A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects

BACKGROUND/OBJECTIVE: FKB327 is a biosimilar of the adalimumab reference product (RP). The primary objective was to assess the relative bioavailability of FKB327 after a single subcutaneous (SC) dose via prefilled syringe (PFS), auto-injector (AI), or vial with a disposable syringe (vial), in healthy subjects. METHODS: This randomized, open-label, parallel-group, single SC-dose study was conducted in 195 healthy male and female subjects who were randomized 1:1:1 to receive FKB327 40 mg via PFS, AI, or vial. The primary pharmacokinetic (PK) parameters, areas under the serum concentration-time curve to the last detectable value (AUC(0-t)) and extrapolated to infinity (AUC(0-∞)), and maximum concentration (C(max)), were compared. Relative bioavailability was established if the ratio of geometric least squares (LS) means of the test product was within the predefined bioequivalence (BE) range of 0.80 to 1.25 of the RP for each comparison. Safety and immunogenicity were assessed. RESULTS: The mean serum FKB327 concentration-time profiles appeared similar across all 3 presentations. AUC(0-t), AUC(0-∞), and C(max) were within the predefined BE range for PFS compared with vial, suggesting comparable bioavailability. AUC(0-∞) and C(max) of AI compared with vial and PFS were fully contained within BE range, although the upper limit of 90% confidence intervals of the geometric LS means ratios for AUC(0-t) was slightly high. Treatment-emergent adverse events in all 3 groups were mild, with no new safety concern with FKB327 identified. Similar immunogenicity was observed among administrations. CONCLUSION: Among all 3 delivery methods, PK characteristics, safety profiles, and immunogenicity were similar. TRIAL REGISTRATION: EU Clinical Trials Registry EudraCTN2014–004469-26, registered October 14, 2014.