A randomized, double-blind, 3-arm, parallel study assessing the pharmacokinetics, safety, tolerability and immunogenicity of AVT04, an ustekinumab candidate biosimilar, in healthy adults
Christopher Wynne, Paul Hamilton, Kristi McLendon, Heimo Stroissnig, Matthew Smith, Paul Duijzings, Ruth Ruffieux, Hendrik Otto, Abid Sattar, Halimu N. Haliduola, Steffen Leutz, Fausto Berti
Abstract
BACKGROUND: This study assessed pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT04, a candidate biosimilar, compared with reference product (RP) ustekinumab (EU-approved and US-licensed Stelara®). METHODS: = 298) were randomized 1:1:1 to receive one 45 mg dose of AVT04, EU-RP, or US-RP. The primary PK parameters were Cmax and AUC0-inf. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means were all contained within the prespecified margins of 80% and 125%. Additional PK parameters, including AUC0-t, were also assessed. Safety and immunogenicity were also assessed until Day 92. RESULTS: After pre-specified protein content normalization, the 90% CI for the ratio of geometric means for primary PK parameters were all contained within the pre-specified bioequivalence margins of 80% and 125%, supporting demonstration of PK similarity between AVT04 and both EU- and US-RP. Secondary PK parameters supported the analysis. Safety and immunogenicity profiles were comparable across all three treatment arms, although the study was not powered to detect small differences in these parameters. CONCLUSION: www.clinicaltrials.gov identifier is NCT04744363.