SM03, an anti-human CD22 monoclonal antibody, for active rheumatoid arthritis: a phase II randomized, double-blind, placebo-controlled study.

OBJECTIVE SM03, a novel chimeric monoclonal antibody specific to B cell-restricted antigen CD22, has been developed to treat rheumatoid arthritis (RA) and other B cell-related diseases. This 24-week Phase II randomized, double-blind, multi-dose, placebo-controlled study aimed to evaluate the efficacy and safety of SM03 in moderately-to-severely active RA patients in China. METHODS One hundred fifty-six patients on background methotrexate were randomized in a 1:1:1 ratio to receive a cumulative dose of 3600 mg (high dose, 600 mg * 6 infusions at weeks 0, 2, 4, 12, 14, and 16) or 2400 mg SM03 (low dose, 600 mg * 4 infusions at weeks 0, 2, 12, and 14), or the placebo. The primary outcome was the 24-week American College of Rheumatology 20% improvement criteria (ACR20) response rate. Safety was also assessed. RESULTS The 24-week ACR20 response rate was significantly higher with high (65.3%, p= 0.002) and low-dose SM03 (56.9%, p= 0.024) than placebo (34.0%), but comparable between the high and low dose group. The rate of adverse events was not statistically different among the high dose group (35.3%), the low dose group (51.9%) and the placebo group (34.6%). Thirteen (12.6%) patients receiving SM03 reported treatment-emergent infections, including 3.9% patients in the high-dose group. No patients reported severe treatment-emergent infections or malignancies. CONCLUSIONS In active RA Chinese patients receiving background methotrexate, SM03 at a cumulative dose of both 2400 mg and 3600 mg is efficacious and well-tolerated throughout the 24 weeks of treatment. Moreover, SM03 has demonstrated a good safety profile. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, https://clinicaltrials.gov, NCT04192617.