Safety and tolerability of IgPro10 in Japanese primary immunodeficiency patients: a registrational study.

Studies investigating the safety of IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, USA) in Japanese patients with primary immunodeficiency (PID) are lacking. This study evaluated safety and tolerability of IgPro10 in Japanese patients with PID. In this prospective, open-label, single-arm, registrational study for Japan, IgPro10 was administered intravenously at pre-study doses of 138-556 mg/kg body weight per 3-/4-weekly dosing cycle for up to 4 months. Frequency and intensity of adverse events (AEs), their relationship to IgPro10 and AE rate per infusion (AERI) were evaluated. Of 11 enrolled patients, 10 completed the study. The median (range) total duration of exposure was 16.14 (4.1-16.3) weeks. Eight patients reported 19 AEs, none severe (based on maximum severity), giving an AERI of 0.442. One AE was deemed related to IgPro10 treatment. Three patients experienced temporally associated AEs. No serious AEs or deaths were reported. Nine patients (90%) who completed the study tolerated flow rates of ≥ 8 mg/kg/min; 5 tolerated 12 mg/kg/min (7.2 mL/kg/h), translating into a threefold decrease in mean infusion time. IgPro10 was well tolerated at a flow rate of up to 12 mg/kg/min. Safety and tolerability findings were consistent with previously reported studies in non-Japanese patients with PID.

Pharmacokinetic properties of Privigen® in Japanese patients with primary immunodeficiency.

This prospective, Phase 3, open-label, study (EudraCT: 2016-001631-12) evaluated pharmacokinetic (PK) characteristics of 3-/4-weekly Privigen® (IgPro10, CSL Behring, King of Prussia, PA, USA) in Japanese patients with PID. PK parameters including serum trough immunoglobulin (IgG) level before next infusion during the wash-in/wash-out phase (Ctrough), area under the concentration-time curve from time point zero to the last time point with quantifiable concentration (AUC0-last), dose-adjusted AUC0-last (dAUC), lowest and highest observed IgG levels (Cmin, Cmax), time to reach Cmax (Tmax), and total clearance (CL) were analyzed for both regimens of Privigen® (dose: 138-554 mg/kg body weight). Ten patients were included in this analysis (3-/4-weekly: n = 2/n = 8). Ctrough levels achieved ranged 7.96-10.05 g/L. Cmax was observed approximately 1 h after the start of the infusion in both regimens. Mean (SD [not applicable for 3-weekly data]) PK parameters: Cmax, 16.60 and 14.20 (5.53) g/L; Cmin, 10.60 and 8.53 (3.89) g/L; AUC0-last, 5971 and 6591 (2633) g*h/L; dAUC, 0.41 and 0.46 (0.19) g*h/L/mg; CL, 2.53 and 2.53 (1.00) mL/h and median Tmax was 1.19 and 1.14 h, for 3-/4-weekly dosing regimens, respectively. Privigen® PK characteristics in Japanese patients were similar between dosing regimens and to previously-reported results in non-Japanese patients with PID.