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

Pulmonary Tuberculosis Clinical Trial

Official title: 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 Recruiting

Clinical Trial 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

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Drug Sensitive Tuberculosis
• Hypersensitivity
• Pulmonary TB
• Pulmonary Tuberculosis
• Tuberculosis
• Tuberculosis, Pulmonary

• NCT number: NCT06058299
• Study type: Interventional
• Source: Global Alliance for TB Drug Development
• Contact: Leandra Lombard
• Phone: +27 83 307 6784
• Email: leandra.lombard@tballiance.org
• Status: Recruiting
• Phase: Phase 2
• Start date: October 24, 2023
• Completion date: June 2026