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 SLE. The primary efficacy endpoint of the trial will be evaluated at 52 weeks. The study will enroll approximately 250 subjects at approximately 55 centers in the United States.

Condition	Intervention	Phase
Lupus Erythematosus, Systemic	Drug: Rituxan (rituximab)	Phase II Phase III

Further Study Details: 

Primary Outcomes: To assess the efficacy of rituximab compared with placebo in achieving and maintaining a major clinical response or partial clinical response in subjects with moderate to severe systemic lupus erythematosus.
Secondary Outcomes: To evaluate the ability of rituximab to decrease overall SLE disease activity, to prolong the time to a moderate or severe flare, to improve quality of life, and to achieve a BILAG C or better at Week 24.
Expected Total Enrollment:  250

Ages Eligible for Study:  16 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Ability and willingness to provide written informed consent and comply with the schedule of protocol assessments
• Diagnosis of Systemic Lupus Erythematosus (SLE) per the current American College of Rheumatology (ACR) criteria at any time prior to screening (at least four criteria must be present, one of which must be a positive antinuclear antibody [ANA])
• Age 16-75 years
• Active disease at screening as defined by one or more domains with a BILAG A score or two or more domains with a BILAG B score that in the investigator''''s judgment is serious enough to warrant potential exposure to immunotherapy
• Stable use of one immunosuppressive drug (100-250 mg/day azathioprine, 50-250 mg/day 6-mercaptopurine, 1-4 gm/day mycophenolate mofetil [MMF], or 7.5-27.5 mg/wk methotrexate [MTX])
• Use of an antimalarial drug (hydroxychloroquine 200 mg every day or twice daily, chloroquine 500 mg every day or every other day, or quinacrine 100 mg every day) unless excluded by a history of antimalarial drug toxicity or not clinically indicated prior to trial screening
• For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, physical barrier) 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, as defined by proteinuria > 1 g/24 hr (or urinary protein to urinary creatinine ratio [Upr/Ucr] > 1) and either presence of red blood cell (RBC) casts or >= 10 RBC/hpf (in the absence of infection or menstrual hematuria at screening)
• 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 (e.g., poorly controlled chronic obstructive pulmonary disease or asthma, cardiovascular disease, accelerated hypertension, major depression) that in the investigator''''s opinion would preclude subject participation
• Concomitant conditions (e.g., asthma, Crohn''''s disease, etc.) that required oral or systemic corticosteroid use within the 52 weeks prior to screening
• 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 IV antibiotics within 8 weeks of screening or oral antibiotics within 2 weeks prior to screening
• History of deep space infection (i.e., fasciitis, abscess, osteomyelitis) within 1 year of screening
• 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 within the past 52 weeks
• Major surgery within 4 weeks prior to screening
• Previous treatment with CAMPATH-1H
• Previous treatment with any B cell-targeted therapy (e.g., anti-CD20, anti-CD22, or anti-BlyS 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 within 90 days prior to screening or change in dose of ongoing immunosuppressive drug within 30 days prior to screening
• Prednisone dose of >= 1 mg/kg/day for more than 7 of the 30 days prior to screening
• Treatment with cyclophosphamide or a calcineurin inhibitor within 12 weeks of screening
• Treatment with a second immunosuppressive or immunomodulatory drug (e.g., sulfasalazine, leflunomide) within 30 days of screening
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x the upper limit of normal
• Amylase or lipase > 2 x the upper limit of normal
• Neutrophils < 1500 uL
• Positive hepatitis surface antigen (BsAg) or hepatitis C serology
• Hemoglobin < 7 g/dL unless caused by autoimmune hemolytic anemia resulting from SLE
• Platelet count < 10,000/uL
• Serum creatinine > 2.5 mg/dL

Please refer to this study by ClinicalTrials.gov identifier  NCT00137969

Trial Information Support Line      888-662-6728 

Alabama
      Rheumatology Associates of N. AL, P.C., Huntsville,  Alabama,  35801,  United States; Recruiting
Arizona
      Arizona Arthritis and Rheumatology Associates, P.C., Paradise Valley,  Arizona,  85253,  United States; Recruiting
California
      Stanford Health Services/Blake Wilbur Clinic, Palo Alto,  California,  94304,  United States; Recruiting
      C. Michael Neuwelt , M.D., San Leandro,  California,  94578,  United States; Recruiting
Florida
      Arthritis and Rheumatic Disease Specialties, Aventura,  Florida,  33180,  United States; Recruiting
Idaho
      Intermountain Research Center, Boise,  Idaho,  83702,  United States; Recruiting
      Coeur d''''Alene Arthritis Clinic, Coeur D Alene,  Idaho,  83814,  United States; Recruiting
Illinois
      University of Chicago, Chicago,  Illinois,  60637,  United States; Recruiting
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160,  United States; Recruiting
Louisiana
      LSU HSC-Shreveport Dept. of Medicine, Shreveport,  Louisiana,  71103,  United States; Recruiting
Massachusetts
      Tufts-New England Medical Center, Boston,  Massachusetts,  02111,  United States; Recruiting
New York
      Division of Rheumatology and Allergy-Clinical Immunology, NS-LIJ Health System, Lake Success,  New York,  11042,  United States; Recruiting
      The Center for Rheumatology, LLP, Albany,  New York,  12206,  United States; Recruiting
      University of Rochester, Rochester,  New York,  14642,  United States; Recruiting
      Columbia University, New York,  New York,  10032,  United States; Recruiting
North Carolina
      Physician''''s East, Greenville,  North Carolina,  27834,  United States; Recruiting
Oklahoma
      Oklahoma Medical Research Foundation, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
      Bone and Joint Hospital Research Department, Oklahoma City,  Oklahoma,  73103,  United States; Recruiting
Pennsylvania
      University of Pennsylvania Medical Center, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      Altoona Center for Clinical Research, Duncansville,  Pennsylvania,  16635,  United States; Recruiting
      Department of Medicine Albert Einstein Medical Center, Philadelphia,  Pennsylvania,  19141,  United States; Recruiting
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
Texas
      Radiant Research, Inc., Dallas,  Texas,  75235,  United States; Recruiting
      Houston Institute for Clinical Research, Houston,  Texas,  77074,  United States; Recruiting
      Texas Research Center, LLP, Sugar Land,  Texas,  77479,  United States; Recruiting
Virginia
      Virginia Commonwealth University CRC, Richmond,  Virginia,  23298,  United States; Recruiting
Washington
      University of Washington, Seattle,  Washington,  98195,  United States; Recruiting
      Seattle Rheumatology Associates, Seattle,  Washington,  98104,  United States; Recruiting

Study chairs or principal investigators

Paul Brunetta, M.D.,  Study Director,  Genentech   

Study ID Numbers:  U2971g
Last Updated:  August 29, 2005
Record first received:  August 26, 2005
ClinicalTrials.gov Identifier:  NCT00137969
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-30