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.

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 ( = 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 and AUC for EMA; C and AUC for FDA and PMDA) were within the prespecified margins of 80.00% and 125.00%. Secondary PK parameters assessed were AUC, T, K, t, V/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% (C [102.23, 113.64]; AUC [107.17, 118.87]; AUC [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.