Seoul National University College of Medicine and Hospital, Seoul, Korea.
Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
Clin Transl Sci. 2021 Jul;14(4):1280-1291. doi: 10.1111/cts.12967. Epub 2021 Mar 2.
This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT-P17 to United States-licensed adalimumab (US-adalimumab) and European Union-approved adalimumab (EU-adalimumab). This double-blind, parallel-group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT-P17, US-adalimumab, or EU-adalimumab. Primary end points were PK equivalence in terms of: area under the concentration-time curve from time zero to infinity (AUC ); AUC from time zero to the last quantifiable concentration (AUC ); and maximum serum concentration (C ). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80-125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT-P17; 103 US-adalimumab; 106 EU-adalimumab), 308 subjects received study drug. AUC , AUC , and C were equivalent among CT-P17, US-adalimumab, and EU-adalimumab, because 90% CIs for the ratios of GLSMs were within the 80-125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single-dose administration of CT-P17, EU-adalimumab, and US-adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars.
本研究旨在证明单剂量的阿达木单抗生物类似药 CT-P17 的药代动力学(PK)等效性,与美国许可的阿达木单抗(US-adalimumab)和欧盟批准的阿达木单抗(EU-adalimumab)。这是一项双盲、平行组、I 期临床试验(clinicaltrials.gov NCT03970824),在 10 家医院(韩国)进行,其中健康受试者(1:1:1)随机接受单次 40mg(100mg/ml)皮下注射 CT-P17、US-adalimumab 或 EU-adalimumab。主要终点是 PK 等效性,包括:从零时间到无穷大的浓度-时间曲线下面积(AUC );从零时间到最后可量化浓度的 AUC ;和最大血清浓度(C )。如果成对比较的几何最小二乘均值(GLSM)的百分比比值的 90%置信区间(CI)在 80-125%的等效区间内,则认为 PK 等效。还评估了其他 PK 终点、安全性和免疫原性。在 312 名随机分组的受试者中(CT-P17 组 103 名;US-adalimumab 组 103 名;EU-adalimumab 组 106 名),308 名受试者接受了研究药物。CT-P17、US-adalimumab 和 EU-adalimumab 之间的 AUC 、 AUC 和 C 等效,因为每个成对比较的 GLSM 比值的 90%CI 在 80-125%的等效区间内。次要 PK 终点、安全性和免疫原性在治疗组之间相似。总之,在健康成年人中,单次给予 CT-P17、EU-adalimumab 和 US-adalimumab 的 PK 等效性得到了证明。安全性和免疫原性特征在治疗组之间具有可比性,与阿达木单抗生物类似物的先前报告一致。