AzTrials
AzTrials

Alpha 1-Antitrypsin DeficiencyPhase 2NCT00263887

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

A Phase 2 study testing Alpha1-Proteinase Inhibitor (Human) and Albumin (Human) 20%, United States Pharmacopeia (USP) in people with Alpha 1-Antitrypsin Deficiency, run by Grifols Therapeutics LLC at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Alpha 1-Antitrypsin Deficiency
What is being tested?
Alpha1-Proteinase Inhibitor (Human) and Albumin (Human) 20%, United States Pharmacopeia (USP)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
77 participants
Where
3 sitesin 3 countries
Study dates
Dec 2003to Jan 2007
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

Denmark1 site

  • Gentofte Hospital Department of Respiratory Medicine

    Hellerup, 2900

Other trials in Denmark

Sweden1 site

  • Department of Pulmonary Medicine, Malmö University Hospital

    Malmö

Other trials in Sweden

United Kingdom1 site

  • Queen Elizabeth Hospital

    Birmingham, England, B15 2TH

Other trials in United Kingdom

About this study

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.

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.

Read the 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®?
Being tested
Alpha1-Proteinase Inhibitor (Human), Albumin (Human) 20%, United States Pharmacopeia (USP)
Keywords
alpha 1 proteinase inhibitor, alpha1 proteinase inhibitor, congenital emphysema, replacement therapy
Medical subject headings
alpha 1-Antitrypsin Deficiency, Congenital lobar emphysema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alpha1-Proteinase Inhibitor (Human)Drug

    Also called Prolastin, alpha-1 antitrypsin (AAT), BAY x 5747, BAY 10-5233

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

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

    Also called Plasbumin®-20, Plasbumin®-20 (Low Aluminum), Albumin (Human) 20%, TAL-05-00008

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

Study groups in NCT00263887
Study groupRoleWhat they receive
Group 1ExperimentalProlastin
Receives: Drug: Alpha1-Proteinase Inhibitor (Human)
Group 2Placebo comparatorNot described
Receives: Drug: Albumin (Human) 20%, United States Pharmacopeia (USP)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 24 or 30 months

Secondary outcomes (6)

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

    Measured: 24 or 30 months

  2. The Frequency of Exacerbations as Determined by Patient Diary.

    Measured: 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)

    Measured: 24 or 30 months

  4. Duration and Severity of the Exacerbations

    Measured: 24 or 30 months

  5. Mortality

    Measured: 24 or 30 months

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

    Measured: 24 or 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2005 (estimated)
  2. Study startDec 2003
  3. Primary completionJan 2007
  4. Study completionJan 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00263887
Sponsor's protocol ID
100533
Status last verified
Aug 2014
First submitted
12 Sep 2005
Last updated
21 Aug 2014
Data monitoring committee
No

Publications

  • 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.

    PubMed 19251783

  • 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.

    PubMed 19196813

  • 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.

    PubMed 19483042

  • 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.

    PubMed 23226015

  • 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.

    PubMed 21617168

  • 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.

    PubMed 20920370

  • 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.

    PubMed 19678952

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpha1-Proteinase Inhibitor (Human) and Albumin (Human) 20%, United States Pharmacopeia (USP) in people with Alpha 1-Antitrypsin Deficiency, run by Grifols Therapeutics LLC at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Denmark, Sweden, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00263887, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in