NCT03306589

Lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Challenge Study on Healthy Subjects

An Open Label Parallel Group Study to Investigate the Optimum Methodology for the Use of LPS or GM-CSF as Challenge Agents on Healthy Participants by Assessing Inflammatory Biomarkers in Cantharidin-induced Skin Blisters, Peripheral Blood, and Urine

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: Male
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Conditions

• Arthritis, Rheumatoid

Interventions

Type	Name	Description
BIOLOGICAL	Cantharidin	5 microliter (µL) of 0.2 percent Cantharidin solution (diluted in acetone) will be applied to all subjects on forearm by topical route.
BIOLOGICAL	Lipopolysaccharide	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.
BIOLOGICAL	Granulocyte-Macrophage Colony-Stimulating Factor	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.
DRUG	Saline Solution	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.

Timeline

• Start date: 2017-08-11
• Primary completion: 2018-01-03
• Completion: 2018-06-20
• First posted: 2017-10-11
• Last updated: 2019-08-08
• Results posted: 2019-08-08

Locations

1 site across 1 country: United Kingdom

Regulatory

• FDA-regulated drug study