A Study to Assess Safety and PK of Liquid Alpha₁-Proteinase Inhibitor (Human) in Treating Alpha₁-Antitrypsin Deficiency
- Conditions
- Alpha₁-Antitrypsin Deficiency
- Interventions
- Biological: Liquid Alpha₁-PIBiological: Prolastin-C
- Registration Number
- NCT02282527
- Lead Sponsor
- Grifols Therapeutics LLC
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence 1 Prolastin-C Subjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C Treatment Sequence 1 Liquid Alpha₁-PI Subjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C Treatment Sequence 2 Liquid Alpha₁-PI Subjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI Treatment Sequence 2 Prolastin-C Subjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI
- Primary Outcome Measures
Name Time Method AUC(0-7 Days) Based on Antigenic Content 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 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.
- Secondary Outcome Measures
Name Time Method AUC(0-7 Days) Based on Functional Activity 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 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.
Number of Subjects With Immunogenicity Response Weeks 1, 9, 17, and 20 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).
Trial Locations
- Locations (6)
University of Miami - Miller School of Medicine
🇺🇸Miami, Florida, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
PMG Research of Wilmington
🇺🇸Wilmington, North Carolina, United States
University of Texas Health Science Center
🇺🇸Tyler, Texas, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Florida Gainesville
🇺🇸Gainesville, Florida, United States