Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients

Inclusion Criteria: * Written informed consent must be obtained before any assessment is performed * Fulfill ≥4 of the 11 American College of Rheumatology 1997 classification criteria for SLE * Patient diagnosed with SLE for at least 6 months prior to screening * Elevated serum titers at screening of ANA (≥1:80) of a pattern consistent with an SLE diagnosis, including at a minimum either anti-double stranded DNA (anti-ds DNA) or anti-Ro (SSA) or anti-La (SSB) or anti-nuclear ribonucleoprotein (anti-RNP) or anti-Smith (anti-Sm) * Currently receiving corticosteroids and/or anti-malarial and/or thalidomide treatment and/or another DMARD on a stable dose according to protocol requirements * SLEDAI-2K score of ≥6 at screening * BILAG 2004 score of one "A" score either in the mucocutaneous or in the musculoskeletal domain or one "B" score in either the mucocutaneous or musculoskeletal domain and at least one "A" or "B" score in a second domain at screening * Weigh at least 40 kg at screening Exclusion Criteria: Cohort 2 (CFZ533/Placebo) only: * Patients who are at significant risk for thromboembolic events based on the following: * History of either thrombosis or 3 or more spontaneous abortions * Presence of lupus anticoagulant or significantly prolonged activated partial thromboplastin time (aPTT) consistent with co-existent anti-phospholipid syndrome and without concurrent prophylactic treatment with aspirin or anticoagulants as per local standard of care All Cohorts: * History of receiving prior to screening: * Within 12 weeks: i.v. corticosteroids, calcineurin inhibitors or other oral DMARD * Within 24 weeks: cyclophosphamide or biologics such as intravenous Ig, plasmapheresis, anti-TNF-a mAb, CTLA4-Fc Ig (abatacept) or BAFF targeting agents (e.g., belimumab) * Any B-cell depleting therapies (e.g., anti-CD20 mAb, anti-CD22 mAb, anti-CD52 mAb) or TACI-Ig (atacicept) administered within 52 weeks prior to screening, and a B-cell count \<50 cells/μ at the time of screening * Evidence of past exposure to tuberculosis as assessed by Quantiferon testing at screening * Presence of human immunodeficiency virus (HIV) infection at screening * Severe organ dysfunction or life threatening disease; ECOG performance status \> 1 at screening * Presence of WHO Class III-IV renal involvement with proliferative disease Presence of severe lupus kidney disease as defined by proteinuria above 6 g/day or equivalent using spot urine protein creatinine ratio, or serum creatinine greater than 2.5 mg/dL (221.05 μmol/L), or requiring immune suppressive induction or maintenance treatment exceeding protocol defined limits * Active viral, bacterial or other infections at the time of screening or enrollment * Receipt of live/attenuated vaccine within a 2-month period before first dosing * Uncontrolled, co-existing serious disease, e.g., uncontrolled hypertension, heart failure, type I diabetes, thyroid disease within 3 months prior to first dosing, or significant, unresolved illness within 2 weeks prior to first dosing * History of hypersensitivity to drugs of similar chemical class * Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Subjects who are HBsAg negative and HBcAb positive are excluded unless negative for HBV DNA. Once past screening and enrolled into study, requirements for monitoring and antiviral treatment are enacted. Subjects with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded.