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 totolerate

• Able and willing to give written informed consent and comply with the requirementsof 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 ofbirth control during treatment and for 16 weeks after completion of treatment

Exclusion Criteria:

• Previous exposure to disease modifying drugs such as azathioprine, mycophenolatemofetil, cyclophosphamide, or cyclosporine.

• Previous exposure to biologic therapies including rituximab, belimumab or otheragents that have been investigated for SLE.

• Active renal or nervous system disease or disease activity fulfilling BILAG Acriteria

• 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 adisease 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 orHepatitis 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-livesof the investigational drug (whichever is longer)

• Receipt of a live vaccine within 30 days prior to baseline or concurrently withbelimumab

• Have a history of an anaphylactic reaction to parenteral administration of contrastagents, 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 atypicalmycobacteria)

• 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 ofchildbearing potential at screening; a urine pregnancy test must be negative < 7days prior to first dose and monthly)

• Lactation

• History of psychiatric disorder that would interfere with normal participation inthis protocol

• Significant cardiac or pulmonary disease (including obstructive pulmonary disease)

• Any other disease, metabolic dysfunction, physical examination finding, or clinicallaboratory finding giving reasonable suspicion of a disease or condition thatcontraindicates the use of an investigational drug or that may affect theinterpretation of the results or render the patient at high risk from treatmentcomplications

• History of malignant neoplasm within the last 5 years with the exception ofadequately treated basal or squamous cell carcinoma of the skin or carcinoma in situof the cervix

• Evidence of serious suicide risk including any history of suicidal behaviour in thelast 6 months and/or any suicidal ideation in the last 2 months or who in theinvestigator'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 ofthe investigator

• Comorbidities requiring corticosteroid therapy, including those which have requiredtwo or more courses of systemic courses of systemic corticosteroids within theprevious 12 months

• Inability to comply with study and follow-up procedures