Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients
Information source: Talecris Biotherapeutics
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Alpha 1-Antitrypsin Deficiency
Intervention: Alpha1-Proteinase Inhibitor (Human) (Drug); Albumin (Human) 20%, USP (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Talecris Biotherapeutics Official(s) and/or principal investigator(s):
Asger Dirksen, MD PHD, Principal Investigator, Affiliation: University of Copenhagen
Summary
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.
Clinical Details
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.
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: The progression rate of emphysema determined by change in lung density measured by annual CT scan of whole lung
Secondary outcome: The frequency of exacerbations as determined by patient diary.The deterioration of the lung function will be assessed by measurement of the change in FEV1 and KCO Duration and severity of the exacerbations Mortality Quality of life with a disease specific instrument, the St George's Respiratory Questionnaire
Detailed description:
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®?
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patient with pulmonary emphysema due to severe congenital AAT deficiency of phenotype
PiZ or other rare genotypes (not MS, MZ or SZ) and AAT serum level < 11 µM or < 80
mg/dL (status to be confirmed by phenotyping and genotyping)
- Inspiratory capacity (VC - ERV) > 1. 2 L and FEV1 < 80% of predicted value post
bronchodilator
- FEV1/VC < 70% of predicted value post-bronchodilator or KCO < 80% of predicted value
post-bronchodilator
- History of at least one exacerbation in the past 2 years
- Written informed consent
Exclusion Criteria:
- 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
Locations and Contacts
Gentofte Hospital Department of Respiratory Medicine, Hellerup 2900, Denmark
Department of Pulmonary Medicine, Malmö University Hospital, Malmö, Sweden
Queen Elizabeth Hospital, Birmingham, England B15 2TH, United Kingdom
Additional Information
FDA Approved Product Labeling Information - Prolastin® FDA Enforcement, Report Index (Class I, Class II Recall, Market Alerts and Medical Product Safety Alerts) FDA Approved Product Labeling Information - Plasbumin®-20 (Low Aluminum) Synopsis of Study Results
Starting date: December 2003
Ending date: January 2007
Last updated: April 1, 2008
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