A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV Lupus Nephritis

Inclusion Criteria

• Diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria.
• Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (LN), with either active or active/chronic disease.
• Proteinuria.
• 16-75 years of age.

Exclusion Criteria

• 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.
• Unstable subjects 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.
• Lack of peripheral venous access.
• Pregnancy or lactation.
• History of severe allergic or anaphylactic reactions to monoclonal antibodies.
• Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude subject participation.
• Concomitant chronic conditions, excluding SLE (eg, asthma, Crohn's disease) that require oral or systemic corticosteroid use in the 52 weeks prior to screening.
• History of renal transplant.
• Known human immunodeficiency virus (HIV) infection.
• Known active infection of any kind (but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives within 4 weeks of randomization or oral anti-infectives within 2 weeks of randomization.
• History of deep space infection within 1 year of screening.
• History of serious recurrent or chronic infection.
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinomas of the skin that have been treated or excised and have resolved).
• Currently active alcohol or drug abuse or history of alcohol or drug abuse within 52 weeks prior to screening.
• Major surgery requiring hospitalization within 4 weeks of screening (excluding diagnostic surgery).
• Treatment with cyclophosphamide or calcineurin inhibitors within the 90 days prior to screening.
• Use of mycophenolate mofetil (MMF) at a dose of > 2 grams daily for longer than the 90 days prior to screening.
• Intolerance or history of allergic reaction to MMF.
• Intolerance or history of allergic reaction to both angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers.
• Use of oral prednisone (or corticosteroid equivalent) at a dose of > 20 mg/day for longer than the 14 days prior to screening.
• Previous treatment with CAMPATH-1H (alemtuzumab).
• Previous treatment with a B-cell targeted therapy.
• Treatment with any investigational agent (including biologic agents approved for other indications) within 28 days of the start of the screening period or 5 half-lives of the investigational drug (whichever is longer).
• Receipt of a live vaccine within the 28 days prior to screening.
• Intolerance or contraindication to oral or IV corticosteroids.
• Current therapy with a nonsteroidal anti-inflammatory agent.
• Positive hepatitis B sAg or hepatitis C serology.