A Study of Quabodepistat-containing Regimen for the Treatment of Drug-resistant Pulmonary Tuberculosis (QUANTUM)

Otsuka

Status and phase: Begins enrollment this month; Phase 3

Conditions: Pulmonary Tuberculosis

Treatments: Drug: BPaQM; Drug: BPaQ; Drug: BPaL; Drug: BPaLM

Study type: Interventional

Funder types: Industry

Identifiers

NCT07209761

323-201-00013

Details and patient eligibility

About

This study aims to assess quabodepistat-based treatment regimen 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.

Full description

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.

Enrollment: 532 estimated patients

Sex: All

Ages: 14+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 14 years or older.
2. Body weight ≥ 30.0 kg.
3. Documented pulmonary TB: Mtb confirmed by Xpert MTB/RIF Ultra semi-quantitative result of 'low', 'medium', or 'high' on the screening sputum sample.
4. Resistant to at least rifampicin by Xpert MTB/RIF Ultra test.
5. Chest radiograph consistent with evidence of active TB disease.
6. Able to provide a sputum sample.
7. For participants of childbearing potential: agreement to use 2 different effective methods of birth control.
8. Willing to have an HIV test.
9. For participants living with HIV: on stable antiretroviral regimen for at least 3 months, viral load < 200 copies/mL, and CD4 count > 100 cells/mL.

Exclusion criteria

1. Known or suspected resistance to any of the drugs administered in the treatment interventions.
2. Prior treatment with bedaquiline, pretomanid, linezolid, delamanid, quabodepistat, or DprE1 inhibitors for 1 or more months within the past 3 months.
3. Clinical evidence of Severe extrapulmonary TB.
4. Specific laboratory test results outside of defined ranges (e.g., ALT or AST > 2.5 x ULN, total bilirubin > 1.5 x ULN).
5. Pre-existing peripheral neuropathy Grade 1 or higher, optic neuritis, or visual impairment.
6. QTcF > 450 msec in male participants (> 470 msec in female participants).
7. History of clinically significant cardiovascular disorders.
8. Known bleeding disorders or family history of bleeding disorders.
9. Pregnant or breastfeeding women.
10. Karnofsky score < 60.
11. Body mass index < 16.0 kg/m2.
12. Evidence of clinically significant metabolic, renal, gastrointestinal, neurological, psychiatric, endocrine, or liver conditions.
13. Active SARS-CoV-2 infection at screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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532 participants in 4 patient groups

BPaQM for Fluoroquinolone-sensitive RR/MDR-TB

Experimental group

Description:

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

Treatment:

Drug: BPaQM

BPaLM for Fluoroquinolone-sensitive RR/MDR-TB

Active Comparator group

Description:

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

Treatment:

Drug: BPaLM

BPaQ for Fluoroquinolone-resistant RR/MDR-TB

Experimental group

Description:

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

Treatment:

Drug: BPaQ

BPaL for Fluoroquinolone-resistant RR/MDR-TB

Active Comparator group

Description:

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

Treatment:

Drug: BPaL