Study of Epratuzumab versus Placebo in subjects with moderate to severe general Systemic Lupus Erythematosus (SLE)

This is a Phase 3, multicenter, placebo-controlled, randomized, double-blind study to evaluate the efficacy, safety, tolerability, and immunogenicity of epratuzumab in subjects with moderate to severe general systemic lupus erythematosus (SLE). The study population consists of subjects (>=18 years of age) receiving a stable dose of corticosteroids (5 to 60mg/day prednisone equivalents) for at least 5 days (±1 day) prior to Week 0 (Visit 2) and the first dose of study drug. Subjects must have a diagnosis of SLE by the American College of Rheumatology (ACR) revised criteria, such that at least 4 (not including Neurologic Disorder) of the 11 criteria are met (if positive for Neurologic Disorder criteria, a total of 5 of the 11 ACR criteria must be met). In addition, subjects must have British Isles Lupus Assessment Group (BILAG) Index (version 2004) level A disease activity in at least 1 body/organ system, or BILAG level B disease activity in at least 2 body/organ systems at Baseline among the BILAG-defined mucocutaneous, musculoskeletal, or cardiorespiratory body systems, and active moderate to severe SLE disease activity as demonstrated by a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score of at least 6. Approximately 1053 subjects will be enrolled to randomize 780 subjects in this study. For each subject, the study will last a maximum of 54 weeks and will consist of a Screening Period (1 to 14 days), a double-blind Treatment Period consisting of four 12-week treatment cycles (48 weeks total), and a Safety Follow-Up Visit for subjects not participating in the open-label extension study, SL0012, at 13 weeks from their final dose of study drug, or a maximum of 4 weeks beyond Week 48 (ie, no later than Week 52). Eligible subjects will be randomized in a 1:1:1 ratio as follows: Epratuzumab 600mg infusions delivered once a week (QW) for a total of 4 weeks (cumulative dose [CMD] 2400mg) over four 12-week treatment cycles (ie, Weeks 0, 1, 2, 3, 12, 13, 14, 15, 24, 25, 26, 27, 36, 37, 38, and 39) Epratuzumab 1200mg infusions delivered every other week (QOW) for a total of 4 weeks (CMD 2400mg) over four 12-week treatment cycles (ie, Weeks 0, 2, 12, 14, 24, 26, 36, and38); and placebo (PBO) infusions delivered QOW for a total of 4 weeks over four 12-week treatment cycles (ie, Weeks 1, 3, 13, 15, 25, 27, 37, and 39) PBO infusions delivered QW for a total of 4 weeks over four 12-week treatment cycles (ie, Weeks 0, 1, 2, 3, 12, 13, 14, 15, 24, 25, 26, 27, 36, 37, 38, and 39) The primary objective of the study is to confirm the clinical efficacy of epratuzumab in the treatment of subjects with moderate to severe general SLE despite standard of care treatments (ie, corticosteroids, and potentially antimalarials and immunosuppressants) continued from Baseline. The secondary objectives of the study are to assess the safety, tolerability, and immunogenicity of epratuzumab, and to assess the steroid-sparing effects of epratuzumab treatment. The exploratory objectives of the study are to assess the pharmacokinetics (PK) of epratuzumab; the effects of epratuzumab treatment on individual components of the combined response index, fatigue associated with moderate to severe SLE, and the health-related quality of life (HRQoL) and utility benefits of epratuzumab treatment.