Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1, Multi-Center, Double-Blind, Single and Double Dose-Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of LymphoStat-B™ (Monoclonal Anti-BLyS Antibody) in Subjects With Systemic Lupus Erythematosus
Brief Summary: The purpose of thie study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of belimumab (LymphoStat-B™)in subjects with SLE.


Options:
A: Key Inclusion Criteria:

* Clinical diagnosis of SLE by ACR criteria
* Stable SLE disease activity
* On stable SLE treatment regimen
* History of measurable autoantibodies

Key Exclusion Criteria:

* Pregnant or nursing
* Received a non-FDA approved investigational agent within last 28 days
* Received cyclosporin, intravenous immunoglobulin (IVIG) or plasmapheresis within last 6 months
* Active lupus nephritis requiring hemodialysis, intravenous cyclophosphamide (Cytoxan™), or high-dose prednisone (\> 100 mg/day) within last 6 months
* Active central nervous system (CNS) lupus requiring medical intervention within last 6 months
* History of renal transplant
* History of clinical evidence of an active significant acute or chronic diseases
* Have required management or hospitalization of any infection within last 4 weeks.
* History of hypogammaglobulinemia or IgA deficiency
* Have current drug or alcohol addiction
* History of or test positive at screening for HIV, Hepatitis B or Hepatitis C
B: Primary Inclusion Criteria

* Clinical diagnosis of SLE
* "Active" SLE disease
* On a stable SLE treatment regimen
* History of measurable autoantibodies

Primary Exclusion Criteria

* Received a non-FDA approved investigational agent within last 28 days
* Cyclosporin, intravenous immunoglobulin (IVIG) or plasmapheresis within last 90 days
* Active lupus nephritis requiring hemodialysis, cyclophosphamide (Cytoxan™), or high-dose prednisone (\> 100 mg/day) within last 90 days
* Active central nervous system (CNS) lupus requiring therapeutic intervention within last 60 days
* History of renal transplant
* History of chronic infection that has been active within last 6 months, herpes zoster within last 90 days or any infection requiring hospitalization or intravenous medication within last 60 days
* History of hypogammaglobulinemia or immunoglobulin A (IgA) deficiency
* Human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C
C: Primary Inclusion Criteria

1. Have completed the LBSL02 trial and achieved a satisfactory response.

Primary Exclusion Criteria

1. Required more than 2 courses of corticosteroids for treatment of severe SLE flares in the last 5 months of LBSL02.
2. Had an SLE flare during the last 30 days of LBSL02 and through the 1st dose in LBSL99.
3. Used any of the following prohibited medications during their participation in LBSL02:

   * Other investigational agents.
   * Biologic therapeutic agents: adalimumab (Humira™), etanercept (Enbrel™), infliximab (Remicade™), and rituximab (Rituxan™).
   * Intravenous cyclophosphamide.
   * Corticosteroids \>100 mg/day prednisone equivalent for reasons other than severe SLE flare.
D: Inclusion Criteria:

* Subjects must be \>=18 years of age at the time of signing the informed consent.
* Subjects who have clinical diagnosis of SLE based on 4 or more of the 11 American College of Rheumatology (ACR) criteria.
* Subjects who have a screening SLEDAI-2K score \>=6 (This refers to the total score. Serological activity, i.e., anti-double stranded deoxyribonucleic acid \[dsDNA\]) positivity and/or hypocomplementemia is not required to be present in SLEDAI-2K assessment, but are scored if present).
* 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.
* Subjects who 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). Documentation may include 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 mm at 48 to 72 hours, regardless of Baccillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold Plus test.
* Significant allergies to humanized monoclonal antibodies.
* 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 deciliter \[mg/dL\]).
* Immunoglobulin G (IgG) less than 250 mg/dL. For Germany only, IgG less than 400mg/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 intramuscular \[IM\]) 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 hours 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- Tumor Necrosis Factor (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 (Investigational agent applies to any drug not approved for sale in the country in which it is being used); IV cyclophosphamide and, for Germany only, oral 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.

Answer: A