The goal of this interventional trial is to evaluate the safety and efficacy of the loading dose regimen 200/100SPaL-4/13 weeks, and the 100SPaL -17 weeks regimen in adults with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis.
Participants (18-65 years) will be randomised 1:1, stratified by country and disease severity, to receive either :
1. a sorfequiline loading-dose regimen (200 mg daily for 4 weeks followed by 100 mg daily for 13 weeks) plus pretomanid 200 mg and linezolid 600 mg daily, or 2. sorfequiline 100 mg daily for 17 weeks plus pretomanid 200 mg and linezolid 600 mg daily. Study treatment is administered orally once daily with food.
The primary objective is to assess safety through 17 weeks of treatment, including treatment-emergent adverse events, ECG findings, vital signs, laboratory assessments, visual acuity, and peripheral neuropathy. Secondary objectives include assessments of efficacy (time to stable sputum culture conversion; favorable outcome and treatment failure/relapse at 26 and 52 weeks after end of treatment) and pharmacokinetics of trial drugs, with exploratory analyses including predictors of culture conversion, exposure-response relationships, and quality of life.
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 k
Karnofsky score < 60 at screening
Any evidence of extrapulmonary TB
Cardiovascular or QT prolongation risk factors Pregnant or breast-feeding
CD4+ count<200 cells/μL.
Parallel
sorfequiline
DrugTwo sorfequiline 100mg tablets taken once daily for 4 weeks then one sorfequiline taken once daily for 13 weeks OR one sorfequiline 100mg tablet taken once daily for 17 weeks (with one 100mg sorfequiline placebo tablet for the first 4 weeks)
Pretomanid
Drugone 200mg tablet taken once daily for 17 weeks
Linezolid
Drugone 600mg tablet taken once daily for 17 weeks
Incidence and characterization of treatment-emergent adverse events (TEAEs)
Includes severity, relationship to study drugs, seriousness, TEAEs leading to discontinuation, and TEAEs leading to death; plus safety monitoring endpoints (ECG, vital signs, clinical labs, visual acuity changes, peripheral neuropathy changes.
Time to stable sputum culture conversion (SSCC) to negative
SSCC defined as two negative cultures at least 7 days apart without an intervening MTB-positive result (protocol definition used for time-to-event analyses). Time Frame: Through 17 weeks of treatment
Proportion with favorable outcome
Favorable outcome assessed post-treatment; protocol includes evaluation at 26 weeks and 52 weeks after end of treatment
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