Randomised, phase I pharmacokinetic study of adalimumab biosimilar CT-P17 (40 mg/0.4 mL) by autoinjector and prefilled syringe in healthy subjects

Antonia Davidson; Darin Brimhall; Jonathan Kay; Edward Keystone; Sang Joon Lee; Sung Hyun Kim; Yun Ju Bae; Eun Jin Choi; Daniel E Furst

doi:10.1111/bcp.14850

Randomised, phase I pharmacokinetic study of adalimumab biosimilar CT-P17 (40 mg/0.4 mL) by autoinjector and prefilled syringe in healthy subjects

Br J Clin Pharmacol. 2021 Nov;87(11):4323-4333. doi: 10.1111/bcp.14850. Epub 2021 May 9.

Authors

Antonia Davidson¹, Darin Brimhall², Jonathan Kay³, Edward Keystone⁴, Sang Joon Lee⁵, Sung Hyun Kim⁵, Yun Ju Bae⁵, Eun Jin Choi⁵, Daniel E Furst^{6

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Affiliations

¹ PPD Development, Austin, Texas, USA.
² PPD Development, Las Vegas, Nevada, USA.
³ University of Massachusetts Medical School and UMass Memorial Medical Center, Worcester, Massachusetts, USA.
⁴ Mount Sinai Hospital, University of Toronto, Toronto, Canada.
⁵ Celltrion, Inc., Incheon, Republic of Korea.
⁶ University of California, Los Angeles, California, USA.
⁷ University of Washington, Seattle, Washington, USA.
⁸ University of Florence, Florence, Italy.

Abstract

Aims: To evaluate pharmacokinetic equivalence and preliminary safety of the adalimumab biosimilar CT-P17 administered via autoinjector (CT-P17 AI) or prefilled syringe (CT-P17 PFS) in healthy subjects.

Methods: This phase I, open-label study (ClinicalTrials.gov: NCT04295356) randomised subjects (1:1) to receive a single 40-mg (100 mg/mL) dose of CT-P17 AI or CT-P17 PFS. Primary endpoint was pharmacokinetic equivalence of CT-P17 AI to CT-P17 PFS for: area under the concentration-time curve from time zero to infinity (AUC_0-inf ); area under the concentration-time curve from time zero to the last quantifiable concentration (AUC_0-last ); maximum serum concentration (C_max ). Equivalence was determined if the 90% confidence interval for the geometric least-squares mean ratio was within the 80-125% equivalence margin. Additional pharmacokinetic endpoints, safety and immunogenicity were evaluated.

Results: Of 193 subjects who were randomised (98 CT-P17 AI; 95 CT-P17 PFS), 180 received study drug. Pharmacokinetic equivalence was demonstrated: 90% confidence intervals were within the 80-125% equivalence margin (AUC_0-inf : 93.98-114.29; AUC_0-last : 91.09-121.86; C_max : 94.08-111.90). Mean serum CT-P17 concentrations, secondary pharmacokinetic parameters and numbers of subjects with antidrug antibodies (ADAs) or neutralising ADAs were comparable between groups. AUC_0-inf , AUC_0-last and C_max were numerically lower for ADA-positive than for ADA-negative subjects (both groups); pharmacokinetic equivalence was also demonstrated among ADA-positive subjects. CT-P17 AI and CT-P17 PFS were well tolerated, with comparable overall safety profiles.

Conclusions: CT-P17 AI and CT-P17 PFS were pharmacokinetically equivalent. Overall safety and immunogenicity were comparable between the 2 delivery devices.

Keywords: biologicals; drug delivery; monoclonal antibodies; pharmacokinetics; phase I.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adalimumab / adverse effects
Area Under Curve
Biosimilar Pharmaceuticals* / adverse effects
Healthy Volunteers
Humans
Syringes
Therapeutic Equivalency
Tomography, X-Ray Computed

Substances

Biosimilar Pharmaceuticals
Adalimumab

Associated data

ClinicalTrials.gov/NCT04295356