An Open-Label, Multiple-Dose Study To Assess The Preliminary Pharmacokinetics, Pharmacodynamics, Clinical Activity, And Safety Of Human Mouse Chimeric Anti-Cd22 Monoclonal Antibody (Sm03) In Patients With Rheumatoid Arthritis

Background: The pharmacokinetics, safety, and clinical activity of antibodies targeting CD22 have been evaluated in systemic lupus erythematosus (SLE) and non-Hodgkin lymphoma (NHL) patients, however, there have been no reports for the rheumatoid arthritis (RA) population. SM03 is a novel chimeric IgG1 monoclonal antibody which targets the B-cell-restricted antigen CD22. This is the first study of the anti-CD22 antibody in RA patients. Objectives: This study was designed to preliminarily evaluate the pharmacokinetics, pharmacodynamics, safety, and clinical activity profiles of the anti-CD22 monoclonal antibody SM03 in Chinese patients with active RA. Materials and methods: This study was an open phase I study in 8 RA patients. Eligible patients received two 600 mg doses of SM03 administered through intravenous infusions given 2 weeks apart and were monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical responses. Results: After multiple doses of SM03, the maximum serum concentration of SM03 was reached within 2 - 4 hours. Mean elimination half-life was 16 days (range: 13 - 22 days). Half of the patients responded according to ACR and DAS28 assessments, and CD19(+) B lymphocyte counts decreased. Upper respiratory tract infections and headaches were the most common adverse events (AEs). No drug-related serious AEs were reported. Conclusion: This study is the first to report on the preliminary pharmacokinetics, pharmacodynamics, clinical activity, and safety of SM03 in RA patients. All AEs were mild or moderate in severity. SM03 showed potential efficacy in RA patients.