Phase 2 Trial Assessing TBAJ876 or Bedaquiline, with Pretomanid and Linezolid in Adults with Drug-sensitive Pulmonary Tuberculosis

NCT06058299 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NC-009
• Study Type: interventional
• Target: 309
• Locations: 5 countries
• Sites: 22

Brief Summary

The goal of this clinical trial is to evaluate 3 dose levels of TBAJ876 for 8 weeks in combination with pretomanid and linezolid, compared to 8 weeks of Isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE), in adult participants with newly diagnosed, smear-positive, pulmonary drug sensitive tuberculosis (DS-TB). The main questions the trial aims to answer are:

• What is the optimal dose of TBAJ876 to continue further in development.
• What is the bactericidal activity of bedaquiline with pretomanid and linezolid (B-Pa-L) compared to 2HRZE and TBAJ876-Pa-L over 8 weeks
• What is the efficacy and safety of the 26-week B-Pa-L regimen compared with the SOC (2HRZE/4HR) in participants with DS-TB. Participants will be seen regularly during treatment (up to 26 weeks) and follow-up (52 weeks post treatment) for safety and efficacy assessments, including but not limited to:
• Safety labs, ECGs, vital signs, physical exams, PK sampling, neuropathy assessments and adverse event monitoring
• Sputum collection

Conditions

Pulmonary TB; Pulmonary Tuberculosis; Drug Sensitive Tuberculosis

Keywords

TBAJ-876; Tuberculosis; pretomanid; bedaquiline; linezolid

Outcome Measures

Primary Outcomes (1)

• Time to stable sputum conversion

  Time to stable sputum culture conversion to negative status using data from weekly cultures through 8 weeks of treatment.

  Through 8 weeks of treatment

Secondary Outcomes (1)

• Favorable Outcome 26 Weeks after End of Treatment

  26 weeks after end of treatment

Study Arms (5)

TBAJ876 25 mg

EXPERIMENTAL

TBAJ876 25 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks

Drug: TBAJ-876; Drug: Pretomanid; Drug: Linezolid; Drug: HR

TBAJ876 50 mg

EXPERIMENTAL

TBAJ876 50 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks

Drug: TBAJ-876; Drug: Pretomanid; Drug: Linezolid; Drug: HR

TBAJ876 100 mg

EXPERIMENTAL

TBAJ876 100 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks

Drug: TBAJ-876; Drug: Pretomanid; Drug: Linezolid; Drug: HR

BPaL

ACTIVE COMPARATOR

Bedaquiline 200 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by bedaquiline 100 mg + pretomanid 200 mg + linezolid 600 mg for 18 weeks

Drug: Pretomanid; Drug: Linezolid; Drug: Bedaquiline

2HRZE/4HR

ACTIVE COMPARATOR

Isoniazid (H) + rifampicin (R) + pyrazinamide (Z), ethambutol (E) for 8 weeks followed by HR for 18 weeks (dose based on participant's weight).

Drug: HRZE; Drug: HR

Interventions

TBAJ-876 DRUG

tablet

TBAJ876 100 mg; TBAJ876 25 mg; TBAJ876 50 mg

Pretomanid DRUG

200 mg

Also known as: PA-824, Dovprela

BPaL; TBAJ876 100 mg; TBAJ876 25 mg; TBAJ876 50 mg

Linezolid DRUG

600 mg

Also known as: Zyvox

BPaL; TBAJ876 100 mg; TBAJ876 25 mg; TBAJ876 50 mg

Bedaquiline DRUG

200 mg for 8 weeks followed by 100 mg for 18 weeks

Also known as: Sirturo, TMC207

BPaL

HRZE DRUG

Isoniazid (H) + rifampicin (R) + pyrazinamide (Z) plus ethambutol (E) fixed dose combination tablets dosed by weight

2HRZE/4HR

HR DRUG

Isoniazid (H) + rifampicin (R) fixed dose combination tablets dosed by weight

2HRZE/4HR; TBAJ876 100 mg; TBAJ876 25 mg; TBAJ876 50 mg

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• DS-TB as defined as sensitive to rifampicin and isoniazid by rapid sputum-based test AND either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB
• Of non-childbearing potential OR using effective birth control methods
• Body weight ≥ 35 kg

You may not qualify if:

• Karnofsky score \< 60 at screening
• Any evidence of extrapulmonary TB
• Cardiovascular or QT prolongation risk factors
• Pregnant or breast-feeding
• Any of the following lab toxicities:
• Platelets \<100,000/mm³
• Creatinine \>1.3 x ULN
• Haemoglobin \<9.5 g/dL or \<95 g/L
• Absolute neutrophil count \<800/mm³
• Serum potassium less than the lower limit of normal for the laboratory.
• ALT and/or AST ≥2.5 x ULN
• Total bilirubin ≥1.6 x ULN
• Direct bilirubin \>1 x ULN
• Haemoglobin A1c ≥8.0%
• Total lipase ≥1.5 x ULN

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (22)

National Center for Tuberculosis and Lung Diseases

Tbilisi, 0101, Georgia

Location

Care Clinical Trial Group Inc.

Dasmariñas, 4114, Philippines

Location

Tropical Disease Foundation

Makati City, 1230, Philippines

Location

Lung Center of the Philippines

Quezon City, 1104, Philippines

Location

Setshaba Research Centre

Soshanguve, Gauteng, 0152, South Africa

Location

TASK Eden

George, George, 6529, South Africa

Location

Madibeng Centre for Research

Brits, 0250, South Africa

Location

TASK Brooklyn

Cape Town, 7405, South Africa

Location

University of Cape Town Lung Institute (UCTLI)

Cape Town, 7700, South Africa

Location

Desmond Tutu Health Foundation

Cape Town, 7750, South Africa

Location

Enhancing Care Foundation

Durban, 4052, South Africa

Location

Synergy Biomed Research Institute (SBRI)

East London, 5201, South Africa

Location

TB and HIV Investigative Network (THINK)

Hillcrest, 3610, South Africa

Location

WITS, Clinical HIV Research Unit (CHRU) Themba Lethu Clinic, Helen Joseph Hospital

Johannesburg, 2092, South Africa

Location

Perinatal HIV Research Unit (PHRU)

Klerksdorp, 2571, South Africa

Location

Isango Lethemba TB Research Unit

Port Elizabeth, 6200, South Africa

Location

The Aurum Institute

Rustenburg, 2999, South Africa

Location

NIMR-MBEYA Medical Research Center

Mbeya, Tanzania

Location

Kilimanjaro Christian Medical Centre

Moshi, Tanzania

Location

National Institute for Medical Research (NIMR)

Mwanza, Tanzania

Location

Case Western Reserve University- Research collaboration Uganda

Kampala, Uganda

Location

Joint Clinical Research Centre (JCRC)

Kampala, Uganda

Location

Related Publications (3)

• Darpo B, Nedelman J, Bruning-Barry R, Hickman D, Kleiman R, Lombardi A, Xue H. Cardiodynamic evaluation of sorfequiline (TBAJ-876): results from a first-in-human study. Antimicrob Agents Chemother. 2026 Jan 30:e0127325. doi: 10.1128/aac.01273-25. Online ahead of print.

  PMID: 41616265 DERIVED

• Olugbosi M, Beumont M, Lombard L, Nedelman J, Timm J, Black T, Bruning-Barry R, Hickman D, Lombardi A, Betteridge M, Egizi E, Marcopulos L, Henderson J, Seidel S, Foraida S, Benhayoun M, Sun E. Protocol for a phase 2, partially blinded, randomized trial assessing the safety and efficacy of sorfequiline or bedaquiline in combination with pretomanid and linezolid in adult participants with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis (NC-009). Trials. 2026 Jan 6. doi: 10.1186/s13063-025-09413-5. Online ahead of print.

  PMID: 41495827 DERIVED

• Komm OD, Tyagi S, Garcia A, Almeida D, Chang Y, Li S-Y, Castillo JR, Converse PJ, Black T, Fotouhi N, Nuermberger EL. Contribution of telacebec to novel drug regimens in a murine tuberculosis model. Antimicrob Agents Chemother. 2025 Jan 31;69(1):e0096224. doi: 10.1128/aac.00962-24. Epub 2024 Dec 9.

  PMID: 39651910 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

TBAJ-876; pretomanid; Linezolid; bedaquiline

Condition Hierarchy (Ancestors)

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)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Morounfolu Olugbosi, MD

  TB Alliance

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: TBAJ-876 and the first 8 weeks of bedaquiline will be blinded. Participants randomized to TBAJ-876 or bedaquiline arms will received active TBAJ-876 (and placebo TBAJ876 to blind the dose) and placebo bedaquiline or placebo TBAJ-876 and active bedaquiline
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants who meet all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1:1:1:1 ratio using an interactive response technology that stratifies based on country and severity of disease (AFB 3+ and/or bilateral cavitation) to 1 of the 5 treatment arms:

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 28, 2023
• Study Start: October 24, 2023
• Primary Completion: December 27, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

PH (3); TA (3); GE (1); ZA (13); UG (2)