ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 10 of 79 for:    ALPHA-1-ANTITRYPSIN DEFICIENCY

A Study to Assess Safety and PK of Liquid Alpha₁-Proteinase Inhibitor (Human) in Treating Alpha₁-Antitrypsin Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02282527
Recruitment Status : Completed
First Posted : November 4, 2014
Results First Posted : March 13, 2017
Last Update Posted : March 13, 2017
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alpha₁-Antitrypsin Deficiency
Interventions Biological: Liquid Alpha₁-PI
Biological: Prolastin-C
Enrollment 32

Recruitment Details This study was performed at 6 investigative centers in the US.
Pre-assignment Details  
Arm/Group Title Liquid Alpha₁-PI/Prolastin-C Prolastin-C/Liquid Alpha₁-PI
Hide Arm/Group Description

Subjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C

Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Subjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions

Period Title: Overall Study
Started 16 16
Completed 15 15
Not Completed 1 1
Reason Not Completed
Lost to Follow-up             0             1
Lack of home health aid             1             0
Arm/Group Title Liquid Alpha₁-PI/Prolastin-C Prolastin-C/Liquid Alpha₁-PI Total
Hide Arm/Group Description

Subjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C

Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Subjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions

Total of all reporting groups
Overall Number of Baseline Participants 16 16 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 16 participants 32 participants
60.7  (7.94) 63.1  (5.93) 61.9  (7.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 32 participants
Female
8
  50.0%
6
  37.5%
14
  43.8%
Male
8
  50.0%
10
  62.5%
18
  56.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 32 participants
Hispanic or Latino
0
   0.0%
1
   6.3%
1
   3.1%
Not Hispanic or Latino
16
 100.0%
15
  93.8%
31
  96.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants 16 participants 32 participants
16 16 32
Alpha1-PI concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/mL
Naive Number Analyzed 1 participants 3 participants 4 participants
0.31 [2]   (NA) 0.21  (0.040) 0.24  (0.059)
Non-naive Number Analyzed 14 participants 13 participants 27 participants
0.72  (0.283) 0.69  (0.215) 0.70  (0.248)
[1]
Measure Analysis Population Description: One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
[2]
The standard deviation was not calculated as only 1 subject was assessed.
1.Primary Outcome
Title AUC(0-7 Days) Based on Antigenic Content
Hide Description The primary PK objective of this study was to demonstrate the bioequivalence of Liquid Alpha₁-PI 60 mg/kg to Prolastin-C 60 mg/kg, as measured by AUC from 0 to 7 days (AUC0-7days) using an antigenic content assay of alpha₁-PI, at approximate steady state in subjects with AATD.
Time Frame pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Liquid Alpha₁-PI Prolastin-C
Hide Arm/Group Description:

Subjects treated with Liquid Alpha₁-PI in each treatment sequence

Liquid Alpha₁-PI: Liquid Alpha1-PI, 60 mg/kg, 8 weekly intravenous infusions

Subjects treated with Prolastin-C in each treatment sequence

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Overall Number of Participants Analyzed 30 28
Mean (Standard Deviation)
Unit of Measure: mg*h/mL
203.20  (23.041) 198.38  (25.230)
2.Secondary Outcome
Title AUC(0-7 Days) Based on Functional Activity
Hide Description The exploratory PK objective of this study was to demonstrate the bioequivalence of Liquid Alpha₁-PI 60 mg/kg to Prolastin-C 60 mg/kg, as measured by AUC from 0 to 7 days (AUC 0-7 days) using a functional activity assay of alpha₁-PI, at approximate steady state in subjects with AATD.
Time Frame pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Liquid Alpha₁-PI Prolastin-C
Hide Arm/Group Description:

Subjects treated with Liquid Alpha₁-PI in each treatment sequence

Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions

Subjects treated with Prolastin-C in each treatment sequence

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Overall Number of Participants Analyzed 30 28
Mean (Standard Deviation)
Unit of Measure: mg*h/mL
171.16  (28.764) 168.50  (27.473)
3.Secondary Outcome
Title Number of Subjects With Immunogenicity Response
Hide Description Blood samples for immunogenicity testing were collected at Weeks 1 (Baseline), 9, 17, and 20. Any samples that tested positive for alpha₁-PI antibodies were tested for neutralizing antibodies and antibody titer. Immunogenicity testing was performed using validated assays in a multitiered approach. Samples collected at Week 1 (Baseline) and at Weeks 9 and 20 were tested for immunogenicity while samples collected at Week 17 were to be tested for immunogenicity only if deemed appropriate (eg, unexpected PK profile).
Time Frame Weeks 1, 9, 17, and 20
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Liquid Alpha₁-PI/Prolastin-C Prolastin-C/Liquid Alpha₁-PI
Hide Arm/Group Description:

Subjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C

Liquid Alpha₁-PI: Liquid Alpha1-PI, 60 mg/kg, 8 weekly intravenous infusions

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Subjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI

Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions

Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions

Overall Number of Participants Analyzed 16 16
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Time Frame 20 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Liquid Alpha₁-PI Prolastin-C
Hide Arm/Group Description Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
All-Cause Mortality
Liquid Alpha₁-PI Prolastin-C
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Liquid Alpha₁-PI Prolastin-C
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/32 (0.00%)      1/31 (3.23%)    
Infections and infestations     
Infective exacerbation of chronic obstructive airways disease  1  0/32 (0.00%)  0 1/31 (3.23%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Liquid Alpha₁-PI Prolastin-C
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/32 (28.13%)      3/31 (9.68%)    
Gastrointestinal disorders     
Diarrhoea  1  2/32 (6.25%)  3 1/31 (3.23%)  1
General disorders     
Fatigue  1  2/32 (6.25%)  2 0/31 (0.00%)  0
Pyrexia  1  2/32 (6.25%)  2 0/31 (0.00%)  0
Infections and infestations     
Nasopharyngitis  1  1/32 (3.13%)  1 2/31 (6.45%)  2
Skin and subcutaneous tissue disorders     
Dermatitis Contact  1  2/32 (6.25%)  2 0/31 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The site may publish results from the study, after providing Sponsor at least 30 days notice prior to submitting a manuscript or other materials related to the study to any outside party. At Sponsor’s request, Site will remove any any confidential information (other than study results), and incorporate all reasonable comments by Sponsor, or delay publication or presentation for a period of up to 120 days to allow Sponsor to protect its interests in any Sponsor’s Inventions.
Results Point of Contact
Name/Title: Henry Li
Organization: Grifols Therapeutics Inc.
Phone: 1-919-316-6042
Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT02282527     History of Changes
Other Study ID Numbers: GTI1402
First Submitted: October 31, 2014
First Posted: November 4, 2014
Results First Submitted: November 11, 2016
Results First Posted: March 13, 2017
Last Update Posted: March 13, 2017