Multi-center, Randomized Trial With I.V. Prolastin® to Evaluate Frequency of Exacerbations and Progression of Emphysema by Means of Multi-slice CT Scans in Patients With Congenital Alpha-1-antitrypsin Deficiency.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 3
- 主要终点
- The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung
研究概览
简要总结
The goal of this trial was to explore the utility of evaluating emphysema progression through CT scans measuring lung density during a 2 year period of weekly infusions of either placebo or human alpha-1-antitrypsin (AAT; Prolastin®). Exacerbation data recorded in patient diaries were also collected. All efficacy data were analyzed for potential use in evaluating Prolastin efficacy in this and other clinical trials.
详细描述
This is a one to one randomized, placebo-controlled, clinical, exploratory study with the aim of collecting information on possible clinical endpoints i.e., the progression of emphysema by lung density measurements with CT scan and frequency of exacerbations that could be used for a subsequent placebo controlled clinical trial. Progression of disease will be investigated in 80 patients with alpha-1-antitrypsin deficiency, who will be treated with human alpha-1-antitrypsin (AAT; Prolastin®) or placebo weekly for two years to analyze the effect of treatment on lung density and exacerbations. Targeted augmentation therapy with weekly infusions of Prolastin® will be a dose of 60 mg/kg body weight (range of 51.72 to 71.43 mg per kg body weight).
Therefore, this study focuses on several questions:
- Is the 15th percentile point calculated by analysis of CT lung histograms a useful endpoint for clinical trials in AAT deficiency?
- Is quantitation of exacerbations in AAT-deficient patients a useful endpoint for clinical trials in AAT deficiency?
- Are there significant differences between the treatments in favor of Prolastin®?
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
- •Patient with pulmonary emphysema due to severe congenital AAT deficiency of phenotype protease inhibitor Z (PiZ) or other rare genotypes (not MS, MZ or SZ) and AAT serum level < 11 microns (µM) or < 80 mg/dL (status to be confirmed by phenotyping and genotyping)
- •Inspiratory capacity (VC - ERV) > 1.2 L and forced expiratory volume at one second (FEV1) < 80% of predicted value post bronchodilator
- •FEV1/VC < 70% of predicted value post-bronchodilator or transfer factor of carbon monoxide (KCO) < 80% of predicted value post-bronchodilator
- •History of at least one exacerbation in the past 2 years
- •Written informed consent
排除标准
- •FEV1 < 25% of predicted value post-bronchodilator
- •Augmentation therapy for more than one month with plasma-derived human alpha 1-antitrypsin (AAT) within the last 2 years
- •History of lung transplant
- •Any lung surgery within the past 2 years
- •On any thoracic surgery waiting list
- •Diagnosis of liver cirrhosis
- •Severe concomitant disease
- •Active pulmonary infection/exacerbations within the last month
- •Active smoking during the last 6 months or plasma positive for cotinine
- •Body weight < 42 kg or > 92 kg
- •Pregnancy or lactation
- •Women of child-bearing potential without adequate contraception
研究组 & 干预措施
Group 1
Prolastin
干预措施: Alpha1-Proteinase Inhibitor (Human) (Drug)
Group 2
干预措施: Albumin (Human) 20%, United States Pharmacopeia (USP) (Drug)
结局指标
主要结局
The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung
时间窗: 24 or 30 months
次要结局
- Change in Lung Density at Each Visit as Measured by Computed Tomography(24 or 30 months)
- Mortality(24 or 30 months)
- The Frequency of Exacerbations as Determined by Patient Diary.(24 or 30 months)
- Quality of Life With a Disease Specific Instrument, the St. George's Respiratory Questionnaire(24 or 30 months)
- Duration and Severity of the Exacerbations(24 or 30 months)
- The Deterioration of the Lung Function Will be Assessed by Measurement of the Change in Forced Expiratory Volume at One Second (FEV1) and Transfer Factor of Carbon Monoxide (KCO)(24 or 30 months)