Phase 2 Open-label Study of Oral Alpibectir with Ethionamide and with Rifampicin, Pyrazinamide, and Ethambutol in Adults with Newly Diagnosed Drug-Susceptible Pulmonary Tuberculosis

What this Trial Is About

Researchers are evaluating the early effects, safety, and dose-response of oral alpibectir combined with ethionamide and other standard tuberculosis drugs in adults with newly diagnosed, drug-susceptible pulmonary tuberculosis. This phase 2 randomized, open-label trial aims to optimize dosing and confirm safety for potential future use as an alternative treatment for isoniazid mono-resistant TB. The study also explores novel biomarkers from sputum and blood samples to improve treatment monitoring beyond traditional methods. The trial includes two sequential cohorts with participants randomly assigned to experimental treatment arms or a standard care control group. All treatments are oral and given once daily for 14 days. Cohort 1 focuses on safety and dose optimization of alpibectir with ethionamide at two dose levels. After an interim safety review, cohort 2 evaluates the safety of combining alpibectir and ethionamide with rifampicin, pyrazinamide, and ethambutol. Participants receive pyridoxine to prevent peripheral neuropathy, and those with HIV may continue selected antiretroviral therapies. Participants will be hospitalized and closely monitored throughout the treatment period, with continuous medical attention and safety assessments. The study measures early bactericidal activity over 14 days using microbiological and molecular tests, as well as pharmacokinetic analyses and biomarker evaluations from sputum and blood samples. Safety, tolerability, and potential drug interactions are carefully assessed to inform future clinical development. Total participation duration covers the 14-day treatment and observation period.

A Study of the Early Effects, Safety, and Acceptability of Oral Alpibectir in Combination With Ethionamide