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Randomized Controlled Trial
. 2021 Nov;87(11):4323-4333.
doi: 10.1111/bcp.14850. Epub 2021 May 9.

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  1 , Darin Brimhall  2 , Jonathan Kay  3 , Edward Keystone  4 , Sang Joon Lee  5 , Sung Hyun Kim  5 , Yun Ju Bae  5 , Eun Jin Choi  5 , Daniel E Furst  6   7   8
Affiliations
Randomized Controlled Trial

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 et al. Br J Clin Pharmacol. 2021 Nov.

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 (AUC0-inf ); area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-last ); maximum serum concentration (Cmax ). 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 (AUC0-inf : 93.98-114.29; AUC0-last : 91.09-121.86; Cmax : 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. AUC0-inf , AUC0-last and Cmax 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.

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Conflict of interest statement

Jonathan Kay has received consultancies, speaker fees and/or honoraria from AbbVie, Alvotech Suisse AG, Boehringer Ingelheim GmbH, Celltrion Healthcare Co. Ltd, Mylan Inc., Merck & Co., Inc., Novartis AG, Samsung Bioepis, Sandoz and UCB. Edward Keystone has received speaker honoraria and/or consultancies from AbbVie, Amgen, Celltrion, Gilead, Janssen, Lilly, Merck, Pfizer, Roche, Samsung Bioepis, Sandoz and Sanofi. Sang Joon Lee, Sung Hyun Kim, Yun Ju Bae and Eun Jin Choi are employed by Celltrion, Inc. Daniel E. Furst has received grant/research support from Corbus, CSL Behring, Galapagos, Gilead, GlaxoSmithKline, Kadmon, PICORI, Pfizer and Talaris, and consultancies from AbbVie, Amgen, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos, Gilead, Novartis, Pfizer, Roche/Genentech and Talaris. Antonia Davidson and Darin Brimhall have no conflicts of interest to report.

Figures

FIGURE 1
FIGURE 1
Subject flow diagram. a Due to out‐of‐range laboratory values or vital signs. AI = autoinjector; PFS = prefilled syringe
FIGURE 2
FIGURE 2
Mean (SD) serum concentrations of CT‐P17 for CT‐P17 AI and CT‐P17 PFS (PK population a). a In the CT‐P17 AI and CT‐P17 PFS groups, 6 and 7 subjects, respectively, were excluded due to absence of ≥3 time points following Cmax. Three subjects (CT‐P17 AI) were excluded due to major protocol deviations (whole volume of study drug was not administered successfully [n = 2] and dosing with morphine in a previous clinical study [n = 1]). AI = autoinjector; Cmax = maximum serum concentration; PFS = prefilled syringe; PK = pharmacokinetic; SD = standard deviation
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