A Randomized, Phase I Pharmacokinetic Study Comparing SB2 and Infliximab Reference Product (Remicade(®)) in Healthy Subjects

Donghoon Shin, Youngdoe Kim, Yoo Seok Kim, Thomas Körnicke, Rainard Fuhr, Donghoon Shin, Youngdoe Kim, Yoo Seok Kim, Thomas Körnicke, Rainard Fuhr

Abstract

Objective: SB2, a biosimilar to infliximab reference product (INF), has an identical amino acid sequence and similar physicochemical functional properties to its reference product. The primary objective of this study is to demonstrate pharmacokinetic (PK) bioequivalence between SB2 and EU-sourced INF (EU-INF), between SB2 and US-sourced INF (US-INF), and between EU-INF and US-INF.

Methods: This study was a randomized, single-blind, three-arm, parallel group study in 159 healthy subjects. All subjects received a single 5 mg/kg intravenous infusion of study drug and then were observed for 10 weeks to study PK, safety and immunogenicity. The primary PK parameters were area under the concentration-time curve (AUC) from time zero to infinity (AUCinf), AUC from time zero to the last quantifiable concentration (AUClast) and maximum concentration (C max). Bioequivalence for the primary PK parameters was to be concluded using an analysis of variance (ANOVA) if the 90 % confidence intervals (CIs) for the ratio of geometric least squares means (LSMeans) of the treatments compared were completely contained within the pre-defined equivalence margin, 0.8-1.25.

Results: All of the 90 % CIs for the geometric LSMean ratios of primary PK parameters for each comparison were within the pre-defined equivalence margin. The proportion of subjects who experienced treatment-emergent adverse events was comparable between treatments. The incidences of anti-drug antibodies between the three treatments were comparable.

Conclusion: This study demonstrated biosimilarity of SB2 to its marketed reference products of infliximab in terms of PK equivalence in healthy subjects. SB2 was generally well tolerated and showed comparable safety and immunogenicity profiles to the reference products (ClinicalTrials.gov Identifier: NCT01922336).

Figures

Fig. 1
Fig. 1
Mean serum concentration-time profiles after single administration of infliximabs. a All subjects’ data included in the pharmacokinetic analysis of SB2, EU-sourced infliximab reference product, and US-sourced infliximab reference product; means of all subjects and ADA subgroups for b SB2, c EU-sourced infliximab reference product, and d US-sourced infliximab reference product. Bars represent standard deviations of all subjects’ data including ADA positive and ADA negative. ADA anti-drug antibody

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