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The study is stopped for Portfolio prioritization.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I & II: GSK2618960 2 milligram per kilogram (mg/kg) | Experimental | GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX) |
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| Part II: Placebo | Placebo Comparator | Placebo will be administered IV with MTX |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2618960 2 mg/kg | Drug | GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 | 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 | 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 | 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. | 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. | Up to Week 29 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 0GG | United Kingdom |
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This is a parallel assignment where in Part II of the study, randomized subject will receive GSK2618960 and placebo drug simultaneously.
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This is a randomized, double blind (sponsor unblind) study and masking will be performed.
| Placebo | Drug | Placebo solution will be administered by IV infusion. |
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| Methotrexate | Drug | 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. |
|
| 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. |
| 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. | 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 | 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. | 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 | 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 | 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 | 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. | 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. | 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. | 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. | 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 | Up to Week 35 |
| 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. |
| 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. | 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. | 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. | 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. | 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. | 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. | 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 | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Up to Day 29 |
| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000705473 | GSK2618960 |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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