Abstract
BackgroundFKB327 has been developed as a biosimilar of the adalimumab reference product (RP). We compared the pharmacokinetics (PK), safety, and immunogenicity of FKB327 with those of the adalimumab RP after a single dose by subcutaneous (SC) injection in Japanese male participants.MethodsTwo randomized, single-blind, single-dose studies were conducted in healthy Japanese male participants to compare PK characteristics between FKB327 and the RP. Study 1 included 130 participants who were randomized in a 1:1 ratio to receive a subcutaneous injection of 40 mg of either FKB327 or the RP into the abdomen. In Study 2, another 130 subjects were randomized in a 1:1 ratio to receive either drug as in Study 1, but the drug administration site was changed to the thigh. The primary PK endpoints of both studies were area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and maximum serum concentration; area under the concentration-time curve from time zero to 360 h was also evaluated as one of the primary endpoints in Study 1. Biosimilarity in terms of pharmacokinetics was determined if the 90% confidence interval of the mean difference in geometric mean ratio of all primary PK parameters was within the prespecified equivalence criteria (0.80–1.25). Immunogenicity and safety were also evaluated as secondary endpoints.ResultsThe serum concentration-time profiles were comparable between the FKB327 and the RP treatment groups in both studies. Primary PK parameters were within the prespecified bioequivalence range in Study 2, although AUC0-t was slightly outside the upper side of the range in Study 1. No differences in safety profile were observed in these studies. The incidence of anti-drug antibodies (ADAs) and impact of ADAs on PK profile were similar among the treatment groups in both studies.ConclusionBiosimilarity between FKB327 and the RP after a single 40-mg SC injection was confirmed in healthy Japanese male participants by modifying the study design.Trial registrationjRCT2071200058 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200058, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200058) and jRCT2071200057 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200057, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200057). Retrospectively registered 25/11/2020.
Highlights
FKB327 has been developed as a biosimilar of the adalimumab reference product (RP)
Adalimumab has been approved as a treatment for rheumatoid arthritis, psoriasis, inflammatory bowel disease, and other chronic immunemediated inflammatory diseases in the United States, the European Union, Japan, and other countries worldwide under the trade name Humira®, hereafter referred to as the reference product (RP) [1,2,3]
Anti-drug antibodies (ADAs) were detected by high-sensitivity Anti-drug antibody (ADA) assay methods used in recent biosimilar studies [5, 6], a low ADApositive ratio was reported in initial studies using a conventional ADA assay method [7]
Summary
We compared the pharmacokinetics (PK), safety, and immunogenicity of FKB327 with those of the adalimumab RP after a single dose by subcutaneous (SC) injection in Japanese male participants. High pharmacokinetic (PK) variability of the drug has been reported after subcutaneous (SC) injection [3, 4]. Anti-drug antibodies (ADAs) were detected by high-sensitivity ADA assay methods used in recent biosimilar studies [5, 6], a low ADApositive ratio was reported in initial studies using a conventional ADA assay method [7]. Given the wider PK variability of the RP, healthy male participants comprising a more homogeneous population without immunosuppressive conditions are considered a more sensitive population in which to assess the PK similarity of its biosimilar product [8,9,10]
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