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

NCT03239600 | Withdrawn Phase 2 DMC

• 1 other identifier: 201579
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Diseases

Keywords

Anti-IL-7 Receptor-alpha Monoclonal Antibody; Safety; GSK2618960; Primary Sjögren's Syndrome

Outcome Measures

Primary Outcomes (18)

• Number of subjects with Adverse Events (AEs): Part 1

  An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

  Up to Week 29

• Number of subjects with abnormal clinical chemistry values: Part 1

  Samples for clinical chemistry tests will be collected as a measure of safety

  Up to Week 29

• Number of subjects with abnormal hematology values: Part 1

  Samples for clinical hematology tests will be collected as a measure of safety

  Up to Week 29

• Number of subjects with abnormal urine analysis values: Part 1

  Samples for Urine analysis tests will be collected as a measure of safety

  Up to Week 29

• Number of subjects with abnormal findings of body temperature: Part 1

  Body temperature will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 29

• Number of subjects with abnormal findings of blood pressure: Part 1

  Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 29

• Number of subjects with abnormal findings of pulse rate: Part 1

  Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 29

• Number of subjects with abnormal findings of respiratory rate: Part 1

  Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 29

• Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1

  Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine

  Up to Week 29

• Number of subjects with AEs: Part 2

  An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

  Up to Week 35

• Number of subjects with abnormal clinical chemistry values: Part 2

  Samples for clinical chemistry tests will be collected as a measure of safety

  Up to Week 35

• Number of subjects with abnormal hematology values: Part 2

  Samples for clinical hematology tests will be collected as a measure of safety

  Up to Week 35

• Number of subjects with abnormal urine analysis values: Part 2

  Samples for Urine analysis tests will be collected as a measure of safety

  Up to Week 35

• Number of subjects with abnormal findings of body temperature: Part 2

  Body temperature will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 35

• Number of subjects with abnormal findings of blood pressure: Part 2

  SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 35

• Number of subjects with abnormal findings of pulse rate: Part 2

  Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 35

• Number of subjects with abnormal findings of respiratory rate: Part 2

  Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.

  Up to Week 35

• Number of subjects with abnormal ECG findings: Part 2

  Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine

  Up to Week 35

Secondary Outcomes (19)

• Plasma concentration of GSK2618960: Part 1

  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

  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

  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

  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

  Up to Week 29

Study Arms (2)

Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)

EXPERIMENTAL

GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)

Drug: GSK2618960 2 mg/kg; Drug: Methotrexate

Part II: Placebo

PLACEBO COMPARATOR

Placebo will be administered IV with MTX

Drug: Placebo; Drug: Methotrexate

Interventions

GSK2618960 2 mg/kg DRUG

GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.

Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)

Placebo DRUG

Placebo solution will be administered by IV infusion.

Part II: Placebo

Methotrexate DRUG

MTX dose between 7.5 to 15 mg will be administered in tablet form once in a week till last dose of GSK2618960 to all subjects in Part I and Part II.

Part I & II: GSK2618960 2 milligram per kilogram (mg/kg); Part II: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 0GG, United Kingdom

Location

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

GSK2618960; Methotrexate

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a randomized, double blind (sponsor unblind) study and masking will be performed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a parallel assignment where in Part II of the study, randomized subject will receive GSK2618960 and placebo drug simultaneously.

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: August 4, 2017
• Study Start: September 19, 2017
• Primary Completion: October 12, 2017
• Study Completion: October 12, 2017
• Last Updated: March 7, 2018

Record last verified: 2018-03

Locations

GB (1)