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

NCT05327803 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: EBO-301
• Study Type: interventional
• Target: 177
• Locations: 4 countries
• Sites: 91

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).

Conditions

MAC Lung Disease; Treatment Refractory MAC Lung Disease

Keywords

NTM; Respiratory Infection; antimycobacterial activity; antimycobacterial agent; antimycobacterial therapy; MAC infections; MAC lung disease; MAC lung infection; MAC pulmonary infection; Mycobacteria; mycobacterial disease; mycobacterium; Mycobacterium Avium Complex; Mycobacterium Avium Complex Infections; Mycobacterium avium complex lung disease; Mycobacterium Infections; Nontuberculous; Nontuberculous mycobacteria / mycobacterial / mycobacterium; Non-tuberculous mycobacteria disease; Non-tuberculous mycobacterial (NTM) infections; Nontuberculous mycobacterial lung disease; Non-tuberculous mycobacterial lung disease; Nontuberculous mycobacterial pulmonary disease; NTM infection; NTM lung disease; NTM Pulmonary Disease; NTM lung infection; Pulmonary MAC disease; Pulmonary MAC lung disease; Pulmonary Mycobacterium Avium Complex disease; Treatment refractory MAC lung disease; Treatment refractory mycobacterial lung disease; Treatment refractory NTM lung disease; Treatment refractory NTM lung infection; Treatment refractory NTM pulmonary disease

Outcome Measures

Primary Outcomes (4)

• Phase 2: Assessment of novel Patient Reported Outcome instrument psychometric properties

  Assessment of novel Patient Report outcomes

  Screening (Day -14 to Day -7) to Month 6 + 1 week

• Phase 2: Percentage of Participants Achieving Clinical Response

  Detection of within-patient changes in symptoms reported in a novel Patient-Reported Outcome (PRO) instrument at Month 3 and Month 6.

  Baseline to Month 6

• Phase 2: Adverse Event Profile of 500 mg Once Daily Dose of Epetraborole

  Percentage of Participants reporting treatment emergent adverse events

  Baseline to Month 16

• Phase 3: Percentage of Participants Achieving Clinical Response

  Detection of within-patient changes in symptoms reported in a novel Patient-Reported Outcome (PRO) instrument at Month 6

  Baseline to Month 6

Secondary Outcomes (23)

• Phase 2: Percentage of Participants Achieving Culture Conversion

  Baseline to Month 6

• Phase 2: Percentage of Participants Achieving Microbiological Improvement

  Baseline to Month 6

• Phase 2: Change from Baseline in QOL-B Respiratory Domain PRO

  Baseline to Month 6

• Phase 2: Change from Baseline in NTM Symptoms Module PRO

  Baseline to Month 6

• Phase 2: Change from Baseline in SGRQ-C PRO

  Baseline to Month 6

Study Arms (2)

epetraborole + OBR

EXPERIMENTAL

epetraborole + Optimized Background Regimen

Drug: Epetraborole

placebo + OBR

PLACEBO COMPARATOR

Placebo + Optimized Background Regimen

Drug: Placebo

Interventions

Epetraborole DRUG

500 mg taken orally QD

Also known as: AN2-501971

epetraborole + OBR

Placebo DRUG

Placebo taken orally QD

placebo + OBR

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 a diagnosis of treatment-refractory MAC lung disease consisting of all of the following (a) Microbiological, (b) Clinical, and (c) Radiographic criteria:
• 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.
• 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
• Radiographic criteria: Non contrast Chest CT scan within 6 months prior to signing the ICF with abnormalities consistent with MAC lung disease.

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.
• 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.
• Patients with creatinine clearance (CrCl) of ≤30 mL/min, as estimated by the Cockcroft Gault formula, at Screening.
• 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.
• 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.
• 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.
• Patients who are pregnant or breastfeeding.
• Patients with a mean QT interval corrected using Fridericia's formula (QTcF) \>480 msec based on triplicate 12-lead ECGs at Screening.
• Patients with an immunodeficiency or an immunocompromised condition and risk for an opportunistic pulmonary infection.
• Patients with an anticipated start of new non-study antimycobacterial therapy to be administered at any time between Screening and Month 6.
• Patients who have received any investigational medication during the 30 days or 5 half-lives, whichever is longer, prior to randomization.
• Patients with any prior exposure to epetraborole.
• 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.

Sponsors & Collaborators

• AN2 Therapeutics, Inc: lead

Study Sites (91)

423032

Birmingham, Alabama, 35233, United States

Location

423037

Tucson, Arizona, 85724, United States

Location

423070

Sacramento, California, 95817, United States

Location

423069

San Francisco, California, 94143, United States

Location

423006

Stanford, California, 94305, United States

Location

423068

Washington D.C., District of Columbia, 20037, United States

Location

423075

Bay Pines, Florida, 33744, United States

Location

423018

DeLand, Florida, 32720, United States

Location

423034

Kissimmee, Florida, 34746, United States

Location

423033

Tampa, Florida, 33606, United States

Location

423054

Tampa, Florida, 33612, United States

Location

423047

Tampa, Florida, 33614, United States

Location

423038

Vero Beach, Florida, 32960, United States

Location

423027

Atlanta, Georgia, 30342, United States

Location

423076

Indianapolis, Indiana, 46202, United States

Location

423029

Iowa City, Iowa, 52242, United States

Location

423015

Kansas City, Kansas, 66205, United States

Location

423063

Wichita, Kansas, 67211, United States

Location

423065

Jefferson, Louisiana, 70121, United States

Location

423042

New Orleans, Louisiana, 70112, United States

Location

423060

Baltimore, Maryland, 21201, United States

Location

423003

Baltimore, Maryland, 21231, United States

Location

423074

Boston, Massachusetts, 02114-2696, United States

Location

423061

Boston, Massachusetts, 02115, United States

Location

423078

Ann Arbor, Michigan, 48109, United States

Location

423031

Rochester, Minnesota, 55902, United States

Location

423008

St Louis, Missouri, 63110, United States

Location

423004

Omaha, Nebraska, 68198, United States

Location

423009

Lebanon, New Hampshire, 03756, United States

Location

423024

Manhasset, New York, 11030, United States

Location

423014

New York, New York, 10017, United States

Location

423013

New York, New York, 10029, United States

Location

423071

Chapel Hill, North Carolina, 27599, United States

Location

423072

Charlotte, North Carolina, 28204, United States

Location

423017

Durham, North Carolina, 27705, United States

Location

423039

Winston-Salem, North Carolina, 27103, United States

Location

423079

Cleveland, Ohio, 44195, United States

Location

423082

Oklahoma City, Oklahoma, 73104, United States

Location

423007

Portland, Oregon, 97239, United States

Location

423002

Philadelphia, Pennsylvania, 19104, United States

Location

423058

Philadelphia, Pennsylvania, 19107, United States

Location

423045

Charleston, South Carolina, 29414, United States

Location

423001

Charleston, South Carolina, 29425, United States

Location

423067

Nashville, Tennessee, 37232, United States

Location

423081

Fort Worth, Texas, 76104, United States

Location

423005

Tyler, Texas, 75708, United States

Location

423012

Charlottesville, Virginia, 22908, United States

Location

423080

Edmonds, Washington, 98026, United States

Location

423011

Milwaukee, Wisconsin, 53226, United States

Location

501005

Concord, New South Wales, 2139, Australia

Location

501007

Birtinya, Queensland, 4575, Australia

Location

501003

Chermside West, Queensland, 4032, Australia

Location

501001

Greenslopes, Queensland, Australia

Location

501008

Perth, Western Australia, 6000, Australia

Location

501004

Clayton, 3168, Australia

Location

501002

South Brisbane, 4101, Australia

Location

215019

Aichi, 465-8620, Japan

Location

215026

Aomori, 036-8563, Japan

Location

215004

Fukuoka, 811-3195, Japan

Location

215025

Fukuoka, 814-0180, Japan

Location

215016

Fukuoka, 819-8555, Japan

Location

215006

Gifu, 502-8558, Japan

Location

215030

Hiroshima, 730-0822, Japan

Location

215014

Hokkaido, 070-8644, Japan

Location

215028

Ibaraki, 319-1113, Japan

Location

215018

Ishikawa, 920-8530, Japan

Location

215020

Ishikawa, 920-8650, Japan

Location

215017

Kanagawa, 236-0051, Japan

Location

215021

Kitakyushu, 806-0034, Japan

Location

215009

Kyoto, 610-0113, Japan

Location

215013

Kyoto, 612-8555, Japan

Location

215022

Mie, 514-1101, Japan

Location

215023

Nagano, 382-8577, Japan

Location

215002

Niigata, 951-8510, Japan

Location

215029

Osaka, 560-8552, Japan

Location

215008

Osaka, 591-8555, Japan

Location

215012

Osaka, 591-8555, Japan

Location

215001

Tokyo, 160-8582, Japan

Location

215005

Tokyo, 162-8655, Japan

Location

215024

Tokyo, 180-8610, Japan

Location

215003

Tokyo, 204-8522, Japan

Location

215027

Tokyo, Japan

Location

215010

Wakayama, 646-8558, Japan

Location

215007

Yamaguchi, Japan

Location

215011

Yokohama, 245-8575, Japan

Location

219003

Gwangju, 61469, South Korea

Location

219005

Incheon, 21431, South Korea

Location

219001

Seongnam-si, 13620, South Korea

Location

219002

Seoul, 03080, South Korea

Location

219007

Seoul, 05505, South Korea

Location

219008

Seoul, South Korea

Location

MeSH Terms

Conditions

Respiratory Tract Infections; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection; Infections

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Mycobacterium Infections, Nontuberculous

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: April 14, 2022
• Study Start: May 20, 2022
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: May 8, 2025

Record last verified: 2024-08

Locations

KR (6); US (49); JP (29); AU (7)