Safety and Tolerability of 120 mg/kg Dose of Alpha1-Proteinase Inhibitor in Alpha-1 Antitrypsin Deficiency: A Multicenter, Randomized, Double-Blind, Crossover Study

Abstract

PURPOSE: Augmentation therapy with 60 mg/kg intravenous (IV) alpha1‐proteinase inhibitor (A1PI) has previously demonstrated a trough serum level of 11 Î1/4M in individuals with alpha‐1 antitrypsin deficiency (AATD). However, patients treated with weekly 60 mg/kg dose still have lower A1PI levels compared to non‐AAT deficient subjects. The safety and tolerability of weekly infusions of 120 mg/kg dose of A1PI in comparison with 60 mg/kg dose in patients with AATD was assessed. METHODS: Thirty adult subjects with AATD and COPD (28 PIZZ, 1 PIZ (Null), and 1 PIZ with an â€at risk†allele); (4 naÃ‐ve and 26 non‐naive), were randomized to receive 60 or 120 mg/kg of Prolastin‐C by weekly IV infusion for 8 weeks, followed by a crossover to the alternate dose for 8 weeks. Safety assessments included adverse events (AEs), pulmonary exacerbations (PEx), vital signs, FEV1, FVC and laboratory evaluations. RESULTS: Twenty‐one subjects (70%) in the 60mg/kg group experienced 60 AEs and 14 subjects (46.7%) in the 120mg/kg group experienced 37 AEs. Nine PEx occurred in 7 subjects (23.3%) of the 60mg/kg group and 6 PEx occurred in 5 subjects (16.7%) in the 120mg/kg group, none severe. The most frequent AEs were PEx in both the 60 mg/kg and 120 mg/kg treatment group. Five drug‐related AEs occurred in 3 (10%) subjects in the 60mg/kg group and 1 drug‐related AE occurred in 1 (3.3%) subject in the 120mg/kg group. No serious AEs occurred during the treatment phase and no subjects discontinued. All immunogenicity test results were negative. There were no safety concerns regarding laboratory assessments, FEV1, FVC or vital signs. CONCLUSIONS: A higher dose of 120 mg/kg Prolastin‐C was safe and well tolerated in subjects with AATD.