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

Last updated: February 13, 2025
Sponsor: Global Alliance for TB Drug Development
Overall Status: Active - Not Recruiting

Phase

2

Condition

Hiv

Lung Disease

Allergy

Treatment

HRZE

Bedaquiline

HR

Clinical Study ID

NCT06058299
NC-009
  • Ages 18-65
  • All Genders

Study 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

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Signed informed consent

  • DS-TB as defined as sensitive to rifampicin and isoniazid by rapid sputum-based testAND 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

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 activityand 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 isindicated, and randomised to the TBAJ876 or the B-Pa-L regimen

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

Study Design

Total Participants: 309
Treatment Group(s): 6
Primary Treatment: HRZE
Phase: 2
Study Start date:
October 24, 2023
Estimated Completion Date:
June 30, 2026

Study 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.

Connect with a study center

  • National Center for Tuberculosis and Lung Diseases

    Tbilisi, 0101
    Georgia

    Site Not Available

  • Care Clinical Trial Group Inc.

    Dasmariñas, 4114
    Philippines

    Site Not Available

  • De La Salle Medical and Health Sciences Institute

    Dasmariñas, 4114
    Philippines

    Site Not Available

  • Tropical Disease Foundation

    Makati City, 1230
    Philippines

    Site Not Available

  • Lung Center of the Philippines

    Quezon City, 1104
    Philippines

    Site Not Available

  • Setshaba Research Centre

    Soshanguve, Gauteng 0152
    South Africa

    Site Not Available

  • Madibeng Centre for Research

    Brits, 0250
    South Africa

    Site Not Available

  • Desmond Tutu Health Foundation

    Cape Town, 7750
    South Africa

    Site Not Available

  • TASK Brooklyn

    Cape Town, 7405
    South Africa

    Site Not Available

  • University of Cape Town Lung Institute (UCTLI)

    Cape Town, 7700
    South Africa

    Site Not Available

  • Setshaba Research Centre

    City Of Tshwane, 0152
    South Africa

    Site Not Available

  • Enhancing Care Foundation

    Durban, 4052
    South Africa

    Site Not Available

  • Synergy Biomed Research Institute (SBRI)

    East London, 5201
    South Africa

    Site Not Available

  • TASK Eden

    George, 6529
    South Africa

    Site Not Available

  • TB and HIV Investigative Network (THINK)

    Hillcrest, 3610
    South Africa

    Site Not Available

  • WITS, Clinical HIV Research Unit (CHRU) Themba Lethu Clinic, Helen Joseph Hospital

    Johannesburg, 2092
    South Africa

    Site Not Available

  • Perinatal HIV Research Unit (PHRU)

    Klerksdorp, 2571
    South Africa

    Site Not Available

  • Isango Lethemba TB Research Unit

    Port Elizabeth, 6200
    South Africa

    Site Not Available

  • The Aurum Institute

    Rustenburg, 2999
    South Africa

    Site Not Available

  • NIMR-MBEYA Medical Research Center

    Mbeya,
    Tanzania

    Site Not Available

  • Kilimanjaro Christian Medical Centre

    Moshi,
    Tanzania

    Site Not Available

  • National Institute for Medical Research (NIMR)

    Mwanza,
    Tanzania

    Site Not Available

  • Case Western Reserve University- Research collaboration Uganda

    Kampala,
    Uganda

    Site Not Available

  • Joint Clinical Research Centre (JCRC)

    Kampala,
    Uganda

    Site Not Available

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