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

• Published in: Clinical and translational science Vol. 14; no. 4; pp. 1280 - 1291
• Main Authors: Yu, Kyung‐Sang, Jang, In‐Jin, Lim, Hyeong‐Seok, Hong, Jang Hee, Kim, Min‐Gul, Park, Min Kyu, Cho, Doo‐Yeoun, Park, Min Soo, Chung, Jae Yong, Ghim, Jong‐Lyul, Lee, SeungHwan, Yoon, Seok Kyu, Kwon, In Sun, Lee, Sang Joon, Kim, Sung Hyun, Bae, Yun Ju, Cha, Jung Bin, Furst, Daniel E., Keystone, Edward, Kay, Jonathan
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2021; John Wiley and Sons Inc; Wiley
• Subjects: Adalimumab - administration & dosage; Adalimumab - adverse effects; Adalimumab - pharmacokinetics; Adult; Area Under Curve; Arthritis; Biological products; Biosimilar Pharmaceuticals - administration & dosage; Biosimilar Pharmaceuticals - adverse effects; Biosimilar Pharmaceuticals - pharmacokinetics; Dictionaries; Double-Blind Method; Drug dosages; Electrocardiography; FDA approval; Female; Healthy Volunteers; Hepatitis; Humans; Immunogenicity; Injections, Subcutaneous; Licenses; Male; Medical laboratories; Middle Aged; Monoclonal antibodies; Patients; Pharmacokinetics; Republic of Korea; Safety; Syphilis; Therapeutic Equivalency; TNF inhibitors; Tuberculosis; Tumor Necrosis Factor Inhibitors - administration & dosage; Tumor Necrosis Factor Inhibitors - adverse effects; Tumor Necrosis Factor Inhibitors - pharmacokinetics; Tumor necrosis factor-TNF; Young Adult; Republic of Korea; United States > US; Europe
• ISSN: 1752-8054; 1752-8062; 1752-8062
• DOI: 10.1111/cts.12967

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 (AUC0–inf); AUC from time zero to the last quantifiable concentration (AUC0–last); and maximum serum concentration (Cmax). 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. AUC0–inf, AUC0–last, and Cmax 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.