Facilitated subcutaneous immunoglobulin 10% at a target dose of 0.4 g/kg/infusion is well tolerated with accelerated or no dose ramp-up in healthy participants

Abstract

IntroductionTransitioning to recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) infusions from intravenous immunoglobulin therapies in primary immunodeficiency disease (PID) is implemented using a gradual dose ramp-up schedule, whereby infusion volumes are increased over a number of weeks to achieve the target dose level (TDL). This study investigated the tolerability and safety of fSCIG 10% at a TDL of 0.4 g/kg/infusion (i.e. 4 mL/kg/infusion) with accelerated and no dose ramp-up schedules in comparison with conventional dose ramp-up. MethodsThis was a phase 1, open-label, single-center trial (NCT04578535). This analysis compared three fSCIG 10% treatment arms at a TDL of 0.4 g/kg/infusion: (i) conventional dose ramp-up from 0.1 g/kg/infusion at Week 1 increasing to the TDL at Week 8; (ii) accelerated dose ramp-up from 0.2 g/kg/infusion at Week 1 increasing to the TDL at Week 5; (iii) the TDL administered without dose ramp-up. Participants were healthy adults aged 19–50 years. The primary endpoint was the tolerability of fSCIG 10% infusions, assessed as the proportion of participants who completed all initiated infusions without interruptions, stoppages or reductions in infusion rate due to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint. ResultsTwenty-four participants (mean [standard deviation] age 35.3 [8.6] years; 62.5% female) were assigned equally to the three treatment arms. All participants completed all initiated infusions except for one participant who experienced a headache resulting in an infusion rate reduction in the conventional dose ramp-up arm. All participants experienced local TEAEs, including infusion site swelling, erythema, pain and pruritus. Systemic TEAEs were experienced by 1/8 (12.5%), 2/8 (25.0%) and 2/8 (25.0%) participants in the conventional, accelerated and no dose ramp-up arms, respectively. All TEAEs were mild in severity. ConclusionsfSCIG 10% at a target dose of 0.4 g/kg/infusion showed a favorable safety and tolerability profile in healthy adults, with comparable tolerability and safety outcomes between the dose ramp-up treatment arms. Accelerated and no dose ramp-up schedules could be considered as potential alternatives to conventional dose ramp-up.Takeda Development Center Americas, Inc. funded this study. Takeda Pharmaceuticals International AG funded writing support.