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

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_0-inf ); AUC from time zero to the last quantifiable concentration (AUC_0-last ); and maximum serum concentration (C_max ). 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_0-inf , AUC_0-last , and C_max 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.

Figure 1

Subject flow diagram. EU‐adalimumab, European Union‐approved adalimumab; US‐adalimumab, United States‐licensed adalimumab. ^†Grade 2 alopecia areata considered related to study drug

Figure 2

Mean (SD) serum concentrations of CT‐P17, EU‐adalimumab, and US‐adalimumab (PK population). EU‐adalimumab, European Union‐approved adalimumab; PK, pharmacokinetic; US‐adalimumab, United States‐licensed adalimumab