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.
- - 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.
- - 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]).
- - 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).
- - 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.