Tolerability and safety of facilitated subcutaneous immunoglobulin 20% in healthy adults: a phase 1 open-label study

Abstract

IntroductionFacilitated subcutaneous immunoglobulin 20% (fSCIG 20%) is human immunoglobulin G (IgG) 20% administered subcutaneously with recombinant human hyaluronidase (rHuPH20). rHuPH20 depolymerizes hyaluronan in subcutaneous tissue, which transiently allows for higher IgG administration volumes. This study assessed the tolerability and safety of fSCIG 20% at various infusion rates and infusion volumes in healthy adults. MethodsThis Phase 1, single-dose, open-label, three-arm study (NCT05059977) included healthy adults aged 19–50 years with a body mass index of 18.0–30.0 kg/m2, and was conducted at one US center. After screening, participants were assigned to one of the three treatment arms (TAs) and dosed sequentially. Participants received fSCIG 20% at a single dose of 0.4 g/kg (TA 1 with in-line warming) or 1 g/kg (TA 2 with in-line warming; TA 3 without warming) on day 1 of a 4-day treatment period. After dosing, participants were followed-up for up to 12 (± 1) weeks. ResultsIn total, 24 participants were enrolled (mean [standard deviation] age 39 [7.3] years; 54.2% male) with eight per treatment arm. All but one participant completed the study. All participants had tolerable fSCIG 20% infusions and achieved the target maximum tolerable infusion rate (300 mL/hour/site). The maximum fSCIG 20% volume per site was 300 mL (achieved by 5 and 7 participants in TAs 2 and 3, respectively). No infusions were stopped or interrupted owing to a treatment-emergent adverse event (TEAE). All participants experienced TEAEs: 107 TEAEs were reported (102 local, 5 systemic), of which 105 TEAEs were related to fSCIG 20% (25, 34 and 46 TEAEs in TAs 1, 2 and 3, respectively). No TEAEs were severe, serious or led to study discontinuation. One TEAE in one participant was of special interest (TA 1; catheter leakage). The most frequent TEAEs were infusion site-related (erythema, swelling, pruritis and pain; all reported by > 50% of participants overall). ConclusionsfSCIG 20% was well tolerated with a favorable safety profile at infusion rates up to 300 mL/hour/site in healthy adults. In-line warming had no substantial impact on tolerability or safety. Takeda Development Center Americas, Inc. funded this study. Takeda Pharmaceuticals International AG funded writing support.