Lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Challenge Study on Healthy Subjects
Status:
Completed
Trial end date:
2018-06-20
Target enrollment:
Participant gender:
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.