Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients - Full Text View

Sponsored by:	Talecris Biotherapeutics
Information provided by:	Talecris Biotherapeutics
ClinicalTrials.gov Identifier:	NCT00263887

Purpose

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.

Condition	Intervention	Phase
Alpha 1-Antitrypsin Deficiency	Drug: Alpha1-Proteinase Inhibitor (Human) Drug: Albumin (Human) 20%, USP	Phase II

Genetics Home Reference related topics: alpha-1 antitrypsin deficiency

MedlinePlus related topics: Alpha-1 Antitrypsin Deficiency CT Scans Emphysema Nuclear Scans

Drug Information available for: Dextrose Aluminum

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
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.

Further study details as provided by Talecris Biotherapeutics:

Primary Outcome Measures:

The progression rate of emphysema determined by change in lung density measured by annual CT scan of whole lung [ Time Frame: 24 or 30 month ]

Secondary Outcome Measures:

The frequency of exacerbations as determined by patient diary. [ Time Frame: 24 or 30 month ]
The deterioration of the lung function will be assessed by measurement of the change in FEV1 and KCO [ Time Frame: 24 or 30 month ]
Duration and severity of the exacerbations [ Time Frame: 24 or 30 month ]
Mortality [ Time Frame: 24 or 30 month ]
Quality of life with a disease specific instrument, the St George's Respiratory Questionnaire [ Time Frame: 24 or 30 month ]

Enrollment:	77
Study Start Date:	December 2003
Study Completion Date:	January 2007

Arms	Assigned Interventions
Group 1: Experimental Prolastin	Drug: Alpha1-Proteinase Inhibitor (Human) Weekly infusion of 60 mg/kg body weight for 2 years
Group 2: Placebo Comparator	Drug: Albumin (Human) 20%, USP Weekly infusion for 2 years. Albumin (Human) 20% will be diluted with 5% glucose to a final concentration of 2.0%.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00263887

Locations

Denmark
Gentofte Hospital Department of Respiratory Medicine
Hellerup, Denmark, 2900
Sweden
Department of Pulmonary Medicine, Malmö University Hospital
Malmö, Sweden
United Kingdom, England
Queen Elizabeth Hospital
Birmingham, England, United Kingdom, B15 2TH

Sponsors and Collaborators

Talecris Biotherapeutics

Investigators

Principal Investigator:

Asger Dirksen, MD PHD

University of Copenhagen

More Information

FDA Approved Product Labeling Information - Prolastin® This link exits the ClinicalTrials.gov site

FDA Enforcement, Report Index (Class I, Class II Recall, Market Alerts and Medical Product Safety Alerts) This link exits the ClinicalTrials.gov site

FDA Approved Product Labeling Information - Plasbumin®-20 (Low Aluminum) This link exits the ClinicalTrials.gov site

Synopsis of Study Results This link exits the ClinicalTrials.gov site

Study ID Numbers:	100533
Study First Received:	September 12, 2005
Last Updated:	April 1, 2008
ClinicalTrials.gov Identifier:	NCT00263887
Health Authority:	Denmark: Danish Medicines Agency; Sweden: Medical Products Agency; United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Talecris Biotherapeutics:

alpha 1 proteinase inhibitor
alpha1 proteinase inhibitor
congenital emphysema
replacement therapy

Study placed in the following topic categories:

Pulmonary Emphysema
Emphysema
Protein C Inhibitor
Alpha 1-Antitrypsin
Protein C

Alpha 1-Antitrypsin Deficiency
Alpha 1-antitrypsin deficiency
Connective Tissue Diseases
Disease Progression

Additional relevant MeSH terms:

Serine Proteinase Inhibitors
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors

Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009