A randomized, adaptive design, double-blind, 3-arm, parallel study assessing the pharmacokinetics and safety of AVT02, a high-concentration (100 mg/mL) Adalimumab biosimilar, in healthy adult subjects (ALVOPAD FIRST)

Background: This study (ALVOPAD FIRST) assessed bioequivalence, safety, and immunogenicity of AVT02, an adalimumab biosimilar, compared with reference product adalimumab (EU- and US-approved Humira (R)). Methods: Healthy subjects (N = 392) were randomized 1:1:1 to receive one 40 mg dose of AVT02, EU-reference product, or US-reference product subcutaneously. An interim analysis was planned when similar to 30 subjects per arm had completed the study, to optimize final sample size. The primary PK parameters were C-max, AUC(0-t), and AUC(0-inf). Bioequivalence was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary pharmacokinetic (PK) parameters were all contained within the prespecified margins of 80% and 125%. Safety and immunogenicity were assessed until Day 64. Results: The 90% CI for the ratio of geometric means for the primary PK parameters, based on Fisher's Combination test analysis, were all contained within the prespecified bioequivalence margins of 80% and 125%, supporting the demonstration of bioequivalence between AVT02 and both EU- and US-reference product. The safety and immunogenicity profiles were comparable across all three treatment arms. Conclusion: PK bioequivalence was supported between AVT02, US-licensed- and EU-approved-reference product adalimumab. Similar safety and immunogenicity were also demonstrated.

Automated summary

This study assessed the bioequivalence, safety, and immunogenicity of AVT02 compared with reference product adalimumab. The results demonstrated bioequivalence between AVT02 and the reference product, and showed similar safety and immunogenicity profiles in all three treatment arms.