A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects.

The study aims to evaluate the pharmacokinetic (PK) similarity of the proposed biosimilar HS628 compared with the reference tocilizumab (Actemra®), also to demonstrate similar safety and immunogenicity profiles in healthy Chinese male subjects. Eighty eligible subjects were randomized into two treatment groups in a 1:1 ratio, to receive a single intravenous (IV) infusion of HS628 or Actemra® at 4 mg/kg over 60 minutes. Blood samples were collected at the scheduled time points for PK and immunogenicity analysis. PK biosimilarity was determined using the standard bioequivalence criteria 80%-125%. Total 77 subjects received the study drug and completed the study. Main PK parameters were similar for the test group and reference group. The ratio of geometric least-squares means (GMR) and its 90% CIs for AUC 0-t , AUC 0-∞ and C max between test group and reference group was 1.06 (1.00-1.12), 1.07 (1.00-1.14) and 1.04 (0.99-1.10), respectively, which was fully within the predefined bioequivalent range 80%-125%. The incidence of treatment emergent adverse events (TEAEs) was similar for HS628 and Actemra® (P>0.05). The most common TEAEs were fibrinogen decreased, neutrophil decreased, pharyngalgia, oral ulcer, leukocyte decreased, erythrocyte sedimentation rate increased. The results of present study provide strong evidence to support the PK similarity and bioequivalence between HS628 and Actemra®. The safety and immunogenicity profiles of HS628 was also shown to be similar to the reference tocilizumab.