Efficacy and Safety of Belimumab in Black Race Patients with Systemic Lupus Erythematosus (SLE)EMBRACE

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:

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 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 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 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.

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.