Epetraborole in Patients With Mycobacterium Abscessus Lung Disease
ConditionMycobacterium Abscessus Infection
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorKevin Winthrop
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Epetraborole
DrugHigh-dose intervention (750mg daily)
Epetraborole
DrugLow-dose intervention (500mg daily)
Placebo
DrugPlacebo intervention (matching the high-dose experimental intervention)
Placebo
DrugPlacebo intervention (matching the low-dose experimental intervention)
Treatment groups
84 Participants
are divided into 4 treatment groupsGroup A: High Dose EpetraboroleExperimental treatment 1 intervention
Group B: Low Dose EpetraboroleExperimental treatment 1 intervention
Group C: High Dose PlaceboPlacebo comparator 1 intervention
Group D: Low Dose PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
Day 1 to Day 842
Sputum culture conversion by Day 84
Defined as 3 consecutive negative cultures one month apart without intervening or subsequent positives
Time frame
Day 1 to Day 843
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
Time frame
Day 1 to Day 844
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
Time frame
Day 1 to Day 84Secondary outcomes
1
Patient Global Impression of Change (PGI-C) at Day 84
The Patient Global Impression of Change Scale has a minimum value of 1 and a maximum value of 7. For this scale, higher scores indicate a worse outcome.
Time frame
Day 1 to Day 842
Patient Global Impression of Severity (PGI-S) at Day 84
The Patient Global Impression of Severity Scale measures severity of a patient's overall status over the previous 7 days. The responses on this scale have a minimum value of 'None' and a maximum value of 'Very severe' related to severity. For this scale, higher scores ('Very severe') indicate a worse outcome.
Time frame
Day 1 to Day 843
Physician Visual Analog Scale (VAS) - Global at Day 84
The Physician Visual Analog Scale - Global has a minimum value of 0 and a maximum value of 10. For this scale, higher scores indicate a worse outcome.
Time frame
Day 1 to Day 844
Physician Visual Analog Scale (VAS) - Respiratory at Day 84
The Physician Visual Analog Scale - Respiratory has a minimum value of 0 and a maximum value of 10. For this scale, higher scores indicate a worse outcome.
Time frame
Day 1 to Day 84Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Kevin Winthrop
Lead sponsor
Oregon Health and Science University
Sponsor institution
AN2 Therapeutics, Inc
Collaborator
Source ClinicalTrials.gov