Kaur Primal, Chow Vincent, Zhang Nan, Moxness Michael, Kaliyaperumal Arunan, Markus Richard
Biosimilars Development, Amgen Inc., Thousand Oaks, California, USA.
Clinical Pharmacology, Modeling and Simulation, Amgen Inc., Thousand Oaks, California, USA.
Ann Rheum Dis. 2017 Mar;76(3):526-533. doi: 10.1136/annrheumdis-2015-208914. Epub 2016 Jul 27.
To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501.
Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC) and the maximum observed concentration (C). Secondary end points included safety and immunogenicity.
AUC and C were similar across the three groups. Geometrical mean ratio (GMR) of AUC was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of C was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUC and C were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups.
Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups.
EudraCT number 2012-000785-37; Results.
证明生物类似药候选药物ABP 501与美国和欧盟的阿达木单抗参比产品在药代动力学（PK）方面的相似性，并评估ABP 501的安全性、耐受性和免疫原性。
随机、单盲、单剂量、三臂、平行组研究；健康受试者被随机分为皮下注射40mg的ABP 501组（n = 67）、美国阿达木单抗组（n = 69）或欧盟阿达木单抗组（n = 67）。主要终点是从时间0外推至无穷大的血清浓度-时间曲线下面积（AUC）和最大观察浓度（C）。次要终点包括安全性和免疫原性。
三组的AUC和C相似。ABP 501与美国阿达木单抗之间AUC的几何平均比（GMR）为1.11，ABP 501与欧盟阿达木单抗之间为1.04。ABP 501与美国阿达木单抗之间C的GMR为1.04，ABP 501与欧盟阿达木单抗之间为0.96。AUC和C的GMR的90%置信区间在预先设定的0.80至1.25的标准PK等效标准范围内。与治疗相关的不良事件为轻度至中度，ABP 501组、美国阿达木单抗组和欧盟阿达木单抗组分别有35.8%、24.6%和41.8%的受试者报告了此类事件；研究组之间抗药抗体（ADAbs）的发生率相似。
本研究结果表明，单次皮下注射40mg后，ABP 501与美国阿达木单抗和欧盟阿达木单抗在PK方面相似。未发现ABP 501有新的安全信号。ABP 501的安全性和耐受性与参比产品相似，三组观察到的ADAb率相似。
EudraCT编号2012 - 000785 - 37；结果
