Pharmacokinetics, Pharmacodynamics and Preliminary Observations for Clinical Activity and Safety of Multiple Doses of Human Mouse Chimeric Anti-CD22 Monoclonal Antibody (SM03) in Chinese Patients with Systemic Lupus Erythematosus

SM03 is a novel recombinant, human/mouse chimeric immunoglobulin G1 monoclonal antibody directed against the CD22 antigen on human B lymphocytes. This was the first study to investigate the pharmacokinetics, pharmacodynamics, immunogenicity, safety and clinical activity of SM03 in patients with systemic lupus erythematosus (SLE). This study was an open, multiple-centre, parallel-group, multiple-ascending-dose, phase I study in 29 SLE patients. Pharmacokinetic assessment was conducted in 22 of these patients. Eligible patients received multiple intravenous infusions of SM03 for 4 weeks (240 mg/m(2), 600 or 900 mg, once weekly) and were monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety and clinical response. After multiple-dose SM03, the maximal serum concentration of SM03 was reached within 3-7 h. The mean elimination half-life was 15 days. The average accumulation ratios of the area under the time-concentration curve and the maximum concentration after the fourth administration of SM03 were 2.0 and 1.5. CD19(+) B-lymphocyte counts were decreased. Infections were the most common adverse events. No drug-related serious adverse events were reported. The therapeutic benefit of SM03 was observed mainly in patients with moderate-to-severe disease activity. Pharmacokinetic exposure increased in a lower-than-dose-proportional manner up to 900 mg. SM03 was well tolerated at doses ranging from 240 mg/m(2) to 900 mg, with no new safety signals identified. SM03 has potential efficacy in Chinese patients with SLE.