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

This study has been completed.
Sponsor:
Information provided by:
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT00263887
First received: September 12, 2005
Last updated: August 7, 2009
Last verified: August 2009
History of Changes
  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 2

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:

U.S. FDA Resources

Further study details as provided by Grifols Therapeutics Inc.:

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
Grifols Therapeutics Inc.
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:

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

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 Grifols Therapeutics Inc.:
alpha 1 proteinase inhibitor
alpha1 proteinase inhibitor
congenital emphysema
replacement therapy

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Alpha 1-Antitrypsin
Emphysema
Pulmonary Emphysema
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Liver Diseases
Digestive System Diseases
 Genetic Diseases, Inborn
Subcutaneous Emphysema
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 June 17, 2013