Trial Outcomes & Findings for A Study to Assess Safety and PK of Liquid Alpha₁-Proteinase Inhibitor (Human) in Treating Alpha₁-Antitrypsin Deficiency (NCT NCT02282527)
NCT ID: NCT02282527
Last Updated: 2017-03-13
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
32 participants
Primary outcome timeframe
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
Results posted on
2017-03-13
Participant Flow
This study was performed at 6 investigative centers in the US.
Participant milestones
| Measure |
Liquid Alpha₁-PI/Prolastin-C
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
|
Prolastin-C/Liquid Alpha₁-PI
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 Study
STARTED
|
16
|
16
|
|
Overall Study
COMPLETED
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Liquid Alpha₁-PI/Prolastin-C
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
|
Prolastin-C/Liquid Alpha₁-PI
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 Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Lack of home health aid
|
1
|
0
|
Baseline Characteristics
One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
Baseline characteristics by cohort
| Measure |
Liquid Alpha₁-PI/Prolastin-C
n=16 Participants
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
|
Prolastin-C/Liquid Alpha₁-PI
n=16 Participants
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
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.7 years
STANDARD_DEVIATION 7.94 • n=16 Participants
|
63.1 years
STANDARD_DEVIATION 5.93 • n=16 Participants
|
61.9 years
STANDARD_DEVIATION 7.00 • n=32 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=16 Participants
|
6 Participants
n=16 Participants
|
14 Participants
n=32 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=16 Participants
|
10 Participants
n=16 Participants
|
18 Participants
n=32 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=16 Participants
|
1 Participants
n=16 Participants
|
1 Participants
n=32 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=16 Participants
|
15 Participants
n=16 Participants
|
31 Participants
n=32 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=16 Participants
|
0 Participants
n=16 Participants
|
0 Participants
n=32 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=16 Participants
|
16 participants
n=16 Participants
|
32 participants
n=32 Participants
|
|
Alpha1-PI concentration
Naive
|
0.31 mg/mL
STANDARD_DEVIATION NA • n=1 Participants • One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
|
0.21 mg/mL
STANDARD_DEVIATION 0.040 • n=3 Participants • One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
|
0.24 mg/mL
STANDARD_DEVIATION 0.059 • n=4 Participants • One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
|
|
Alpha1-PI concentration
Non-naive
|
0.72 mg/mL
STANDARD_DEVIATION 0.283 • n=14 Participants • One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
|
0.69 mg/mL
STANDARD_DEVIATION 0.215 • n=13 Participants • One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
|
0.70 mg/mL
STANDARD_DEVIATION 0.248 • n=27 Participants • One subject in the Liquid Alpha₁-PI/Prolastin -C non-naïve population was missing baseline alpha₁-PI concentration due to sample instability.
|
PRIMARY outcome
Timeframe: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post doseThe 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.
Outcome measures
| Measure |
Liquid Alpha₁-PI
n=30 Participants
Subjects treated with Liquid Alpha₁-PI in each treatment sequence
Liquid Alpha₁-PI: Liquid Alpha1-PI, 60 mg/kg, 8 weekly intravenous infusions
|
Prolastin-C
n=28 Participants
Subjects treated with Prolastin-C in each treatment sequence
Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
|
|---|---|---|
|
AUC(0-7 Days) Based on Antigenic Content
|
203.20 mg*h/mL
Standard Deviation 23.041
|
198.38 mg*h/mL
Standard Deviation 25.230
|
SECONDARY outcome
Timeframe: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post doseThe 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.
Outcome measures
| Measure |
Liquid Alpha₁-PI
n=30 Participants
Subjects treated with Liquid Alpha₁-PI in each treatment sequence
Liquid Alpha₁-PI: Liquid Alpha1-PI, 60 mg/kg, 8 weekly intravenous infusions
|
Prolastin-C
n=28 Participants
Subjects treated with Prolastin-C in each treatment sequence
Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
|
|---|---|---|
|
AUC(0-7 Days) Based on Functional Activity
|
171.16 mg*h/mL
Standard Deviation 28.764
|
168.50 mg*h/mL
Standard Deviation 27.473
|
SECONDARY outcome
Timeframe: Weeks 1, 9, 17, and 20Blood 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).
Outcome measures
| Measure |
Liquid Alpha₁-PI
n=16 Participants
Subjects treated with Liquid Alpha₁-PI in each treatment sequence
Liquid Alpha₁-PI: Liquid Alpha1-PI, 60 mg/kg, 8 weekly intravenous infusions
|
Prolastin-C
n=16 Participants
Subjects treated with Prolastin-C in each treatment sequence
Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
|
|---|---|---|
|
Number of Subjects With Immunogenicity Response
|
0 Participants
|
0 Participants
|
Adverse Events
Liquid Alpha₁-PI
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Prolastin-C
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Liquid Alpha₁-PI
n=32 participants at risk
Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions
|
Prolastin-C
n=31 participants at risk
Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
|
|---|---|---|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.00%
0/32 • 20 weeks
|
3.2%
1/31 • Number of events 1 • 20 weeks
|
Other adverse events
| Measure |
Liquid Alpha₁-PI
n=32 participants at risk
Liquid Alpha₁-PI: Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions
|
Prolastin-C
n=31 participants at risk
Prolastin-C: Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
|
|---|---|---|
|
General disorders
Fatigue
|
6.2%
2/32 • Number of events 2 • 20 weeks
|
0.00%
0/31 • 20 weeks
|
|
General disorders
Pyrexia
|
6.2%
2/32 • Number of events 2 • 20 weeks
|
0.00%
0/31 • 20 weeks
|
|
Infections and infestations
Nasopharyngitis
|
3.1%
1/32 • Number of events 1 • 20 weeks
|
6.5%
2/31 • Number of events 2 • 20 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
2/32 • Number of events 3 • 20 weeks
|
3.2%
1/31 • Number of events 1 • 20 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
6.2%
2/32 • Number of events 2 • 20 weeks
|
0.00%
0/31 • 20 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER