Oral Omadacycline vs. Placebo in Adults With NTM Pulmonary Disease Caused by Mycobacterium Abscessus Complex (MABc)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and tolerability of oral omadacycline as compared to placebo in the treatment of adults with Nontuberculous Mycobacterial (NTM) pulmonary disease caused by Mycobacterium abscessus complex (MABc)

Detailed Description
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The total duration of subject participation in the study is approximately 5 months which includes a total duration of study treatment for approximately 3 months (84 days). Eligible participants will be randomized 1.5:1 to receive 3 months of treatment with either omadacycline or placebo (monotherapy). The study will use a double-dummy design in order to maintain the study blinding.

Official Title
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A Ph. 2, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy, Safety, & Tolerability of Oral Omadacycline in Adults With NTM Pulmonary Disease Caused by Mycobacterium Abscessus Complex

Conditions
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Mycobacterium Infections, Nontuberculous, Mycobacterium Abscessus Infection, Nontuberculous Mycobacterial Lung Disease, Nontuberculous Mycobacterial Pulmonary Infection

Intervention / Treatment
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* Drug: Omadacycline Oral Tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Has a diagnosis of Nontuberculous Mycobacterial pulmonary disease caused by MABc Has at least 2 of the following NTM-infection symptoms present at Screening and Baseline: chronic cough, coughing up blood (hemoptysis), wheezing, chest pain, frequent throat clearing, phlegm or sputum production, shortness of breath, fatigue, fever, night sweats, poor appetite, and/or weight loss. At least 1 positive pulmonary (sputum) culture for MABc in the 6 months prior to Screening and 1 positive culture at Screening Radiographic evidence of MABc infection via computed tomography (CT) scan of the chest within 3 months prior to Screening In the opinion of the investigator, guideline-directed antibiotic therapy for treatment of MABc will not be required within the next 3 months, and a delay, in order for the subject to participate in a placebo-controlled clinical trial, is considered reasonable and clinically acceptable Additional inclusion criteria as per protocol Key Exclusion Criteria: Has received antibiotic treatment within 6 months prior to Screening for MABc or MAC Has received systemic or inhaled antibiotic therapy (other than chronic macrolide therapy) within 4 weeks prior to Screening Has any of the following medical conditions: Active pulmonary malignancy, or any type of malignancy requiring chemotherapy or radiation within 1 year prior to Screening Active allergic bronchopulmonary mycosis, or any other condition requiring chronic treatment with systemic corticosteroids within 90 days prior to Screening Radiologic evidence of cavitary disease Known active pulmonary tuberculosis Cystic fibrosis History of lung transplantation Another advanced lung disease with a known percent predicted forced expiratory volume in 1 second < 30%. Disseminated or extra-pulmonary NTM disease Has been previously treated with omadacycline Has a history of hypersensitivity or allergic reaction to tetracyclines Additional exclusion criteria as per protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omadacycline 300 mg PO<br>omadacycline 150 mg tablets (x 2) administered orally, once daily, q24h | Drug: Omadacycline Oral Tablet<br>* omadacycline 300 mg orally, once daily (150 mg tablets x 2)<br>* Other names: Nuzyra;|
| Placebo Comparator: Placebo PO<br>Placebo tablets resembling omadacycline (x 2) administered once daily, q24h | Drug: Placebo<br>* placebo tablets resembling omadacycline orally, once daily (x 2 tablets)<br>* Other names: placebo tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response on NTM Symptom Assessment Scale at Day 84 | Improvement in severity of at least 50% of symptoms present at baseline | Day 1 to Day 84/EOT | 
| Reported adverse events (AEs) | To assess reported adverse events | Day 1 to Day 84/EOT | 
| Changes from baseline in laboratory tests | To assess the incidents of abnormal hematology, biochemistry, coagulation and urinalysis assessments following 84 days of IP administration | Day 1 to Day 84/EOT | 
| Clinically significant (CS), outside normal range laboratory tests | To assess the incidents of CS abnormal hematology, biochemistry, coagulation and urinalysis assessments following 84 days of IP administration | Day 1 to Day 84/EOT | 
| Changes from baseline in vital signs | To assess the incidents of abnormal heart rate and blood pressure assessments following 84 days of IP administration | Day 1 to Day 84/EOT | 
| Clinically significant (CS) vital signs | To assess the incidents of CS heart rate and blood pressure following 84 days of IP administration | Day 1 to Day 84/EOT | 
| Changes from baseline in electrocardiogram (ECG) | To assess the incidents of abnormal heart rate, cardiac rhythm, PR interval, RR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration | Day 1 to Day 84/EOT | 
| Clinically significant (CS) electrocardiogram (ECG) findings | To assess the incidents of CS and QTc interval assessments following 84 days of IP administration | Day 1 to Day 84/EOT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the total score of the Quality of Life - Bronchiectasis (QOL-B) questionnaire |  | Day 1 to Day 84/EOT | 
| Change from baseline in global score and individual domain scores of the St. George Respiratory Questionnaire (SGRQ) |  | Day 1 to Day 84/EOT | 
| Change from baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) |  | Day 1 to Day 84/EOT | 
| Change from baseline in Patient Clinical Impression of Severity (PGI-S) |  | Day 1 to Day 84/EOT | 
| Change from baseline in Patient Clinical Impression of Change (PGI-C) |  | Day 1 to Day 84/EOT | 
| Change from baseline in Clinical Global Impression - Severity of Illness (CGI-S) |  | Day 1 to Day 84/EOT | 
| Change from baseline in Clinical Global Impression - Improvement (CGI-I) |  | Day 1 to Day 84/EOT | 
| Patients reporting no new symptoms with a severity worse than mild on the NTM Symptom Assessment Questionnaire |  | Day 1 to Day 84/EOT | 
| Decrease in quantitative sputum culture at Day 84 |  | Day 1 to Day 84/EOT | 
| Time to growth in liquid medium only |  | Day 1 to Day 84/EOT | 
| Time to first negative sputum culture |  | Day 1 to Day 84/EOT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nontuberculous Mycobacteria (NTM), Mycobacterium abscessus complex (MABc), NTM pulmonary disease, NTM lung disease