Lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Challenge Study on Healthy Subjects
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 1

Summary: 
      This exploratory study aims to assess exposure of healthy subjects to systemic challenge with
      either LPS or GM-CSF. This will be done by measuring inflammatory mediators and cellular
      activation markers both in circulation and in skin blisters induced by exposure to
      cantharidin (an agent that causes blisters). LPS is often used to induce inflammation whereas
      GM-CSF is a cytokine and a key mediator in inflammatory diseases. In this 2 parts study,
      subjects will have 2 sessions in each part. Part I of the study is a dose-exploration phase
      and part II will be a continuation phase to draw more precise outcomes. In session 1,
      subjects will be randomized to receive either LPS or GM-CSF and will have 2 blisters induced
      on each forearm followed by blood draws and a blister harvest on each forearm at 24 and 48
      hours post-induction. After a minimum of 14 days blister healing period, subjects will return
      for session 2. In part I, Up to 6 cohorts will be tested and all cohorts will have 2
      sessions. For Part I, initially Cohort 1 will proceed with session 1. After their blister
      healing period, Cohort 1 will return for their session 2 visit in two groups (Group A and
      Group B) on different days. Group A will be dosed on the same day (one with LPS and one with
      GM-CSF) and Group B will be dosed on a different day (one with LPS and one with GM-CSF) after
      group A. Dose-escalation in Cohort 2-6 will be continued until the well tolerated dose has
      been determined. The same dose will be administered to an additional Cohort in Part II and
      the same 2-session design will be used. Approximately 24-30 healthy subjects will be enrolled
      for the study and the total duration of the study for each subject will be approximately 13
      weeks from screening to follow up.
    


Intervention name(s): Cantharidin; Lipopolysaccharide; Granulocyte-Macrophage Colony-Stimulating Factor; Saline Solution
Intervention type(s): Biological; Biological; Biological; Drug
Intervention description(s): 5 microliter (µL) of 0.2 percent Cantharidin solution (diluted in acetone) will be applied to all subjects on forearm by topical route.; 0.5 to 4 ng/kg body weight of LPS formulated as suspension in normal saline will be administered to randomized subjects via intravenous (IV) route in dose-escalation manner.; 5 to 15 µg/kg of GM-CSF will be administered to randomized subjects via subcutaneous (SC) route in the abdominal region in dose-escalation manner.; 0.9 percent sodium chloride will be administered via IV route to all subjects at a rate of 250 mL/hour for 4 hours prior to dosing with LPS and 8 hours after dosing with LPS.
Intervention MeSH terms: Molgramostim; Sargramostim; Cantharidin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects in 2 separate groups will be randomized to receive either LPS or GM-CSF at the same time.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Inflammation; GM-CSF; LPS; Skin blisters; Healthy subjects; cantharidin