A Multi-Center, Open-Label Trial to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Subcutaneously Administered Belimumab, a Human Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Participants With Systemic Lupus Erythematosus (SLE)
A Multi-Center, Open-Label Trial to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Subcutaneously Administered Belimumab, a Human Monoclonal Anti-BLyS Antibody, Plus Standard Therapy 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 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;
Body weight >=15 kg.
Male and/or female;
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;
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;
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;
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;
Have received any of the following within 30 days of Day 1;
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.
Saint Augustin, 53757, Germany