Phase 2 Trial Assessing TBAJ876 or Bedaquiline, with Pretomanid and Linezolid in Adults with Drug… (NCT06058299) | Clinical Trial Compass
Active — Not RecruitingPhase 2
Phase 2 Trial Assessing TBAJ876 or Bedaquiline, with Pretomanid and Linezolid in Adults with Drug-sensitive Pulmonary Tuberculosis
Georgia, Philippines, South Africa309 participantsStarted 2023-10-24
Plain-language 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
Who can participate
Age range18 Years – 65 Years
SexALL
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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…