VDJ-001

Tocilizumab, a humanized IL-6R monoclonal antibody, has been used in autoimmune diseases closely related to humoral immunity. This report aims to evaluate the efficacy and safety in patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG). We performed a prospective, open-label, single-arm study in patients with gMG in a 48-week follow-up. All patients were AChR+ and were given tocilizumab by intravenous infusion at a dose of 8 mg/kg at intervals of 4 weeks. The primary endpoint was mean change from baseline in quantitative MG (QMG) score at week 12. The secondary endpoints were mean changes from baseline in MG activities of daily living (MG-ADL) score, AChR-ab titers, and the dosage of oral prednisone at week 12. At week 48, QMG, MG-ADL, and the use of prednisone were also evaluated. Fourteen gMG patients were enrolled and all of them completed the study. Tocilizumab treatment started 8 (4-192) months after the onset of gMG. During tocilizumab treatment, the QMG score was significantly decreased from 15.5 (interqualile range, 9-26) at baseline to 4 (0-9) at week 12 (p < 0.001). The change of ADL was decreased from 14.5(11-19) at baseline to 4 (0-19) at week 12 (p < 0.001) and the change of AChR-ab titers from 15 (7.5-19) at baseline to 6.8 (11.6-4.3) at week 12 (p < 0.001). The dosage of prednisone decreased from baseline 60 (20-65) mg/d to 30 (30-50) mg/d at week 12 (p < 0.001). By the end of the study, the QMG score was 2 (0-7) and MG-ADL score was 1.5 (0-6). 12 (85.7%) patients achieved minimal manifestations. 4 (28.6%) patients were able to discontinue prednisone. No patients experienced exacerbation at the end of the study. No serious adverse events were observed during follow-up. Tocilizumab treatment was associated with a good clinical response and safety over a 48-week observation period, as evidenced by significant improvements in QMG and MG-ADL.

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).