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CompletedNCT02282527Updated Mar 13, 2017Results posted

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

A Phase 2/3 interventional study of Liquid Alpha₁-PI and Prolastin-C in Alpha₁-Antitrypsin Deficiency, sponsored by Grifols Therapeutics LLC. Completed at 6 sites in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2017-03-13.

Sponsored by Grifols Therapeutics LLC · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
32
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

Grifols Therapeutics Inc. conducted a multi-center, randomized, double-blind, crossover study to evaluate the safety, immunogenicity, and pharmacokinetics (PK) of Liquid Alpha₁-PI compared to the currently licensed product, Prolastin-C, in subjects with Alpha₁-Antitrypsin Deficiency (AATD).

02

Conditions studied

  • Alpha₁-Antitrypsin Deficiency
03

In context

Alpha 1-Antitrypsin Deficiency

94 studies on the registry are indexed under Alpha 1-Antitrypsin Deficiency; 5 are open to participants now.

This study's enrollment of 32 is above the median of 27 across 58 interventional studies indexed under Alpha 1-Antitrypsin Deficiency.

Browse Alpha 1-Antitrypsin Deficiency studies →

Lead sponsor

Grifols Therapeutics LLC is the lead sponsor of 43 studies on the registry; 4 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.

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

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Be between 18 and 70 years of age, inclusive
  • Had a diagnosis of congenital AATD
  • Had a documented total alpha₁-PI level \< 11 µM. If the total alpha₁-PI level had yet to be documented, a blood draw for total alpha₁-PI level was obtained at the Screening Visit
  • Had a post-bronchodilator Forced expiratory volume in 1 second (FEV1) ≥ 30% and \< 80% of predicted and FEV1/forced vital capacity (FVC) \< 70%
  • If the subject had received alpha₁-PI augmentation therapy of any kind, he/she must have been be willing to discontinue that treatment at the Week 1 (Baseline) Visit and remain off any kind of alpha₁-PI treatment, other than the investigational products for this study, while participating in the study

Exclusion criteria

Exclusion Criteria:

  • Subject had a moderate or severe pulmonary exacerbation during the 4 weeks before the Week 1 (Baseline) Visit
  • History of lung or liver transplant
  • Any lung surgery during the past 2 years (excluding lung biopsy)
  • Liver cirrhosis confirmed by biopsy
  • Elevated liver enzymes (aspartate transaminase [AST], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]) equal to or greater than 2.5 times the upper limit of normal
  • Severe concomitant disease (e.g., congestive heart failure, clinically significant pulmonary fibrosis, malignant disease [with the exception of skin cancers other than melanoma], history of acute hypersensitivity pneumonitis reaction, or current chronic hypersensitivity pneumonitis)
  • Females who were pregnant, breastfeeding or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or abstinence) throughout the study
  • Known previous infection with or clinical signs and symptoms consistent with current hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
  • Smoking during the past 6 months or a positive urine cotinine test at the Screening Visit that is due to smoking
  • Participation in another investigational drug study within one month prior to the Week 1 (Baseline) Visit
  • History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s)
  • Use of systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e.,10 mg every 2 days) within the 4 weeks prior to the Week 1 (Baseline) Visit inhaled steroids are not considered systemic steroids)
  • Use of systemic or aerosolized antibiotics for an exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit
  • Known selective or severe Immunoglobulin A (IgA) deficiency
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
32 participants (actual)

Study arms

  • Other
    Treatment Sequence 1

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

    Biological: Liquid Alpha₁-PI · Biological: Prolastin-C

  • Other
    Treatment Sequence 2

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

    Biological: Liquid Alpha₁-PI · Biological: Prolastin-C

Interventions

  • BiologicalLiquid Alpha₁-PI

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

  • BiologicalProlastin-C

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

06

What researchers measure

Primary outcomes

  1. AUC(0-7 Days) Based on Antigenic Content

    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

Secondary outcomes

  1. AUC(0-7 Days) Based on Functional Activity

    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

  2. Number of Subjects With Immunogenicity Response

    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

07

Results

Posted Mar 13, 2017

Participant flow

This study was performed at 6 investigative centers in the US.

Participant flow — Overall Study
MilestoneLiquid Alpha₁-PI/Prolastin-CProlastin-C/Liquid Alpha₁-PI
Started1616
Completed1515
Not completed11
Withdrew: Lost to follow-up01
Withdrew: Lack of home health aid10

Outcome measures

PrimaryAUC(0-7 Days) Based on Antigenic Content

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
Reported as:
Mean · mg*h/mL
AUC(0-7 Days) Based on Antigenic Content
mg*h/mLLiquid Alpha₁-PIProlastin-C
AUC(0-7 Days) Based on Antigenic Content203.20 ± 23.041198.38 ± 25.230
SecondaryAUC(0-7 Days) Based on Functional Activity

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
Reported as:
Mean · mg*h/mL
AUC(0-7 Days) Based on Functional Activity
mg*h/mLLiquid Alpha₁-PIProlastin-C
AUC(0-7 Days) Based on Functional Activity171.16 ± 28.764168.50 ± 27.473
SecondaryNumber of Subjects With Immunogenicity Response

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
Reported as:
Count of participants · Participants
Number of Subjects With Immunogenicity Response
ParticipantsLiquid Alpha₁-PI/Prolastin-CProlastin-C/Liquid Alpha₁-PI
Number of Subjects With Immunogenicity Response00

Adverse events

Collected over 20 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Liquid Alpha₁-PI—0/32 (0%)9/32 (28.1%)
Prolastin-C—1/31 (3.2%)3/31 (9.7%)
Most frequent serious events
Most frequent serious events
EventLiquid Alpha₁-PIProlastin-C
Infective exacerbation of chronic obstructive airways diseaseInfections and infestations0/321/31
Most frequent other events
Most frequent other events
EventLiquid Alpha₁-PIProlastin-C
NasopharyngitisInfections and infestations1/322/31
FatigueGeneral disorders2/320/31
PyrexiaGeneral disorders2/320/31
DiarrhoeaGastrointestinal disorders2/321/31
Dermatitis ContactSkin and subcutaneous tissue disorders2/320/31

Baseline characteristics

Age, Continuous
Age, Continuous(years)Liquid Alpha₁-PI/Prolastin-CProlastin-C/Liquid Alpha₁-PITotal
Mean60.7 ± 7.9463.1 ± 5.9361.9 ± 7.00
Sex: Female, Male
Sex: Female, Male(Participants)Liquid Alpha₁-PI/Prolastin-CProlastin-C/Liquid Alpha₁-PITotal
Female8614
Male81018
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Liquid Alpha₁-PI/Prolastin-CProlastin-C/Liquid Alpha₁-PITotal
Hispanic or Latino011
Not Hispanic or Latino161531
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Liquid Alpha₁-PI/Prolastin-CProlastin-C/Liquid Alpha₁-PITotal
United States161632
Alpha1-PI concentration
Alpha1-PI concentration(mg/mL)Liquid Alpha₁-PI/Prolastin-CProlastin-C/Liquid Alpha₁-PITotal
Naive0.31 ± NA0.21 ± 0.0400.24 ± 0.059
Non-naive0.72 ± 0.2830.69 ± 0.2150.70 ± 0.248
08

Study locations

6 sites
  • National Jewish Health
    Denver, Colorado 80206, United States
  • University of Florida Gainesville
    Gainesville, Florida 32610, United States
  • University of Miami - Miller School of Medicine
    Miami, Florida 33136, United States
  • PMG Research of Wilmington
    Wilmington, North Carolina 28401, United States
  • Oregon Health and Science University
    Portland, Oregon 97239, United States
  • University of Texas Health Science Center
    Tyler, Texas 75708, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 13, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02282527
Lead sponsor
Grifols Therapeutics LLC
Responsible party
Sponsor
First posted
Nov 4, 2014
Start date
Oct 2014
Primary completion
Jan 2016
Completion
Jan 2016
Results posted
Mar 13, 2017
Last update
Mar 13, 2017

Oversight

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

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