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

A Multi-center, Randomized, Double-blind, Crossover Study to Assess the Safety and Pharmacokinetics of Liquid Alpha₁-Proteinase Inhibitor (Human) Compared to Prolastin®-C in Subjects With Alpha₁-Antitrypsin Deficiency

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).

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:

• 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