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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00263887
Recruitment Status : Completed
First Posted : December 9, 2005
Results First Posted : August 21, 2014
Last Update Posted : August 21, 2014
Information provided by (Responsible Party):
Grifols Therapeutics LLC

September 12, 2005
December 9, 2005
September 24, 2009
August 21, 2014
August 21, 2014
December 2003
January 2007   (Final data collection date for primary outcome measure)
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 ]
The progression rate of emphysema determined by change in lung density measured by annual CT scan of whole lung
Complete list of historical versions of study NCT00263887 on Archive Site
  • Change in Lung Density at Each Visit as Measured by Computed Tomography [ Time Frame: 24 or 30 months ]
  • The Frequency of Exacerbations as Determined by Patient Diary. [ Time Frame: 24 or 30 months ]
  • 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 ]
  • Duration and Severity of the Exacerbations [ Time Frame: 24 or 30 months ]
  • Mortality [ Time Frame: 24 or 30 months ]
  • Quality of Life With a Disease Specific Instrument, the St. George's Respiratory Questionnaire [ Time Frame: 24 or 30 months ]
  • 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 as determined by diary cards
  • Mortality
  • Quality of life with a disease specific instrument, the St George's Respiratory Questionnaire
Not Provided
Not Provided
Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients (EXACTLE)
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.
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.

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®?
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Alpha 1-Antitrypsin Deficiency
  • 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
  • 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
  • Experimental: Group 1
    Intervention: Drug: Alpha1-Proteinase Inhibitor (Human)
  • Placebo Comparator: Group 2
    Intervention: Drug: Albumin (Human) 20%, United States Pharmacopeia (USP)

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
January 2007
January 2007   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Denmark,   Sweden,   United Kingdom
Not Provided
Not Provided
Grifols Therapeutics LLC
Grifols Therapeutics LLC
Not Provided
Principal Investigator: Asger Dirksen, MD PHD University of Copenhagen
Grifols Therapeutics LLC
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP