A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults

This study (NCT05876949) compared the pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Xgeva). Healthy male participants (<i>N</i> = 208, including 24 Japanese participants) were randomized 1:1 to receive one 120 mg dose of 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_max and AUC_0-t were within 80.00% and 125.00%. Additional PK parameters included AUC_0-inf, t_max, K_el, t_1/2, V_z/F, and CL/F. Safety and immunogenicity were also assessed. The 90% CIs for the ratio of geometric means for the primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (C_max [98.26, 110.00]; AUC_0-t [102.30, 113.60]), supporting demonstration of PK similarity. Consistency between Japanese participants and the overall population was shown. Safety and immunogenicity profiles were comparable between the two treatment arms. Results supported demonstration of PK similarity between AVT03 and RP. AVT03 had a safety and immunogenicity profile comparable to RP. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05876949); and 2022 -003,659-32 (EudraCT).