A Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE) - BLISS-BELIEVE

Inclusion Criteria:

- Subjects must be >=18 years of age at the time of signing the informed consent.

- Subjects who have a clinical diagnosis of SLE according to the American College of
Rheumatology (ACR) criteria.

- Subjects who have a screening SLEDAI-2K score >=6 (serological activity, that is
[i.e.], anti-dsDNA) positivity and/or hypocomplementemia, is scored in the SLEDAI-2K).

- Subjects who have unequivocally positive autoantibody test results defined as an
anti-nuclear (ANA) titer >=1:80 and/or a positive anti-dsDNA (>=30 International Units
per milliliter [IU/mL]) serum antibody test from 2 independent time points as follows:
Positive test results from 2 independent time points within the study screening
period. Screening results must be based on the study's central laboratory results or
One positive historical test result and 1 positive test result during the screening
period.

- Concomitant medications are on a stable SLE treatment regimen consisting of any of
these medications (alone or in combination) for a period of at least 30 days prior to
Day 1 (i.e. day of first dose of study treatment) with the exception that switching
one agent for another of the same class for tolerability or availability reasons,
which will be allowed within 30 days of Day 1: Corticosteroids (prednisone or
prednisone equivalent); For those subjects on alternating daily doses of steroids, use
the average of 2 daily doses to calculate the average daily steroid dose; Any
immunosuppressant or immunomodulatory agents including methotrexate, azathioprine,
leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil
hydrochloride, and mycophenolate sodium), calcineurin inhibitors (example [e.g.]
tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine,
mizoribine, or thalidomide; Anti-malarials (e.g., hydroxychloroquine, chloroquine,
quinacrine); Non steroidal anti-inflammatory drugs (NSAIDs).

- Male and/or female. A female subject is eligible to participate if she is not pregnant
not breastfeeding, and at least one of the these conditions applies: Not a woman of
childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive
guidance during the treatment period and for at least 16 weeks after the last dose of
belimumab, or at least 12 months after the last dose of rituximab or
rituximab-placebo.

- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.

Exclusion Criteria:

- Symptomatic herpes zoster within 3 months prior to screening.

- Evidence of active or latent tuberculosis (TB) as documented by medical history and
examination, chest X-rays (posterior, anterior, and lateral), and TB testing: either a
positive tuberculin skin test (TST; defined as a skin induration >=5 millimeter [mm]
at 48 to 72 hours [hrs], regardless of Baccillus Calmette-Guerin [BCG] or other
vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.

- Significant allergies to humanized monoclonal antibodies.

- Clinically significant multiple or severe drug allergies and/or history of
hypersensitivity to belimumab and/or rituximab or known to have titers of human
anti-mouse antibody or history of hypersensitivity reactions when treated with other
diagnostic or therapeutic monoclonal antibodies.

- Lymphoma, leukemia, or any malignancy within the past 5 years (yrs) except for basal
cell or squamous epithelial carcinomas of the skin that have been resected with no
evidence of metastatic disease for 3 yrs.

- Alanine transferase (ALT) greater than 2 times upper limit of normal (ULN).

- Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is
acceptable if bilirubin is fractionated and direct bilirubin less than 35%).

- Immunoglobulin A (IgA) deficiency (IgA level less than 10 milligram per decilitre
[mg/dL]).

- Immunoglobulin G (IgG) less than 250 mg/dL.

- Neutrophils less than 1.5 times 10^9.

- Current unstable liver or biliary disease per investigator assessment defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
gastric varices, persistent jaundice, or cirrhosis.

- Severe heart failure (New York Heart Association Class IV) or other severe,
uncontrolled cardiac disease.

- QT interval corrected (QTc) greater than 450 millisecond (msec) or QTc greater than
480 msec in subjects with bundle branch block.

- Subjects who have a history of a major organ transplant (e.g., heart, lung, kidney,
liver) or hematopoietic stem cell/marrow transplant.

- Subjects who have clinical evidence of significant unstable or uncontrolled acute or
chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic,
gastrointestinal, hepatic, renal, neurological, psychiatric, malignancy, or infectious
diseases) which, in the opinion of the principal investigator, could confound the
results of the study or put the subject at undue risk.

- Subjects who have an acute or chronic infection requiring management as : Currently on
any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus,
herpes simplex virus, herpes zoster, or atypical mycobacteria); Hospitalization for
treatment of infection within 60 days of Day 1; subjects who had infection requiring
treatment with parenteral (IV or IM) antibiotics (antibacterials, antivirals,
anti-fungals, or anti-parasitic agents) within 60 days of Day 1. Prophylactic
anti-infective treatment is allowed.

- Subjects who have severe lupus kidney disease (defined by proteinuria greater than 6
gram (g)/24 hr or equivalent using spot urine protein to creatinine ratio, or serum
creatinine greater than 2.5 mg/dL), or have severe active nephritis requiring
induction therapy not permitted by protocol (e.g., IV cyclophosphamide), or have
required hemodialysis or high dose prednisone or equivalent (greater than 100 mg/day)
within 90 days of Day 1.

- Subjects who have severe active central nervous system (CNS) lupus (including
seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA),
cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of
Day 1.

- Subjects who have a planned surgical procedure, laboratory abnormality, or condition
(e.g., poor venous access) that, in the opinion of the principal investigator, makes
the subject unsuitable for the study.

- Subjects who have evidence of serious suicide risk, including any history of suicidal
behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the
Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 2 months or who, in the
investigator's opinion, pose a significant suicide risk.

- Subjects who have a history of an anaphylaxis reaction to parenteral administration of
contrast agents, human or murine proteins, or monoclonal antibodies.

- Subjects who have received live vaccine(s) within 1 month prior to screening, or plans
to receive such vaccines during the screening period or during the study.

- Subjects who have received any of the these prior/concomitant therapy within 364 days
of Day 1: Belimumab; Rituximab; Abatacept; Any B cell targeted therapy (anti-cluster
of differentiation-20 [CD] agents other than rituximab, anti CD22 [epratuzumab],
anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], Trans-membrane activator
and calcium-modulator and cytophilin ligand interactor [TACI] Fc, anti B-cell
activating factor [BAFF] (LY2127399), anti-Interferon alpha agents or anti-BLyS other
than belimumab); A biologic investigational agent other than B cell targeted therapy
(e.g., abetimus sodium, anti CD40L antibody [BG9588/ IDEC 1311]). (Investigational
agent applies to any drug not approved for sale in the country in which it is being
used).

- Subjects who have required 3 or more courses of systemic corticosteroids within 364
days of Day 1. (Topical or inhaled steroids are permitted).

- Subjects who have received any of these within 90 days of Day 1: Anti-TNF therapy
(e.g., adalimumab, etanercept, infliximab); Interleukin-1 receptor antagonist
(anakinra); Intravenous immunoglobulin (IVIG); High dose prednisone or equivalent
(greater than 100 mg/day); Plasmapheresis.

- Subjects who have received any of the these within 60 days of Day 1: A non-biologic
investigational agent; IV cyclophosphamide; Any steroid injection (e.g., intramuscular
[IM], intraarticular, or IV).

- Positive immunodeficiency virus (HIV) antibody test.

- Positive serology for Hepatitis B (HB), defined as HB surface antigen positive
(HBsAg+) OR HB core antibody positive (HBcAb+).

- Positive Hepatitis C (HCV) antibody test.

- Subjects who have current drug or alcohol dependence, or a history of drug or alcohol
abuse or dependence within 364 days prior to Day 1.

- Sensitivity to any of the study treatments, or components thereof, or drug or other
allergy that, in the opinion of the investigator, contraindicates participation in the
study.

- Unable to administer study treatment (belimumab) by SC injection and has no other
reliable resource to administer the injection.