Epetraborole in Patients With Mycobacterium Abscessus Lung Disease

Summary

This double-blind, randomized, placebo-controlled, parallel-group, multicenter, prospective, investigator-initiated trial will evaluate epetraborole (EBO) monotherapy in the treatment of adults with Mycobacterium abscessus complex (MABc) Lung Disease (LD) of mild to moderate severity. For this study, two EBO oral dose regimens will be studied in patients with MABc-LD, each compared to a placebo group (ie, 4 treatment groups): 500 mg daily and 750 mg daily. Detailed inclusion and exclusion criteria attempt to identify only those patients who have acceptable risks based upon the EBO preclinical findings, phase 1, phase 2, and Phase 3 experience; standard-of-care procedures; and the specified procedures of the study. Following receipt of informed consent, and a Screening period, eligible patients will be randomized to one of the 4 treatment groups to receive active or matched placebo EBO tablets for 84 days. Patients will be assessed for clinical and microbiological evidence of efficacy. At selected investigative sites, patients will undergo sparse PK sampling. Safety and tolerability will be determined by standard clinical and laboratory assessment, with oversight by a qualified and appropriately constituted Data Safety Monitoring Board (DSMB). Data collected during the study will be analyzed per a comprehensive Statistical Analysis Plan (SAP). The study will be registered on clinicaltrials.gov. The total duration of patient participation is approximately 6 months.

Timeline

Start

2026-03-30

Primary completion

2027-12

Completion

2028-05

Publications

• Background National Cancer Institute. (2017). Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. https://doi.org/10.33329/ctcae.v5.0
• Background Bowman CJ, Becourt-Lhote N, Boulifard V, Cordts R, Corriol-Rohou S, Enright B, Erkman L, Harris J, Hartmann A, Hilpert J, Kervyn S, Mattson B, Morford L, Muller M, Powell M, Sobol Z, Srinivasan R, Stark C, Thompson KE, Turner KJ, Barrow P. Science-Based Approach to Harmonize Contraception Recommendations in Clinical Trials and Pharmaceutical Labels. Clin Pharmacol Ther. 2023 Feb;113(2):226-245. doi: 10.1002/cpt.2602. Epub 2022 May 5.
• Background Kaneko T, Otoshi R, Sekine A, Baba T, Yamada C, Haga S, Tagami Y, Sawazumi T, Takemura T, Komatsu S, Hagiwara E, Ogura T. Drug-related pneumonitis caused by amikacin liposome inhalation suspension: One pathologically proven case and single-center experience. Respir Investig. 2024 Jul;62(4):513-516. doi: 10.1016/j.resinv.2024.04.003. Epub 2024 Apr 13.
• Background Rimal B, Lippincott CK, Panthi CM, Xie Y, Keepers TR, Alley M, Lamichhane G. Efficacy of epetraborole against Mycobacteroides abscessus in a mouse model of lung infection. Antimicrob Agents Chemother. 2024 Aug 7;68(8):e0064824. doi: 10.1128/aac.00648-24. Epub 2024 Jul 17.
• Background Li L, Henkle E, Youngquist BM, Seo S, Hamed K, Melnick D, Lyon CJ, Jiang L, Zelazny AM, Hu TY, Winthrop KL, Ning B. Serum Cell-Free DNA-based Detection of Mycobacterium avium Complex Infection. Am J Respir Crit Care Med. 2024 May 15;209(10):1246-1254. doi: 10.1164/rccm.202303-0401OC.
• Background Griffith DE, Adjemian J, Brown-Elliott BA, Philley JV, Prevots DR, Gaston C, Olivier KN, Wallace RJ Jr. Semiquantitative Culture Analysis during Therapy for Mycobacterium avium Complex Lung Disease. Am J Respir Crit Care Med. 2015 Sep 15;192(6):754-60. doi: 10.1164/rccm.201503-0444OC.
• Background Eckburg PB, Clarke D, Long J, et al. 2022. Tolerability and pharmacokinetics of oral epetraborole at the predicted therapeutic dosage for Mycobacterium avium complex (MAC) lung disease: a phase 1b dose-ranging and food effect study. In ID week. Washington DC
• Background Griffith DE, Daley CL. Treatment of Mycobacterium abscessus Pulmonary Disease. Chest. 2022 Jan;161(1):64-75. doi: 10.1016/j.chest.2021.07.035. Epub 2021 Jul 24.
• Background Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ Jr, Andrejak C, Bottger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL. Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline. Clin Infect Dis. 2020 Aug 14;71(4):e1-e36. doi: 10.1093/cid/ciaa241.
• Background Strnad L, Winthrop KL. Treatment of Mycobacterium abscessus Complex. Semin Respir Crit Care Med. 2018 Jun;39(3):362-376. doi: 10.1055/s-0038-1651494. Epub 2018 Aug 2.
• Background Diel R, Ringshausen F, Richter E, Welker L, Schmitz J, Nienhaus A. Microbiological and Clinical Outcomes of Treating Non-Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Review and Meta-Analysis. Chest. 2017 Jul;152(1):120-142. doi: 10.1016/j.chest.2017.04.166. Epub 2017 Apr 28.

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Indications