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NCT Number: NCT07209761

A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis

This study aims to assess quabodepistat-based treatment regimens for RR/MDR-TB. The study will enroll adults and adolescents with rifampicin-resistant or multidrug-resistant pulmonary TB. The main goal is to see if a new drug called quabodepistat, when combined with other TB drugs, can shorten treatment duration to 4 months and be as effective and safer than current WHO endorsed treatment regimen given for 6-months. The study will compare different drug combinations in two groups of patients: those whose TB is sensitive to fluoroquinolones and those whose TB is resistant to fluoroquinolones. Participants will be randomly assigned to receive either the new treatment or the standard treatment. The study will last for 16 months for each participant and will measure how well the treatments work and how safe they are.

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Key information

Conditions

Pulmonary Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Lung Diseases Mycobacterium Infections Respiratory Tract Diseases Respiratory Tract Infections Tuberculosis Tuberculosis, Pulmonary

Age range

14 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Capital Medical University - Beijing Chest Hospital, Beijing, Beijing Municipality, China

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About this study

This is a Phase 3, randomized, open-label, multicenter trial evaluating quabodepistat-containing regimens for rifampicin-resistant/multidrug-resistant (RR/MDR) pulmonary tuberculosis (TB).

The study aims to enroll 532 participants aged 14 years and older.

The study has two main cohorts:

Fluoroquinolone-sensitive RR/MDR-TB (432 participants):

  • Experimental arm: BPaQM (bedaquiline, pretomanid, quabodepistat, moxifloxacin) for 4 months
  • Control arm: BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) for 6 months

Fluoroquinolone-resistant RR/MDR-TB (100 participants):

  • Experimental arm: BPaQ (bedaquiline, pretomanid, quabodepistat) for 6 months
  • Control arm: BPaL (bedaquiline, pretomanid, linezolid) for 6 months

The primary efficacy endpoint is an unfavorable outcome by 12 months post-randomization.

Secondary endpoints include time to unfavorable outcome, time to sputum culture conversion, and safety/tolerability assessments. Participants will be followed for 16 months post-randomization.

The study will be conducted at approximately 40 sites in up to 12 countries.

An independent Data Monitoring Committee and Endpoint Adjudication Committee will be used in the study.

The trial aims to evaluate if quabodepistat-containing regimens can shorten treatment duration to 4 months for fluoroquinolone-sensitive RR/MDR-TB and provide a safer alternative to linezolid-containing regimens for both fluoroquinolone-sensitive and fluoroquinolone-resistant RR/MDR-TB.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥14 years
  • Body weight ≥30.0 kg
  • Able to provide written informed consent (if under 18, requires both participant assent and parent/guardian consent)
  • Documented pulmonary TB: Mtb confirmed by Xpert MTB/RIF Ultra (semi-quantitative result of 'low', 'medium', or 'high')
  • Rifampicin resistance confirmed by Xpert MTB/RIF Ultra test
  • Chest radiograph consistent with active TB disease
  • Able to provide sputum sample
  • Participants of childbearing potential must use 2 different approved birth control methods during treatment and for 12 weeks after last dose
  • Willing to have HIV test (unless previous positive result confirmed)
  • For HIV-positive participants: On stable antiretroviral regimen (dolutegravir, lamivudine/emtricitabine, tenofovir) for ≥3 months, Viral load <200 copies/mL, and CD4 count >100 cells/mL

Exclusion criteria

  • Known/suspected resistance to BDQ, PMD, LZD, or QBS
  • Prior treatment with BDQ, PMD, LZD, DLM, QBS, or DprE1 inhibitors for ≥1 month within past 3 months
  • Severe extrapulmonary TB
  • Abnormal laboratory values: ALT/AST >2.5×ULN, Total bilirubin >1.5×ULN, eGFR <60 mL/min/1.73m², Hemoglobin <8 g/dL, Platelets <100,000 cells/mm³, WBC <2.0×10⁹/L, ANC <1000 cells/μL, and HbA1c >9.0%
  • Pre-existing peripheral neuropathy (≥Grade 1), optic neuritis, or visual impairment
  • Co-enrollment in other therapeutic trials
  • QTcF >450 msec (males) or >470 msec (females)
  • Clinically significant cardiovascular disorders
  • Bleeding disorders
  • Conditions interfering with X-ray or sputum assessment
  • Drug allergies/hypersensitivity to study medications
  • Pregnancy or breastfeeding
  • Positive drug screen (case-by-case assessment for some substances)
  • Serious mental disorders
  • Karnofsky score <60
  • BMI <16.0 kg/m²
  • Significant comorbidities (metabolic, renal, gastrointestinal, neurological, psychiatric, endocrine, liver)
  • Pulmonary conditions other than TB (silicosis, fibrosis)
  • Active SARS-CoV-2 infection
  • Use of prohibited medications
  • Blood/plasma donation within 30 days
  • Current use of herbal remedies or traditional medicines

Treatment and study plan

BPaQM

Drug

Bedaquiline 400 mg once daily for 2 weeks then 100 mg once daily for 15 weeks + Pretomanid 200 mg QD for 17 weeks + Quabodepistat 30 mg once daily for 17 weeks + Moxifloxacin 400 mg once daily for 17 weeks

Other names: Bedaquiline, Pretomanid, Quabodepistat, Moxifloxacin

BPaLM

Drug

Bedaquiline 400 mg once daily for 2 weeks then 200 mg thrice a week for 24 weeks + Pretomanid 200 mg QD for 26 weeks + Linezolid 600 mg once daily for 26 weeks + Moxifloxacin 400 mg once daily for 26 weeks

Other names: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin

BPaQ

Drug

Bedaquiline 400 mg once daily for 2 weeks then 100 mg once daily for 24 weeks + Pretomanid 200 mg QD for 26 weeks + Quabodepistat 30 mg once daily for 26 weeks

Other names: Bedaquiline, Pretomanid, Quabodepistat

BPaL

Drug

Bedaquiline 400 mg once daily for 2 weeks then 200 mg thrice a week for 24 weeks + Pretomanid 200 mg QD for 26 weeks + Linezolid 600 mg once daily for 26 weeks

Other names: Bedaquiline, Pretomanid, Linezolid

Primary outcomes

  1. Proportion of participants with unfavorable outcome.

    Time frame: From randomization to Month 12

    Unfavorable outcome is defined as a participant experiencing at least one of the following: death, treatment failure, change in regimen, or sputum culture with growth of Mycobacterium tuberculosis at certain timepoints as follows: Failure to achieve SCC at the end of the treatment period that results in a change in anti-mycobacterial therapy or Relapse during the follow-up period (i.e., the period from end of treatment to Month 12 post-randomization.

  2. Incidence of Grade ≥3 Treatment-Emergent Adverse Events, Serious Adverse Events, or Adverse Events Leading to Dose Reduction or Discontinuation (Safety and Tolerability).

    Time frame: From first dose to 2 weeks after end of treatment (Week 17 for BPaQM; Week 26 for BPaLM, BPaQ, BPaL)

    A participant experiencing at least one of the following: Grade 3 toxicity or higher treatment-emergent adverse events (TEAEs), serious TEAEs, or TEAEs leading to dose reduction or discontinuation.

Secondary outcomes

  1. Time to first occurrence of any event meeting the unfavorable outcome definition.

    Time frame: From randomization to Month 12

    Time to the first occurrence of any event listed under the primary efficacy endpoint.

  2. Time to sputum culture conversion.

    Time frame: From randomization to end of treatment (Week 17 for BPaQM; Week 26 for BPaLM, BPaQ, BPaL)

    Time from randomization to the first of two consecutive negative sputum cultures taken at least 1 week apart.

  3. Proportion of participants with sputum culture conversion.

    Time frame: At Week 8 and at end of treatment (Week 17 for BPaQM; Week 26 for BPaLM, BPaQ, BPaL)

    Proportion of participants achieving sputum culture conversion, defined as two consecutive negative cultures taken at least 1 week apart.

  4. Proportion of participants with microbiological relapse.

    Time frame: From end of treatment (Week 17 for BPaQM; Week 26 for BPaLM, BPaQ, BPaL) to Month 12 post-randomization

    Proportion of microbiological relapse.

  5. Proportion of participants with adverse events of special interest (AESIs).

    Time frame: From first dose to 2 weeks after end of treatment (Week 17 for BPaQM; Week 26 for BPaLM, BPaQ, BPaL)

    AESIs include QTc interval prolongation, hepatotoxicity, peripheral neuropathy, optic neuritis, and hematological toxicity.

  6. Proportion of participants with treatment-emergent adverse events (TEAEs).

    Time frame: From randomization through Week 68

    Proportion of participants with TEAEs, Grade 3 or higher TEAEs, and serious TEAEs.

  7. Proportion of time during treatment spent without adverse events.

    Time frame: From randomization to end of treatment (Week 17 for BPaQM; Week 26 for BPaLM, BPaQ, BPaL)

    Measure of difference in AE-free time during treatment between experimental and standard of care arms.

  8. Proportion of participants who are lost to follow-up.

    Time frame: From randomization through Week 68

    Measure of participant retention throughout the study period.

  9. Proportion of participants with TB-related death.

    Time frame: From randomization through Week 68

    Mortality specifically related to tuberculosis.

  10. Plasma concentrations of each analyte at scheduled visits.

    Time frame: From randomization through Week 17 (BPaQM and BPaQ only)

    Plasma concentrations of trial drugs in experimental arms.

Other outcomes

  1. To evaluate health-related quality of life measures in the experimental and SoC arms.

    Time frame: From baseline to Week 52 and end of treatment (Week 17 for BPaQM; Week 26 for BPaLM, BPaQ, BPaL)

    Changes from baseline in SF-36v2 Physical and Mental Component Summary scores, SF-6D utility score, SGRQ Total score and subscores (Symptoms, Activity, and Impacts), CAAT total score and subscores (symptom burden items and daily impacts items), and descriptive summaries of PRO-CTCAE adverse event frequency, severity, and interference over time.

  2. To estimate the difference in the proportion of unfavorable outcomes between the investigational and SoC arms at specified timepoints.

    Time frame: At 10 months post-treatment completion and at 16 months post-randomization

    Proportion of participants with unfavorable outcome at specified timepoints beyond the primary endpoint assessment at 12 months post-randomization to evaluate durability of treatment effect.

  3. To estimate the difference in the proportion of microbiological relapse between the investigational and SoC arms at specified timepoints.

    Time frame: At 10 months post-treatment completion and at 16 months post-randomization

    Proportion of participants with microbiological relapse at specified timepoints beyond the primary endpoint assessment at 12 months post-randomization to evaluate durability of treatment effect.

  4. To evaluate the development of resistance and cross-resistance to anti-TB drugs in all treatment arms.

    Time frame: From baseline through Week 68

    Proportion of participants developing drug resistance during the trial and proportion of participants developing cross-resistance between bedaquiline and quabodepistat during the trial, as determined by phenotypic drug susceptibility testing and genotyping.

Study contacts

Contact information is provided by the study sponsor or research team.

Otsuka Call Center

CONTACT

[email protected]

+1 844-687-8522

Sponsors and collaborators

Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Industry

Registry information

Official study title

A Phase 3, Randomized, Open-label, Multicenter Trial to Evaluate the Efficacy, Safety, and Tolerability of 4-month and 6-month Quabodepistat-containing Regimens for Rifampicin-resistant/Multidrug-resistant Pulmonary Tuberculosis

Acronym: QUANTUM-TB

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Oct 7, 2025
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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