A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus

Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II/III Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With Moderate to Severe Systemic Lupus Erythematosus

This is a Phase II/III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab compared with placebo when combined with a single stable background immunosuppressive medication in subjects with moderate to severe systemic lupus erythematosus (SLE). The primary efficacy endpoint of the trial will be evaluated at 52 weeks.

Inclusion Criteria:

• Diagnosis of systemic lupus erythematosus (SLE).
• Active disease at screening.
• Stable use of one immunosuppressive drug.
• Use of an antimalarial drug.
• For subjects of reproductive potential (males and females), use of a reliable means of contraception throughout their study participation.

Exclusion Criteria:

• Unstable patients with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions.
• Active moderate to severe glomerulonephritis.
• Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE.
• Lack of peripheral venous access.
• Pregnant women or nursing (breast feeding) mothers.
• History of severe, allergic, or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Significant, uncontrolled medical disease in any organ system not related to SLE that in the investigator's opinion would preclude subject participation.
• Concomitant conditions that require oral or systemic corticosteroid use.
• Known human immunodeficiency virus (HIV) infection.
• Known active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics.
• History of deep space infection.
• History of serious recurrent or chronic infection.
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ.
• Active alcohol or drug abuse, or history of alcohol or drug abuse.
• Major surgery.
• Previous treatment with CAMPATH-1H antibody.
• Previous treatment with any B cell-targeted therapy.
• Treatment with any investigational agent within 28 days of screening (Day -7) or 5 half-lives of the investigational drug (whichever is longer).
• Receipt of a live vaccine within 28 days prior to screening.
• Intolerance or contraindication to oral or IV corticosteroids.
• Use of a new immunosuppressive drug prior to screening or change in dose of ongoing immunosuppressive drug prior to screening.
• Prednisone dose of ≥ 1 mg/kg/day prior to screening.
• Treatment with cyclophosphamide or a calcineurin inhibitor.
• Treatment with a second immunosuppressive or immunomodulatory drug.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x the upper limit of normal.