Safety Profile of High IgPro20 Infusion Parameters in Patients with Primary Immunodeficiency (PID): Results from The Forced Upward Titration HILO Study

Abstract

The Hizentra Label Optimization (HILO) study (NCT03033745) assessed safety and tolerability of increasing infusion rates/volumes of subcutaneous IgPro20 (Hizentra®) in PID patients. In this open-label nonrandomized phase 4 study, patients receiving IgPro20 were assigned to: Pump-assisted Volume Cohort (n=15; 25–50 mL/injection site, weekly); Pump-assisted Flow Rate Cohort (n=18; 25–100 mL/h/injection site, weekly); or Manual Push Flow Rate Cohort (n=16; 30–120 mL/h/injection site; 2–7 infusions/week). Assignments were based on prior experience with pump-assisted infusions at the highest approved IgPro20 parameters or frequent manual push infusions (∼25 mL/h). Treatment-emergent adverse events (TEAEs) were evaluated. The rate of TEAEs/infusion was low across cohorts: 0.145, 0.228, and 0.085 in the Pump-Assisted Volume Cohort, the Pump-Assisted Flow Rate Cohort, and the Manual Push Flow Rate Cohort, respectively. There were no clinically meaningful differences in TEAE frequency, type, intensity, or duration among cohorts, and rates of TEAEs/infusion did not increase with increasing infusion parameters. Most TEAEs were mild/moderate infusion site reactions (ISRs). Causally-related ISRs occurred in 4 patients (26.7%) in the Pump-Assisted Volume Cohort (0.079/infusion); 1 patient discontinued due to mild injection site pain. In the Pump-Assisted Flow Rate Cohort, 8 patients (44.4%) had related ISRs (0.131/infusion); 1 patient (5.6%) reported 2 severe related ISRs, but none discontinued. In the Manual Push Flow Rate Cohort, 6 patients (37.5%) had related ISRs (0.043/infusion); 1 patient (6.3%) had a severe, unrelated serious TEAE (suicide attempt) leading to discontinuation. High infusion parameters for pump-assisted and manual push subcutaneous IgPro20 infusions were tolerated well.