A Phase 2, Proof-of-concept, Multicentre, Double-blind, Randomised, Dose-ascending, Sequential Group, Placebo-controlled Study to Evaluate the Mechanistic Effect, Safety, and Tolerability of 12 Weeks Twice Daily Oral Administration of Alvelestat (MPH966) in Participants With Alpha-1 Antitrypsin Deficiency.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 26
- 主要终点
- Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo
研究概览
简要总结
The purpose of this study is to investigate the effect of alvelestat (an oral neutrophil elastase inhibitor) on blood and sputum biomarkers in patients with PiZZ, null or rare variant phenotype/genotype alpha-1 anti-trypsin deficient lung disease. Change in a number of different blood and sputum biomarkers related to lung damage, inflammation and elastase activity will be measured over a 12 week period. The effect on lung function and respiratory symptoms will also be measured.
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)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a confirmed diagnosis of alpha-1-anti-trypsin deficiency and a PiZZ, null or other rare geno/phenotype and serum anti-alpha1 antitrypsin levels of less than 11uM
- •FEV1 ≥20% predicted
- •Computerised tomography (CT) scan evidence of emphysema
- •Non-smokers
排除标准
- •Primary diagnosis of bronchiectasis
- •An ongoing acute exacerbation of the underlying lung disease
- •Underlying liver disease or abnormal liver function tests
- •Previous augmentation therapy within 6 months of dosing
研究组 & 干预措施
Placebo oral tablet
干预措施: Placebo Oral Tablet (Drug)
Alvelestat oral tablet - dose 1
MPH966
干预措施: Alvelestat oral tablet - dose 1 (Drug)
Alvelestat oral tablet - dose 2
MPH966
干预措施: Alvelestat oral tablet - dose 2 (Drug)
结局指标
主要结局
Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo
时间窗: 12 weeks
Within-individual change from baseline up to end of treatment in: * Blood neutrophil elastase activity * Blood Aα-Val 360 levels * Plasma desmosine/isodesmosine levels
次要结局
- Change from baseline on other blood biomarkers of neutrophil elastase activity(12 weeks)