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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05327803




Registration number
NCT05327803
Ethics application status
Date submitted
24/03/2022
Date registered
14/04/2022
Date last updated
14/02/2024

Titles & IDs
Public title
Study of Epetraborole in Patients With Treatment-refractory MAC Lung Disease
Scientific title
A Phase 2/3, Randomized, Double-blind, Placebo-controlled, Multicenter, Prospective Study to Assess the Efficacy, Safety, and Pharmacokinetics of Orally Administered Epetraborole in Patients With Treatment-refractory Mycobacterium Avium Complex Lung Disease
Secondary ID [1] 0 0
EBO-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
MAC Lung Disease 0 0
Treatment Refractory MAC Lung Disease 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Epetraborole
Treatment: Drugs - Placebo

Experimental: epetraborole + OBR - epetraborole + Optimized Background Regimen

Placebo Comparator: placebo + OBR - Placebo + Optimized Background Regimen


Treatment: Drugs: Epetraborole
500 mg taken orally QD

Treatment: Drugs: Placebo
Placebo taken orally QD
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 2: Assessment of novel Patient Reported Outcome instrument psychometric properties
Timepoint [1] 0 0
Screening (Day -14 to Day -7) to Month 6 + 1 week
Primary outcome [2] 0 0
Phase 2: Percentage of Participants Achieving Clinical Response
Timepoint [2] 0 0
Baseline to Month 6
Primary outcome [3] 0 0
Phase 2: Adverse Event Profile of 500 mg Once Daily Dose of Epetraborole
Timepoint [3] 0 0
Baseline to Month 16
Primary outcome [4] 0 0
Phase 3: Percentage of Participants Achieving Clinical Response
Timepoint [4] 0 0
Baseline to Month 6
Secondary outcome [1] 0 0
Phase 2: Percentage of Participants Achieving Culture Conversion
Timepoint [1] 0 0
Baseline to Month 6
Secondary outcome [2] 0 0
Phase 2: Percentage of Participants Achieving Microbiological Improvement
Timepoint [2] 0 0
Baseline to Month 6
Secondary outcome [3] 0 0
Phase 2: Change from Baseline in QOL-B Respiratory Domain PRO
Timepoint [3] 0 0
Baseline to Month 6
Secondary outcome [4] 0 0
Phase 2: Change from Baseline in NTM Symptoms Module PRO
Timepoint [4] 0 0
Baseline to Month 6
Secondary outcome [5] 0 0
Phase 2: Change from Baseline in SGRQ-C PRO
Timepoint [5] 0 0
Baseline to Month 6
Secondary outcome [6] 0 0
Phase 2: Concordance Analysis of PRO-based Clinical Response and Microbiological Response
Timepoint [6] 0 0
Baseline to Month 6
Secondary outcome [7] 0 0
Phase 2: Percentage of Participants with Reinfection
Timepoint [7] 0 0
Baseline to Month 16
Secondary outcome [8] 0 0
Phase 2: Percentage of Participants with Relapse
Timepoint [8] 0 0
Baseline to Month 16
Secondary outcome [9] 0 0
Phase 2: Maximum plasma concentration (Cmax) of epetraborole
Timepoint [9] 0 0
Day 1 and Day 29
Secondary outcome [10] 0 0
14. Phase 2: Area Under the Plasma Concentration-Time Curve from Time Point 0 Hours Until 24 hours [AUC(0-24)] post dose
Timepoint [10] 0 0
Day 29
Secondary outcome [11] 0 0
Phase 2: Volume of distribution (Vd) of epetraborole
Timepoint [11] 0 0
Day 29
Secondary outcome [12] 0 0
Phase 3: Percentage of Participants Achieving Culture Conversion
Timepoint [12] 0 0
Baseline to Month 6
Secondary outcome [13] 0 0
Phase 3: Percentage of Participants Achieving Microbiological Improvement
Timepoint [13] 0 0
Baseline to Month 6
Secondary outcome [14] 0 0
Phase 3: Change from Baseline in QOL-B Respiratory Domain PRO
Timepoint [14] 0 0
Baseline to Month 6
Secondary outcome [15] 0 0
Phase 3: Change from Baseline in NTM Symptoms Module PRO
Timepoint [15] 0 0
Baseline to Month 6
Secondary outcome [16] 0 0
Phase 3: Change from Baseline in SGRQ-C PRO
Timepoint [16] 0 0
Baseline to Month 6
Secondary outcome [17] 0 0
Phase 3: Concordance Analysis of PRO-based Clinical Response and Microbiological Response
Timepoint [17] 0 0
Baseline to Month 6
Secondary outcome [18] 0 0
Phase 3: Percentage of Participants with Reinfection
Timepoint [18] 0 0
Baseline to Month 16
Secondary outcome [19] 0 0
Phase 3: Percentage of Participants with Relapse
Timepoint [19] 0 0
Month 6, End of Therapy and Late Follow-up
Secondary outcome [20] 0 0
Phase 3: Adverse Event Profile of 500 mg Once Daily Dose of Epetraborole
Timepoint [20] 0 0
Baseline to Month 16
Secondary outcome [21] 0 0
Phase 3: Maximum plasma concentration (Cmax) of epetraborole
Timepoint [21] 0 0
Day 1 and Day 29
Secondary outcome [22] 0 0
Phase 3: Area Under the Plasma Concentration-Time Curve from Time Point 0 Hours Until 24 hours [AUC(0-24)] post dose
Timepoint [22] 0 0
Day 29
Secondary outcome [23] 0 0
Phase 3: Volume of distribution (Vd) of epetraborole
Timepoint [23] 0 0
Day 29

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2026
Actual
Sample size
Target
314
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
501005 - Concord
Recruitment hospital [2] 0 0
501007 - Birtinya
Recruitment hospital [3] 0 0
501003 - Chermside West
Recruitment hospital [4] 0 0
501001 - Greenslopes
Recruitment hospital [5] 0 0
501008 - Perth
Recruitment hospital [6] 0 0
501004 - Clayton
Recruitment hospital [7] 0 0
501002 - South Brisbane
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4575 - Birtinya
Recruitment postcode(s) [3] 0 0
4032 - Chermside West
Recruitment postcode(s) [4] 0 0
- Greenslopes
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Minnesota
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Nebraska
Country [18] 0 0
United States of America
State/province [18] 0 0
New Hampshire
Country [19] 0 0
United States of America
State/province [19] 0 0
New Jersey
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Ohio
Country [23] 0 0
United States of America
State/province [23] 0 0
Oklahoma
Country [24] 0 0
United States of America
State/province [24] 0 0
Oregon
Country [25] 0 0
United States of America
State/province [25] 0 0
Pennsylvania
Country [26] 0 0
United States of America
State/province [26] 0 0
South Carolina
Country [27] 0 0
United States of America
State/province [27] 0 0
Tennessee
Country [28] 0 0
United States of America
State/province [28] 0 0
Texas
Country [29] 0 0
United States of America
State/province [29] 0 0
Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
United States of America
State/province [31] 0 0
Wisconsin
Country [32] 0 0
Japan
State/province [32] 0 0
Aichi
Country [33] 0 0
Japan
State/province [33] 0 0
Aomori
Country [34] 0 0
Japan
State/province [34] 0 0
Fukuoka
Country [35] 0 0
Japan
State/province [35] 0 0
Gifu
Country [36] 0 0
Japan
State/province [36] 0 0
Hiroshima
Country [37] 0 0
Japan
State/province [37] 0 0
Hokkaido
Country [38] 0 0
Japan
State/province [38] 0 0
Ibaraki
Country [39] 0 0
Japan
State/province [39] 0 0
Ishikawa
Country [40] 0 0
Japan
State/province [40] 0 0
Kanagawa
Country [41] 0 0
Japan
State/province [41] 0 0
Kitakyushu
Country [42] 0 0
Japan
State/province [42] 0 0
Kyoto
Country [43] 0 0
Japan
State/province [43] 0 0
Mie
Country [44] 0 0
Japan
State/province [44] 0 0
Nagano
Country [45] 0 0
Japan
State/province [45] 0 0
Niigata
Country [46] 0 0
Japan
State/province [46] 0 0
Osaka
Country [47] 0 0
Japan
State/province [47] 0 0
Tokyo
Country [48] 0 0
Japan
State/province [48] 0 0
Wakayama
Country [49] 0 0
Japan
State/province [49] 0 0
Yamaguchi
Country [50] 0 0
Japan
State/province [50] 0 0
Yokohama
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Gwangju
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Incheon
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Seongnam-si
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AN2 Therapeutics, Inc
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05327803
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries