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CompletedNCT00263887Updated Aug 21, 2014Results posted

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

A Phase 2 interventional study of Alpha1-Proteinase Inhibitor (Human) and Albumin (Human) 20%, United States Pharmacopeia (USP) in Alpha 1-Antitrypsin Deficiency, sponsored by Grifols Therapeutics LLC. Completed at 3 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-08-21.

Sponsored by Grifols Therapeutics LLC (part of Grifols) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
77
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

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®?
02

Conditions studied

  • Alpha 1-Antitrypsin Deficiency

Keywords

  • alpha 1 proteinase inhibitor
  • alpha1 proteinase inhibitor
  • congenital emphysema
  • replacement therapy
03

In context

Lead sponsor

Grifols Therapeutics LLC is the lead sponsor of 46 studies on the registry; 4 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 13 (100%) have results posted.

First submitted before Grifols Therapeutics LLC became part of Grifols.

Browse Grifols Therapeutics LLC studies →All Grifols studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
77 participants (actual)

Study arms

  • Experimental
    Group 1

    Prolastin

    Drug: Alpha1-Proteinase Inhibitor (Human)

  • Placebo comparator
    Group 2

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

Interventions

  • DrugAlpha1-Proteinase Inhibitor (Human)

    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

  • DrugAlbumin (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%.

    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

06

What researchers measure

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

    Time frame: 24 or 30 months

Secondary outcomes

  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

07

Results

Posted Aug 21, 2014

Participant flow

Multicenter study with 3 sites in Denmark, Sweden, and the United Kingdom.

Participant flow — Overall Study
MilestoneProlastin (60 mg/kg Body Weight)Placebo
Started3839
Completed3532
Not completed37
Withdrew: Withdrawal by subject11
Withdrew: Lung transplantation12
Withdrew: Too ill to attend visit10
Withdrew: Adverse event02
Withdrew: Disease progression01
Withdrew: Lack of efficacy01

Outcome measures

PrimaryThe 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
Reported as:
Mean · g/L
The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung
g/LProlastin (60 mg/kg Body Weight)Placebo
Baseline47.980 ± 19.07245.477 ± 16.949
Endpoint45.085 ± 19.43341.354 ± 16.260
Change from Baseline-2.895 ± 4.739-4.124 ± 4.147
Statistical analysis
  • Prolastin (60 mg/kg Body Weight) vs Placebo · ANCOVA · p = 0.049
SecondaryChange in Lung Density at Each Visit as Measured by Computed Tomography
Time frame:
24 or 30 months
Reported as:
Mean · g/L

Results for this outcome have not been posted.

SecondaryThe Frequency of Exacerbations as Determined by Patient Diary.
Time frame:
24 or 30 months

Results for this outcome have not been posted.

SecondaryThe 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

Results for this outcome have not been posted.

SecondaryDuration and Severity of the Exacerbations
Time frame:
24 or 30 months

Results for this outcome have not been posted.

SecondaryMortality
Time frame:
24 or 30 months

Results for this outcome have not been posted.

SecondaryQuality of Life With a Disease Specific Instrument, the St. George's Respiratory Questionnaire
Time frame:
24 or 30 months

Results for this outcome have not been posted.

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Prolastin (60 mg/kg Body Weight)—9/38 (23.7%)37/38 (97.4%)
Placebo—15/39 (38.5%)38/39 (97.4%)
Most frequent serious events
Showing 10 of 31
Most frequent serious events
EventProlastin (60 mg/kg Body Weight)Placebo
PneumoniaInfections and infestations3/384/39
Atrial fibrillationCardiac disorders2/380/39
PneumothoraxRespiratory, thoracic and mediastinal disorders2/380/39
Pulmonary embolismRespiratory, thoracic and mediastinal disorders0/382/39
ConstipationGastrointestinal disorders1/380/39
Gastrooesophageal reflux diseaseGastrointestinal disorders1/380/39
Biliary colicHepatobiliary disorders1/380/39
Gallbladder disorderHepatobiliary disorders1/381/39
MalariaInfections and infestations1/380/39
Upper limb fractureInjury, poisoning and procedural complications1/380/39
Most frequent other events
Showing 10 of 63
Most frequent other events
EventProlastin (60 mg/kg Body Weight)Placebo
NasopharyngitisInfections and infestations24/3822/39
PneumoniaInfections and infestations12/389/39
HeadacheNervous system disorders9/3810/39
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders8/383/39
Pain in extremityMusculoskeletal and connective tissue disorders2/386/39
SinusitisInfections and infestations5/385/39
Back painMusculoskeletal and connective tissue disorders5/382/39
DiarrhoeaGastrointestinal disorders3/385/39
Chest painGeneral disorders2/385/39
Oedema peripheralGeneral disorders1/385/39

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Prolastin (60 mg/kg Body Weight)PlaceboTotal
<=18 years000
Between 18 and 65 years333467
>=65 years5510
Age, Continuous
Age, Continuous(years)Prolastin (60 mg/kg Body Weight)PlaceboTotal
Mean54.68 ± 8.2955.26 ± 9.6854.97 ± 9.03
Sex: Female, Male
Sex: Female, Male(Participants)Prolastin (60 mg/kg Body Weight)PlaceboTotal
Female132336
Male251641
Region of Enrollment
Region of Enrollment(participants)Prolastin (60 mg/kg Body Weight)PlaceboTotal
Denmark181735
United Kingdom121426
Sweden8816
Severity of COPD at baseline
Severity of COPD at baseline(participants)Prolastin (60 mg/kg Body Weight)PlaceboTotal
None224
Mild123
Moderate10818
Severe192039
Very Severe6713
08

Study locations

3 sites
  • Gentofte Hospital Department of Respiratory Medicine
    Hellerup, 2900, Denmark
  • Department of Pulmonary Medicine, Malmö University Hospital
    Malmö, Sweden
  • Queen Elizabeth Hospital
    Birmingham, England B15 2TH, United Kingdom
09

References and documents

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 ↗
10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Dec 2003, a primary completion of Jan 2007 and a completion of Jan 2007. It does not say whether these dates are actual or estimated.

Results were first posted in Aug 2014, 7 years 7 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 12, 2005
First posted
Dec 9, 2005
Start
Dec 2003
Primary completionActual
Jan 2007
CompletionActual
Jan 2007
Results first posted
Aug 21, 2014
Last update
Aug 21, 2014
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 21, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00263887
Lead sponsor
Grifols Therapeutics LLC
Responsible party
Sponsor
First posted
Dec 9, 2005
Start date
Dec 2003
Primary completion
Jan 2007
Completion
Jan 2007
Results posted
Aug 21, 2014
Last update
Aug 21, 2014

Study contacts

Asger Dirksen, MD PHD
principal investigator · University of Copenhagen

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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