A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)

March 6, 2018 updated by: GlaxoSmithKline

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Cambridge, United Kingdom, CB2 0GG
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
Drug: GSK2618960 2 mg/kg
GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
Drug: Methotrexate
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.
Placebo Comparator: Part II: Placebo
Placebo will be administered IV with MTX
Drug: Methotrexate
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.
Drug: Placebo
Placebo solution will be administered by IV infusion.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of subjects with Adverse Events (AEs): Part 1
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Number of subjects with abnormal findings of pulse rate: Part 1
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Up to Week 35

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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
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
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
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
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
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
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
Time Frame: Up to Week 29
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
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
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
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
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
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
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
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
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Week 35
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
Time Frame: Up to Day 29
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 19, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 12, 2017

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 12, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 19, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 7, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201579

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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