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

NCT00263887 | Completed Phase 2 Results

• 1 other identifier: 100533
• Study Type: interventional
• Target: 77
• Locations: 3 countries
• Sites: 3

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Keywords

alpha 1 proteinase inhibitor; alpha1 proteinase inhibitor; congenital emphysema; replacement therapy

Outcome Measures

Primary Outcomes (1)

• The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung

  24 or 30 months

Secondary Outcomes (6)

• Change in Lung Density at Each Visit as Measured by Computed Tomography

  24 or 30 months

• The Frequency of Exacerbations as Determined by Patient Diary.

  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)

  24 or 30 months

• Duration and Severity of the Exacerbations

  24 or 30 months

• Mortality

  24 or 30 months

Study Arms (2)

Group 1

EXPERIMENTAL

Prolastin

Drug: Alpha1-Proteinase Inhibitor (Human)

Group 2

PLACEBO COMPARATOR

Drug: Albumin (Human) 20%, United States Pharmacopeia (USP)

Interventions

Alpha1-Proteinase Inhibitor (Human) DRUG

Weekly infusion of 60 mg/kg body weight for 2 years

Also known as: Prolastin, alpha-1 antitrypsin (AAT), BAY x 5747, BAY 10-5233, TAL-05-00007, NDC 13533-601-30, NDC 13533-601-35

Group 1

Albumin (Human) 20%, United States Pharmacopeia (USP) DRUG

Weekly infusion for 2 years. Albumin (Human) 20% will be diluted with 5% glucose to a final concentration of 2.0%.

Also known as: 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

Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (3)

Gentofte Hospital Department of Respiratory Medicine

Hellerup, 2900, Denmark

Location

Department of Pulmonary Medicine, Malmö University Hospital

Malmo, Sweden

Location

Queen Elizabeth Hospital

Birmingham, England, B15 2TH, United Kingdom

Location

Related Publications (7)

• Brand P, Schulte M, Wencker M, Herpich CH, Klein G, Hanna K, Meyer T. Lung deposition of inhaled alpha1-proteinase inhibitor in cystic fibrosis and alpha1-antitrypsin deficiency. Eur Respir J. 2009 Aug;34(2):354-60. doi: 10.1183/09031936.00118408. Epub 2009 Feb 27.

  PMID: 19251783 RESULT

• 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 alpha1-antitrypsin deficiency. Eur Respir J. 2009 Jun;33(6):1345-53. doi: 10.1183/09031936.00159408. Epub 2009 Feb 5.

  PMID: 19196813 RESULT

• 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. doi: 10.1183/09031936.00026409. No abstract available.

  PMID: 19483042 RESULT

• Vijayasaratha K, Stockley RA. Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:789-96. doi: 10.2147/COPD.S31797. Epub 2012 Nov 27.

  PMID: 23226015 DERIVED

• 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 Aalpha-Val360, a specific marker of neutrophil elastase activity in vivo. Thorax. 2011 Aug;66(8):686-91. doi: 10.1136/thx.2010.154690. Epub 2011 May 26.

  PMID: 21617168 DERIVED

• 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(1):136. doi: 10.1186/1465-9921-11-136.

  PMID: 20920370 DERIVED

• 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(1):75. doi: 10.1186/1465-9921-10-75.

  PMID: 19678952 DERIVED

Related Links

• FDA Approved Product Labeling Information - Prolastin®
• FDA Approved Product Labeling Information - Plasbumin®-20 (Low Aluminum)

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Congenital lobar emphysema

Interventions

alpha 1-Antitrypsin; Albumins

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Results Point of Contact

• Title: Henry Li
• Organization: Talecris Biotherapeutics

henry.li@grifols.com

1-800-520-2807

Study Officials

• Asger Dirksen, MD PHD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: December 9, 2005
• Study Start: December 1, 2003
• Primary Completion: January 1, 2007
• Study Completion: January 1, 2007
• Last Updated: August 21, 2014
• Results First Posted: August 21, 2014

Record last verified: 2014-08

Locations

DK (1); SE (1); GB (1)