Sorfequiline-based Regimens in Adults With Newly Diagnosed Drug-sensitive Pulmonary TB

Overview

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.

This is a phase 2, randomised, multi-center, partially blinded, clinical trial conducted in 2 treatment arms. The trial will be performed at multiple centers in South Africa and Tanzania in at approximately 100 participants with DS-TB who meet all the inclusion criteria and none of the exclusion criteria, aged 18 to 65, inclusive. Participants will be randomised to one of the 2 sorfequiline, pretomanid and linezolid containing regimens and will be randomised in 1:1 ratio based on country and severity of disease (AFB 3+ and/or bilateral cavitation). T The trial will consist of the following periods: 1. Screening period: Screening visit, up to 11 days prior to randomisation (Day 1) 2. Treatment Period: approximately 100 participants will be randomised equally to the 2 treatment arms below: * Sorfequiline 200 mg + pretomanid 200 mg + linezolid 600 mg for 4 weeks followed by sorfequiline 100 mg for 13 weeks * Sorfequiline 100 mg + pretomanid 200 mg + linezolid 600 mg for 17 week 3. Follow-up Period: 52 weeks after end of treatment