A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, pharmacodynamic, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (60 mg/mL) in healthy male adults.
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Abstract
Background: This study compared pharmacokinetic (PK) similarity, pharmacodynamic, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Prolia).
Methods: Healthy male participants (N = 209) were randomized 1:1 to receive one 60 mg dose of either AVT03 or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters (Cmax and AUC0-inf for EMA; Cmax and AUC0-t for FDA and PMDA) were within the prespecified margins of 80.00% and 125.00%. Secondary PK parameters assessed were AUC0-24, Tmax, Kel, t1/2, Vz/F, and CL/F. The serum biomarker of bone resorption, CTX-1 was evaluated to compare pharmacodynamic (PD) profiles. Safety and immunogenicity were also assessed.
Results: The 90% CI for the ratio of geometric means for primary PK parameters was contained between the pre-specified margins of 80.00% and 125.00% (Cmax [102.23, 113.64]; AUC0-inf [107.17, 118.87]; AUC0-t [107.72, 120.42]), supporting demonstration of PK similarity between AVT03 and RP. Secondary PK parameters supported the analysis. PD, safety and immunogenicity profiles were comparable between the two arms.
Conclusion: Results supported a demonstration of PK similarity between AVT03 and RP denosumab. Comparable PD, safety and immunogenicity profiles were also shown.
Clinical trial registration: The clinical trial is registered at https://www.clinicaltrials.gov under identifier NCT05126784.
期刊介绍：
Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development.
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Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies
Drug Evaluations reviewing the clinical and pharmacological data on a particular drug
Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials
The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
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