Back to resultsA Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
Primary Purpose
Autoimmune Diseases
Status
Withdrawn
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
GSK2618960 2 mg/kg
Placebo
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Autoimmune Diseases focused on measuring Anti-IL-7 Receptor-alpha Monoclonal Antibody, Safety, GSK2618960, Primary Sjögren's Syndrome
Eligibility Criteria
Inclusion Criteria:
- Part I and Part II: Male and females aged 18-70
- Part I and Part II: pSS diagnosis according to the American-European Consensus Group Criteria
- Part I and Part II: Documented previous biopsy evidence of salivary gland inflammation consistent with pSS and/or documented history of anti-Ro and/or anti-La antibodies
- Part II: Has any of the following abnormalities at screening: hypergammaglobulinaemia [serum Immunoglobulin G (IgG) greater than or equal to 16 gram per liter (g/L); Presence of Rheumatoid factor (RF); Anti Nuclear Antibodies (ANA) titer greater than or equal to 320:1.
- Stimulated whole salivary flow greater than 0.1 milliliter per minute (mL/min) at screening.
- Symptomatic oral dryness greater than or equal to 5 out of 10 on Visual Analogue Scale (VAS) scale and/or Schirmer test less than 10 millimeter (mm) at screening.
Exclusion Criteria:
- Part I and II: Secondary Sjögren's Syndrome
- Part I and II: Receiving cyclophosphamide, other biologic, immunosuppressive or immunomodulatory treatments
- Part I and II: Active infections, or history of recurrent infections
- Part I and II: History of significant medical illness
- Part I and II: History of lymphoma
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
Part II: Placebo
Arm Description
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
Placebo will be administered IV with MTX
Outcomes
Primary Outcome Measures
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.
Number of subjects with abnormal clinical chemistry values: Part 1
Samples for clinical chemistry tests will be collected as a measure of safety
Number of subjects with abnormal hematology values: Part 1
Samples for clinical hematology tests will be collected as a measure of safety
Number of subjects with abnormal urine analysis values: Part 1
Samples for Urine analysis tests will be collected as a measure of safety
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.
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.
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.
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.
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
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.
Number of subjects with abnormal clinical chemistry values: Part 2
Samples for clinical chemistry tests will be collected as a measure of safety
Number of subjects with abnormal hematology values: Part 2
Samples for clinical hematology tests will be collected as a measure of safety
Number of subjects with abnormal urine analysis values: Part 2
Samples for Urine analysis tests will be collected as a measure of safety
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.
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.
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.
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.
Number of subjects with abnormal ECG findings: Part 2
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Secondary Outcome Measures
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.
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.
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.
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.
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.
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 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.
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.
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
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03239600
Brief Title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
Official Title
A Two Part Phase IIa Study, to Evaluate the Safety and Tolerability, Pharmacokinetics, Proof of Mechanism and Potential for Efficacy of an Anti-IL-7 Receptor-α Monoclonal Antibody (GSK2618960) in the Treatment of Primary Sjögren's Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Withdrawn
Why Stopped
The study is stopped for Portfolio prioritization.
Study Start Date
September 19, 2017 (Actual)
Primary Completion Date
October 12, 2017 (Actual)
Study Completion Date
October 12, 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Diseases
Keywords
Anti-IL-7 Receptor-alpha Monoclonal Antibody, Safety, GSK2618960, Primary Sjögren's Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a parallel assignment where in Part II of the study, randomized subject will receive GSK2618960 and placebo drug simultaneously.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This is a randomized, double blind (sponsor unblind) study and masking will be performed.
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
Arm Type
Experimental
Arm Description
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
Arm Title
Part II: Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered IV with MTX
Intervention Type
Drug
Intervention Name(s)
GSK2618960 2 mg/kg
Intervention Description
GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo solution will be administered by IV infusion.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of subjects with Adverse Events (AEs): Part 1
Description
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
Title
Number of subjects with abnormal clinical chemistry values: Part 1
Description
Samples for clinical chemistry tests will be collected as a measure of safety
Time Frame
Up to Week 29
Title
Number of subjects with abnormal hematology values: Part 1
Description
Samples for clinical hematology tests will be collected as a measure of safety
Time Frame
Up to Week 29
Title
Number of subjects with abnormal urine analysis values: Part 1
Description
Samples for Urine analysis tests will be collected as a measure of safety
Time Frame
Up to Week 29
Title
Number of subjects with abnormal findings of body temperature: Part 1
Description
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
Time Frame
Up to Week 29
Title
Number of subjects with abnormal findings of blood pressure: Part 1
Description
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
Title
Number of subjects with abnormal findings of pulse rate: Part 1
Description
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
Time Frame
Up to Week 29
Title
Number of subjects with abnormal findings of respiratory rate: Part 1
Description
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
Time Frame
Up to Week 29
Title
Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
Description
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Time Frame
Up to Week 29
Title
Number of subjects with AEs: Part 2
Description
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
Title
Number of subjects with abnormal clinical chemistry values: Part 2
Description
Samples for clinical chemistry tests will be collected as a measure of safety
Time Frame
Up to Week 35
Title
Number of subjects with abnormal hematology values: Part 2
Description
Samples for clinical hematology tests will be collected as a measure of safety
Time Frame
Up to Week 35
Title
Number of subjects with abnormal urine analysis values: Part 2
Description
Samples for Urine analysis tests will be collected as a measure of safety
Time Frame
Up to Week 35
Title
Number of subjects with abnormal findings of body temperature: Part 2
Description
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
Time Frame
Up to Week 35
Title
Number of subjects with abnormal findings of blood pressure: Part 2
Description
SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.
Time Frame
Up to Week 35
Title
Number of subjects with abnormal findings of pulse rate: Part 2
Description
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
Time Frame
Up to Week 35
Title
Number of subjects with abnormal findings of respiratory rate: Part 2
Description
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
Time Frame
Up to Week 35
Title
Number of subjects with abnormal ECG findings: Part 2
Description
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Time Frame
Up to Week 35
Secondary Outcome Measure Information:
Title
Plasma concentration of GSK2618960: Part 1
Description
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
Title
Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1
Description
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
Title
Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
Description
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
Title
Area under the curve (AUC) of GSK2618960: Part 1
Description
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
Title
Number of incidences of Anti-drug antibody (ADA) formation: Part 1
Description
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
Title
Number of titres of ADA: Part 1
Description
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
Title
Time to onset of ADA: Part 1
Description
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
Title
Number of incidences of ADA neutralization: Part 1
Description
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
Title
Plasma concentration of GSK2618960 : Part 2
Description
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
Title
Cmax of GSK2618960: Part 2
Description
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
Title
Cmin of GSK2618960: Part 2
Description
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
Title
AUC of GSK2618960: Part 2
Description
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
Title
Number of incidences of ADA formation: Part 2
Description
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
Title
Number of titres of ADA: Part 2
Description
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
Title
Time to onset of ADA: Part 2
Description
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
Title
Number of incidences of ADA neutralization: Part 2
Description
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
Title
Receptor occupancy (RO) on circulating T cells: Part 2
Description
Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.
Time Frame
Up to Week 35
Title
Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2
Description
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
Title
Change from Baseline in Focus score: Part 2
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Part I and Part II: Male and females aged 18-70
Part I and Part II: pSS diagnosis according to the American-European Consensus Group Criteria
Part I and Part II: Documented previous biopsy evidence of salivary gland inflammation consistent with pSS and/or documented history of anti-Ro and/or anti-La antibodies
Part II: Has any of the following abnormalities at screening: hypergammaglobulinaemia [serum Immunoglobulin G (IgG) greater than or equal to 16 gram per liter (g/L); Presence of Rheumatoid factor (RF); Anti Nuclear Antibodies (ANA) titer greater than or equal to 320:1.
Stimulated whole salivary flow greater than 0.1 milliliter per minute (mL/min) at screening.
Symptomatic oral dryness greater than or equal to 5 out of 10 on Visual Analogue Scale (VAS) scale and/or Schirmer test less than 10 millimeter (mm) at screening.
Exclusion Criteria:
Part I and II: Secondary Sjögren's Syndrome
Part I and II: Receiving cyclophosphamide, other biologic, immunosuppressive or immunomodulatory treatments
Part I and II: Active infections, or history of recurrent infections
Part I and II: History of significant medical illness
Part I and II: History of lymphoma
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Cambridge
ZIP/Postal Code
CB2 0GG
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
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