A Randomised Controlled Trial Comparing the Pharmacokinetics and Tolerability of the Proposed Adalimumab Biosimilar MSB11022 Delivered via Autoinjector and Pre-filled Syringe in Healthy Subjects

Abstract

Introduction: The aim of the study was to demonstrate the bioequivalence, and compare the safety and tolerability of MSB11022, a proposed biosimilar of adalimumab, when delivered by either an autoinjector (AI) or a pre-filled syringe (PFS). Methods: In this pharmacokinetic (PK), parallel group, open-label study, 216 healthy volunteers were randomised 1:1 to receive a single subcutaneous injection of a 40 mg/0.8 mL dose of MSB11022 administered via AI or PFS. Coprimary PK endpoints were maximum observed concentration (Cmax), area under the concentration–time curve (AUC) from time 0 to the last quantifiable concentration (AUC0–t), and AUC from time 0 extrapolated to infinity (AUC0–inf). PK equivalence between the AI and PFS administration methods was declared if the 90% confidence intervals (CIs) for the ratio of geometric least square means was entirely contained within the 80–125% equivalence margin for all coprimary endpoints. Safety and tolerability were also evaluated. Results: The 90% CI for the three coprimary PK endpoints (Cmax, AUC0–t and AUC0–inf) were entirely contained within the predefined equivalence margins of 80–125%. Mean serum concentration–time profiles were similar following injection via AI or PFS. Treatment-emergent adverse events (TEAEs) were comparable across both treatment groups. Study device-related TEAEs were reported by 11.3% and 13.1% of subjects in the AI and PFS treatment groups, respectively. Study drug-related TEAEs were reported by 28.3% and 34.6% of subjects in the AI and PFS treatment groups, respectively. Few subjects experienced injection-site reactions, mainly pain and erythema, regardless of the administration method. Conclusion: Delivery of MSB11022 via an AI is bioequivalent to delivery via a PFS. The safety and tolerability profile of MSB11022 was comparable across administration methods. The development of an AI for MSB11022 provides a choice of self-injection devices available to patients, potentially improving treatment compliance. Trial Registration: ClinicalTrials.gov trial identifier: NCT04018599.