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

Mycobacterium Infections, Nontuberculous Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04922554
• Other study ID #: PTK0796-NTM-20203
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 15, 2021
• Est. completion date: July 2024

Study information

• Verified date: February 2024
• Source: Paratek Pharmaceuticals Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Lung Diseases
• Mycobacterium Abscessus Infection
• Mycobacterium Infections
• Mycobacterium Infections, Nontuberculous
• Nontuberculous Mycobacterial Lung Disease
• Nontuberculous Mycobacterial Pulmonary Infection

Intervention

Drug:
• Omadacycline Oral Tablet
omadacycline 300 mg orally, once daily (150 mg tablets x 2)
• Placebo
placebo tablets resembling omadacycline orally, once daily (x 2 tablets)

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Einstein/Montefiore Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	St. Francis Medical Institute	Clearwater	Florida
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Wisconsin Hospitals and Clinics	Madison	Wisconsin
United States	University of Miami	Miami	Florida
United States	Northwell Health	New Hyde Park	New York
United States	Louisiana State University Medical Center Health Sciences Center-New Orleans Section of Pulmonary/Critical Care & Allergy/Immunology	New Orleans	Louisiana
United States	Oregon Health & Science University	Portland	Oregon
United States	Stanford University	Stanford	California
United States	University of South Florida	Tampa	Florida
United States	The University of Texas Health Science Center at Tyler	Tyler	Texas
United States	Infectious Disease Consultants of the Treasure Coast	Vero Beach	Florida
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Paratek Pharmaceuticals Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Reported adverse events (AEs)	To assess reported adverse events	Day 1 to Day 84/EOT
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Change from baseline in the total score of the Quality of Life - Bronchiectasis (QOL-B) questionnaire		Day 1 to Day 84/EOT
Secondary	Change from baseline in global score and individual domain scores of the St. George Respiratory Questionnaire (SGRQ)		Day 1 to Day 84/EOT
Secondary	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
Secondary	Change from baseline in Patient Clinical Impression of Severity (PGI-S)		Day 1 to Day 84/EOT
Secondary	Change from baseline in Patient Clinical Impression of Change (PGI-C)		Day 1 to Day 84/EOT
Secondary	Change from baseline in Clinical Global Impression - Severity of Illness (CGI-S)		Day 1 to Day 84/EOT
Secondary	Change from baseline in Clinical Global Impression - Improvement (CGI-I)		Day 1 to Day 84/EOT
Secondary	Patients reporting no new symptoms with a severity worse than mild on the NTM Symptom Assessment Questionnaire		Day 1 to Day 84/EOT
Secondary	Decrease in quantitative sputum culture at Day 84		Day 1 to Day 84/EOT
Secondary	Time to growth in liquid medium only		Day 1 to Day 84/EOT
Secondary	Time to first negative sputum culture		Day 1 to Day 84/EOT