In China, Belimumab (GSK1550188) will be developed for a dosing regimen of once-monthly intravenous (IV) infusion for the treatment of SLE. This open-label, single dose study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of belimumab in Chinese SLE subjects. A total of approximately 20 subjects will be enrolled to receive IV infusion of 10 milligrams per kilogram (mg/kg) GSK1550188 on Day 0 for the treatment of SLE. Subjects will be followed for 84 days after the administration of drug.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Belimumab will be provided as white uniform lyophilized cake in vials with unit dose strength of 400 mg/vial plus excipients (citric acid/sodium citrate/sucrose/polysorbate) for reconstitution in 4.8 milliliter sterile water for injection (SWFI). Belimumab will be administered as 10 mg/kg intravenous infusion for over 1 hour on Day 0.
GSK Investigational Site
Shanghai, China
GSK Investigational Site
Suzhou, China
Maximum Observed Concentration (Cmax) of Belimumab
Blood samples were collected at the indicated timepoints to calculate Cmax of belimumab.
Time frame: Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0 to t]) and Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0 to Inf]) of Belimumab
Blood samples were collected at the indicated timepoints to calculate AUC (0 to t) and AUC (0 to inf) of belimumab.
Time frame: Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose
Terminal Phase Half-life (t1/2) of Belimumab
Blood samples were collected at the indicated time points to calculate t1/2 of belimumab.
Time frame: Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose
Terminal Phase Rate Constant (Lambda z) of Belimumab
Blood samples were collected at the indicated time points to calculate lambda z of belimumab.
Time frame: Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose
Systemic Clearance (CL) of Belimumab
Blood samples were collected at the indicated time points to calculate CL of belimumab.
Time frame: Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose
Volume of Distribution (Vz) of Belimumab
Blood samples were collected at the indicated time points to calculate Vz of belimumab.
Time frame: Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose
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Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant, or associated with liver injury and impaired liver function.
Time frame: Up to Day 84
Change From Baseline to Day 84 in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Vital signs included SBP and DBP. SBP and DBP were measured with the participant in the sitting position. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Vital Sign- Pulse Rate
Vital signs included pulse rate. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Vital Sign- Temperature
Vital signs included temperature. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Number of Participants With Abnormal-clinically Significant 12-lead Electrocardiogram (ECG) Findings
ECG parameters included heart rate, PR interval, QRS interval, QT interval and corrected QT (QTc) interval. Number of participants with abnormal-clinically significant 12-lead ECG findings are presented.
Time frame: Up to Day 84
Change From Baseline to Day 84 in Clinical Chemistry Parameters- Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase
Clinical chemistry parameters included ALT, ALP, AST, GGT and lactate dehydrogenase. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Clinical Chemistry Parameters- Albumin and Protein
Clinical chemistry parameters included albumin and protein. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Clinical Chemistry Parameters- Bilirubin, Creatinine, Direct Bilirubin, Indirect Bilirubin and Urate
Clinical chemistry parameters included bilirubin, creatinine, direct bilirubin, indirect bilirubin and urate. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Clinical Chemistry Parameters- Calcium, Calcium Corrected, Carbon Dioxide, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea and Glucose
Clinical chemistry parameters included calcium, calcium corrected, carbon dioxide, chloride, magnesium, phosphate, potassium, sodium, urea and glucose. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Hematology Parameter- Erythrocytes
Hematology parameter included erythrocytes. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Hematology Parameter- Hematocrit
Hematology parameter included hematocrit. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Change From Baseline to Day 84 in Hematology Parameter- Hemoglobin
Hematology parameter included hemoglobin. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Number of Participants With Positive Urinalysis Dipstick Results
Urinalysis was done by the dipstick method to detect the presence of protein, glucose, ketones and occult blood in urine. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine occult blood, urine protein and urine ketones can be read as negative, Trace, 1+, 2+, 3+ and 4+, indicating proportional concentrations in the urine sample; results for urinalysis parameter of urine glucose can be read as negative, Trace, 1+ or 1/4 gram per Liter (g/L), 2+ or 1/2 g/L, 3+ or 1 g/L and 4+ indicating proportional concentrations in the urine sample. \*a indicates two participants did not take the urinalysis test at Day 14 on scheduled date but took an unscheduled sample at the next visit (Day 21) and \*b indicates one participant did not take the urinalysis test at Day 28 on scheduled date but took an unscheduled sample at the next visit (Day 42). Only those participants with positive results have been presented.
Time frame: Day 0 (24 hours), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84
Percent Change From Baseline to Day 84 in B Cell Subsets (Cluster of Differentiation [CD]19 and CD 20+) for Pharmacodynamic Assessment
Immunoglobulin B cell subsets included CD19 and CD 20+. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value. Percent change from Baseline was calculated as 100 multiplied by \[(Post-Baseline Visit Value minus Baseline) / Baseline\]. Pharmacodynamic population comprised of participants who received the study medication and for whom pharmacodynamic data was available.
Time frame: Baseline (pre-dose on Day 0) to Day 84
Percent Change From Baseline to Day 84 in B Cell Subsets (CD20+/27+ Memory and CD20+/27-naïve) for the Pharmacodynamic Assessment
Immunoglobulin B cell subset included CD20+/27+ memory and CD20+/27-naïve. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value. Percent change from Baseline was calculated as 100 multiplied by \[(Post-Baseline Visit Value minus Baseline) / Baseline\].
Time frame: Baseline (pre-dose on Day 0) to Day 84
Percent Change From Baseline to Day 84 in Immunoglobulins B Cell Subset (Normalized [Norm] CD19+/27BRIGHT[Br]/38Br SLE Subset, Norm CD20+/138+Plasmacytoid, Norm CD20+/69+Activated and Norm CD20-/CD138+Plasma Cell) for Pharmacodynamic Assessment
Immunoglobulin B cell subset inlcuded Norm CD19+/27Br/38Br SLE subset, Norm CD20+/138+plasmacytoid, Norm CD20+/69+activated and Norm CD20-/CD138+plasma cell. Baseline was pre-dose on Day 0. Change from Baseline was defined as the post-Baseline value minus the Baseline value. Percent change from Baseline was calculated as 100 multiplied by \[(Post-Baseline Visit Value minus Baseline) / Baseline\].
Time frame: Baseline (pre-dose on Day 0) to Day 84