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

NCT06058299 | Active Not Recruiting Phase 2 Results 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

sorfequiline; Tuberculosis; pretomanid; bedaquiline; linezolid; TBAJ876

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Stable Sputum Conversion by 8 Weeks,

  Kaplan Meir estimates of proportion participants with stable sputum culture conversion (SCCC) to negative by 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)

S 25 mg + Pa 200 mg +L 600 mg for 8 weeks followed by HR for 7 to 18 weeks

EXPERIMENTAL

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

Drug: sorfequiline; Drug: Pretomanid; Drug: Linezolid; Drug: HR

S 50 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks

EXPERIMENTAL

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

Drug: sorfequiline; Drug: Pretomanid; Drug: Linezolid; Drug: HR

S 100 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks

EXPERIMENTAL

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

Drug: sorfequiline; Drug: Pretomanid; Drug: Linezolid; Drug: HR

B 200 mg + Pa 200 mg +L 600 mg for 8 weeks followed by B 100 mg + Pa 200 mg + L 600 mg for 18 weeks

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

IH + R + Z + E for 8 weeks followed by HR for 18 weeks (dose based on participant's weight).

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

sorfequiline DRUG

tablet

Also known as: TBAJ876

S 100 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 25 mg + Pa 200 mg +L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 50 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks

HRZE DRUG

fixed doe combination tablets

Also known as: Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E)

IH + R + Z + E for 8 weeks followed by HR for 18 weeks (dose based on participant's weight).

Pretomanid DRUG

tablet

Also known as: PA-824, Dovprela

B 200 mg + Pa 200 mg +L 600 mg for 8 weeks followed by B 100 mg + Pa 200 mg + L 600 mg for 18 weeks; S 100 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 25 mg + Pa 200 mg +L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 50 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks

Linezolid DRUG

tablet

Also known as: Zyvox

B 200 mg + Pa 200 mg +L 600 mg for 8 weeks followed by B 100 mg + Pa 200 mg + L 600 mg for 18 weeks; S 100 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 25 mg + Pa 200 mg +L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 50 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks

Bedaquiline DRUG

tablet

Also known as: Sirturo, TMC207

B 200 mg + Pa 200 mg +L 600 mg for 8 weeks followed by B 100 mg + Pa 200 mg + L 600 mg for 18 weeks

HR DRUG

fixed dose combination tablets

Also known as: Isoniazid (H), Rifampicin R)

IH + R + Z + E for 8 weeks followed by HR for 18 weeks (dose based on participant's weight).; S 100 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 25 mg + Pa 200 mg +L 600 mg for 8 weeks followed by HR for 7 to 18 weeks; S 50 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks

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

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

TASK Eden

George, 6529, 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)

• 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;27(1):102. doi: 10.1186/s13063-025-09413-5.

  PMID: 41495827 BACKGROUND

• 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 Mar 4;70(3):e0127325. doi: 10.1128/aac.01273-25. Epub 2026 Jan 30.

  PMID: 41616265 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

Related Links

• NC-009 Protocol Description
• NC-009 Week 8 Interim Analysis Results

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

TBAJ-876; pretomanid; Linezolid; bedaquiline; Isoniazid; Protons; Rifampin; Pyrazinamide; Ethambutol

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; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines

Results Point of Contact

• Title: Mourounfolu Olugbosi
• Organization: TB Alliance

morounfolu.olugbosi@tballiance.org

+27 79 045 4917

Study Officials

• Morounfolu Olugbosi, MD

  TB Alliance

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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 31, 2023
• Primary Completion: December 27, 2024
• Study Completion (Estimated): February 1, 2027
• Last Updated: June 24, 2026
• Results First Posted: June 24, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Finalized results are published following completion of the trial. At that time, requests for the IPD can be made to C-Path.
• Access Criteria: Requests for the IPD can be made to C-Path at https://c-path.org/tools-platforms/tb-pacts/

Locations

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