Feasibility Assessment of Facilitated Subcutaneous Immunoglobulin 1.0 G/Kg with Abbreviated Dose Ramp-Up and without Ramp-Up: A Phase 1 Tolerability and Safety Study in Healthy Adults (P6-4.003)

Abstract

<h3>Objective:</h3> To assess the feasibility of infusions of facilitated subcutaneous immunoglobulin (fSCIG; immunoglobulin infusion with recombinant human hyaluronidase) at a 1.0g/kg target dose via an abbreviated dose ramp-up or no ramp-up versus conventional ramp-up in healthy participants, based on tolerability and safety outcomes. <h3>Background:</h3> When transitioning from intravenous to facilitated subcutaneous dosing, dose ramp-up is used to incrementally increase infusion volumes to achieve target doses, acclimating patients to high-volume infusions. <h3>Design/Methods:</h3> This phase 1, open-label, single-center trial enrolled healthy adults aged 19–50 years (NCT04578535). Participants were assigned into three fSCIG arms (each with a 1.0g/kg target dose): (1) conventional dose ramp-up (0.25g/kg [Week 1] to 1.0g/kg [Week 8]), (2) abbreviated dose ramp-up (0.50g/kg [Week 1] to 1.0g/kg [Week 5]), or (3) 1.0g/kg without ramp-up. fSCIG tolerability (primary endpoint) was assessed as the proportion of participants completing all initiated infusions without interruptions or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety endpoints included the rates of TEAEs per person-year. <h3>Results:</h3> Overall, 27 participants were enrolled (mean age 34.9 years); with 8, 9, and 10 participants in the conventional, abbreviated, and no ramp-up arms, respectively. Participants completed all initiated infusions. No discontinuations due to TEAEs occurred but discontinuations were proportionally highest in the no ramp-up group. In total, 69.7, 74.0 and 99.7 TEAEs occurred per person-year in the conventional, abbreviated and no ramp-up arms, respectively. No serious or severe TEAEs occurred. <h3>Conclusions:</h3> fSCIG was well-tolerated in healthy adults with or without dose ramp-up at a 1.0 g/kg target dose, but the higher proportion of discontinuations in the no ramp-up arm may provide indirect evidence of better tolerability with ramp-up. The feasibility of abbreviated ramp-up was demonstrated by the lower TEAE rates seen in the dose ramp-up arms. Therefore, administration schedules can be individualized according to physician discretion based on tolerability. <b>Disclosure:</b> Zhaoyang Li has received personal compensation for serving as an employee of Takeda. Andras Nagy has nothing to disclose. Mr. Khaskhely has nothing to disclose. Mr. Lindner has received personal compensation for serving as an employee of Takeda. Mr. Lindner has stock in Takeda. Kimberly Duff has nothing to disclose. Dr. Garcia has received personal compensation for serving as an employee of Takeda Pharmaceutical Company Limited. Dr. Garcia has stock in Takeda Pharmaceutical Company Limited. Dr. AY has received personal compensation for serving as an employee of Takeda. Dr. Rondon has nothing to disclose. Prof. Yel has received personal compensation for serving as an employee of Takeda. Prof. Yel has stock in Takeda. Prof. Yel has received publishing royalties from a publication relating to health care.