Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)

This study has been completed.
Sponsor:
Information provided by:
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00396006
First received: November 3, 2006
Last updated: March 3, 2011
Last verified: March 2011
Results First Received: December 15, 2010  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Alpha 1-Antitrypsin Deficiency
Intervention: Biological: Alpha1-Proteinase Inhibitor

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited at 5 hospital sites in New Zealand and Australia. The period studied was 1 year and 2 months.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
21 participants enrolled: 4 were screen failures (i.e., did not meet inclusion/exclusion criteria), 3 were discontinued due to unevaluable baseline bronchoalveolar lavage (BAL) samples, and 1 subject withdrew consent prior to receiving investigational product.

Reporting Groups
  Description
Participants Treated With ARALAST Fraction IV-1 (Fr. IV-1) Weekly infusions of ARALAST Fr. IV-1 were administered to participants at a dosage of 60 mg/kg

Participant Flow:   Overall Study
    Participants Treated With ARALAST Fraction IV-1 (Fr. IV-1)  
STARTED     13  
COMPLETED     13  
NOT COMPLETED     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Participants Treated With ARALAST Fr. IV-1 No text entered.

Baseline Measures
    Participants Treated With ARALAST Fr. IV-1  
Number of Participants  
[units: participants]
  13  
Age  
[units: participants]
 
<=18 years     0  
Between 18 and 65 years     10  
>=65 years     3  
Age  
[units: years]
Median ( Full Range )
  59.6  
  ( 36.0 to 76.1 )  
Gender  
[units: participants]
 
Female     6  
Male     7  
Region of Enrollment  
[units: participants]
 
Australia     8  
New Zealand     5  



  Outcome Measures
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1.  Primary:   Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level   [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ]

2.  Primary:   The Number of Adverse Events (AEs) Related to the Infusion of ARALAST Fr. IV 1 Administered at a Rate of 0.2 mL/kg/Min   [ Time Frame: During 8 consecutive weeks of treatment ]

3.  Primary:   Number of Changes in the Rate of Infusion   [ Time Frame: During 8 consecutive weeks of treatment ]

4.  Secondary:   Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels   [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ]

5.  Secondary:   Change in in the Ratio of BAL ELF α1-PI to Human Neutrophil Elastase (HNE) Complex Concentration   [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ]

6.  Secondary:   Change in the α1-PI Plasma Level   [ Time Frame: Blood samples were collected at baseline and after 8 consecutive weeks of treatment ]

7.  Secondary:   Change in the Plasma Antineutrophil Elastase Capacity (ANEC) Level   [ Time Frame: Blood samples were collected at baseline and after 8 consecutive weeks of treatment ]

8.  Secondary:   Clinically Significant Changes in Vital Signs From Pre- to Post-Infusion   [ Time Frame: During 8 consecutive weeks of infusion ]

9.  Other Pre-specified:   Change in the BAL ELF Free Neutrophil Elastase Level   [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ]

10.  Other Pre-specified:   Ratio of Post- to Pre-treatment BAL ELF Total Neutrophil Elastase Level   [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ]

11.  Other Pre-specified:   Ratio of Post- to Pre-treatment BAL ELF Interleukin 8 (IL-8) Level   [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ]

12.  Other Pre-specified:   Change in the BAL ELF Tumor Necrosis Factor-alpha (TNF-α) From Baseline to Post-treatment   [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ]


  Serious Adverse Events
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Time Frame 1 year, 2 months
Additional Description No text entered.

Reporting Groups
  Description
Intent to Treat Treated participants with relevant assessments, e.g. if pre- and post-treatment BAL procedures were required to assess the parameter, then the participant had both evaluable BAL procedures.

Serious Adverse Events
    Intent to Treat  
Total, serious adverse events    
# participants affected / at risk     1/13 (7.69%)  
Investigations    
Hepatitis A antibody positive 1 [2]  
# participants affected / at risk     1/13 (7.69%)  
# events     1  
1 Term from vocabulary, MedDRA (Unspecified)
[2] Not related to investigational product. This participant had received 2 Hepatitis A vaccinations in the year prior to enrollment.




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Isoelectric focusing (IEF) analyses that were intended to compare the profile of plasma α1-PI & ELF α1-PI were not carried out due to fact that ELF samples were either missing, insufficient or too dilute for such assays.


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