Clinical trial NCT04922554: Oral Omadacycline Vs. Placebo in Adults with NTM Pulmonary Disease Caused by Mycobacterium Abscessus Complex (MABc)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mycobacterium Infections, Nontuberculous
Mycobacterium Abscessus Infection
Nontuberculous Mycobacterial Lung Disease
Nontuberculous Mycobacterial Pulmonary Infection
Keywords: Nontuberculous Mycobacteria (NTM)
Mycobacterium abscessus complex (MABc)
NTM pulmonary disease
NTM lung disease
Lead sponsor: Paratek Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2021-06-10
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Response on NTM Symptom Assessment Scale at Day 84
timeFrame: Day 1 to Day 84/EOT
measure: Reported adverse events (AEs)
timeFrame: Day 1 to Day 84/EOT
measure: Changes from baseline in laboratory tests
timeFrame: Day 1 to Day 84/EOT
measure: Clinically significant (CS), outside normal range laboratory tests
timeFrame: Day 1 to Day 84/EOT
measure: Changes from baseline in vital signs
timeFrame: Day 1 to Day 84/EOT
measure: Clinically significant (CS) vital signs
timeFrame: Day 1 to Day 84/EOT
measure: Changes from baseline in electrocardiogram (ECG)
timeFrame: Day 1 to Day 84/EOT
measure: Clinically significant (CS) electrocardiogram (ECG) findings
timeFrame: Day 1 to Day 84/EOT
Secondary outcomes:
measure: Change from baseline in the total score of the Quality of Life - Bronchiectasis (QOL-B) questionnaire
timeFrame: Day 1 to Day 84/EOT
measure: Change from baseline in global score and individual domain scores of the St. George Respiratory Questionnaire (SGRQ)
timeFrame: Day 1 to Day 84/EOT
measure: Change from baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a)
timeFrame: Day 1 to Day 84/EOT
measure: Change from baseline in Patient Clinical Impression of Severity (PGI-S)
timeFrame: Day 1 to Day 84/EOT
measure: Change from baseline in Patient Clinical Impression of Change (PGI-C)
timeFrame: Day 1 to Day 84/EOT
measure: Change from baseline in Clinical Global Impression - Severity of Illness (CGI-S)
timeFrame: Day 1 to Day 84/EOT
measure: Change from baseline in Clinical Global Impression - Improvement (CGI-I)
timeFrame: Day 1 to Day 84/EOT
measure: Patients reporting no new symptoms with a severity worse than mild on the NTM Symptom Assessment Questionnaire
timeFrame: Day 1 to Day 84/EOT
measure: Decrease in quantitative sputum culture at Day 84
timeFrame: Day 1 to Day 84/EOT
measure: Time to growth in liquid medium only
timeFrame: Day 1 to Day 84/EOT
measure: Time to first negative sputum culture
timeFrame: Day 1 to Day 84/EOT
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Clearwater
country: United States
facility: St. Francis Medical Institute
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Vero Beach
country: United States
facility: Infectious Disease Consultants of the Treasure Coast
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: New Orleans
country: United States
facility: Louisiana State University Medical Center Health Sciences Center-New Orleans Section of Pulmonary/Critical Care & Allergy/Immunology
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Einstein/Montefiore Medical Center
state: New York
city: New Hyde
country: United States
facility: Northwell Health
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics
state: Wisconsin
Study officials:
affiliation: Paratek Pharmaceuticals Inc
name: Amy Manley
role: STUDY_CHAIR
References: