Abstract
Background: This study aimed to investigate the pharmacokinetics, safety, and immunogenicity of recombinant humanized anti-human IL-6R monoclonal antibody injection, LZM008, and evaluate the pharmacokinetic similarity between LZM008 and tocilizumab (ACTEMRA(®)) in Chinese healthy male subjects. Research design and methods: In this randomized, double-blinded, paralleled, two-center Phase I clinical trial, 96 subjects were randomized with a 1:1 ratio to receive 4 mg/kg intravenous dose of LZM008 or ACTEMRA(®) and evaluated for 28 days. The pharmacokinetic bioequivalence was assessed by the maximum serum concentration (C(max)), the area under the serum concentration-time curve (AUC) from time 0 to the last detectable drug concentration (AUC(0-t)), and AUC(0-∞). The statistical analysis was conducted using SAS Enterprise Guide statistical software. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Anti-drug antibodies (ADAs) were measured by a bridged electrochemiluminescence immunoassay. Results: LZM008 (N = 49) and ACTEMRA(®) (N = 47) groups showed similar pharmacokinetic properties. After a single intravenous infusion of 4 mg/kg LZM008, the C(max) and AUC(0-∞) values of LZM008 reached 87.99 μg/mL and 11,526.70 h*μg/mL, respectively, with T(max) 1.98 h, and the half-life (t(1/2)) was 83.45 h. The 90% confidence intervals of ratios for C(max), AUC(0-t), and AUC(0-∞) were within the range of 80.00%-125.00%. After infusion, one (2.0%) subject in the LZM008 group and three (6.4%) subjects in the ACTEMRA(®) group showed positive ADA test results. The incidence of treatment emergent adverse events (TEAEs) was comparable in LZM008 and ACTEMRA(®) groups (98.0% versus 100%), with the decrease in blood fibrinogen and neutrophil counts being the most common TEAEs. Conclusion: The pharmacokinetic characteristics and immunogenicity exhibited by LZM008 were similar to those of the reference product, ACTEMRA(®). The safety profiles of LZM008 were similar in the two groups with mild-moderate adverse effects. Trial Registration: The trial is registered at www.chinadrugtrials.org.cn (CTR20190889).