Discussion
swelling, erythema, TEAEs, pruritis, pain, PIDs
ADVERSE EVENTS, INFLAMMATION, ERYTHEMA, HAND SWELLING
This phase 1, open-label study assessed the tolerability and safety profile of fSCIG 20%, which combines the benefits of both IVIG and SCIG therapies while offering smaller infusion volumes for the same dose than less-concentrated treatments, less frequent infusions, and reduced infusion duration and needle sticks than with conventional SCIG. Infusions of warmed and unwarmed fSCIG 20% were well-tolerated in all participants at rates of up to 300 mL/h/site, with favorable safety profiles. These findings are of particular importance when considering the potential benefits to patients offered by fSCIG 20% in terms of increased convenience and reduced treatment burden and the potential opportunities for individualized treatment and improved patient convenience.Assessing the safety, tolerability, and infusion parameters of immunoglobulin therapies under development in healthy participants provides critical data when determining an optimal administration strategy and in understanding their potential safety and tolerability in future studies in larger patient populations. The tolerability of fSCIG 20% infusion seen in this analysis was favorable, despite higher infusion rates and increased concentration when compared with conventional SCIG 20% [All participants experienced TEAEs; nearly all TEAEs were related to fSCIG 20% infusions, and all were CTCAE grade 1, indicating that they were mild in severity. In keeping with results from the current analysis, previous studies of fSCIG 10% and conventional SCIG 20% reported that TEAEs were most frequently mild in severity [Nearly all TEAEs were local infusion site reactions, and all participants experienced local infusion site reactions in this study, most frequently infusion site erythema and swelling, which is consistent with administration of conventional SCIG. Local infusion site reactions most often reported by previous patient studies of fSCIG 10% and conventional SCIG 20% include infusion site erythema, pain, pruritis, swelling, inflammation, and discomfort [Warming of IgG 20% may potentially reduce the viscosity of concentrated IgG therapies and improve tolerability. In this study, all infusions were tolerated, and a maximum tolerable infusion rate of 300 mL/h/site was achieved in all treatment arms, with and without inline warming. Although the unwarmed arm at the 1 g/kg dose level appeared to be associated with a slightly greater number of TEAEs, all TEAEs were mild in severity. It should also be noted that seven of the eight patients required two infusion sites owing to dose. Based on the findings of this study, and considering the complexity and reduced patient convenience of using a warming device (important factors in patient preference for SCIG therapies [The strengths of this study include the application of the sequential and sentinel study design to ensure optimal tolerability and safety assessment and comparison of warmed and unwarmed treatment. This study also included healthy participants, who are often included in studies of monoclonal antibodies [This study was limited by a relatively small sample size and inclusion of only a small number of participants who received unwarmed fSCIG 20%. The study also included healthy participants who may have not received prior immunoglobulin therapy and received only a single dose of fSCIG 20%; the frequency and characteristics of adverse events in these participants may, therefore, be different in some cases to those of patients who regularly receive IgRT. Nonetheless, results support further evaluation of fSCIG 20% in patients with PIDs. Further clinical development will aim to identify the optimal method of administration for fSCIG 20% that provides the best patient experience, reduces treatment burden, and shortens infusion times compared with existing IgRT, as well as allowing for individualized treatment regimens.