Study of Epetraborole in Patients With Treatment-refractory MAC Lung Disease

NCT ID: NCT05327803

Last Updated: 2025-05-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-20
• Study Completion Date: 2024-12-18

Brief Summary

This is a pivotal Phase 2/3, double-blind, placebo-controlled study of epetraborole + OBR (Optimized Background Regimen) versus placebo + OBR in patients with treatment-refractory MAC lung disease. This study will enroll adult patients with treatment-refractory MAC lung disease who meet all eligibility criteria (including clinical, radiographic, and microbiological criteria).

Detailed Description

In the Phase 2 part of the study, approximately 80 patients will be randomized in a 1:1 ratio (40 patients receiving active epetraborole tablets and 40 patients receiving matching placebo tablets). The Phase 2 part of the study includes a blinded psychometric analysis plan to assess the psychometric properties of a novel PRO instrument. In addition, symptom-based clinical responses will be assessed using blinded data, to inform the measurement of clinical response in the Phase 3 part of the study.

The Phase 3 part of the study will test the superiority of epetraborole + OBR compared to placebo + OBR. In this part of the study, approximately 234 patients are planned to be randomized in a 2:1 ratio (156 patients receiving active epetraborole tablets and 78 patients receiving matching placebo tablets). The current symptom-based clinical response definition (using the novel PRO) in Phase 3 is a placeholder to be verified after Phase 2 analyses based on data through Month 6. In addition, the Sponsor will determine if the sample size for Phase 3 should be adjusted and will verify the Phase 3 epetraborole dosage regimen based on the observed plasma epetraborole exposure.

Phase 3 data analyses will include a review of patient-reported outcomes, microbiological, safety, and PK data collected at multiple time points through Month 6. Patients in Phase 3 will continue double-blinded study drug for 12 months after the first negative MAC culture that defines sputum culture conversion; study drug will be discontinued in patients who remain MAC culture positive despite 6 months of therapy with study drug.

Conditions

MAC Lung Disease; Treatment Refractory MAC Lung Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

epetraborole + OBR

epetraborole + Optimized Background Regimen

Group Type: EXPERIMENTAL

Epetraborole

Intervention Type: DRUG

500 mg taken orally QD

placebo + OBR

Placebo + Optimized Background Regimen

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo taken orally QD

Interventions

Epetraborole

500 mg taken orally QD

Intervention Type: DRUG

Placebo

Placebo taken orally QD

Intervention Type: DRUG

Other Intervention Names

AN2-501971

Eligibility Criteria

Inclusion Criteria

1. Male or female patients who are 18 years of age or older.

2. Willing and able to provide written informed consent.

3. Patients with a diagnosis of treatment-refractory MAC lung disease consisting of all of the following (a) Microbiological, (b) Clinical, and (c) Radiographic criteria:

1. Microbiological criteria:

• One Pre-Study MAC-positive respiratory specimen. Documentation of a MAC positive specimen collected per standard of care within 6 months prior to signing the informed consent form (ICF).
• One Screening MAC-positive expectorated or induced sputum sample.

2. Clinical criteria: At least 2 of the following patient-reported clinical symptoms:

• Cough with sputum production
• Cough without sputum
• Chest congestion
• Hemoptysis
• Dyspnea
• Fatigue
• Night sweats or unusual sweating

3. Radiographic criteria: Non contrast Chest CT scan within 6 months prior to signing the ICF with abnormalities consistent with MAC lung disease.

4. OBR criteria: An OBR is a combination regimen that consists of ≥2 antimycobacterial agents. The patient-specific OBR must be administered for a minimum duration of 6 consecutive months that is either ongoing at the time of Screening or was stopped or paused no more than 12 months before screening. The OBR regimen administered during Screening must be continued after randomization.

4. Patients who are willing to comply with all the study activities and procedures throughout the duration of the study and comply with all planned study visits and study procedures from Screening through the LFU Visit.

5. All patients must agree to use an effective method of birth control.

6. Patients expected to survive with continued antimycobacterial therapy and appropriate supportive care from Screening through the LFU Visit, in the judgment of the Investigator.

Exclusion Criteria

1. 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.

2. Patients with active pulmonary malignancy or any malignancy that required or would require chemotherapy or radiation therapy within 1 year prior to randomization through the LFU Visit.

3. Patients with creatinine clearance (CrCl) of ≤30 mL/min, as estimated by the Cockcroft Gault formula, at Screening.

4. Patients with hemoglobin <10.0 g/dL or <6.2 mmol/L at Screening; donation of blood or plasma within 28 days prior to randomization; or symptomatic loss of blood or hemorrhage within 28 days prior to randomization.

5. Patients with severe hemoptysis within 28 days prior to randomization, defined as >100 mL over any 24-hour period or severe or extremely severe hemoptysis.

6. Patients with severe hepatic impairment, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total bilirubin >2 × ULN, or clinical signs of cirrhosis or end-stage hepatic disease.

7. Patients who are pregnant or breastfeeding.

8. Patients with a mean QT interval corrected using Fridericia's formula (QTcF) >480 msec based on triplicate 12-lead ECGs at Screening.

9. Patients with an immunodeficiency or an immunocompromised condition and risk for an opportunistic pulmonary infection.

10. Patients with an anticipated start of new non-study antimycobacterial therapy to be administered at any time between Screening and Month 6.

11. Patients who have received any investigational medication during the 30 days or 5 half-lives, whichever is longer, prior to randomization.

12. Patients with any prior exposure to epetraborole.

13. Patients with any condition that, in the opinion of the Investigator, interferes with the ability to safely complete the study or adhere to study requirements, including the patient's inability or unwillingness to comply with all study assessments and visits.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AN2 Therapeutics, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

423032

Birmingham, Alabama, United States

423037

Tucson, Arizona, United States

423070

Sacramento, California, United States

423069

San Francisco, California, United States

423006

Stanford, California, United States

423068

Washington D.C., District of Columbia, United States

423075

Bay Pines, Florida, United States

423018

DeLand, Florida, United States

423034

Kissimmee, Florida, United States

423033

Tampa, Florida, United States

423054

Tampa, Florida, United States

423047

Tampa, Florida, United States

423038

Vero Beach, Florida, United States

423027

Atlanta, Georgia, United States

423076

Indianapolis, Indiana, United States

423029

Iowa City, Iowa, United States

423015

Kansas City, Kansas, United States

423063

Wichita, Kansas, United States

423065

Jefferson, Louisiana, United States

423042

New Orleans, Louisiana, United States

423060

Baltimore, Maryland, United States

423003

Baltimore, Maryland, United States

423074

Boston, Massachusetts, United States

423061

Boston, Massachusetts, United States

423078

Ann Arbor, Michigan, United States

423031

Rochester, Minnesota, United States

423008

St Louis, Missouri, United States

423004

Omaha, Nebraska, United States

423009

Lebanon, New Hampshire, United States

423024

Manhasset, New York, United States

423014

New York, New York, United States

423013

New York, New York, United States

423071

Chapel Hill, North Carolina, United States

423072

Charlotte, North Carolina, United States

423017

Durham, North Carolina, United States

423039

Winston-Salem, North Carolina, United States

423079

Cleveland, Ohio, United States

423082

Oklahoma City, Oklahoma, United States

423007

Portland, Oregon, United States

423002

Philadelphia, Pennsylvania, United States

423058

Philadelphia, Pennsylvania, United States

423045

Charleston, South Carolina, United States

423001

Charleston, South Carolina, United States

423067

Nashville, Tennessee, United States

423081

Fort Worth, Texas, United States

423005

Tyler, Texas, United States

423012

Charlottesville, Virginia, United States

423080

Edmonds, Washington, United States

423011

Milwaukee, Wisconsin, United States

501005

Concord, New South Wales, Australia

501007

Birtinya, Queensland, Australia

501003

Chermside West, Queensland, Australia

501001

Greenslopes, Queensland, Australia

501008

Perth, Western Australia, Australia

501004

Clayton, , Australia

501002

South Brisbane, , Australia

215019

Aichi, , Japan

215026

Aomori, , Japan

215004

Fukuoka, , Japan

215025

Fukuoka, , Japan

215016

Fukuoka, , Japan

215006

Gifu, , Japan

215030

Hiroshima, , Japan

215014

Hokkaido, , Japan

215028

Ibaraki, , Japan

215018

Ishikawa, , Japan

215020

Ishikawa, , Japan

215017

Kanagawa, , Japan

215021

Kitakyushu, , Japan

215009

Kyoto, , Japan

215013

Kyoto, , Japan

215022

Mie, , Japan

215023

Nagano, , Japan

215002

Niigata, , Japan

215029

Osaka, , Japan

215008

Osaka, , Japan

215012

Osaka, , Japan

215001

Tokyo, , Japan

215005

Tokyo, , Japan

215024

Tokyo, , Japan

215003

Tokyo, , Japan

215027

Tokyo, , Japan

215010

Wakayama, , Japan

215007

Yamaguchi, , Japan

215011

Yokohama, , Japan

219003

Gwangju, , South Korea

219005

Incheon, , South Korea

219001

Seongnam-si, , South Korea

219002

Seoul, , South Korea

219007

Seoul, , South Korea

219008

Seoul, , South Korea

Countries

United States; Australia; Japan; South Korea

Other Identifiers

EBO-301

Identifier Type: -

Identifier Source: org_study_id