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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Belimumab 200 mg/mL will be administered as SC injection in left or right thigh and the abdomen.
GSK Investigational Site
Cincinnati, Ohio, United States
GSK Investigational Site
Rosario, Argentina
GSK Investigational Site
Berlin, Germany
GSK Investigational Site
Saint Augustin, Germany
GSK Investigational Site
Kagoshima, Japan
GSK Investigational Site
Kanagawa, Japan
GSK Investigational Site
San Luis Potosí City, Mexico
GSK Investigational Site
Rotterdam, Netherlands
GSK Investigational Site
Barcelona, Spain
GSK Investigational Site
Madrid, Spain
...and 1 more locations
Observed Belimumab Concentrations at Week 12
Blood samples were collected for measurement of serum concentrations of belimumab. Observed belimumab concentrations at Week 12 is presented.
Time frame: At Week 12
Estimated Average Concentration (Cavg) of Belimumab at Steady State
Blood samples were collected for measurement of serum concentrations of belimumab at steady state. Average concentrations were analyzed and reported for all time-points from Week 1 through Week 60.
Time frame: Pre dose on Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52, and Week 60
Estimated Maximum Concentration (Cmax) of Belimumab at Steady State
Blood samples were collected for measurement of serum concentrations of belimumab at steady state. Cmax was analyzed and reported for all time-points from Week 1 through Week 60.
Time frame: Pre dose on Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52, and Week 60
Estimated Minimum Concentration (Cmin) of Belimumab at Steady State
Blood samples were collected for measurement of serum concentrations of belimumab at steady state. Cmin was analyzed and reported for all time-points from Week 1 through Week 60.
Time frame: Pre dose on Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 52, and Week 60
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Time frame: Up to Week 68
Number of Participants With Serious Adverse Events (SAEs)
A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death.
Time frame: Up to Week 68
Number of Participants With Adverse Events of Special Interest (AESIs)
AESI included post-injection systemic reactions and hypersensitivity reactions, infections, malignancies, and depression/suicidality/self-injury. AESIs were followed until the event is resolved, stabilized, otherwise explained, or the participant is lost to follow-up.
Time frame: Up to Week 68
Percent Change From Baseline in Complement C3 and Complement C4 at Week 12 and Week 52
Blood samples were collected from participants to assess complement C3 and complement C4 levels. Baseline status are defined as low complement \[C3 less than (\<) 90 milligrams per deciliter (mg/dL)\] or normal/high (C3 \>= 90 mg/dL) and low (C4 \< 13 mg/dL) or normal/high (C4 \>= 13 mg/dL) respectively. Percent change from Baseline was calculated by subtracting the Baseline value from value at Week 12 and 52 divided by the Baseline value X 100.
Time frame: Baseline (Day 1), Week 12 and Week 52
Percent Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (dsDNA) Antibodies at Week 12 and Week 52
Blood samples were collected for anti-dsDNA- antibody biomarker analysis. Baseline status are defined as positive (Anti-dsDNA antibody \>= 30 International Units Per Milliliter (IU/mL)) or negative (Anti-dsDNA antibody\< 30 IU/mL). Percent change from Baseline was calculated by subtracting the Baseline value from value at Week 12 and 52 divided by the Baseline value X 100.
Time frame: Baseline (Day 1), Week 12 and Week 52
Percent Change From Baseline in CD19+ Total B Cells and CD20+ B Cells at Week 12 and Week 52
Blood samples were collected for biomarker analysis. B cell subsets included CD19+ total B cells and CD 20+ B cells. Percent change from Baseline was calculated by subtracting the Baseline value from value at Week 12 and 52 divided by the Baseline value X 100.
Time frame: Baseline (Day 1), Week 12 and Week 52
Percent Change From Baseline in Naïve B Cells and Memory B Cells at Week 12 and Week 52
Blood samples were collected for biomarker analysis and included CD20+ CD27- Naïve B cells and CD20+ CD27+ memory B cell. Percent change from Baseline was calculated by subtracting the Baseline value from value at Week 12 and 52 divided by the Baseline value X 100.
Time frame: Baseline (Day 1), Week 12 and Week 52
Percent Change From Baseline in in CD27bright CD38bright Plasma Blasts at Week 12 and Week 52
Blood samples were collected for CD27bright CD38bright Plasma blasts biomarker analysis. Percent change from Baseline was calculated by subtracting the Baseline value from value at Week 12 and 52 divided by the Baseline value X 100.
Time frame: Baseline (Day 1), Week 12 and Week 52
Percent Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 12
Blood samples were collected for analysis of immunoglobulins: Immunoglobulin A (IgA), Immunoglobulin G (IgG), and Immunoglobulin M (IgM). Percent change from Baseline was calculated by subtracting the Baseline value from value at Week 12 divided by the Baseline value X 100.
Time frame: Baseline (Day 1) and Week 12
Percent Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 52
Blood samples were collected for analysis of immunoglobulins: Immunoglobulin A (IgA), Immunoglobulin A (IgG), and Immunoglobulin M (IgM). Percent change from Baseline was calculated by subtracting the Baseline value from value at Week 52 divided by the Baseline value X 100.
Time frame: Baseline (Day 1) and Week 52
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