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: Completed
• 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 (Actual): 66
• Phase: Phase 2

Contacts and Locations

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
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84	A clinical responder is defined as a participant who shows improvement in at least 50% of baseline symptoms on the NTM Symptom Assessment Questionnaire at the Day 84 Visit. This self-administered tool assesses 12 common NTM symptoms, each rated on a 4-point scale (absent, mild, moderate, severe), reflecting the participant's overall impression over the past week. The questionnaire is completed solely by the participant, without any interpretation from clinicians or site staff.	Day 1 to Day 84
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84 With no Deterioration in Severity of Symptoms That Were Present at Baseline.	A clinical responder is defined as a participant who shows improvement in at least 50% of baseline symptoms with no deterioration of symptoms present at baseline on the NTM Symptom Assessment Questionnaire at the Day 84 Visit. This self-administered tool assesses 12 common NTM symptoms, each rated on a 4-point scale (absent, mild, moderate, severe), reflecting the participant's overall impression over the past week. The questionnaire is completed solely by the participant, without any interpretation from clinicians or site staff.	Day 1 to Day 84
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	A TEAE is an adverse event that occurred on or after first dose of test article and those existing AEs that worsened on or after first dose of test article. An SAE is an adverse event that results in death, is life-threatening, requires hospitalization or extends an existing one, causes significant or lasting disability/incapacity, or leads to a congenital anomaly or birth defect. Additionally, events that may not meet these criteria but are medically significant can also be classified as SAEs.	From screening period (up to 8 weeks prior to randomization) through Day 114 (at any study timepoint)
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers	To assess the incidents of abnormal hepatic and enzymatic biomarkers following 84 days of IP administration	Day 1 (Baseline) to Day 84/EOT
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter	Laboratory PCS event is defined as at least a 2 grade increase from baseline based on the Division of Microbiology and Infectious Diseases (DMID) v5.0.	Day 1 through Day 84 (at any study timepoint)
Change From Baseline in Systolic and Diastolic Blood Pressure	To assess the incidents of abnormal blood pressure assessments following 84 days of IP administration	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in Heart Rate	To assess the incidents of abnormal heart rate following 84 days of IP administration	Day 1 (Baseline) to Day 84/EOT
Number of Participants With PCS Threshold Vital Signs Measurement	To assess the incidents of PCS heart rate and blood pressure following 84 days of IP administration	Day 1 through Day 84 (at any study timepoint)
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval	To assess the incidents of cardiac rhythm, PR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration	Day 1 (Baseline) to Day 84/EOT
Number of Participants With PCS QTcF Value	To assess the incidents of PCS and QTc interval assessments following 84 days of IP administration	Day 1 through Day 84/EOT (at any study timepoint)

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 - Emotional Functioning Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain	The QOL-B is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for participants with non-cystic fibrosis bronchiectasis using a series of 37 questions. The QOL-B includes domains for physical functioning, role functioning, vitality, emotional functioning, social functioning, treatment burden, health perceptions and respiratory symptoms. For each domain, scores will be standardized on a 0 to 100 scale and higher scores represent better outcomes.	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score	The SGRQ is a disease-specific, 50-item instrument designed to measure the impact of obstructive airways disease on overall health, daily life, and perceived well-being in participants. It consists of three domains: Symptoms (distress from respiratory symptoms), Activity (limitations in mobility and physical activity), and Impacts (effects on employment, self-management, and medication needs). Scores range from 0 (no impairment) to 100 (maximum impairment) for each domain. The SGRQ Total Score is calculated by dividing the total score values of all positive responses across all domains in the questionnaire by the maximum possible total score that a participant could have achieved, and then multiplying the result by 100. Higher scores indicate worse health status	Day 1 (Baseline) to Day 84/EOT
Change From Baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) Score	The PROMIS Fatigue is a self-administered questionnaire that assesses fatigue and its impact on physical, mental, and social activities. The fatigue short form is universal rather than disease-specific and assesses fatigue over the past 7 days. Participants respond to each of the 7 items using a 5-point Likert scale (e.g., "Not at all" to "Very much") and item responses are summed to produce a raw total score. Raw scores are converted to T-scores using standardized PROMIS scoring tables. The average change in PROMIS Fatigue T-scores was calculated for each study arm. The PROMIS Fatigue T-score is a standardized score (mean = 50, SD = 10) where higher scores indicate greater fatigue severity. A negative change from baseline (i.e., lower T-scores over time) indicates improvement in fatigue symptoms, whereas a positive change (i.e., higher T-scores) indicates worsening of fatigue.	Day 1 (Baseline) to Day 84/EOT
Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C)	The PGI-C is a self-administered, single question assessed using a 7-point scale that measures a participant's perceived change in clinical status and overall improvement. Participants with improvement includes: Very much improved, much improved, minimally improved; participants without improvement include: no change, minimally worse, much worse, very much worse.	Day 1 to Day 84/EOT
Number of Participants Reporting "Not Present or Mild Severity" in Patient Clinical Impression of Severity (PGI-S)	The PGI-S is a self-administered, single question assessed using a 7-point scale that measures a participant's perception of disease severity. Participants with severity Not present or Mild include: not present, very mild, mild; Participants with severity Moderate or Severe include: moderate, moderately severe, severe, extremely severe.	Day 84/EOT
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S)	The CGI-S is administered by an experienced clinician who is familiar with the disease under study. The CGI-S is a 1-item observer-rated scale that rates illness severity based upon observed and reported symptoms, behavior, and function over the past seven days.	Day 84/EOT
Number of Participants With Clinical Global Impression - Improvement (CGI-I)	The CGI-I is a single-item, observer-rated measure using a 7-point scale to assess overall improvement in a participant's condition due to drug treatment. Participants with improvement includes: very much improved, much improved, minimally improved; participants without improvement include: no change, minimally worse, much worse, very much worse.	Day 1 to Day 84/EOT
Number of Participants With New Symptoms With a Severity Worse Than Mild on the NTM Symptom Assessment Questionnaire at Any Time Post-baseline	The NTM symptom assessment questionnaire is a self-administered tool which assesses 12 common NTM symptoms on a 4-point scale (absent, mild, moderate, severe), reflecting the participant's overall impression over the past week. The questionnaire is completed solely by the participant, without any interpretation from clinicians or site staff.	Day 1 through Day 84 (at any study timepoint)
Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84	Semi-quantitative score is derived based on growth in liquid medium, growth on agar plate, and colony count on agar plate; the score ranges from 0 to 6. A reduction in the semi-quantitative score reflects a decrease in the quantitative mycobacterial load.	Day 1 to Day 84
Time to Growth in Liquid Medium Only	Time to growth in liquid medium only is defined as the number of days from the date of study drug administration to the date of the first assessment where growth is detected in liquid medium only. The analysis was based on Kaplan Meier Estimation for Growth in Liquid Medium Only (Day). If there is no culture result indicating growth in liquid medium only and the culture plates are negative, the date of the first negative culture is used for determination of time to growth in liquid medium only.	Day 1 through Day 84 (at any study timepoint)
Time to First Negative Sputum Culture	Time to first negative sputum culture is defined as the number of days from the date of study drug administration to the date of the first negative sputum culture. The analysis was based on Kaplan Meier Estimation for Negative Sputum Culture (Day).	Day 1 through Day 84 (at any study timepoint)

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 (Actual): June 17, 2024
• Study Completion (Actual): July 17, 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): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

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; Disease Attributes; Respiratory Tract Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; 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
• product manufactured in and exported from the U.S.: No