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

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacterial Lung Disease; Mycobacterium Abscessus Infection; Nontuberculous Mycobacterial Pulmonary Infection
• Intervention / Treatment: Drug: Omadacycline Oral Tablet; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alissa Sirbu; Phone Number: 617.459.5307; Email: alissa.sirbu@paratekpharma.com
• Study Contact Backup: Name: Amy Manley; Phone Number: 484.682.4976; Email: amy.manley@paratekpharma.com

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University Hospital
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • University of South Florida
    • Vero Beach, Florida, United States, 32960
      • Infectious Disease Consultants of the Treasure Coast
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory University School of Medicine
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Medical Center Health Sciences Center-New Orleans Section of Pulmonary/Critical Care & Allergy/Immunology
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Einstein/Montefiore Medical Center
    • New Hyde Park, New York, United States, 11042
      • Northwell Health
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
  • Texas
    • Tyler, Texas, United States, 75708
      • The University of Texas Health Science Center at Tyler
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Paratek Pharmaceuticals Inc
• Investigators: Study Chair: Amy Manley, Paratek Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: June 5, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: NTM lung disease; Nontuberculous Mycobacteria (NTM); Mycobacterium abscessus complex (MABc); NTM pulmonary disease
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Lung Diseases; Infections; Communicable Diseases; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous
• Other Study ID Numbers: PTK0796-NTM-20203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No