NCT04643587已完成1 期
A Phase 1, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Exploratory Efficacy of Nebulized CSL787 in Healthy Subjects and Subjects With Non-Cystic Fibrosis Bronchiectasis (NCFB)
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 64
- 试验地点
- 3
- 主要终点
- Number of subjects with treatment emergent adverse events (TEAEs) - overall, severity and causality
研究概览
简要总结
This study is a prospective, multicenter, randomized, double-blind, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and exploratory efficacy of nebulized CSL787 after administrations of single (SAD) ascending doses in healthy subjects and multiple (MAD) ascending doses in subjects with NCFB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- 是
入选标准
- •Male or female, aged ≥ 18 years at the time of providing written informed consent
- •For Part A (SAD) Only:
- •Healthy and free of medical conditions that could in the opinion of the investigator affect's the subject's participation in the study or the interpretation of results.
- •For Part B (MAD) Only:
- •Diagnosis of NCFB made by a respiratory physician, confirmed per CT showing bronchial wall dilatation with or without bronchial wall thickening, with a FEV1 ≥ 40% of the predicted value regarding age, height, gender, ethnicity, and FEV1 ≥ 1 L (pre-bronchodilator values) at the Screening Visit.
- •No antibiotic use within 1 month before the Screening Visit.
- •Presence of one or more of the following bacteria (H. influenzae, P. aeruginosa, M. catarrhalis, S. pneumoniae, members of Enterobacterales family or S. aureus) in the sputum culture at the Screening Visit.
- •Has been fully vaccinated against COVID-19 (as per country recommendations) at least 7 days prior to Day 1
排除标准
- •Evidence of a clinically significant medical condition, disorder, or disease, including but not limited to any of the following: hepatic (hepatitis, cirrhosis); biliary; renal; cardiac; bronchopulmonary; vascular; hematologic; gastrointestinal; allergy; endocrine / metabolic (diabetes, thyroid disorders, adrenal disease); neurologic; psychiatric; immunodeficiency; cancer.
- •History of chronic respiratory disease (eg, COPD or bronchiectasis) or current asthma with regular treatment including occasional use of an inhaler for exercise induced asthma.
- •Current moderate-severe allergic disease (eg, allergic rhinitis) with regular treatment.
- •Diagnosis of cystic fibrosis, mycobacterial disease, connective tissue disease, or alpha-1 antitrypsin deficiency as underlying disease for bronchiectasis.
- •Oral/parenteral corticosteroid 28 days before the Screening Visit until EOS Visit. Use of long acting bronchodilators (long acting muscarinic antagonists (LAMA) and / or long acting beta2 agonists (LABA) and/or inhaled corticosteroids that have been at a stable dose for at least 3 months before the Screening Visit is permitted; inhalation with hypertonic saline solution is permitted up to and including Day -
- •Any systemic or inhaled antibiotic for acute pulmonary exacerbation within 1 month before the Screening Visit until EOS Visit.
研究组 & 干预措施
CSL787 (MAD dose 3)
Experimental
Inhalation by mouth of a nebulized aerosol in NCFB subjects
干预措施: CSL787 (Biological)
Placebo
Placebo Comparator
Inhalation by mouth of a nebulized aerosol
干预措施: Placebo (Drug)
CSL787 (SAD dose 1)
Experimental
Inhalation by mouth of a nebulized aerosol in healthy subjects
干预措施: CSL787 (Biological)
CSL787 (SAD dose 2)
Experimental
Inhalation by mouth of a nebulized aerosol in healthy subjects
干预措施: CSL787 (Biological)
CSL787 (SAD dose 3)
Experimental
Inhalation by mouth of a nebulized aerosol in healthy subjects
干预措施: CSL787 (Biological)
CSL787 (SAD dose 4)
Experimental
Inhalation by mouth of a nebulized aerosol in healthy subjects
干预措施: CSL787 (Biological)
CSL787 (MAD dose 1)
Experimental
Inhalation by mouth of a nebulized aerosol in NCFB subjects
干预措施: CSL787 (Biological)
CSL787 (MAD dose 2)
Experimental
Inhalation by mouth of a nebulized aerosol in NCFB subjects
干预措施: CSL787 (Biological)
结局指标
主要结局
Number of subjects with treatment emergent adverse events (TEAEs) - overall, severity and causality
时间窗: Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients)
Percent of subjects with TEAEs - overall, severity and causality
时间窗: Up to 8 days (healthy volunteers); Up to 21 days (NCFB patients)
次要结局
- Time of maximum concentration (Tmax) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- Apparent volume of distribution during the elimination phase (V/F) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- Terminal elimination half-life (T1/2) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- Cmax of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- Ctrough of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- AUCtau of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- Accumulation Ratio (AR) for Cmax of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- AR for Ctrough of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- Apparent total clearance of the drug (CL/F) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- Tmax of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- V/F of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- AR for AUCtau of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- Maximum concentration (Cmax) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- Area under the concentration-time curve from time 0 to 24 hours (AUC0-24h) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- Area under the concentration-time curve from time 0 to last quantifiable time point (AUC0-last) of CSL787 in sputum and serum in healthy subjects(Up to 8 days from inhalation)
- T1/2 of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
- CL/F of CSL787 in sputum and serum of NCFB subjects(On Day 14, after last dose)
研究者
研究点 (3)
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