Efficacy and safety of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency diseases

Hirokazu Kanegane, Kohsuke Imai, Masafumi Yamada, Hidetoshi Takada, Tadashi Ariga, Martin Bexon, Mikhail Rojavin, Wilson Hu, Midori Kobayashi, John-Philip Lawo, Shigeaki Nonoyama, Toshiro Hara, Toshio Miyawaki, Hirokazu Kanegane, Kohsuke Imai, Masafumi Yamada, Hidetoshi Takada, Tadashi Ariga, Martin Bexon, Mikhail Rojavin, Wilson Hu, Midori Kobayashi, John-Philip Lawo, Shigeaki Nonoyama, Toshiro Hara, Toshio Miyawaki

Abstract

Purpose: Intravenous (IVIG) and subcutaneous (SCIG) immunoglobulin infusions are widely used for the treatment of patients with primary immunodeficiency (PID) worldwide. This prospective, multicenter, open-label, single-arm Phase III study evaluated the efficacy, tolerability, and safety of IgPro20 (Hizentra®; L-proline-stabilized 20 % human SCIG) in adult and pediatric Japanese patients with PID.

Methods: Patients received three IVIG infusions at 3-4-week intervals followed by a dose-equivalent switch to weekly SCIG infusions. A 12-week wash-in/wash-out period was followed by a 12-week SCIG efficacy period. The primary efficacy endpoint was the comparison of total serum IgG trough levels during the IVIG and SCIG efficacy periods by calculating the geometric mean ratio (GMR).

Results: The GMR of IgG trough levels on SCIG versus IVIG was 1.09 (2-sided 90% confidence interval: 1.06-1.13). No serious bacterial infections were reported. Eleven patients (52.4%) had infectious episodes with an overall rate of 2.98 infections/patient/year; 7 patients (33.3%) missed school/work/daycare due to infection (3.48 days/patient/year). Sixteen patients (76.2%) were treated with antibiotics for an adverse event (AE; 47.6%) or prophylaxis (23.8%), resulting in 167.42 days/patient/year of antibiotic use. During SCIG treatment, 24 patients (96.0%) had 269 AEs (0.461 AEs per/infusion) including local reactions as the most common AE (20 patients, 80.0%). Local tolerability of IgPro20 was assessed as "very good" or "good" after 85.4% of SCIG infusions. One patient (4.0%) experienced a serious AE of moderate severity (bacterial infection) that was considered unrelated to study medication.

Conclusion: IgPro20 was effective and well tolerated in Japanese patients with PID.

Figures

Fig. 1
Fig. 1
Study design. Patients received three mandatory IVIG infusions at 3- or 4-week intervals (times for 4-week intervals are shown in brackets), followed by 24 weekly SCIG infusions during the wash-in/wash-out period (Weeks 1–12) and SCIG efficacy period (Weeks 13–25). There were two follow-up visits: completion visit (Week 25) and viral safety follow-up visit 12–17 weeks after completion. The horizontal curve schematically represents the expected fluctuations of serum IgG levels before (dashed curve) and during the SCIG efficacy period (solid curve)
Fig. 2
Fig. 2
Patient disposition. All 25 screened patients were enrolled into the study and received mandatory IVIG treatment. One patient discontinued from the study during the SCIG wash-in/wash-out period, leaving 24 patients who completed the study
Fig. 3
Fig. 3
Mean total serum IgG trough levels (PPS). Mean total serum IgG trough levels are shown for the PPS (N = 21). The number of patients with available IgG levels differed from the original patient number in the PPS at Week 20 (N = 20; *) and Week 24 (N = 18; **). Error bars represent the standard error of the mean

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