Study of Subcutaneous (SC) Belimumab in Pediatric Participants With Systemic Lupus Erythematosus (SLE)
Study of Subcutaneous (SC) Belimumab in Pediatric Participants With Systemic Lupus Erythematosus (SLE)
The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and
 pharmacodynamics (PD) of repeat doses of 200 milligrams per milliliter (mg/mL) belimumab
 administered via SC injection in pediatric participants 5 to 17 years of age with SLE on a
 background of standard of care therapy. This bridging PK study is part of an extrapolation
 strategy to support the use of SC belimumab in pediatric SLE participants, based on the
 completed adult SLE study with SC belimumab and the pediatric SLE study with intravenous (IV)
 belimumab. Part A is an open label 12-week treatment phase where participants will be
 enrolled and allocated to treatment cohorts based on their body weight at baseline. The dose
 and dosing regimens selected for SC administration in this pediatric population are intended
 to achieve a similar average exposure as observed with the weekly 200 mg SC dosing regimen in
 adult SLE patients. Part B is an optional 40-week open-label continuation phase, open to all
 participants who have completed Part A. Dosing of SC belimumab may continue at the same
 frequency in Part B or may require a change in frequency according to changes in participant
 body weight. The total duration of the study will be 68 weeks including a 12-Week open label
 treatment phase (Part A), an optional 40-week open-label continuation phase (Part B) and
 16-week follow-up.
Inclusion Criteria:

 -  Participant must be between 5 and 17 years of age inclusive, at the time of Day 1.

 -  Participants who meet the 1997 American College of Rheumatology (ACR) criteria for the
 classification of SLE;

 -  Have or have had in series 4 or more of the 11 ACR criteria for the
 classification of SLE.

 -  Have active SLE disease defined as a safety of estrogen in lupus erythematosus
 national assessment (SELENA) systemic lupus erythematosus disease activity index
 (SLEDAI) score >=6 at screening.

 -  Have documented positive autoantibody test results within the study screening period,
 defined as an anti-nuclear antibody (ANA) titre >= 1:80 and/or a positive anti-dsDNA
 (>=30 international units per milliliter [IU/mL]) serum antibody test based on either
 the study's central laboratory results or the local laboratory results. Only
 unequivocally positive values as defined in the laboratory's reference range are
 acceptable; borderline values will not be accepted

 -  Are on a stable SLE treatment regimen, "Stable treatment at Baseline" consists of any
 of the following medications (alone or in combination) administered for a period of at
 least 30 days prior to Day 1;

 -  Corticosteroids [prednisone or prednisone equivalent up to 0.5 milligram per
 kilogram per day (mg/kg/day)], for those participants 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 or thalidomide.

 -  Anti-malarials (e.g. hydroxychloroquine, chloroquine, quinacrine).

 -  Non-steroidal anti-inflammatory drugs (NSAIDs)

 -  New SLE therapy must not be added within 30 days of Day 1.

 -  Body weight >=15 kg.

 -  Male and/or female;

 -  Contraceptive use by men or women should be consistent with local regulations
 regarding the methods of contraception for those participating in clinical
 studies.

 -  No contraceptive measures are required for male participants.

 -  A female participant is eligible to participate if she is not pregnant or
 breastfeeding, and at least one of the following conditions applies, Is not a
 woman of childbearing potential (WOCBP) or Is a WOCBP and is using a
 contraceptive method that is highly effective, with a failure rate of <1%, during
 the belimumab treatment period and for at least 16 weeks, corresponding to the
 time needed to eliminate any study intervention(s) (e.g., 5 terminal half-lives),
 after the last dose of study intervention. The investigator should evaluate the
 effectiveness of the contraceptive method in relationship to the first dose of
 study intervention.

 -  A WOCBP must have a negative highly sensitive pregnancy test (serum or as
 required by local regulations) within 35 days before the first dose of belimumab.

 -  The investigator is responsible for review of medical history, menstrual history,
 and recent sexual activity to decrease the risk for inclusion of a woman with an
 early undetected pregnancy.

 -  Participant signs and dates a written age appropriate assent form (in accordance with
 applicable regulations) and the parent or legal guardian (or emancipated minor) that
 has the ability to understand the requirements of the study, provides written informed
 consent (including consent for the use and disclosure of research-related health
 information) that the participant will comply with the study protocol procedures
 (including required study visits).

 Exclusion Criteria:

 -  Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula
 of less than 30 milliliter/minute (mL/min).

 -  Have acute severe nephritis defined as significant renal disease (e.g., the presence
 of urinary sediments and other laboratory abnormalities) that, in the opinion of the
 study investigator, may lead to the participant requiring induction therapy during the
 first 12 weeks of the trial.

 -  Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or
 hematopoetic 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 investigator, could confound the results of the study or
 put the participant 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 investigator, makes the participant unsuitable for the
 study.

 -  Have a history of malignant neoplasm within the last 5 years.

 -  Have evidence of serious suicide risk including any history of suicidal behavior in
 the last 6 months, or who in the investigator's opinion, pose a significant suicide
 risk.

 -  Have a history of a primary immunodeficiency.

 -  Have an immunoglobulin A (IgA) deficiency (IgA level <10 milligrams per deciliter
 [mg/dL]).

 -  Have acute or chronic infections requiring management, as follows;

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

 -  Use of parenteral [IV or Intramuscular (IM)] antibiotics (antibacterials,
 antivirals, anti-fungals, or anti parasitic agents) for infection within 60 days
 of Day 1.

 -  Have a Grade 3 or greater laboratory abnormality based on the protocol defined adverse
 event and laboratory value severity grade scale except for the following that are
 allowed;

 -  Stable Grade 3 prothrombin time (PT) secondary to 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 hypoalbuminemia due to lupus nephritis, and not related to liver
 disease or malnutrition.

 -  Any grade proteinuria.

 -  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 the alanine amininotransferase (ALT)
 and or aspartate aminotransferase (AST) must be <= Grade 2.

 -  Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3
 leukopenia, due to SLE.

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

 -  Have ever received treatment with belimumab.

 -  Have received any of the following within 364 days of Day 1;

 -  Treatment with any B-cell targeted therapy [e.g., rituximab, other anti-CD20
 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], B lymphocyte stimulator
 (BLyS)-receptor fusion protein [BR3], transmembrane activator attached to the Fc
 portion of an immunoglobulin [TACI Fc]).

 -  Abatacept.

 -  Any biologic investigational agent.

 -  Have required 3 or more courses of systemic corticosteroids for concomitant conditions
 (e.g., asthma, atopic dermatitis) within 90 days of Day 1 (topical or inhaled steroids
 are permitted).

 -  Have received any of the following within 90 days of Day 1;

 -  Anti-tumor necrosis factor (TNF) therapy (e.g., adalimumab, etanercept,
 infliximab).

 -  Interleukin-1 receptor antagonist (anakinra).

 -  Intravenous immunoglobulin (IVIG).

 -  Plasmapheresis.

 -  Have received any of the following within 30 days of Day 1;

 -  IV cyclophosphamide.

 -  A non-biologic investigational agent (30 day window or 5 half-lives, whichever is
 greater).

 -  Any new immunosuppressive/immunomodulatory agent.

 -  High dose prednisone or equivalent (>1.5 mg/kg/day) or any intramuscular or
 intravenous steroid injection.

 -  Have received a live or live-attenuated vaccine within 30 days of Day 1.

 -  Have 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.

 -  Have required renal replacement therapy (e.g. hemodialysis, peritoneal dialysis)
 within 90 days of Day 1 or are currently on renal replacement therapy.

 -  Participation in an interventional clinical study either concurrently or within 6
 months of screening. Participation in an observational study may be permitted.

 -  Positive immunodeficiency virus (HIV) antibody test

 -  Hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as Hepatitis B
 surface antigen positive (HBsAg+) or Hepatitis B core antibody positive (HBcAb+)

 -  Hepatitis C: Positive test for Hepatitis C antibody confirmed on an additional blood
 sample by ribonucleic acid (RNA) polymerase chain reaction (PCR) assay. Participants
 who are positive for Hepatitis C antibody and negative when the Hepatitis C RNA-PCR
 assay is performed on an additional sample will be eligible to participate.
 Participants who are positive for Hepatitis C antibody and have a positive result for
 the Hepatitis C virus (HCV) when the Hepatitis C RNA PCR assay is performed on the
 additional sample will not be eligible to participate. (Institution or country
 specific guidelines for blood sample volume limits must be followed in collection of
 the additional blood sample).

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

 -  Are unable or unlikely, in the opinion of the investigator, to administer belimumab by
 SC injection and have no reliable source to administer the injection

 -  Children in Care: A Child in Care (CiC) is a child who has been placed under the
 control or protection of an agency, organization, institution or entity by the courts,
 the government or a government body, acting in accordance with powers conferred on
 them by law or regulation. The definition of a CiC can include a child cared for by
 foster parents or living in a care home or institution, provided that the arrangement
 falls within the definition above. The determination of whether a child meets the
 definition of CiC should be made with the study centre staff in consultation with the
 responsible institutional review board (IRB)/Ethics Committee.