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

May 29, 2026 updated by: Global Alliance for TB Drug Development

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

309

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Georgia
      • Tbilisi, Georgia, 0101
        • National Center for Tuberculosis and Lung Diseases
  • Philippines
      • Dasmariñas, Philippines, 4114
        • Care Clinical Trial Group Inc.
      • Makati City, Philippines, 1230
        • Tropical Disease Foundation
      • Quezon City, Philippines, 1104
        • Lung Center Of The Philippines
  • South Africa
      • Brits, South Africa, 0250
        • Madibeng Centre for Research
      • Cape Town, South Africa, 7700
        • University of Cape Town Lung Institute (UCTLI)
      • Cape Town, South Africa, 7405
        • TASK Brooklyn
      • Cape Town, South Africa, 7750
        • Desmond Tutu Health Foundation
      • Durban, South Africa, 4052
        • Enhancing Care Foundation
      • East London, South Africa, 5201
        • Synergy Biomed Research Institute (SBRI)
      • George, South Africa, 6529
        • TASK Eden
      • Hillcrest, South Africa, 3610
        • TB and HIV Investigative Network (THINK)
      • Johannesburg, South Africa, 2092
        • WITS, Clinical HIV Research Unit (CHRU) Themba Lethu Clinic, Helen Joseph Hospital
      • Klerksdorp, South Africa, 2571
        • Perinatal HIV Research Unit (PHRU)
      • Port Elizabeth, South Africa, 6200
        • Isango Lethemba TB Research Unit
      • Rustenburg, South Africa, 2999
        • The Aurum Institute
    • Gauteng
      • Soshanguve, Gauteng, South Africa, 0152
        • Setshaba Research Centre
  • Tanzania
      • Mbeya, Tanzania
        • NIMR-MBEYA Medical Research Center
      • Moshi, Tanzania
        • Kilimanjaro Christian Medical Centre
      • Mwanza, Tanzania
        • National Institute for Medical Research (NIMR)
  • Uganda
      • Kampala, Uganda
        • Joint Clinical Research Centre (JCRC)
      • Kampala, Uganda
        • Case Western Reserve University- Research collaboration Uganda

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: S 25 mg + Pa 200 mg +L 600 mg for 8 weeks followed by HR for 7 to 18 weeks
sorfequiline 25 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks
Drug: sorfequiline
tablet
Other Names:
  • TBAJ876
Drug: Pretomanid
tablet
Other Names:
  • PA-824
  • Dovprela
Drug: Linezolid
tablet
Other Names:
  • Zyvox
Drug: HR
fixed dose combination tablets
Other Names:
  • Isoniazid (H)
  • Rifampicin R)
Experimental: S 50 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks
sorfequiline 50 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks
Drug: sorfequiline
tablet
Other Names:
  • TBAJ876
Drug: Pretomanid
tablet
Other Names:
  • PA-824
  • Dovprela
Drug: Linezolid
tablet
Other Names:
  • Zyvox
Drug: HR
fixed dose combination tablets
Other Names:
  • Isoniazid (H)
  • Rifampicin R)
Experimental: S 100 mg + Pa 200 mg + L 600 mg for 8 weeks followed by HR for 7 to 18 weeks
sorfequiline 100 mg + pretomanid 200 mg + linezolid 600 mg for 8 weeks followed by HR for 7 to 18 weeks
Drug: sorfequiline
tablet
Other Names:
  • TBAJ876
Drug: Pretomanid
tablet
Other Names:
  • PA-824
  • Dovprela
Drug: Linezolid
tablet
Other Names:
  • Zyvox
Drug: HR
fixed dose combination tablets
Other Names:
  • Isoniazid (H)
  • Rifampicin R)
Active Comparator: 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
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
tablet
Other Names:
  • PA-824
  • Dovprela
Drug: Linezolid
tablet
Other Names:
  • Zyvox
Drug: Bedaquiline
tablet
Other Names:
  • Sirturo
  • TMC207
Active Comparator: IH + R + Z + E for 8 weeks followed by HR for 18 weeks (dose based on participant's weight).
Isoniazid (H) + rifampicin (R) + pyrazinamide (Z), ethambutol (E) for 8 weeks followed by HR for 18 weeks (dose based on participant's weight).
Drug: HR
fixed dose combination tablets
Other Names:
  • Isoniazid (H)
  • Rifampicin R)
Drug: HRZE
fixed doe combination tablets
Other Names:
  • Isoniazid (H)
  • Pyrazinamide (Z)
  • Ethambutol (E)
  • Rifampicin (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants With Stable Sputum Conversion by 8 Weeks,
Time Frame: Through 8 weeks of treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Favorable Outcome 26 Weeks After End of Treatment
Time Frame: 26 weeks after end of treatment
Proportion of participants with a favorable outcome at 26 weeks after the end of treatment.
26 weeks after end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Global Alliance for TB Drug Development

Investigators

  • Study Director: Morounfolu Olugbosi, MD, TB Alliance

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 31, 2023

Primary Completion (Actual)

December 27, 2024

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

September 22, 2023

First Submitted That Met QC Criteria

September 22, 2023

First Posted (Actual)

September 28, 2023

Study Record Updates

Last Update Posted (Actual)

June 24, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NC-009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

There is an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The results of this trial may be published or presented at scientific meetings. If this is foreseen, the investigator agrees to submit all manuscripts or abstracts to TB Alliance before submission. This allows TB Alliance to protect proprietary information and to provide comments; such consent will not be withheld unreasonably

IPD Sharing Time Frame

Finalized results are published following completion of the trial. At that time, requests for the IPD can be made to C-Path.

IPD Sharing Access Criteria

Requests for the IPD can be made to C-Path at https://c-path.org/tools-platforms/tb-pacts/

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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