<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03239600</url>
  </required_header>
  <id_info>
    <org_study_id>201579</org_study_id>
    <nct_id>NCT03239600</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the safety, tolerability and PK of repeat dose administration of&#xD;
      GSK2618960 in the treatment of pSS. The study will contain two parts, Part I will be open&#xD;
      label and Part II will be randomized, double-blind. The minimum duration of Part I &amp; Part II&#xD;
      of the study will be 26 and 32 weeks respectively.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The study is stopped for Portfolio prioritization.&#xD;
  </why_stopped>
  <start_date type="Actual">September 19, 2017</start_date>
  <completion_date type="Anticipated">October 12, 2017</completion_date>
  <primary_completion_date type="Actual">October 12, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a parallel assignment where in Part II of the study, randomized subject will receive GSK2618960 and placebo drug simultaneously.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>This is a randomized, double blind (sponsor unblind) study and masking will be performed.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with Adverse Events (AEs): Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal clinical chemistry values: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <description>Samples for clinical chemistry tests will be collected as a measure of safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal hematology values: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <description>Samples for clinical hematology tests will be collected as a measure of safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal urine analysis values: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <description>Samples for Urine analysis tests will be collected as a measure of safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of body temperature: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <description>Body temperature will be measured in a semi-supine position after at least a 5-minute rest.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of blood pressure: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of pulse rate: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <description>Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of respiratory rate: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <description>Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <description>Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with AEs: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal clinical chemistry values: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Samples for clinical chemistry tests will be collected as a measure of safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal hematology values: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Samples for clinical hematology tests will be collected as a measure of safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal urine analysis values: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Samples for Urine analysis tests will be collected as a measure of safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of body temperature: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Body temperature will be measured in a semi-supine position after at least a 5-minute rest.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of blood pressure: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of pulse rate: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings of respiratory rate: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal ECG findings: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of GSK2618960: Part 1</measure>
    <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</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1</measure>
    <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</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1</measure>
    <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</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of GSK2618960: Part 1</measure>
    <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</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of incidences of Anti-drug antibody (ADA) formation: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of titres of ADA: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to onset of ADA: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of incidences of ADA neutralization: Part 1</measure>
    <time_frame>Up to Week 29</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of GSK2618960 : Part 2</measure>
    <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</time_frame>
    <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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of GSK2618960: Part 2</measure>
    <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</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin of GSK2618960: Part 2</measure>
    <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</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of GSK2618960: Part 2</measure>
    <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</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of incidences of ADA formation: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of titres of ADA: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to onset of ADA: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of incidences of ADA neutralization: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Receptor occupancy (RO) on circulating T cells: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <description>Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2</measure>
    <time_frame>Up to Week 35</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Focus score: Part 2</measure>
    <time_frame>Up to Day 29</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Autoimmune Diseases</condition>
  <arm_group>
    <arm_group_label>Part I &amp; II: GSK2618960 2 milligram per kilogram (mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part II: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered IV with MTX</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2618960 2 mg/kg</intervention_name>
    <description>GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.</description>
    <arm_group_label>Part I &amp; II: GSK2618960 2 milligram per kilogram (mg/kg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo solution will be administered by IV infusion.</description>
    <arm_group_label>Part II: Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <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.</description>
    <arm_group_label>Part I &amp; II: GSK2618960 2 milligram per kilogram (mg/kg)</arm_group_label>
    <arm_group_label>Part II: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Part I and Part II: Male and females aged 18-70&#xD;
&#xD;
          -  Part I and Part II: pSS diagnosis according to the American-European Consensus Group&#xD;
             Criteria&#xD;
&#xD;
          -  Part I and Part II: Documented previous biopsy evidence of salivary gland inflammation&#xD;
             consistent with pSS and/or documented history of anti-Ro and/or anti-La antibodies&#xD;
&#xD;
          -  Part II: Has any of the following abnormalities at screening: hypergammaglobulinaemia&#xD;
             [serum Immunoglobulin G (IgG) greater than or equal to 16 gram per liter (g/L);&#xD;
             Presence of Rheumatoid factor (RF); Anti Nuclear Antibodies (ANA) titer greater than&#xD;
             or equal to 320:1.&#xD;
&#xD;
          -  Stimulated whole salivary flow greater than 0.1 milliliter per minute (mL/min) at&#xD;
             screening.&#xD;
&#xD;
          -  Symptomatic oral dryness greater than or equal to 5 out of 10 on Visual Analogue Scale&#xD;
             (VAS) scale and/or Schirmer test less than 10 millimeter (mm) at screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Part I and II: Secondary Sjögren's Syndrome&#xD;
&#xD;
          -  Part I and II: Receiving cyclophosphamide, other biologic, immunosuppressive or&#xD;
             immunomodulatory treatments&#xD;
&#xD;
          -  Part I and II: Active infections, or history of recurrent infections&#xD;
&#xD;
          -  Part I and II: History of significant medical illness&#xD;
&#xD;
          -  Part I and II: History of lymphoma&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0GG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>June 19, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>March 6, 2018</last_update_submitted>
  <last_update_submitted_qc>March 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anti-IL-7 Receptor-alpha Monoclonal Antibody</keyword>
  <keyword>Safety</keyword>
  <keyword>GSK2618960</keyword>
  <keyword>Primary Sjögren's Syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sjogren's Syndrome</mesh_term>
    <mesh_term>Autoimmune Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methotrexate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03239600
org study id: 201579
nct id: NCT03239600
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a parallel assignment where in Part II of the study, randomized subject will receive GSK2618960 and placebo drug simultaneously.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: This is a randomized, double blind (sponsor unblind) study and masking will be performed.
measure: Number of subjects with Adverse Events (AEs): Part 1
time frame: Up to Week 29
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.
measure: Number of subjects with abnormal clinical chemistry values: Part 1
time frame: Up to Week 29
description: Samples for clinical chemistry tests will be collected as a measure of safety
measure: Number of subjects with abnormal hematology values: Part 1
time frame: Up to Week 29
description: Samples for clinical hematology tests will be collected as a measure of safety
measure: Number of subjects with abnormal urine analysis values: Part 1
time frame: Up to Week 29
description: Samples for Urine analysis tests will be collected as a measure of safety
measure: Number of subjects with abnormal findings of body temperature: Part 1
time frame: Up to Week 29
description: Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
measure: Number of subjects with abnormal findings of blood pressure: Part 1
time frame: Up to Week 29
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.
measure: Number of subjects with abnormal findings of pulse rate: Part 1
time frame: Up to Week 29
description: Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
measure: Number of subjects with abnormal findings of respiratory rate: Part 1
time frame: Up to Week 29
description: Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
measure: Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
time frame: Up to Week 29
description: Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
measure: Number of subjects with AEs: Part 2
time frame: Up to Week 35
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.
measure: Number of subjects with abnormal clinical chemistry values: Part 2
time frame: Up to Week 35
description: Samples for clinical chemistry tests will be collected as a measure of safety
measure: Number of subjects with abnormal hematology values: Part 2
time frame: Up to Week 35
description: Samples for clinical hematology tests will be collected as a measure of safety
measure: Number of subjects with abnormal urine analysis values: Part 2
time frame: Up to Week 35
description: Samples for Urine analysis tests will be collected as a measure of safety
measure: Number of subjects with abnormal findings of body temperature: Part 2
time frame: Up to Week 35
description: Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
measure: Number of subjects with abnormal findings of blood pressure: Part 2
time frame: Up to Week 35
description: SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.
measure: Number of subjects with abnormal findings of pulse rate: Part 2
time frame: Up to Week 35
description: Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
measure: Number of subjects with abnormal findings of respiratory rate: Part 2
time frame: Up to Week 35
description: Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
measure: Number of subjects with abnormal ECG findings: Part 2
time frame: Up to Week 35
description: Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
measure: Plasma concentration of GSK2618960: Part 1
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
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.
measure: Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1
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
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.
measure: Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
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
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.
measure: Area under the curve (AUC) of GSK2618960: Part 1
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
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.
measure: Number of incidences of Anti-drug antibody (ADA) formation: Part 1
time frame: Up to Week 29
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.
measure: Number of titres of ADA: Part 1
time frame: Up to Week 29
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.
measure: Time to onset of ADA: Part 1
time frame: Up to Week 29
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.
measure: Number of incidences of ADA neutralization: Part 1
time frame: Up to Week 29
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.
measure: Plasma concentration of GSK2618960 : Part 2
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
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
measure: Cmax of GSK2618960: Part 2
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
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.
measure: Cmin of GSK2618960: Part 2
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
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.
measure: AUC of GSK2618960: Part 2
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
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.
measure: Number of incidences of ADA formation: Part 2
time frame: Up to Week 35
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.
measure: Number of titres of ADA: Part 2
time frame: Up to Week 35
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.
measure: Time to onset of ADA: Part 2
time frame: Up to Week 35
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.
measure: Number of incidences of ADA neutralization: Part 2
time frame: Up to Week 35
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.
measure: Receptor occupancy (RO) on circulating T cells: Part 2
time frame: Up to Week 35
description: Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.
measure: Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2
time frame: Up to Week 35
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.
measure: Change from Baseline in Focus score: Part 2
time frame: Up to Day 29
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.
arm group label: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
arm group type: Experimental
description: GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
arm group label: Part II: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered IV with MTX
intervention type: Drug
intervention name: GSK2618960 2 mg/kg
description: GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
arm group label: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
intervention type: Drug
intervention name: Placebo
description: Placebo solution will be administered by IV infusion.
arm group label: Part II: Placebo
intervention type: Drug
intervention name: Methotrexate
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.
arm group label: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
arm group label: Part II: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Sjogren's Syndrome
mesh term: Autoimmune Diseases
mesh term: Methotrexate