Safety of bi-weekly infusion of A1-PI augmentation therapy in RAPID

Background The RAPID trial showed that infusion of alpha 1 -proteinase inhibitor (A 1 -PI; 60mg/kg/week) slows lung density decline in A 1 -PI-deficient patients (Chapman et al., Lancet, In Press). Aim To assess the safety of bi-weekly infusion of 120mg/kg A 1 -PI (Zemaira ® , CSL Behring) given to cover 2-week periods when patients were unable to receive weekly dosing. Methods Subjects were monitored for 7 days post biweekly 120mg/kg A 1 -PI infusion and the profile of adverse events (AEs) compared with placebo. Results In total, 75 of 93 subjects (80.6%) received 333 bi-weekly infusion of 120mg/kg A 1 -PI (3.9% of 8,538 total infusions), and 70 of 87 subjects (80.5%) received 374 bi-weekly placebo infusions (5.2% of 7,192 total infusions). Predicted C max was 45.1µM after 120mg/kg and 28.5µM after 60mg/kg. The number of AEs after 120mg/kg A 1 -PI was comparable to placebo. Three serious AEs (bladder cancer; transurethral prostatectomy; chest pain) occurred with 120mg/kg A 1 -PI and none with placebo. None were considered related to treatment. Conclusions Bi-weekly 120mg/kg A 1 -PI infusion was well tolerated, with an AE profile comparable to placebo. This short-term option enhances convenience for patients in the future.