a study to assess safety and pk of liquid alpha₁-proteinase inhibitor (human) in treating alpha₁-antitrypsin deficiency

Conditions: Alpha₁-Antitrypsin Deficiency

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).


Eligibility criteria:
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