Comparison of SB17 and reference ustekinumab in healthy adults: Arandomized, double-blind, single-dose, phase I study.

Abstract

This study compared the pharmacokinetic (PK) characteristics of SB17 (Samsung Bioepis, Incheon, Republic of Korea), a proposed biosimilar of ustekinumab (UST) against reference UST (Stelara, Janssen Biotech, Horsham, PA, USA). This double-blind, three-arm, parallel-group, single-dose study randomized 201 healthy adult subjects 1:1:1 to receive 45 mg of SB17, European Union-sourced UST (EU-UST) or United States of America-sourced UST (US-UST) via subcutaneous (SC) injection. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUCinf) and maximum serum concentration (Cmax). Safety, tolerability, and immunogenicity were investigated. All 90% confidence intervals (CIs) for the ratios of AUCinf and Cmax between groups were within the predefined bioequivalence margin of 0.8 - 1.25. The geometric LSMeans ratios of AUCinf and Cmax were 0.99 and 0.90 for SB17/EU-UST, 1.01 and 0.94 for SB17/US-UST, and 1.02 and 1.05 for EU-UST/US-UST, respectively. The proportion of subjects with treatment-emergent adverse events (TEAEs) was comparable between SB17, EU-UST, and US-UST (68.7, 58.2, and 65.7%). No deaths, serious adverse events (SAEs), or severe TEAEs were reported. The incidence of subjects testing positive for post-dose anti-drug antibodies (ADAs) was 26.9%, 34.3%, and 34.3% in the SB17, EU-UST, and US-UST groups, respectively. Among the subjects with a positive ADA result at day 99/end of study, 53.8% (SB17 n = 5, EU-UST n = 12, and US-UST n = 11) were positive for neutralizing antibodies (NAbs). This study demonstrated bioequivalence of SB17, EU-UST, and US-UST in terms of PK. Safety, tolerability, and immunogenicity were also comparable between all groups.