NCT06058299

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

A Phase 2, Partially-blinded, Randomised Trial Assessing the Safety and Efficacy of TBAJ-876 or Bedaquiline, in Combination with Pretomanid and Linezolid in Adult Participants with Newly Diagnosed, Drug-sensitive, Smear-positive Pulmonary Tuberculosis

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 309 (actual)
• Sponsor: Global Alliance for TB Drug Development · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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

Detailed description

Participants will be treated up to 26 weeks with either: * TBAJ876 25 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks * TBAJ876 50 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks * TBAJ876 100 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks * 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 * Isoniazid (H) + rifampicin (R) + pyrazinamide (Z), ethambutol (E) for 8 weeks followed by HR for 18 weeks (dose based on participant's weight). TBAJ876 and bedaquiline will be blinded during the first 8 weeks of trial treatment; participants randomised to the TBAJ876 or bedaquiline arms will receive open-label pretomanid and linezolid. Participants randomised to the 2HRZE/4HR arm will receive open-label HRZE. After receiving 8 weeks of treatment, participants randomised to the TBAJ876-Pa-L treatment arms will receive open-label HR for at least 7 weeks. Treatment completion will be allowed at Week 15 in participants randomised to the TBAJ876-Pa-L arms, if the below criteria are met: * Week 8 or EOT Make-up Period 1 sputum MGIT culture is negative, and * The participant has no TB-related symptoms by Week 15. Participants with symptoms that have a more likely alternative explanation are eligible to complete treatment at Week 15. If the MGIT result is MTB positive and/or there are still TB symptom(s), participants will continue to receive HR (in the 3 TBAJ876 arms) and will complete 18 weeks of treatment with HR, for a total of 26 weeks of treatment. After receiving 8 weeks of trial treatment, all participants randomised to the HRZE arm will receive open-label HR for 18 weeks, for a total of 26 weeks of treatment. After receiving 8 weeks of treatment, a participants randomised to the B-Pa-L arm will receive open-label bedaquiline 100 mg (a reduction from the 200 mg daily dose in the first 8 weeks), pretomanid 200 mg, and linezolid 600 mg daily for 18 weeks, for a total of 26 weeks of trial treatment.

Conditions

• Pulmonary TB
• Pulmonary Tuberculosis
• Drug Sensitive Tuberculosis

Interventions

Type	Name	Description
DRUG	TBAJ-876	tablet
DRUG	Pretomanid	200 mg
DRUG	Linezolid	600 mg
DRUG	Bedaquiline	200 mg for 8 weeks followed by 100 mg for 18 weeks
DRUG	HRZE	Isoniazid (H) + rifampicin (R) + pyrazinamide (Z) plus ethambutol (E) fixed dose combination tablets dosed by weight
DRUG	HR	Isoniazid (H) + rifampicin (R) fixed dose combination tablets dosed by weight

Timeline

• Start date: 2023-10-24
• Primary completion: 2024-12-27
• Completion: 2026-06-01
• First posted: 2023-09-28
• Last updated: 2025-02-17

Locations

22 sites across 5 countries: Georgia, Philippines, South Africa, Tanzania, Uganda

Regulatory

• FDA-regulated drug study