A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial

This phase 2a, single-center, open-label, randomized trial assessed the early bactericidal activity (EBA), safety, and pharmacokinetics of ganfeborole in participants with untreated, rifampicin-susceptible pulmonary tuberculosis. Ganfeborole (1/5/15/30 mg) or standard of care was administered daily for 14 days to 75 males. Numerical reductions in sputum colony-forming units were observed with 5, 15, and 30 mg ganfeborole. Adverse events were comparable across groups and grade 1 or 2. Post-hoc analysis of PET/CT scans showed treatment responses, and transcriptional analysis revealed an association with neutrophil-dominated modules at 30 mg. Ganfeborole shows potential for tuberculosis combination therapy.

Andreas H. Diacon, Clifton E. Barry III, Alex Carlton, Ray Y. Chen, Matt Davies, Veronique de Jager, Kim Fletcher, Gavin C. K. W. Koh, Irina Kontsevaya, Jan Heyckendorf, Christoph Lange, Maja Reimann, Sophie L. Penman, Rhona Scott, Gareth Maher-Edwards, Simon Tiberi, Georgios Vlasakakis, Caryn M. Upton, David Barros Aguirre