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

NCT07209761 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 323-201-00013jRCT2031260045
• Study Type: interventional
• Target: 532
• Locations: 8 countries
• Sites: 35

Brief 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.

Conditions

Pulmonary Tuberculosis

Keywords

Pulmonary Tuberculosis; Quabodepistat; Bedaquiline; Pretomanid; Linezolid; Moxifloxacin; Fluoroquinolone-sensitive TB; Fluoroquinolone-resistant TB; Drug-resistant TB; Shortened TB treatment

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with unfavorable outcome.

  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.

  From randomization to Month 12

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

  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.

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

Secondary Outcomes (10)

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

  From randomization to Month 12

• Time to sputum culture conversion.

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

• Proportion of participants with sputum culture conversion.

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

• Proportion of participants with microbiological relapse.

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

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

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

Other Outcomes (4)

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

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

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

  At 10 months post-treatment completion and at 16 months post-randomization

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

  At 10 months post-treatment completion and at 16 months post-randomization

Study Arms (4)

BPaQM for Fluoroquinolone-sensitive RR/MDR-TB

EXPERIMENTAL

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

Drug: BPaQM

BPaLM for Fluoroquinolone-sensitive RR/MDR-TB

ACTIVE COMPARATOR

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

Drug: BPaLM

BPaQ for Fluoroquinolone-resistant RR/MDR-TB

EXPERIMENTAL

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

Drug: BPaQ

BPaL for Fluoroquinolone-resistant RR/MDR-TB

ACTIVE COMPARATOR

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

Drug: BPaL

Interventions

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

Also known as: Bedaquiline, Pretomanid, Quabodepistat, Moxifloxacin

BPaQM for Fluoroquinolone-sensitive RR/MDR-TB

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

Also known as: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin

BPaLM for Fluoroquinolone-sensitive RR/MDR-TB

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

Also known as: Bedaquiline, Pretomanid, Quabodepistat

BPaQ for Fluoroquinolone-resistant RR/MDR-TB

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

Also known as: Bedaquiline, Pretomanid, Linezolid

BPaL for Fluoroquinolone-resistant RR/MDR-TB

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (35)

Capital Medical University - Beijing Chest Hospital

Beijing, Beijing Municipality, 101100, China

RECRUITING

Fuzhou Tuberculosis Prevention and Control Hospital of Fujian Province

Fuzhou, Fujian, 350008, China

NOT YET RECRUITING

The Third People's Hospital of Shenzhen

Shenzhen, Guangdong, 518112, China

NOT YET RECRUITING

Wuhan Institute of Tuberculosis Control (Wuhan Pulmonary Hospital)

Wuhan, Hubei, 430032, China

NOT YET RECRUITING

The Second Hospital of Nanjing

Nanjing, Jiangsu, 210003, China

NOT YET RECRUITING

Shandong Public Health Clinical Center

Jinan, Shandong, 250102, China

NOT YET RECRUITING

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, 200040, China

NOT YET RECRUITING

Shanghai Pulmonary Hospital - Pneumology

Shanghai, Shanghai Municipality, 200433, China

NOT YET RECRUITING

Public Health Clinical Center of Chengdu

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

National Center for Tuberculosis and Lung Disease

Tbilisi, 0101, Georgia

RECRUITING

Japan Anti-Tuberculosis Association Fukujuji Hospital

Kiyose, Tokyo, 204-8522, Japan

NOT YET RECRUITING

IMSP Institutul de Ftiziopneumologie Chiril Draganiuc - Phthisiopneumology

Chisinau, Chisinau City, MD-2025, Moldova

RECRUITING

Socios en Salud Sucursal Peru

La Molina, Lima region, 15012, Peru

NOT YET RECRUITING

Centro de Investigación del Hospital de Emergencias de Villa el Salvador

Villa El Salvador, Lima region, 15837, Peru

NOT YET RECRUITING

Hospital Sergio E. Bernales

Lima, 15313, Peru

NOT YET RECRUITING

Silang Specialist Medical Center

Silang, Cavite, 4118, Philippines

RECRUITING

Jose B. Lingad Memorial Regional Hospital

San Fernando City, Central Luzon (Region III), 2000, Philippines

NOT YET RECRUITING

Tropical Disease Foundation

Makati City, National Capital Region, 1772, Philippines

RECRUITING

Lung Center Of The Philippines

Quezon City, National Capital Region, 1100, Philippines

NOT YET RECRUITING

Synergy Biomed Research Institute

East London, Eastern Cape, 5241, South Africa

RECRUITING

Isango Lethemba TB Res Unit (CHRU) - Jose Pearson TB Hospital

Port Elizabeth, Eastern Cape, 6003, South Africa

RECRUITING

The Aurum Institute - Tembisa Hospital Clinical Research Centre

Johannesburg, Gauteng, 1632, South Africa

RECRUITING

Clinical HIV Research Unit (CHRU) - Helen Joseph Hospital

Johannesburg, Gauteng, 2092, South Africa

RECRUITING

Sizwe Clinical Research Site (CHRU) - Sizwe Tropical Disease Hospital,

Johannesburg, Gauteng, 2131, South Africa

RECRUITING

Setshaba Research Center

Pretoria, Gauteng, 0152, South Africa

NOT YET RECRUITING

Perinatal HIV Research Unit (PHRU) - Chris Hani Baragwanath Academic Hospital

Soweto, Gauteng, 1835, South Africa

NOT YET RECRUITING

Centre for the AIDS Programme of Research in South Africa (CAPRISA)

Durban, KwaZulu-Natal, 4013, South Africa

RECRUITING

Klerksdorp/Tshepong Hospital Complex, Tshepong Hospital, MDR Unit

Klerksdorp, North West, 2574, South Africa

RECRUITING

The Aurum Institute - Rustenburg

Rustenburg, North West, 0299, South Africa

NOT YET RECRUITING

Brooklyn Chest Hospital

Belville, Western Cape, 7405, South Africa

NOT YET RECRUITING

UCT - Lung Infection and Immunity Unit

Cape Town, Western Cape, 7700, South Africa

NOT YET RECRUITING

UCT Lung Institute

Cape Town, Western Cape, 7700, South Africa

RECRUITING

The Catholic University of Korea, Incheon St. Mary's Hospital

Incheon, Incheon Metropolitan City, 21431, South Korea

NOT YET RECRUITING

Pusan National University Hospital

Busan, Pusan-Kwangyokshi, 49241, South Korea

NOT YET RECRUITING

Asan Medical Center - Pulmonology

Seoul, Seoul Teugbyeolsi, 05505, South Korea

NOT YET RECRUITING

Related Links

• Otsuka Clinical Trials Website
• Otsuka Clinical Trial Transparency

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

bedaquiline; pretomanid; Moxifloxacin; Linezolid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Simbarashe G Takuva, MD, MSc.

  Study Sponsor

  STUDY DIRECTOR

Central Study Contacts

Otsuka Call Center

CONTACT

+1 844-687-8522; Otsuka-ProfessionalServices@otsuka-us.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study with blinded endpoint adjudication of the primary efficacy outcome. Certain sponsor team members will be blinded to treatment assignments to minimize potential bias as much as possible
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study has two parallel cohorts based on fluoroquinolone sensitivity status, each with an experimental arm and a control arm.

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: October 7, 2025
• Study Start: October 16, 2025
• Primary Completion (Estimated): May 28, 2027
• Study Completion (Estimated): September 29, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform: https://vivli.org/ourmember/Otsuka/

Locations

PE (3); ZA (13); MO (1); JP (1); PH (4); KR (3); CN (9); GE (1)