A randomized phase-I pharmacokinetic trial comparing the potential biosimilar tocilizumab (QX003S) with the reference product (Actemra(®)) in Chinese healthy subjects

PURPOSE: QX003S is a biosimilar candidate for the reference tocilizumab, Actemra®. We investigated the tolerance, variability, and pharmacokinetics (PK) of QX003S biosimilar in healthy Chinese male subjects. DESIGN: A randomised, double-blind, two-arm, parallel study was performed to examine the bioequivalence of QX003S (8 mg/kg) with that of Actemra® as a reference drug. RESULTS: QX003S (N = 40) and Actemra® (N = 40) groups exhibited similar PK properties. The inter-subject variability ranged from 14.95% to 18.78%. The 90% confidence intervals of the ratios for C(max), AUC(0–t) andAUC(0–∞) in both groups were within the range of 80–125%. After administration, the number of subjects who tested positive for anti-drug antibodies (ADA) in the QX003S group and Actemra® groups was 6 (14.3%) and 14 (34.1%), respectively. Adverse reactions occurred in 100% and 97.6% subjects in the QX003S and Actemra® groups, respectively. The most common adverse reactions were decrease in fibrinogen level and neutrophil and leukocyte counts. CONCLUSION: The PK characteristics and immunogenicity exhibited by QX003S were similar to that of the reference product, Actemra®. The safety profile was similar in the two treatment groups with mild-moderate adverse effects. TRIAL REGISTRATION: The trial is registered at Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html#CTR20190002): KEY POINTS: This was the first clinical report of a new proposed tocilizumab biosimilar, QX003S. This phase-I randomized, controlled study compared pharmacokinetics, variability,immunogenicity, and safety of QX003S vs. the approved tocilizumab product (Actemra@). The results demonstrate bioequivalence between BAT1806 and the reference products (Actemra@), as well as comparable immunogenicity, safety and tolerability profiles.