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

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ClinicalTrials.gov Identifier: NCT00263887
Recruitment Status : Completed
First Posted : December 9, 2005
Results First Posted : August 21, 2014
Last Update Posted : August 21, 2014
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Alpha 1-Antitrypsin Deficiency Drug: Alpha1-Proteinase Inhibitor (Human) Drug: Albumin (Human) 20%, United States Pharmacopeia (USP) Phase 2

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®?
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (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.
Study Start Date : December 2003
Actual Primary Completion Date : January 2007
Actual Study Completion Date : January 2007

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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%, 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%.
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


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Change in Lung Density at Each Visit as Measured by Computed Tomography [ Time Frame: 24 or 30 months ]
  2. The Frequency of Exacerbations as Determined by Patient Diary. [ Time Frame: 24 or 30 months ]
  3. 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 ]
  4. Duration and Severity of the Exacerbations [ Time Frame: 24 or 30 months ]
  5. Mortality [ Time Frame: 24 or 30 months ]
  6. Quality of Life With a Disease Specific Instrument, the St. George's Respiratory Questionnaire [ Time Frame: 24 or 30 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with pulmonary emphysema due to severe congenital AAT deficiency of phenotype protease inhibitor Z (PiZ) or other rare genotypes (not MS, MZ or SZ) and AAT serum level < 11 microns (µM) or < 80 mg/dL (status to be confirmed by phenotyping and genotyping)
  • Inspiratory capacity (VC - ERV) > 1.2 L and forced expiratory volume at one second (FEV1) < 80% of predicted value post bronchodilator
  • FEV1/VC < 70% of predicted value post-bronchodilator or transfer factor of carbon monoxide (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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00263887


Locations
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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 LLC
Investigators
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Principal Investigator: Asger Dirksen, MD PHD University of Copenhagen
More Information
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Publications of Results:

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

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Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT00263887    
Other Study ID Numbers: 100533
First Posted: December 9, 2005    Key Record Dates
Results First Posted: August 21, 2014
Last Update Posted: August 21, 2014
Last Verified: August 2014
Keywords provided by Grifols Therapeutics LLC:
alpha 1 proteinase inhibitor
alpha1 proteinase inhibitor
congenital emphysema
replacement therapy
Additional relevant MeSH terms:
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Alpha 1-Antitrypsin Deficiency
Pulmonary Emphysema
Emphysema
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Liver Diseases
 Digestive System Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Alpha 1-Antitrypsin
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action