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

Sponsor:	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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:

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: Albumins, human

U.S. FDA Resources

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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

Enrollment:	77
Study Start Date:	December 2003
Study Completion Date:	January 2007
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 Prolastin	Drug: Alpha1-Proteinase Inhibitor (Human) Weekly infusion of 60 mg/kg body weight for 2 years Other Names: Prolastin alpha-1 antitrypsin (AAT) BAY x 5747 BAY 10-5233 TAL-05-00007 NDC 13533-601-30 NDC 13533-601-35
Placebo Comparator: Group 2	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%. Other Names: Plasbumin®-20 Plasbumin®-20 (Low Aluminum) Albumin (Human) 20% TAL-05-00008 TAL-05-00024 BAY 34-9255 NDC 3533-683-20 NDC 1533-683-71 NDC 13533-691-20 NDC 13533-691-71

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
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

Additional 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

Publications:

Brand P, Schulte M, Wencker M, Herpich CH, Klein G, Hanna K, Meyer T. Lung deposition of inhaled {alpha}1-proteinase inhibitor in CF and {alpha}1-antitrypsin deficiency. Eur Respir J. 2009 Feb 27; [Epub ahead of print]

Dirksen A, Piitulainen E, Parr DG, Deng C, Wencker M, Shaker SB, Stockley RA. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha-1 antitrypsin deficiency. Eur Respir J. 2009 Feb 5; [Epub ahead of print]

Soriano JB, Miravitlles M. Your racing horses will help you to quit: a lesson for COPD and alpha1-antitrypsin deficiency research. Eur Respir J. 2009 Jun;33(6):1244-6. No abstract available.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Carter RI, Mumford RA, Treonze KM, Finke PE, Davies P, Si Q, Humes JL, Dirksen A, Piitulainen E, Ahmad A, Stockley RA. The fibrinogen cleavage product A?-Val360, a specific marker of neutrophil elastase activity in vivo. Thorax. 2011 Aug;66(8):686-91. Epub 2011 May 26.

Stockley RA, Parr DG, Piitulainen E, Stolk J, Stoel BC, Dirksen A. Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry. Respir Res. 2010 Oct 5;11:136.

Parr DG, Dirksen A, Piitulainen E, Deng C, Wencker M, Stockley RA. Exploring the optimum approach to the use of CT densitometry in a randomised placebo-controlled study of augmentation therapy in alpha 1-antitrypsin deficiency. Respir Res. 2009 Aug 13;10:75.

Responsible Party:	Gerald Klein, MD, Chief Medical Officer, Vice President of Medical and Clinical Affairs, Talecris Biotherapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT00263887 History of Changes
Other Study ID Numbers:	100533
Study First Received:	September 12, 2005
Last Updated:	August 7, 2009
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

Additional relevant MeSH terms:

Emphysema
Pulmonary Emphysema
Alpha 1-Antitrypsin Deficiency
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Liver Diseases
Digestive System Diseases
Genetic Diseases, Inborn

Subcutaneous Emphysema
Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012