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CT-P17 与高浓度(100mg/ml)参考阿达木单抗的药代动力学等效性:一项在健康受试者中的随机 I 期研究。

Pharmacokinetic equivalence of CT-P17 to high-concentration (100 mg/ml) reference adalimumab: A randomized phase I study in healthy subjects.

机构信息

Seoul National University College of Medicine and Hospital, Seoul, Korea.

Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.

出版信息

Clin Transl Sci. 2021 Jul;14(4):1280-1291. doi: 10.1111/cts.12967. Epub 2021 Mar 2.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc71/8301575/6fec754631b7/CTS-14-1280-g001.jpg

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