A Phase 3 Clinical Study to Evaluate the Long-Term Safety and Tolerability of 20% IGSC for Japanese Patients with PID

Background Subcutaneous immunoglobulin (Ig20Gly) is an effective and safe immunoglobulin replacement therapy for primary immunodeficiency disorders (PIDs), allowing home self-administration. While the efficacy and safety of 20% subcutaneous immunoglobulin (Ig20Gly) have been reported in Europe, North America, and Japan, data on long-term administration, particularly biweekly dosing, were limited. This study (TAK-664-3002) is a phase 3 open-label trial evaluating the safety and tolerability of long-term Ig20Gly administration (weekly or biweekly dosing) in Japan. Methods Twelve PID patients who completed the preceding study (TAK-664-3001) were enrolled. They continued receiving Ig20Gly in either the weekly group (5 patients) or the biweekly group (7 patients) and were followed. The primary endpoints were long-term safety and tolerability; secondary endpoints included pharmacokinetics, efficacy, and treatment preference. Results The median treatment duration was 893.5 days (range: 226–1,037 days). A total of 159 adverse events were reported in all 12 patients; however, only 15 events in 3 patients (25.0%) were judged to be related to the study drug. The majority of reported adverse events were mild to moderate in severity. There were no severe or serious related adverse events and no adverse events leading to discontinuation of the drug or withdrawal from the trial. The overall adverse event rate was 6.0 events per patient-year, and the related adverse event rate was 0.6 events per patient-year, both showing a decreasing trend with long-term administration. Serum IgG trough levels (geometric mean) at the end of the trial were maintained at stable, high levels: 11.0 g/L (1,100 mg/dL) in the weekly group and 8.98 g/L (898 mg/dL) in the biweekly group. No acute serious bacterial infections were observed, with an annual infection rate of 1.32 events per patient. The patient desire to continue treatment was 100% (5/5 patients) in the weekly group and 71% (5/7 patients) in the biweekly group. Conclusion Long-term administration of Ig20Gly once weekly or biweekly demonstrated efficacy, safety, and good tolerability in Japanese PID patients. These trial results support the usefulness of long-term Ig20Gly use in Japanese patients and are consistent with existing reports.