Trial of Belimumab in Early Lupus

Inclusion criteria

• Diagnosis of SLE per current ACR classification criteria
• Date of SLE diagnosis within 2 years of screening
• ANA positive (with a titer ≥ 80)
• anti-ds DNA antibody positive
• Mild to moderate disease activity define by a SLEDAI-2K ≥4
• Stable corticosteroid dose in the 4 weeks prior to screening ≤ 30mg/day.
• If on methotrexate, dose must be stable for 4 weeks
• Concomitant treatment with hydroxychloroquine unless documented inability to tolerate
• Able and willing to give written informed consent and comply with the requirements of the study protocol
• Negative serum pregnancy test (for women of child bearing potential)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for 16 weeks after completion of treatment

Exclusion criteria

• Previous exposure to disease modifying drugs such as azathioprine, mycophenolate mofetil, cyclophosphamide, or cyclosporine.
• Previous exposure to biologic therapies including rituximab, belimumab or other agents that have been investigated for SLE.
• Active renal or nervous system disease or disease activity fulfilling BILAG A criteria
• Use of high dose steroids (\>0.5 mg/kg/ day) within the 4 weeks prior to screening
• Expectation (by the investigator) that the subject will require treatment with a disease modifying drug within the first 52 weeks of the study
• Hemoglobin: \< 8.0 gm/dL
• Platelets: \< 50,000/mm
• ANC \< 1.0 x 103/mm
• AST or ALT \>2.5 x Upper Limit of Normal unless related to primary disease.
• Creatinine clearance ≤ 25ml/min per 1.73 m2
• Positive Hepatitis B or C serology (Hep B Surface antigen, Hep B core Ab or Hepatitis C antibody)
• History of positive HIV (HIV conducted during screening if applicable)
• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
• Receipt of a live vaccine within 30 days prior to baseline or concurrently with belimumab
• Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies
• Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria)
• Hospitalization for treatment of infection within 60 days of Day 0.
• Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 0
• History of serious recurrent or chronic infection
• Lack of peripheral venous access
• History of drug, alcohol, or chemical abuse within 365 days prior to Day 0
• Pregnancy (a negative serum pregnancy test must be obtained for all women of childbearing potential at screening; a urine pregnancy test must be negative \< 7 days prior to first dose and monthly)
• Lactation
• History of psychiatric disorder that would interfere with normal participation in this protocol
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• History of malignant neoplasm within the last 5 years with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• Evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk
• History of a primary immunodeficiency
• Have a significant IgG deficiency (IgG level \< 400 mg/dL)
• Have an IgA deficiency (IgA level \< 10 mg/dL)
• Have any other clinically significant abnormal laboratory value in the opinion of the investigator
• Comorbidities requiring corticosteroid therapy, including those which have required two or more courses of systemic courses of systemic corticosteroids within the previous 12 months
• Inability to comply with study and follow-up procedures