Efficacy and safety of hyaluronidase-facilitated subcutaneous immunoglobulin 10% in US pediatric patients with primary immunodeficiency disease

Abstract

IntroductionThis study assessed the efficacy and safety of facilitated subcutaneous immunoglobulin (fSCIG; immunoglobulin G [IgG] 10% and recombinant human hyaluronidase [rHuPH20]) in US pediatric patients with primary immunodeficiency disease (PIDD). MethodsThis phase 3, open-label, prospective study (NCT03277313) was conducted at 17 centers in the US. Patients were eligible for enrollment if they were aged 2 to <16 years, diagnosed with PIDD requiring immunoglobulin replacement therapy and had received a consistent IgG dose for ≥3 months prior to screening. Patients received fSCIG 10% using a dose ramp-up over ≤6 weeks (Epoch 1) followed by fSCIG 10% treatment every 3 or 4 weeks for ≤3 years (Epoch 2). The primary endpoint, rate of acute serious bacterial infections (ASBIs), was compared with the regulatory-defined threshold (< 1.0 ASBIs per patient-year). ResultsFinal data were provided by 44 patients for Epoch 1 (mean age [range] 9.0 [3–15] years, 59.1% male) and 43 patients for Epoch 2; 34 patients completed the study. Two ASBIs (both bacterial pneumonia) were reported in the same patient. The mean rate of ASBIs (0.04 events/patient-year [99% upper confidence interval: 0.20]) was significantly lower than the regulatory-defined threshold. The mean rate of all infections was 3.12 events/patient-year. Stable mean serum trough IgG levels were maintained during Epoch 2 (10.4, 9.2, and 9.2 g/L at Months 0, 6 and 12, respectively). Excluding infections, 336 fSCIG-related treatment-emergent adverse events (TEAEs) were reported in 34 patients (Epochs 1 and 2 combined); most were mild (247 events in 32 patients) and two TEAEs in two patients were severe (celiac disease flare and headache). One serious TEAE of tonsillar hypertrophy was considered unrelated to fSCIG 10%. One patient developed anti-rHuPH20 binding antibodies (titer ≥160) without neutralizing anti-rHuPH20 antibodies. At end of Epoch 2, the majority of patients stated that they would choose to continue fSCIG 10%. ConclusionsfSCIG 10% effectively prevented ASBIs in US pediatric patients with PIDD with a safety profile consistent with previous clinical studies. Takeda Development Center Americas, Inc. and Baxalta funded this study. Takeda Pharmaceuticals International AG funded writing support.