This is a Phase 1, randomized, placebo-controlled, double-blind, dose-escalation study of repeat SC doses of AMG 557 in adults with Systemic Lupus Erythematosus.

Inclusion Criteria:

• Before any study-specific procedure, the appropriate written informed consent must be obtained;
• Men and women, between the ages of 18 and 70 years old, inclusive, at the time of randomization;
• Diagnosis of SLE as defined by the most recent ACR criteria, including a positive ANA at screening or documented positive ANA (the titer should be at least 1:80) in the past.
• SLE duration of at least six months, as diagnosed by a physician;
• Stable disease, defined as no change in SLE therapy within the previous 30 days; and, in the opinion of the investigator, no anticipated need for a change in SLE therapy will be required while the subject is enrolled in the study;
• Normal or clinically acceptable ECG (12-lead reporting ventricular rate and PR, QRS, QT, QTc) at screening and Day -1 based on the opinion of the investigator;
• Body mass index from 18 to 40 kg/m2 at screening;
• Able and willing to complete entire study according to study schedule.
• Immunizations up to date, with a minimum of tetanus, diphtheria, pertussis (td/Tdap), pneumococcal (polysaccharide) and influenza (during flu season) vaccinations, as determined by the Principal Investigator.

Exclusion Criteria:

• Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies (confirmed by PCR or RIBA);
• Have had signs or symptoms of a viral, bacterial or fungal infection within 30 days of study randomization;
• Evidence of active or latent tuberculosis as assessed by PPD or Quantiferon testing at screening;
• Have donated blood or experienced a loss of blood >500mL within 4 weeks of randomization;
• History of ethanol or drug abuse within the last one year prior to randomization;
• Evidence of significant renal insufficiency, defined by:

The glomerular fitration rate < 50 mL/min using the Cockroft and Gault equation;

• Evidence of liver disease (eg, serum ALT or AST > 2x upper limit of normal);
• Total WBC <3000 x 106/L;
• Neutrophil count < 1500 x106/L
• Platelet count <75,000 x 106/L
• Hemoglobin <10g/dL
• Any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of SLE) that would, by it progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures in the medical judgment of the investigator. This includes any age related co-morbidites such as presence of congestive heart failure, angina, chronic obstructive pulmonary disease, asthma, and malignancies (other than resected squamous and basal cell carcinoma of the skin).
• Presence or history of vasculitis (comprising internal organs or extremities or leading to peripheral neuropathy) within the last 3 years, presence or history of active CNS lupus (defined as seizure disorder, cerebral vascular accident, psychosis ascribed to SLE , encephalitis, meningitis, and myelitis) requiring therapy within the last 3 years;
• Uncontrolled hypertension (Blood pressure > 150/95);
• Poorly controlled diabetes (HbA1c > 8%);
• Any history of granulomatous disease including autoimmune granulomatous vasculitis and sarcoidosis;
• Underlying condition that predisposes the subject to infections (eg, history of splenectomy);
• Any disorder or condition that prevents the subject from providing truly informed consent;
• Prior administration of any other biologic that primarily targets the immune system (eg, Lymphostat-B, TACI-Ig, or CTLA4-Ig) in the past 9 months. This includes prior administration of AMG 557;
• Presence of AMG 557 anti-bodies;
• Prior administration of rituximab > 9 months with CD19+ B cells <5/µL;
• Administration of cyclophosphamide (or any other alkylating agent), cyclosporine, tacrolimus, or sirolimus, or > 100 mg/day prednisone or equivalent in the 6 months prior to randomization;
• Participated in an investigational drug trial involving a monoclonal antibody (not targeting the immune system) within 3 months or 5 half-lives, whichever time period is longer, prior to randomization;
• Participated in any another investigational drug or device trial within the previous 30 days or 5 half-lives, whichever time period is longer, prior to randomization;
• Administration of >10 mg/day prednisone (or equivalent) in the 30 days prior to randomization;
• Known sensitivity to mammalian derived products;
• Unwilling to practice an effective method of double-barrier contraception as determined by the investigator for the duration of the study;
• Positive serum hCG at screening or positive urine hCG on D-1; or females who are currently lactating;
• Known allergies to shellfish or any excipients found in KLH;
• Previous immunization with KLH.