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

• Status: Recruiting
• Trial end date: 2026-06-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Global Alliance for TB Drug Development
• Treatments: Bedaquiline; Linezolid

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Total amylase ≥1.5 x ULN

• CPK >3 x ULN (if >3 x ULN, enquire about the participant's recent strenuous activity and consider repeating the test within the screening window)

• TSH >1 x ULN

• Positive results at screening for HBsAg, HAV IgM, or hepatitis C antibodies

For participants living with HIV only:

• CD4+ count<200 cells/μL.

• WHO Clinical Stage 4 HIV disease

• Participant does not agree to use DTG/TFV/3TC during trial if ARV therapy is indicated, and randomised to the TBAJ876 or the B-Pa-L regimen

• If initiation of ARV therapy is indicate, participants who are known to be intolerant, non-responsive to DTG/TFV/3TC or have DTG/TFV/3TC as a contraindication.