Safety, Pharmacokinetics and Pharmacodynamics of Epratuzumab in Japanese Patients with Moderate-to-Severe Systemic Lupus Erythematosus: Results from a Phase 1/2 Randomized Study

Objectives: This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care.Methods: Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100mg every other week [Q2W], 400mg Q2W, 600mg every week [QW], or 1200mg Q2W) administered during an initial 4-week dosing period. Adverse events (AEs), pharmacokinetics and pharmacodynamics were assessed.Results: Nineteen of 20 patients completed the study. All placebo patients and 13 of 16 epratuzumab patients reported1 AE, 2 of 16 epratuzumab patients reported a serious AE. C-max and AUC increased proportionally with dose after first and last infusion, t(1/2) was similar across groups (approximate to 13 days). Epratuzumab treatment was associated with decreased CD22 mean fluorescence intensity in total B cells (CD19(+)CD22(+)) and unswitched memory B cells (CD19(+)IgD(+)CD27(+)). Small-to-moderate decreases were observed in total B cell (CD20(+)) count.Conclusions: Epratuzumab was well-tolerated, with no new safety signals identified. The pharmacokinetics appeared linear after first and last infusions. Treatment with epratuzumab was associated with CD22 downregulation and with small-to-moderate decreases in total B cell count.