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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 17
- 主要终点
- Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84
研究概览
简要总结
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)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Omadacycline 300 mg PO
omadacycline 150 mg tablets (x 2) administered orally, once daily, q24h
干预措施: Omadacycline Oral Tablet (Drug)
Placebo PO
Placebo tablets resembling omadacycline (x 2) administered once daily, q24h
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Clinical Response on NTM Symptom Assessment Scale at Day 84
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
时间窗: 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)
时间窗: 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
时间窗: Day 1 (Baseline) to Day 84/EOT
To assess the incidents of abnormal heart rate following 84 days of IP administration
次要结局
- Change From Baseline in the Total Score of the QOL-B Questionnaire - Vitality Domain(Day 1 (Baseline) to Day 84/EOT)
- Change From Baseline in Global Score and Individual Domain Scores of the SGRQ - Total Score(Day 1 (Baseline) to Day 84/EOT)
- Number of Participants With Improvement in Patient Clinical Impression of Change (PGI-C)(Day 1 to Day 84/EOT)
- Number of Participants Reporting "Not Present or Mild Severity" in Patient Clinical Impression of Severity (PGI-S)(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(Day 1 through Day 84 (at any study timepoint))
- Change From Baseline in the Total Score of the QOL-B Questionnaire - Respiratory Symptoms Domain(Day 1 (Baseline) to Day 84/EOT)
- Change From Baseline in the Total Score of the QOL-B Questionnaire - Role Functioning Domain(Day 1 (Baseline) to Day 84/EOT)
- 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)
- Change From Baseline in the Total Score of the QOL-B Questionnaire - Health Perceptions Domain(Day 1 (Baseline) to Day 84/EOT)
- Change From Baseline in the Total Score of the QOL-B Questionnaire - Physical Functioning Domain(Day 1 (Baseline) to Day 84/EOT)
- Change From Baseline in the Total Score of the QOL-B Questionnaire - Social Functioning Domain(Day 1 (Baseline) to Day 84/EOT)
- Change From Baseline in the Total Score of the QOL-B Questionnaire - Treatment Burden Domain(Day 1 (Baseline) to Day 84/EOT)
- Number of Participants With Clinical Global Impression - Severity of Illness (CGI-S)(Day 84/EOT)
- Time to Growth in Liquid Medium Only(Day 1 through Day 84 (at any study timepoint))
- Time to First Negative Sputum Culture(Day 1 through Day 84 (at any study timepoint))
- 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)
- Number of Participants With Clinical Global Impression - Improvement (CGI-I)(Day 1 to Day 84/EOT)
- Number of Participants With Decreased Semi-Quantitative Score of Mycobacterial Sputum Culture From Day 1 to Day 84(Day 1 to Day 84)