Protocol for a phase 2, partially blinded, randomized trial assessing the safety and efficacy of sorfequiline or bedaquiline in combination with pretomanid and linezolid in adult participants with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis (NC-009).

introductionIn 2023, tuberculosis (TB) returned to being the world's leading cause of death from a single infectious agent. Current standard of care for drug-sensitive tuberculosis (DS-TB) treatment has a long duration with risk of poor compliance and outcomes and increased risk of development of resistant strains. Sorfequiline (S) is a second-generation diarylquinoline with the potential to contribute both to increased efficacy and improved safety and to a shorter TB treatment regimen for both DS-TB and drug-resistant DR-TB. METHODS AND ANALYSIS: NC-009 is a phase 2, multicentre, partially blinded, randomized clinical trial conducted in five treatment arms, including three doses of sorfequiline in combination with pretomanid and linezolid for 8 weeks followed by 7 or 18 weeks of HR depending on the participant meeting criteria to stop treatment at week 15. There is also a BPaL arm and standard of care arm, both for a 26-week treatment duration. The study population is smear-positive, DS-TB. The primary objective of the study is to determine the optimal dose of sorfequiline to move forward to a potential phase 3 study based on efficacy and safety data. The study is being conducted in Georgia, South Africa, Tanzania, Uganda, and the Philippines in accordance with ICH-GCP and after approval of all relevant country health authorities and ethics committees. DISCUSSION: NC-009 is a first in-patient, dose-ranging, phase 2 trial of sorfequiline, with an innovative design combining ph2a, ph2b, and ph2c elements that simultaneously allow for dose selection, preliminary evaluation of treatment duration, robust collection of safety data, evaluation of drug-drug interaction with antiretroviral medications, and pharmacokinetic assessment of study drugs. The study is currently ongoing. TRIAL REGISTRATION NUMBER {4}: ClinicalTrials.gov NCT06058299. Registered on 09 September 2023.