Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients (EXACTLE)
|Alpha 1-Antitrypsin Deficiency||Drug: Alpha1-Proteinase Inhibitor (Human) Drug: Albumin (Human) 20%, United States Pharmacopeia (USP)||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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.|
- The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung [ Time Frame: 24 or 30 months ]
- Change in Lung Density at Each Visit as Measured by Computed Tomography [ Time Frame: 24 or 30 months ]
- The Frequency of Exacerbations as Determined by Patient Diary. [ Time Frame: 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) [ Time Frame: 24 or 30 months ]
- Duration and Severity of the Exacerbations [ Time Frame: 24 or 30 months ]
- Mortality [ Time Frame: 24 or 30 months ]
- Quality of Life With a Disease Specific Instrument, the St. George's Respiratory Questionnaire [ Time Frame: 24 or 30 months ]
|Study Start Date:||December 2003|
|Study Completion Date:||January 2007|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
Experimental: Group 1
Drug: Alpha1-Proteinase Inhibitor (Human)
Weekly infusion of 60 mg/kg body weight for 2 years
|Placebo Comparator: Group 2||
Drug: Albumin (Human) 20%, United States Pharmacopeia (USP)
Weekly infusion for 2 years. Albumin (Human) 20% will be diluted with 5% glucose to a final concentration of 2.0%.
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®?
Please refer to this study by its ClinicalTrials.gov identifier: NCT00263887
|Gentofte Hospital Department of Respiratory Medicine|
|Hellerup, Denmark, 2900|
|Department of Pulmonary Medicine, Malmö University Hospital|
|Queen Elizabeth Hospital|
|Birmingham, England, United Kingdom, B15 2TH|
|Principal Investigator:||Asger Dirksen, MD PHD||University of Copenhagen|