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
Condition: Lupus Nephritis
MeSH terms: Nephritis; Lupus Nephritis
Intervention: Rituximab; Placebo; Mycophenolate mofetil; Methylprednisolone; Diphenhydramine; Acetaminophen; Prednisone
Intervention description: Rituximab was provided as a sterile solution for injection.; Placebo was provided as a sterile solution for injection.
Intervention MeSH terms: Acetaminophen; Diphenhydramine; Promethazine; Mycophenolic Acid; Prednisone; Methylprednisolone; Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 144.0
Sex: All
Minimum age: 16 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Class IV LN; Lupus; LUNAR; LN

Summary:

      This was a Phase III, randomized, double-blind, placebo-controlled, multicenter study to
      evaluate the efficacy and safety of rituximab in combination with mycophenolate mofetil (MMF)
      compared with placebo in combination with MMF in subjects diagnosed with International
      Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis.
    

Eligibility criteria:

        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.