Pharmacokinetics, Pharmacodynamics, Safety, and Clinical Activity of Multiple Doses of RCT‐18 in Chinese Patients With Systemic Lupus Erythematosus

Abstract RCT‐18 is a novel recombinant fusion protein that blocks the activity of a B‐lymphocyte stimulator and a proliferation‐inducing ligand. This was a randomized, single‐blind, and placebo‐controlled phase 1 study in 12 patients with systemic lupus erythematosus. Eligible patients were randomized 3:1 to receive multiple subcutaneous doses of RCT‐18 for 4 weeks (180 mg, once weekly) or placebo and monitored over an 84‐day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical activity. After multiple‐dose RCT‐18, the maximal serum concentration (C max ) of total and free RCT‐18 was reached within 1 to 2 days. Mean elimination half‐life for total RCT‐18 and free RCT‐18 was 11.4 to 26.4 days and 2.4 to 26.5 days, respectively. Slight accumulation was found after multiple subcutaneous administrations. The average accumulation ratios of AUC and C max after the fourth administration of RCT‐18 were 2.0 and 1.7 for total RCT‐18, and 1.8 and 1.6 for free RCT‐18. The formation and elimination of BLyS‐RCT‐18 complex were much slower, with a time to C max of 14 to 46 days. Pharmacokinetic characteristics of RCT‐18 in SLE patients were similar to those in patients with rheumatoid arthritis. No positive reaction was detected in the immunogenicity assessments. RCT‐18 was biologically active, according to serum immunoglobulin and B‐cell levels. Treatment‐related IgM and IgA reduction was found during this study. CD19 + , IgD + , and CD27 + B‐cell counts were increased after administration and decreased subsequently. SLE patients treated with RCT‐18 were more prone to infections, including moderate and severe infections. Lower dosages of RCT‐18 should be considered in further clinical development.