A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
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
Otsuka Pharmaceutical Development & Commercialization, Inc.
532 participants
Oct 16, 2025
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria10
- 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 Criteria22
- 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
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Interventions
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
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
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
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
Locations(33)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07209761