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

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 (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.

Publication types

  • Clinical Trial, Phase I
  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab* / administration & dosage
  • Adalimumab* / adverse effects
  • Adalimumab* / pharmacokinetics
  • Adult
  • Area Under Curve
  • Biosimilar Pharmaceuticals* / administration & dosage
  • Biosimilar Pharmaceuticals* / adverse effects
  • Biosimilar Pharmaceuticals* / pharmacokinetics
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Republic of Korea
  • Therapeutic Equivalency
  • Tumor Necrosis Factor Inhibitors* / administration & dosage
  • Tumor Necrosis Factor Inhibitors* / adverse effects
  • Tumor Necrosis Factor Inhibitors* / pharmacokinetics
  • Young Adult

Substances

  • Adalimumab
  • Biosimilar Pharmaceuticals
  • Tumor Necrosis Factor Inhibitors
  • CT-P17

Associated data

  • ClinicalTrials.gov/NCT03970824

Grants and funding