuberculosis and Rifampicin-resistant Tuberculosis, run by Shanghai Pulmonary Hospital, Shanghai, China at 2 sites in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multidrug-Resistant Tuberculosis, Rifampicin-resistant Tuberculosis, MDR-TB
- What is being tested?
- Acetohydroxamic Acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesChina
- Study dates
- 21 Feb 2026to 30 Nov 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites
Anhui Chest Hospital
Hefei, Anhui, 230000
Wang Hua, MD, 0551-6362-3114, 1726553540@qq.com
Wang Hua, MD, 0551-6362-3114
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, 200433
liu yidian, MD, 021-65115006, liuyidian115@139.com
Fan Liping, 021-65115006, fkyyflp@163.com
About this study
Official title: Acetohydroxamic Acid Combined With a Short-Course Regimen for the Treatment of Multidrug-Resistant Tuberculosis: A Phase II Clinical Trial
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.
Read the 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.
- Being tested
- Acetohydroxamic Acid, Placebo
- Keywords
- Acetohydroxamic Acid, Short-Course Regimen, BDLLfxC, BDCZ, DNA Repair, RP2D, Phase II
- Medical subject headings
- Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetohydroxamic AcidDrug
Acetohydroxamic acid administered according to the protocol-defined dose and schedule, in combination with a short-course anti-tuberculosis regimen.
PlaceboDrug
Matching placebo identical in appearance, packaging, and administration schedule to acetohydroxamic acid, administered with the same short-course anti-tuberculosis regimen.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Day 14
Secondary outcomes (1)
Time to sputum culture conversion
Time from treatment initiation to the first of two consecutive negative Mycobacterium tuberculosis sputum cultures collected at least 24 hours apart, assessed using standardized culture methods.
Measured: Baseline to Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2026
- Study start21 Feb 2026 (estimated)
- Primary completion28 Feb 2027 (estimated)
- Study completion30 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Multidrug-Resistant TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, yidian liu, Shanghai Pulmonary Hospital, Shanghai, China
- Investigators
- liu yidian, Principal investigator, Shanghai Pulmonary Hospital, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07393438
- Sponsor's protocol ID
- AHA-PLUS-MDRTB-2026
- Other IDs
- 2025ZD1802404
- Acronym
- AHA-PLUS
- Status last verified
- Jan 2026
- First submitted
- 19 Jan 2026
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The plan for sharing individual participant data (IPD) has not yet been finalized. Data sharing will depend on institutional policies, ethical approvals, and resource availability at the time of study completion.
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.
PubMed 37848028Griffith 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.
PubMed 23442WHO 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/
PubMed 36630546