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

Primary Purpose

Alpha 1-Antitrypsin Deficiency

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Alpha1-Proteinase Inhibitor (Human)

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

About this trial

This is an interventional treatment trial for Alpha 1-Antitrypsin Deficiency focused on measuring alpha 1 proteinase inhibitor, alpha1 proteinase inhibitor, congenital emphysema, replacement therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Gentofte Hospital Department of Respiratory Medicine
Department of Pulmonary Medicine, Malmö University Hospital
Queen Elizabeth Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group 1

Group 2

Arm Description

Prolastin

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

The Frequency of Exacerbations as Determined by Patient Diary.

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)

Duration and Severity of the Exacerbations

Mortality

Quality of Life With a Disease Specific Instrument, the St. George's Respiratory Questionnaire

Full Information

NCT ID

NCT00263887

First Posted

September 12, 2005

Last Updated

August 5, 2014

Sponsor

Grifols Therapeutics LLC

1. Study Identification

Unique Protocol Identification Number

NCT00263887

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

August 2014

Overall Recruitment Status

Completed

Study Start Date

December 2003 (undefined)

Primary Completion Date

January 2007 (Actual)

Study Completion Date

January 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Grifols Therapeutics LLC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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®?

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alpha 1-Antitrypsin Deficiency

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

77 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

Prolastin

Arm Title

Group 2

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Alpha1-Proteinase Inhibitor (Human)

Other Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

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

Time Frame

24 or 30 months

Title

The Frequency of Exacerbations as Determined by Patient Diary.

Time Frame

24 or 30 months

Title

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

Title

Duration and Severity of the Exacerbations

Time Frame

24 or 30 months

Title

Mortality

Time Frame

24 or 30 months

Title

Quality of Life With a Disease Specific Instrument, the St. George's Respiratory Questionnaire

Time Frame

24 or 30 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Asger Dirksen, MD PHD

Organizational Affiliation

University of Copenhagen

Official's Role

Principal Investigator

Facility Information:

Facility Name

Gentofte Hospital Department of Respiratory Medicine

City

Hellerup

ZIP/Postal Code

2900

Country

Denmark

Facility Name

Department of Pulmonary Medicine, Malmö University Hospital

City

Malmö

Country

Sweden

Facility Name

Queen Elizabeth Hospital

City

Birmingham

State/Province

England

ZIP/Postal Code

B15 2TH

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

19251783

Citation

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.

Results Reference

result

PubMed Identifier

19196813

Citation

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.

Results Reference

result

PubMed Identifier

19483042

Citation

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.

Results Reference

result

PubMed Identifier

23226015

Citation

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.

Results Reference

derived

PubMed Identifier

21617168

Citation

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.

Results Reference

derived

PubMed Identifier

20920370

Citation

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.

Results Reference

derived

PubMed Identifier

19678952

Citation

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.

Results Reference

derived

Links:

URL

http://www.talecris-pi.info/inserts/Prolastin.pdf

Description

FDA Approved Product Labeling Information - Prolastin®

URL

http://www.talecris-pi.info/inserts/plasbumin20la.pdf

Description

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

Learn more about this trial

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

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