PEARL-SC Trial: A Study of the Efficacy, Safety, and Tolerability of A 623 Administration in Subjects With Systemic Lupus Erythematosus (PEARL-SC)

• B cell reduction [ Time Frame: Various timepoints through Week 52 ]
• Time to first flare [ Time Frame: Various timepoints through Week 52 ]
• FACIT-fatigue score [ Time Frame: Various timepoints through Week 52 ]
• Reduction in prednisone dose [ Time Frame: Various timepoints through Week 52 ]
• Change in IgG, IgM,C3 and C4 [ Time Frame: Various timepoints through Week 52 ]
• Flare rates [ Time Frame: Various timepoints through Week 52 ]
• SRI, using improvements of SELENA-SLEDAI of 5, 6, 7, 8 and 9 [ Time Frame: Various timepoints through Week 52 ]

• B cell reduction [ Time Frame: Various timepoints through Week 52 ]
  The percent reduction from baseline in total B cells at the time of assessment
• Time to first flare [ Time Frame: Various timepoints through Week 52 ]
  Time to first flare after randomization
• FACIT-fatigue score [ Time Frame: Various timepoints through Week 52 ]
  Change in FACIT score from baseline
• Reduction in prednisone dose [ Time Frame: Various timepoints through Week 52 ]
  The percent of subjects with a reduction in average prednisone dose
• Change in IgG, IgM,C3 and C4 [ Time Frame: Various timepoints through Week 52 ]
  Change in IgG, IgM, C3, C4 and anti-ds DNA values from baseline and post-baseline time periods

• Drug: A-623
  High dose given subcutaneously once a week for up to 52 weeks
• Drug: A-623
  Low dose given subcutaneously once a week for up to 52 weeks
• Drug: A-623
  High dose given subcutaneously once every 4 weeks for up to 52 weeks
• Other: Placebo Comparator
  Placebo comparator is a matched volume given subcutaneously once a week or once every 4 weeks for up to 52 weeks

• Experimental: A-623 high dose weekly
  Intervention: Drug: A-623
• Experimental: A-623 low dose weekly
  Intervention: Drug: A-623
• Experimental: A-623 high dose every 4 weeks
  Intervention: Drug: A-623
• Placebo Comparator: Placebo
  Intervention: Other: Placebo Comparator

Inclusion Criteria:

• Diagnosis of SLE by American College of Rheumatology guidelines.
• On stable SLE treatment
• Active SLE disease
• Serologically active
• 18 years of age or older
• Receiving stable doses of prednisone between 7.5 mg and 40 mg per day

Exclusion Criteria:

• Severe active vasculitis, active central nervous system lupus, active lupus nephritis, uncontrolled hypertension, or uncontrolled diabetes.
• Known to be positive for HIV and/or positive at the screening visit for hepatitis B, or hepatitis C.
• Liver disease.
• Anemia, neutropenia, or thrombocytopenia.
• Malignancy within past 5 years
• Active infection requiring hospitalization or treatment with parenteral antibiotics within the past 60 days or history of repeated herpetic viral infections.
• History of active tuberculosis or a history of tuberculosis infection.
• Participation in the active treatment arm of any Phase 2 or Phase 3 clinical trial for a molecule that primarily targets the B cell pathway in the past 18 months.
• Prior administration of any B cell depleting therapy in the past 18 months.
• Pregnant or nursing
• History of congenital immunodeficiency