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

Phase 2

Completed

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

Interventions: Drug: Placebo
Drug: Omadacycline Oral Tablet

Registration Number: NCT04922554

Lead Sponsor: Paratek Pharmaceuticals Inc

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo PO	Placebo	Placebo tablets resembling omadacycline (x 2) administered once daily, q24h
Omadacycline 300 mg PO	Omadacycline Oral Tablet	omadacycline 150 mg tablets (x 2) administered orally, once daily, q24h

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84	Day 1 to 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.
Change From Baseline in Systolic and Diastolic Blood Pressure	Day 1 (Baseline) to Day 84/EOT	To assess the incidents of abnormal blood pressure assessments following 84 days of IP administration
Number of Participants With PCS Threshold Vital Signs Measurement	Day 1 through Day 84 (at any study timepoint)	To assess the incidents of PCS heart rate and blood pressure following 84 days of IP administration
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval	Day 1 (Baseline) to Day 84/EOT	To assess the incidents of cardiac rhythm, PR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers	Day 1 (Baseline) to Day 84/EOT	To assess the incidents of abnormal hepatic and enzymatic biomarkers following 84 days of IP administration
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter	Day 1 through Day 84 (at any study timepoint)	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.
Number of Participants With PCS QTcF Value	Day 1 through Day 84/EOT (at any study timepoint)	To assess the incidents of PCS and QTc interval assessments following 84 days of IP administration
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.	Day 1 to Day 84	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From screening period (up to 8 weeks prior to randomization) through Day 114 (at any study timepoint)	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.
Change From Baseline in Heart Rate	Day 1 (Baseline) to Day 84/EOT	To assess the incidents of abnormal heart rate following 84 days of IP administration

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain	Day 1 (Baseline) to Day 84/EOT	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.
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score	Day 1 (Baseline) to Day 84/EOT	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
Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C)	Day 1 to Day 84/EOT	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.
Number of Participants Reporting "Not Present or Mild Severity" in Patient Clinical Impression of Severity (PGI-S)	Day 84/EOT	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.
Number of Participants With New Symptoms With a Severity Worse Than Mild on the NTM Symptom Assessment Questionnaire at Any Time Post-baseline	Day 1 through Day 84 (at any study timepoint)	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.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain	Day 1 (Baseline) to Day 84/EOT	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.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain	Day 1 (Baseline) to Day 84/EOT	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.
Change From Baseline in the Total Score of the Quality of Life - Bronchiectasis (QOL-B) Questionnaire - Emotional Functioning Domain	Day 1 (Baseline) to Day 84/EOT	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.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain	Day 1 (Baseline) to Day 84/EOT	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.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain	Day 1 (Baseline) to Day 84/EOT	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.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain	Day 1 (Baseline) to Day 84/EOT	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.
Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain	Day 1 (Baseline) to Day 84/EOT	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.
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S)	Day 84/EOT	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.
Time to Growth in Liquid Medium Only	Day 1 through Day 84 (at any study timepoint)	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.
Time to First Negative Sputum Culture	Day 1 through Day 84 (at any study timepoint)	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).
Change From Baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) Score	Day 1 (Baseline) to Day 84/EOT	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.
Number of Participants With Clinical Global Impression - Improvement (CGI-I)	Day 1 to Day 84/EOT	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.
Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84	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.

Trial Locations

Locations (17): Stanford University
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Stanford, California, United States
Georgetown University Hospital
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Washington, District of Columbia, United States
St. Francis Medical Institute
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Clearwater, Florida, United States
University of Miami
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Miami, Florida, United States
University of South Florida
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Tampa, Florida, United States
Infectious Disease Consultants of the Treasure Coast
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Vero Beach, Florida, United States
Emory University School of Medicine
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Atlanta, Georgia, United States
Louisiana State University Medical Center Health Sciences Center-New Orleans Section of Pulmonary/Critical Care & Allergy/Immunology
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New Orleans, Louisiana, United States
Johns Hopkins University
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Baltimore, Maryland, United States
Dartmouth-Hitchcock Medical Center
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Lebanon, New Hampshire, United States
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Stanford University
🇺🇸Stanford, California, United States