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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03239600
Recruitment Status : Withdrawn (The study is stopped for Portfolio prioritization.)
First Posted : August 4, 2017
Last Update Posted : March 7, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Autoimmune Diseases Drug: GSK2618960 2 mg/kg Drug: Placebo Drug: Methotrexate Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a randomized, double blind (sponsor unblind) study and masking will be performed.
Primary Purpose: Treatment
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
Actual Study Start Date : September 19, 2017
Actual Primary Completion Date : October 12, 2017
Estimated Study Completion Date : October 12, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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: Placebo
Placebo solution will be administered by IV infusion.

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.




Primary Outcome Measures :
  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03239600


Locations
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United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 0GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03239600    
Other Study ID Numbers: 201579
First Posted: August 4, 2017    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Anti-IL-7 Receptor-alpha Monoclonal Antibody
Safety
GSK2618960
Primary Sjögren's Syndrome
Additional relevant MeSH terms:
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Sjogren's Syndrome
Autoimmune Diseases
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Immune System Diseases
Methotrexate
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists