This study aims to evaluate the safety, tolerability and PK of repeat dose administration of GSK2618960 in the treatment of pSS. The study will contain two parts, Part I will be open label and Part II will be randomized, double-blind. The minimum duration of Part I \& Part II of the study will be 26 and 32 weeks respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
Placebo solution will be administered by IV infusion.
MTX dose between 7.5 to 15 mg will be administered in tablet form once in a week till last dose of GSK2618960 to all subjects in Part I and Part II.
GSK Investigational Site
Cambridge, United Kingdom
Number of subjects with Adverse Events (AEs): Part 1
An AE is any untoward medical occurrence in a subject, 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.
Time frame: Up to Week 29
Number of subjects with abnormal clinical chemistry values: Part 1
Samples for clinical chemistry tests will be collected as a measure of safety
Time frame: Up to Week 29
Number of subjects with abnormal hematology values: Part 1
Samples for clinical hematology tests will be collected as a measure of safety
Time frame: Up to Week 29
Number of subjects with abnormal urine analysis values: Part 1
Samples for Urine analysis tests will be collected as a measure of safety
Time frame: Up to Week 29
Number of subjects with abnormal findings of body temperature: Part 1
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
Time frame: Up to Week 29
Number of subjects with abnormal findings of blood pressure: Part 1
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured in a semi-supine position after at least a 5-minute rest.
Time frame: Up to Week 29
Number of subjects with abnormal findings of pulse rate: Part 1
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
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Time frame: Up to Week 29
Number of subjects with abnormal findings of respiratory rate: Part 1
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
Time frame: Up to Week 29
Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Time frame: Up to Week 29
Number of subjects with AEs: Part 2
An AE is any untoward medical occurrence in a subject, 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.
Time frame: Up to Week 35
Number of subjects with abnormal clinical chemistry values: Part 2
Samples for clinical chemistry tests will be collected as a measure of safety
Time frame: Up to Week 35
Number of subjects with abnormal hematology values: Part 2
Samples for clinical hematology tests will be collected as a measure of safety
Time frame: Up to Week 35
Number of subjects with abnormal urine analysis values: Part 2
Samples for Urine analysis tests will be collected as a measure of safety
Time frame: Up to Week 35
Number of subjects with abnormal findings of body temperature: Part 2
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
Time frame: Up to Week 35
Number of subjects with abnormal findings of blood pressure: Part 2
SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.
Time frame: Up to Week 35
Number of subjects with abnormal findings of pulse rate: Part 2
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
Time frame: Up to Week 35
Number of subjects with abnormal findings of respiratory rate: Part 2
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
Time frame: Up to Week 35
Number of subjects with abnormal ECG findings: Part 2
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Time frame: Up to Week 35
Plasma concentration of GSK2618960: Part 1
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
Time frame: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
Time frame: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
Time frame: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
Area under the curve (AUC) of GSK2618960: Part 1
Blood samples will be collected prior to start and at the end of infusion at indicated time points and will be analyzed for PK parameters.
Time frame: Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
Number of incidences of Anti-drug antibody (ADA) formation: Part 1
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 29
Number of titres of ADA: Part 1
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 29
Time to onset of ADA: Part 1
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 29
Number of incidences of ADA neutralization: Part 1
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 29
Plasma concentration of GSK2618960 : Part 2
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters
Time frame: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
Cmax of GSK2618960: Part 2
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
Time frame: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
Cmin of GSK2618960: Part 2
Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
Time frame: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
AUC of GSK2618960: Part 2
Blood samples will be collected prior to start and at the end of infusion at indicated time points and will be analyzed for PK parameters.
Time frame: Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
Number of incidences of ADA formation: Part 2
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 35
Number of titres of ADA: Part 2
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 35
Time to onset of ADA: Part 2
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 35
Number of incidences of ADA neutralization: Part 2
Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
Time frame: Up to Week 35
Receptor occupancy (RO) on circulating T cells: Part 2
Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.
Time frame: Up to Week 35
Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2
Blood samples will be collected from subjects at indicated time points to measure phosphorylation of STAT 5 in response to ex vivo IL-7 stimulation.
Time frame: Up to Week 35
Change from Baseline in Focus score: Part 2
Salivary glands for immunohistochemistry analysis will be evaluated for general appearance and total inflammatory infiltrate (focus score). Salivary gland biopsy will be performed at Baseline and blood samples will be collected at indicated time points.
Time frame: Up to Day 29