This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab in combination with MMF compared with placebo in combination with mycophenolate mofetil (MMF) in subjects diagnosed with ISN/RPS 2003 Class III or IV Lupus Nephritis.

Inclusion Criteria:

• Diagnosis of SLE according to current ACR criteria
• Diagnosis of ISN/RPS 2003 Class III or IV 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 (e.g., asthma, Crohn's disease) that require oral or systemic corticosteroid use in the 52 weeks prior to screening
• History of renal transplant
• Known 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 CYC or calcineurin inhibitors within the 90 days prior to screening
• Use of 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
• 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