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)
Brief Title
Oral Omadacycline vs. Placebo in Adults With 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Mycobacterium Infections, Nontuberculous
Mycobacterium Abscessus Infection
Nontuberculous Mycobacterial Lung Disease
Nontuberculous Mycobacterial Pulmonary Infection
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
Nontuberculous Mycobacteria (NTM)
Mycobacterium abscessus complex (MABc)
NTM pulmonary disease
NTM lung disease
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04922554
Org Class
Industry
Org Full Name
Paratek Pharmaceuticals Inc
Org Study Id
PTK0796-NTM-20203
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84
Outcome Time Frame
Day 1 to Day 84
Outcome Description
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.
Outcome Measure
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.
Outcome Time Frame
Day 1 to Day 84
Outcome Description
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.
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Outcome Time Frame
From screening period (up to 8 weeks prior to randomization) through Day 114 (at any study timepoint)
Outcome Description
To assess the incidents of abnormal hepatic and enzymatic biomarkers following 84 days of IP administration
Outcome Measure
Change From Baseline in Laboratory Test Parameters - Hepatic and Enzymatic Biomarkers
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Description
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.
Outcome Measure
Number of Participants With Potentially Clinically Significant (PCS) Laboratory Parameter
Outcome Time Frame
Day 1 through Day 84 (at any study timepoint)
Outcome Description
To assess the incidents of abnormal blood pressure assessments following 84 days of IP administration
Outcome Measure
Change From Baseline in Systolic and Diastolic Blood Pressure
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Description
To assess the incidents of abnormal heart rate following 84 days of IP administration
Outcome Measure
Change From Baseline in Heart Rate
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Description
To assess the incidents of PCS heart rate and blood pressure following 84 days of IP administration
Outcome Measure
Number of Participants With PCS Threshold Vital Signs Measurement
Outcome Time Frame
Day 1 through Day 84 (at any study timepoint)
Outcome Description
To assess the incidents of cardiac rhythm, PR interval, QRS interval, QT interval and QTc interval assessments following 84 days of IP administration
Outcome Measure
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, and QTcF Interval
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Description
To assess the incidents of PCS and QTc interval assessments following 84 days of IP administration
Outcome Measure
Number of Participants With PCS QTcF Value
Outcome Time Frame
Day 1 through Day 84/EOT (at any study timepoint)
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the Quality of Life - Bronchiectasis (QOL-B) Questionnaire - Emotional Functioning Domain
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain
Outcome Description
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
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score
Outcome Description
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.
Outcome Time Frame
Day 1 (Baseline) to Day 84/EOT
Outcome Measure
Change From Baseline in Patient-Reported Outcomes Measurement Information System Short Form v1.0 - Fatigue 7a Daily (PROMIS-7a) Score
Outcome Description
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.
Outcome Time Frame
Day 1 to Day 84/EOT
Outcome Measure
Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C)
Outcome Description
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.
Outcome Time Frame
Day 84/EOT
Outcome Measure
Number of Participants Reporting "Not Present or Mild Severity" in Patient Clinical Impression of Severity (PGI-S)
Outcome Description
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.
Outcome Time Frame
Day 84/EOT
Outcome Measure
Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S)
Outcome Description
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.
Outcome Time Frame
Day 1 to Day 84/EOT
Outcome Measure
Number of Participants With Clinical Global Impression - Improvement (CGI-I)
Outcome Description
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.
Outcome Time Frame
Day 1 through Day 84 (at any study timepoint)
Outcome Measure
Number of Participants With New Symptoms With a Severity Worse Than Mild on the NTM Symptom Assessment Questionnaire at Any Time Post-baseline
Outcome Description
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.
Outcome Time Frame
Day 1 to Day 84
Outcome Measure
Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84
Outcome Description
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.
Outcome Time Frame
Day 1 through Day 84 (at any study timepoint)
Outcome Measure
Time to Growth in Liquid Medium Only
Outcome Description
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).
Outcome Time Frame
Day 1 through Day 84 (at any study timepoint)
Outcome Measure
Time to First Negative Sputum Culture
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Eric Meyerowitz
Investigator Email
emeyerowit@montefiore.org
Investigator Phone
631-338-4592
Categories Mesh Debug
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
MeSH Terms
MYCOBACTERIUM INFECTIONS, NONTUBERCULOUS
MYCOBACTERIUM INFECTIONS
ACTINOMYCETALES INFECTIONS
GRAM-POSITIVE BACTERIAL INFECTIONS
BACTERIAL INFECTIONS
BACTERIAL INFECTIONS AND MYCOSES
INFECTIONS
OMADACYCLINE
COUNTERFEIT DRUGS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS