Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
The purpose of this study is to evaluate the efficacy, safety, and tolerability of belimumab
 in adult patients of black race with systemic lupus erythematosus (SLE; lupus).
Study participants receive stable standard therapy for lupus in addition to receiving either
 placebo (no active medicine) or belimumab. The controlled period of the study is 52 weeks.
 The random assignment in this study is "2 to 1" which means that for every 3 participants, 2
 will receive belimumab and 1 will receive placebo. Participants who successfully complete the
 52-week study may enter into a 6-month open-label extension. All participants in the
 open-label extension receive belimumab plus standard therapy.
Inclusion criteria:

 -  At least 18 years of age.

 -  Self-identified black race.

 -  Have a clinical diagnosis of SLE according to the American College of Rheumatology
 (ACR) criteria

 -  Have active SLE disease defined as a SELENA SLEDAI score >= 8 at screening

 -  Have 2 unequivocally positive autoantibody test results defined as a positive
 antinuclear antibody (ANA) test [i.e., titer >= 1:80 by human epithelial cell line 2
 (HEp-2) immunofluorescence assay (IFA) and/or positive enzyme immunoassay (EIA)]
 and/or a positive anti- double stranded deoxyribonucleic acid (dsDNA) (>= 30
 international units [IU]/milliliter [mL]) serum antibody test as follows:

 -  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.

 Historical documentation of a positive ANA test (e.g., HEp-2 IFA or EIA) or anti-dsDNA (eg,
 anti-dsDNA by any validated commercial assay) must include the date and type of the test,
 the name of the testing laboratory, numerical reference range, and a key that explains
 values provided as positive versus negative OR negative, equivocal/borderline positive).
 Only unequivocally positive values as defined in the laboratory's reference range are
 acceptable; borderline values will not be accepted.

 -  On a stable SLE treatment regimen consisting of any of the following medications
 (alone or in combination) for a period of at least 30 days prior to Day 0 (i.e., day
 of 1st dose of study agent):

 -  Corticosteroids (prednisone or prednisone equivalent, up to 40 mg/day): For
 subjects on SLE combination therapy, their stable steroid dose must be fixed
 within the range of 0 to 40 mg/day (prednisone or prednisone equivalent). For
 subjects whose only SLE treatment is steroids, their stable steroid dose must be
 fixed within the range of 7.5 to 40 mg/day (prednisone or prednisone equivalent).
 For those subjects on alternating day doses of steroids, use the average of 2
 daily doses to calculate the average daily steroid dose.

 -  Other immunosuppressive or immunomodulatory agents including methotrexate,
 azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil,
 mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin
 inhibitors (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).

 Note:

 -  Pre-existing SLE medications must be stable for at least 30 days prior to Day 0.

 -  Corticosteroids may be added as new medication or their doses adjusted only up to 30
 days prior to Day 0.

 -  New SLE therapy other than corticosteroids must not be added within 60 days of Day 0.

 -  A female subject is eligible to enter the study if she is:

 -  Not pregnant or nursing;

 -  Of non-childbearing potential defined as: pre-menopausal females with a
 documented tubal ligation, hysterectomy, documented hysteroscopic tubal occlusion
 procedure with follow-up confirmation of bilateral tubal occlusion, or documented
 bilateral oophorectomy, OR postmenopausal defined as 12 months of spontaneous
 amenorrhea with an appropriate clinical profile [e.g., > 45 years, in the absence
 of hormone replacement therapy or other cause for amenorrhea]; in questionable
 cases obtain a blood sample for follicle stimulating hormone (FSH) and estradiol
 simultaneously to confirm. Diagnostic levels for FSH and estradiol vary by
 specific laboratories/assays;

 -  OR is of child-bearing potential with negative pregnancy test as determined by
 serum human chorionic gonadotrophin (hCG) test at screening and urine hCG test
 prior to dosing AND agrees to use one of the contraception methods for 2 weeks
 prior to the day of dosing to sufficiently minimize the risk of pregnancy at that
 point. Female subjects must agree to use contraception until 16 weeks following
 the last dose of study agent.

 -  OR has only same-sex partners, when this is her preferred and usual lifestyle.

 -  Have the ability to understand the requirements of the study, provide written
 informed consent (including consent for the use and disclosure of
 research-related health information), and comply with the study protocol
 procedures (including required study visits).

 Exclusion criteria:

 -  Have received treatment with anti-B lymphocyte stimulator (BLyS) [belimumab] at any
 time.

 -  Have received any of the following within 364 days of Day 0:

 -  Abatacept

 -  Other B cell targeted therapy (e.g., rituximab, other anti-cluster of
 differentiation [CD] 20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab],
 BLyS-receptor fusion protein [BR3], TACI-Fc, or anti-B-cell activating factor
 [BAFF] (LY2127399).

 -  A biologic investigational agent other than B cell targeted therapy (e.g.,
 abetimus sodium, anti-CD40L antibody [BG9588/IDEC-131]).

 -  Have required 3 or more courses of systemic corticosteroids for concomitant conditions
 (e.g., asthma, atopic dermatitis) within 364 days of Day 0. (Topical or inhaled
 steroids are permitted.)

 -  Have received any of the following within 90 days of Day 0:

 -  Anti-tumor necrosis factor (TNF) therapy (eg, adalimumab, certolizumab pegol,
 etanercept, golimumab, infliximab).

 -  Intravenous (IV) cyclophosphamide

 -  Interleukin-1 receptor antagonist (anakinra).

 -  Intravenous immunoglobulin (IVIG).

 -  High dose prednisone or equivalent (> 100 mg/day).

 -  Plasmapheresis.

 -  Have received any of the following within 60 days of Day 0:

 -  A non-biologic investigational agent.

 -  Any new immunosuppressive/immunomodulatory agent, anti-malarial, or NSAID Note:
 New inhaled and topical steroids and new topical immunosuppressive agents (e.g.,
 eye drops, topical creams) are allowed. Any NSAID use for < 1 week is allowed.

 -  Any steroid injection (e.g., intramuscular, intraarticular, or intravenous).

 -  Have received any of the following within 30 days of Day 0:

 -  A live vaccine.

 -  A change in dose of a corticosteroid, other immunosuppressive/immunomodulatory
 agent, anti-malarial, or NSAID

 -  Have severe lupus kidney disease (defined by proteinuria > 6 grams/24 hour or
 equivalent using spot urine protein to creatinine ratio, or serum creatinine > 2.5
 mg/deciliter [dL]), or have severe active nephritis requiring acute therapy not
 permitted by protocol (e.g., IV cyclophosphamide within 90 days of Day 0), or have
 required hemodialysis or high-dose prednisone (> 100 mg/day) within 90 days of Day 0.

 -  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 0.

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

 -  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, 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.

 -  Have a planned surgical procedure or a history of any other medical disease (e.g.,
 cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access)
 that, in the opinion of the principal investigator, makes the subject unsuitable for
 the study.

 -  Have a history of malignant neoplasm within the last 5 years, except for adequately
 treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the
 uterine cervix.

 -  Have required management of acute or chronic infections, as follows:

 -  Currently on any suppressive therapy for a chronic infection (such as
 tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster,
 and atypical mycobacteria).

 -  Hospitalization for treatment of infection within 60 days of Day 0.

 -  Use of parenteral (IV or intramuscular [IM]) antibiotics (antibacterials,
 antivirals, anti-fungals, or anti-parasitic agents) within 60 days of Day 0.

 -  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
 screening Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 2 months or who,
 in the investigator's opinion, pose a significant suicide risk.

 -  Have current drug or alcohol abuse or dependence, or a history of drug or alcohol
 abuse or dependence within 364 days prior to Day 0.

 -  Have a historically positive test or test positive at screening for human
 immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis
 B core antibody, or hepatitis C antibody.

 -  Have an immunoglobulin (Ig)A deficiency (IgA level < 10 mg/dL).

 -  Have a grade 3 or greater laboratory abnormality based on the adverse event

 -  Severity grading tables except for the following that are allowed:

 -  Stable grade 3 prothrombin time (PT) secondary to anticoagulant, e.g., warfarin,
 treatment.

 -  Stable grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and
 not related to liver disease or anti-coagulant therapy.

 -  Stable grade 3/4 proteinuria (<=6 grams/24 hour equivalent by spot urine protein
 to creatinine ratio allowed).

 -  Stable grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver
 disease or malnutrition.

 -  Stable grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis,
 and not related to alcoholic liver disease, uncontrolled diabetes, or viral
 hepatitis. If present, any abnormalities in alanine transaminase (ALT) and/or
 aspartate transaminase (AST) must be <=grade 2.

 -  Stable grade 3 hemoglobin reduction due to lupus.

 -  Stable grade 3 neutropenia or stable grade 3 white blood cell count.

 -  Have a history of an anaphylactic reaction to parenteral administration of contrast
 agents, human or murine proteins, or monoclonal antibodies.