Completed

Study Description:

This study is a phase I, randomised, double blind (sponsor unblinded), placebo-controlled, single ascending dose study GSK2831781 administered by IV. GSK2831781 is a humanized Antibody Dependent Cell Cytotoxicity (ADCC) enhanced monoclonal afucosylated antibody that is specific to the Lymphocyte Activation Gene-3 (LAG-3) protein. This is the first administration of GSK2831781 in humans and will evaluate in two parts the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of single IV doses of GSK2831781 administered to healthy subjects previously vaccinated with Bacillus Calmette Guérin (BCG) (Part A delayed type hypersensitivity [DTH] cohorts) and patients with plaque psoriasis (Part B). The inclusion of DTH and psoriasis subjects to explore the mechanism in biopsies and clinical response endpoints in these populations, as well as investigate systemic biomarkers will provide useful information prior to conducting studies in other immune-inflammatory disease which will involve more invasive tissue biopsies. Measuring the pharmacology of GSK2831781 using the depletion of LAG-3+ T-cells in skin biopsies from Tuberculin Purified Protein Derivative (PPD) skin challenge and lesional skin biopsies from patients with psoriasis, will be helpful in understanding of the dose response relationship, which will be important for designing future studies in immuno-inflammatory diseases, including psoriasis. Approximately 67 subjects will be enrolled to complete dosing and critical assessments. The subject numbers will be split to approximately 40 healthy subjects (Part A) and 27 patients with psoriasis (Part B).

GSK Study ID:

200630


ClinicalTrials.gov Identifier:

NCT02195349


Has Results Available Below
EudraCT Number:

2014-000312-33


Study Overview

Medical Conditions

Psoriasis

Product

GSK2831781;SKF71899

Collaborators

Parexel


Date

July 2014 to March 2018

Type

Interventional

Phase

1


Gender

All

Age

18 years - 75 years

Accepts Healthy Volunteers

Yes


This study has Protocol and Result summary on ClinicalTrial.gov. Click here to learn more.

Locations

  • Central Contact :

    US GSK Clinical Trials Call Center

  • Central Contact Phone:

    877-379-3718

  • Central Contact Email:

    [email protected]

Germany, Berlin, Berlin 14050Completed
Germany, Nordrhein-Westfalen, Bonn 53127Completed
United Kingdom, London Completed

Study Design

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Study Design: Single Group Assignment
  • Study Classification: Not Available
  • Masking: Not Available
  • Masked Subject: Yes
  • Masked Caregiver: No
  • Masked Investigator: Yes
  • Masked Assessor: No
Primary Outcomes:

  • Assessment of safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (No DTH) by measuring Vital signs
    Timeframe: Up to Day 189

  • Assessment of safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (DTH) by measuring Vital signs
    Timeframe: Up to Day 219

  • Assessment of Safety and tolerability of single IV doses of GSK2831781 in psoriasis patients by measuring Vital signs
    Timeframe: Up to Day 300

  • Assessment of safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (No DTH) by measuring 12-Lead Electrocardiogram (ECG)
    Timeframe: Up to Day 189

  • Assessment of safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (DTH) by measuring 12-Lead ECGs
    Timeframe: Up to Day 219

  • Assessment of safety and tolerability of single IV doses of GSK2831781 in psoriasis patients by measuring 12-Lead ECGs
    Timeframe: Up to Day 300

  • Safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (No DTH) as assessed by number of subjects with adverse events (AE)
    Timeframe: Up to Day 365

  • Safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (DTH) as assessed by number of subjects with AEs
    Timeframe: Up to Day 365

  • Safety and tolerability of single IV doses of GSK2831781 in volunteers with psoriasis, as assessed by number of subjects with AEs
    Timeframe: Up to Day 365

  • Assessment of Safety and tolerability of single IV doses of GSK2831781 in healthy subjects (No DTH) by measuring inflammatory cytokine levels
    Timeframe: Pre-dose, and at 6, 12, 24 and 48 hours post dose

  • Assessment of Safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (DTH) by measuring inflammatory cytokine levels
    Timeframe: Pre-dose, and at 6, 12, 24 and 48 hours post dose

  • Assessment of Safety and tolerability of single IV doses of GSK2831781 in psoriasis patients by measuring inflammatory cytokine levels
    Timeframe: At pre-dose, and at 6, 12, 24 and 48 hours post dose

  • Assessment of safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (no DTH) by measuring Laboratory safety data
    Timeframe: Up to Day 189

  • Assessment of safety and tolerability of single IV doses of GSK2831781 in healthy volunteers (DTH) by measuring Laboratory safety data
    Timeframe: Up to Day 219

  • Assessment of safety and tolerability assessment of single IV doses of GSK2831781 in psoriasis patients by measuring Laboratory safety data
    Timeframe: Up to Day 300

Secondary Outcomes:

  • Change from baseline [Tuberculin Purified Protein Derivative (PPD) 1st challenge] of induration diameter from re-challenge at 3 days post-dose, in healthy volunteers (DTH)
    Timeframe: Baseline (Day1) and Day32

  • Duration of induration in the re-challenge (healthy volunteers DTH model)
    Timeframe: Day 30

  • Change from baseline (PPD 1st challenge) of Lymphocyte Activation Gene (LAG)-3+ cells in biopsies of re-challenged skin at 3 days post dose in healthy volunteers (DTH)
    Timeframe: Baseline(Day 1) and Day 32

  • Change from baseline in LAG-3+ cells in lesional biopsies of psoriasis patients at Day 29 measured by IHC.
    Timeframe: Baseline and Day 29

  • Composite of GSK2831781 PK parameters following single IV dose in healthy volunteers (no DTH) for 0.0003mg/kg Cohort
    Timeframe: Pre dose, at 0.5, 1, 2, 4, 6, 8, 12 and 24, hours post dose and Follow up (Day 29)

  • Composite of GSK2831781 PK parameters following single IV dose in healthy volunteers (no DTH) for 0.0015mg/kg Cohort
    Timeframe: Pre dose, at 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post dose and Follow up (Day 43)

  • Composite of GSK2831781 PK parameters following single IV dose in healthy volunteers (no DTH) for 0.0075mg/kg Cohort
    Timeframe: Pre dose, at 0.5, 1, 2, 4, 6, 8, 12, 24, 48,72, 168 hours, Day 15 post dose and Follow up (Day 85)

  • Composite of GSK2831781 PK parameters following single IV dose in healthy volunteers (no DTH) for 0.04mg/kg Cohort
    Timeframe: Pre dose, At 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 168 hours, Days 15, 22, 29, 43, 57 post dose and Follow up (Day 147)

  • Composite of GSK2831781 PK parameters following single IV dose in healthy volunteers (no DTH) for 0.15mg/kg Coh
    Timeframe: Pre dose, At 0.5, 1, 2, 4, 6, 8, 12, 24, 48,72, 168 hours, Days 15, 22, 43, 85 post dose and Follow up (Day 189)

  • Composite of GSK2831781 PK parameters following single IV dose in healthy volunteers (DTH) for 0.15mg/kg Cohort
    Timeframe: Pre dose, At 0.5, 1, 2, 4, 6, 8, 12, 24, 48,72, 168 hours, Days 15, 22, 43, 85 post dose and Follow up (Day 219)

  • Composite of GSK2831781 PK parameters following single IV dose for patients with psoriasis in 0.5mg/kg cohort
    Timeframe: Pre dose, at 0.5, 1, 2, 4, 6, 8, 12, 24, 48,72,168 hours, Days 15, 22, 29, 43, 85, 121 post dose and Follow up (Day 230)

  • Composite of GSK2831781 PK parameters following single IV dose in patients with psoriasis for 1.5mg/kg cohort
    Timeframe: Pre dose, At 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72,168 hours, Days 15, 22, 29, 36, 43, 57, 85, 121 post dose and Follow up (Day 270)

  • Composite of GSK2831781 PK parameters following single IV dose in subjects with psoriasis for 5mg/kg cohort
    Timeframe: Pre dose, At 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72,168 hours, Days 15, 22, 29, 43, 57, 71, 85, 121 post dose and Follow up (Day 300)

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of healthy volunteers (no DTH) For 0.0003MG/KG Cohort
    Timeframe: Up to Day 29

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of healthy subjects (no DTH) For 0.0015MG/KG Cohort
    Timeframe: Up to Day 43

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of healthy volunteers (no DTH) For 0.0075MG/KG Cohort
    Timeframe: Up to Day 85

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of healthy volunteers (no DTH) For 0.004MG/KG Cohort
    Timeframe: Up to Day 147

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of healthy volunteers (no DTH) For 0.15MG/KG Cohort
    Timeframe: Up to Day 189

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of healthy volunteers (DTH) For 0.15MG/KG Cohort
    Timeframe: Up to Day 219

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of volunteers with psoriasis in 0.5 MG/KG cohort
    Timeframe: Up to Day 230

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of patients with psoriasis in 1.5 MG/KG cohort
    Timeframe: Up to Day 270

  • Immunogenicity of single IV dose of GSK2831781, measured in terms of antibodies to GSK2831781 in serum of patients with psoriasis in 5 MG/KG cohort
    Timeframe: Up to Day 300

  • To evaluate the effect of a single IV dose of GSK2831781 on disease activity in patients with psoriasis by measuring the change from baseline and actual Psoriasis Area Severity Index (PASI) scores at Day 15, 29, 43, 85 and 121
    Timeframe: Baseline, Up to Day 300

  • To evaluate the effect of a single IV dose of GSK2831781on disease activity in psoriasis patients by measuring the proportion of subjects achieving >=50 % and >=75 % improvement from baseline in PASI score at Day 15, 29, 43, 85 and 121 (PASI 50 and 75)
    Timeframe: Baseline, Up to Day 300

  • To evaluate the effect of a single IV dose of GSK2831781on disease activity in patients with psoriasis by measuring the change from baseline and actual Psoriatic Lesion Severity Scores (PLSS) at Day 15, 29, 43, 85 and 121
    Timeframe: Baseline, Up to Day 300

  • Change from baseline and actual Physical Global Assessment (PGA) scores in patients with psoriasis at Day 15, 29, 43, 85 and 121
    Timeframe: Baseline, Up to Day 121

  • Proportion of patients in each PGA score category among patients with psoriasis, at Day 15, 29, 43, 85 and 121
    Timeframe: Baseline, Up to Day 121

Arms:
  • 3

Interventions:

  • Biological/Vaccine: GSK2831781
  • Biological/Vaccine: Placebo

Keyword:

  • Tuberculin Purified Protein Derivative, Delayed Type Hypersensitivity, Biopsy, Induration, First time in human, T-cells, LAG-3, safety, GSK2831781, psoriasis
Inclusion / Exclusion Criteria: Click to view inclusion/exclusion criteria:
Enrollment: 67