Shin Donghoon, Kim Youngdoe, Kim Yoo Seok, Körnicke Thomas, Fuhr Rainard
Samsung Bioepis Co., Ltd., 107 Chemdan-daero, Yeonsu-gu, Incheon, Republic of Korea.
PAREXEL International Early Phase Clinical Unit, Berlin, Germany.
BioDrugs. 2015 Dec;29(6):381-8. doi: 10.1007/s40259-015-0150-5.
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.
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.
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.
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).
SB2是英夫利昔单抗参比产品（INF）的生物类似药，其氨基酸序列与参比产品相同，理化功能特性相似。本研究的主要目的是证明SB2与欧盟来源的INF（EU-INF）、SB2与美国来源的INF（US-INF）以及EU-INF与US-INF之间的药代动力学（PK）生物等效性。
本研究是一项针对159名健康受试者的随机、单盲、三臂平行组研究。所有受试者接受一次5mg/kg的研究药物静脉输注，然后观察10周以研究PK、安全性和免疫原性。主要PK参数为从时间零点至无穷大的浓度-时间曲线下面积（AUCinf）、从时间零点至最后可定量浓度的AUC（AUClast）和最大浓度（Cmax）。如果所比较治疗的几何最小二乘均值（LSMeans）之比的90%置信区间（CIs）完全包含在预先定义的等效范围内（0.8 - 1.25），则使用方差分析（ANOVA）得出主要PK参数的生物等效性结论。
每次比较的主要PK参数几何LSMean比值的所有90% CIs均在预先定义的等效范围内。各治疗组中出现治疗突发不良事件的受试者比例相当。三种治疗之间抗药抗体的发生率相当。
本研究证明了SB2在健康受试者的PK等效性方面与其已上市的英夫利昔单抗参比产品具有生物相似性。SB2总体耐受性良好，并且在安全性和免疫原性方面与参比产品相当（ClinicalTrials.gov标识符：NCT01922336）。
