Clinical Trial: Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of GSK2646264 in Cutaneous Lupus Erythematosus Patients

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Double-blind (Sponsor Unblinded) Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of Repeat Dosing of GSK2646264 in Cutaneous L

Brief Summary:

This study is designed to examine safety, tolerability, pharmacokinetics, pharmacodynamics and clinical effect of repeat dosing of GSK2646264 in patients with subacute and chronic cutaneous lupus erythematosus (CLE) lesions and in acute CLE like lesions induced by photoprovocation (PV).

Current study is two group study. In Group A, Patients with fewer than two active lesions will be enrolled and exposed to photoprovocation (PV) for 3 consecutive days. Patients that develop PV lesions at any time during this period, as determined by the local investigative team, will receive 1% strength GSK2646264 on 1 lesion and placebo on 1 lesion daily and either 1% strength GSK2646264 or placebo on an area of uninvolved skin, for skin pharmacokinetic (PK) of study drug, for 28 days.

In Group B, Patients that have a minimum of 2 active existing CLE lesions as determined by the investigators will be enrolled into group B and have one lesion treated with 1% GSK2646264 and 1 lesion with placebo.

A completed patient will be defined as a subject who receives at least 25 days of study drug and completes the end of treatment biopsy (at day 28) and assessment. Thereafter patients will be followed for 28 days in Group A only or until complete resolution of induced PV lesions, as determined by the investigator.


Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Number of participants with abnormal hematology parameters in Group A [ Time Frame: Approximately 14 weeks ]
    The hematology parameters included are platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, basophils.
  • Number of participants with abnormal hematology parameters in Group B [ Time Frame: Approximately 12 weeks ]
    The hematology parameters included are platelet count, RBC count, hemoglobin, hematocrit, MCV, MCH, neutrophils, lymphocytes, monocytes, eosinophils, basophils.
  • Number of participants with abnormal clinical chemistry parameters in Group A [ Time Frame: Approximately 14 weeks ]
    Clinical chemistry parameters included are blood urea nitrogen (BUN), creatinine, glucose, potassium, sodium, calcium, Aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase, total and direct bilirubin, total protein, albumin, thyroid-stimulating hormone (TSH), free T4, free T3
  • Number of participants with abnormal clinical chemistry parameters in Group B [ Time Frame: Approximately 12 weeks ]
    Clinical chemistry parameters included are BUN, creatinine, glucose, potassium, sodium, calcium, AST, ALT, alkaline phosphatase, total and direct bilirubin, total protein, albumin, TSH, free T4, free T3
  • Number of participants with abnormal urinalysis parameters in Group A [ Time Frame: Approximately 14 weeks ]
    Same as current

    Current Secondary Outcome:

    • Change from baseline of components of a modified RCLASI- composite clinical activity score [ Time Frame: Baseline, Day 14 and Day 28 ]
      The RCLASI (Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index) will be used to assess disease activity.
    • Change from baseline in interferon (IFN) Messenger-Ribonucleaic Acid (mRNA) signature in skin biopsies in PV and existing CLE lesions [ Time Frame: Baseline and Day 28 ]
      Lesional inflammation in lupus erythematosus is driven through the activation of IFN via the innate pathway. SYK mRNA is known to be stimulated by the IFN pathway.
    • Cmax of GSK2646264 [ Time Frame: Day 1, Day 2-13, Day 14, Day 21-27, Day 28, Day 29-42, Day 43-56 ]
      PK parameter will include maximum observed concentration (Cmax)
    • AUC(0- Tau) of GSK2646264 [ Time Frame: Day 1, Day 2-13, Day 14, Day 21-27, Day 28, Day 29-42, Day 43-56 ]
      PK parameter will include area under the concentration-time curve (AUC) over the dosing interval (0- Tau)
    • t1/2 of GSK2646264 [ Time Frame: Day 1, Day 2-13, Day 14, Day 21-27, Day 28, Day 29-42, Day 43-56 ]
      PK parameter will include Terminal phase half life (t1/2)


    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: August 30, 2016
    Date Started: January 1, 2017
    Date Completion: June 1, 2018
    Last Updated: April 27, 2017
    Last Verified: April 2017