Epetraborole in Patients With Mycobacterium Abscessus Lung Disease

NCT07301320 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: REBOUND Trial
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mycobacterium Abscessus Infection

Keywords

NTM; nontuberculous mycobacteria; Mycobacterium abscessus; M. abscessus; abscessus

Outcome Measures

Primary Outcomes (6)

• Clinical Response (NTM Symptom Evaluation Instrument) at Day 84

  Improvement in severity of at least 50% of the symptoms present at baseline and no deterioration in severity of symptoms present at baseline

  Day 1 to Day 84

• Sputum culture conversion by Day 84

  Defined as 3 consecutive negative cultures one month apart without intervening or subsequent positives

  Day 1 to Day 84

• Decrease in semi-quantitative sputum culture counts at Day 84

  Defined as improvement in sputum colony count category as defined by Griffith et al, 2015

  Day 1 to Day 84

• Change from baseline in Quality of Life - Bronchiectasis (QOL-B) Respiratory Domain at Day 84

  QOL-B Domain scores range from 0 to 100, with higher scores indicating better health-related quality of life

  Day 1 to Day 84

• Change from baseline in MACrO2 PRO at Day 84

  MACrO2 scores range from 0 to 100, with lower scores indicating better symptom-related quality of life

  Day 1 to Day 84

• Sputum culture conversion by Day 56

  Defined as 2 consecutive negative cultures collected one month apart without intervening or subsequent positives

  Day 1 to Day 56

Secondary Outcomes (9)

• Patient Global Impression of Change (PGI-C) at Day 84

  Day 1 to Day 84

• Patient Global Impression of Severity (PGI-S) at Day 84

  Day 1 to Day 84

• Physician Visual Analog Scale (VAS) - Global at Day 84

  Day 1 to Day 84

• Physician Visual Analog Scale (VAS) - Respiratory at Day 84

  Day 1 to Day 84

• NTM Symptoms Scale (NTM-SS) Questionnaire at Day 84

  Day 1 to Day 84

Study Arms (4)

High Dose Epetraborole

EXPERIMENTAL

This arm is a daily treatment regimen of a 750mg oral dose of Epetraborole.

Drug: Epetraborole

Low Dose Epetraborole

EXPERIMENTAL

This arm is a daily treatment regimen of a 500mg oral dose of Epetraborole.

Drug: Epetraborole

High Dose Placebo

PLACEBO COMPARATOR

This arm is a daily treatment regimen of a placebo, matching the high dose experimental arm.

Drug: Placebo

Low Dose Placebo

PLACEBO COMPARATOR

This arm is a daily treatment regimen of a placebo, matching the low dose experimental arm.

Drug: Placebo

Interventions

Placebo DRUG

Placebo intervention (matching the high-dose experimental intervention)

High Dose Placebo

Epetraborole DRUG

High-dose intervention (750mg daily)

High Dose Epetraborole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients who are 18 years of age or older.
• Willing and able to provide written informed consent.
• Patients with MABc lung disease, meeting the following (a) Microbiological, (b) Clinical, (c) Radiographic
• a. Microbiological criteria: i. Documentation of at least 1 Pre-Study MABc-positive respiratory specimen (sputum or deep bronchial specimen) collected per standard of care within 6 months prior to signing the consent form.
• ii. At least 1 Screening MABc-positive expectorated or induced sputum sample. b. Clinical criteria: At least 2 of the following patient-reported clinical symptoms: i. Chest pain ii. Chronic cough iii. Coughing up blood iv. Fatigue v. Fever (documented by thermometer) vi. Mucus (sputum) production vii. Night sweats (drenching perspiration with no other obvious etiology, e.g. perimenopausal) viii. Poor appetite ix. Shortness of breath x. Weight loss (unintentional, more than 5% of usual weight in 6 to 12 months) c. Radiographic criteria: Non-contrast chest CT scan within 4 months prior to signing the ICF (Pre-Study chest CT) or within the Screening Period (Screening chest CT) with abnormalities consistent with MABc-LD based on local interpretation (e.g. Investigator or local radiologist).
• Patients who, in the opinion of the investigator, will not require initiation of guideline-directed antibiotic therapy for treatment of MABc-LD within the next 6 months, and for whom a delay, in order for the subject to participate in a placebo-controlled clinical trial, is considered both reasonable and clinically acceptable.
• Patients who are willing to comply with all the study activities and procedures throughout the duration of the study.
• Patients must agree to use an effective method of birth control, if applicable, as follows: Females of childbearing potential (FOCPs; defined in Appendix 1, Contraception Requirements) must commit to either sexual abstinence or use of at least 2 medically accepted, effective methods of birth control (defined in Contraception Requirements) from Screening through the EOS Visit
• Males who are sexually active with a FOCP must agree to use an effective barrier method of contraception (defined in Contraception Requirements) from Screening through the EOS Visit
• Patients expected to survive with continued antimycobacterial therapy and appropriate supportive care from Screening through the LFU Visit, in the judgment of the Investigator.

You may not qualify if:

• Patients with a presence of any suspected or confirmed disease or condition at Screening or the time of randomization that, in the opinion of the Investigator, may confound the assessment of symptom-based clinical response, including, but not limited to, the following:
• Radiographic presence of cavitary disease (defined as a patient with one or more cavities \>2 cm internal diameter)
• Cystic fibrosis or other inherited disorders of airway ciliary dysfunction (e.g., primary ciliary dyskinesia)
• Active allergic bronchopulmonary mycosis
• Anticipated or planned lung surgery for treatment of MABc lung disease
• Disseminated MABc infection, or other known or suspected non-pulmonary source of infection (e.g., infective endocarditis, osteomyelitis, meningitis, or urinary tract infection) requiring non-study antimicrobial therapy
• Concomitant pulmonary infection requiring antimicrobial therapy, including infection caused by fungi, viruses, non-MABc mycobacteria (e.g., Mycobacterium tuberculosis, Mycobacterium avium intracellulare, Mycobacterium avium complex, Mycobacterium kansasii), or other bacteria (e.g., Pseudomonas aeruginosa, Staphylococcus aureus).
• Note: Patients with MABc lung disease and concomitant non-MABc lung infection requiring antimicrobial therapy must complete the antimicrobial treatment for the non-MABc infection prior to randomization. Patients with respiratory specimen cultures that contain growth of non-MABc organisms that are deemed by the Investigator to be respiratory tract colonizers and who do not require or receive specific antimicrobial therapy may remain eligible. The Investigator should discuss such cases with the Study Investigator prior to randomization and provide rationale for study eligibility in the source document.
• Patients on brensocatib who have not been on a stable dose for at least 12 weeks.
• Patients with active pulmonary malignancy (primary or metastatic) or any malignancy that required or would require chemotherapy or radiation therapy within 1 year prior to randomization through the LFU Visit.
• Patients with creatinine clearance (CrCl) of \<30 mL/min, as estimated by the Cockcroft-Gault formula, at Screening: Estimated CrCl (mL/min) = (140 - Age \[years\]) × Actual Body Weight \[kg\] × \[0.85 if Female\]) / (72 × Serum Creatinine \[mg/dL\]).
• Patients with any of the following hematological findings:
• Hemoglobin \<11.0 g/dL or \<6.83 mmol/L.
• Donation of blood or plasma within 28 days prior to randomization; or symptomatic loss of blood or hemorrhage within 28 days prior to randomization.
• Pre-existing (inborn or acquired) disorder of hematopoiesis that could substantially worsen the effect of EBO on hemoglobin levels or potentially prevent hemoglobin recovery post cessation of treatment, for example, thalassemia, sickle cell disease, hemolytic anemia, Inherited bone marrow failure syndromes, myelodysplastic or myeloproliferative disorders, bone marrow transplantation

Sponsors & Collaborators

• Kevin Winthrop: lead
• AN2 Therapeutics, Inc: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Related Publications (11)

• 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.

  PMID: 35388453 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.

  PMID: 38615375 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.

  PMID: 39016592 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.

  PMID: 38190702 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.

  PMID: 26068042 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.

  PMID: 34314673 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. Erratum In: Clin Infect Dis. 2020 Dec 31;71(11):3023. doi: 10.1093/cid/ciaa1062.

  PMID: 32628747 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.

  PMID: 30071551 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.

  PMID: 28461147 BACKGROUND

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Kevin L Winthrop, MD, MPH

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Felicity Coulter, PhD

CONTACT

503-494-2565; rebound@ohsu.edu

Brandy Peacock, DAOM, MAcOM

CONTACT

(503) 494-8022; rebound@ohsu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigator, the Sponsor, and the Funder will be blinded to treatment group assignments throughout the study. The Sponsor (e.g., clinical supply manager etc.) will have a designated randomization administrator who will maintain the randomization codes in accordance with standard operating procedures to ensure the blind is properly maintained. Only Sponsor personnel who require knowledge of treatment assignments will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: December 24, 2025
• Study Start: March 30, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)