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
This study compared pharmacokinetic (PK) similarity, pharmacodynamic, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Prolia). Healthy male participants (<i>N</i> = 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 (C<sub>max</sub> and AUC<sub>0-inf</sub> for EMA; C<sub>max</sub> and AUC<sub>0-t</sub> for FDA and PMDA) were within the prespecified margins of 80.00% and 125.00%. Secondary PK parameters assessed were AUC<sub>0–24</sub>, T<sub>max</sub>, K<sub>el</sub>, t<sub>1/2</sub>, V<sub>z</sub>/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. 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% (C<sub>max</sub> [102.23, 113.64]; AUC<sub>0-inf</sub> [107.17, 118.87]; AUC<sub>0-t</sub> [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. Results supported a demonstration of PK similarity between AVT03 and RP denosumab. Comparable PD, safety and immunogenicity profiles were also shown. The clinical trial is registered at https://www.clinicaltrials.gov under identifier NCT05126784.
Publication Details
- Journal
- Figshare
- Published
- 2025-01-01
- DOI
- https://doi.org/10.6084/m9.figshare.29062245.v1
- Primary Topic
- Biosimilars and Bioanalytical Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00