Evaluation of the Immunopharmacology of EDP1815 and EDP2939
- Conditions
- KLH and Imiquimod Induced Skin Inflammation in Healthy Volunteers
- Interventions
- Registration Number
- NCT05682222
- Lead Sponsor
- Evelo Biosciences, Inc.
- Brief Summary
A single-center, randomized, double-blind, placebo-controlled, multiple dose platform trial.
- Detailed Description
This study will evaluate the pharmacodynamic effects of multiple doses of EDP1815 and EDP2939 on immunological responses to keyhole limpet hemocyanin (KLH) and imiquimod (IMQ) dermal challenges in healthy volunteers.
EDP1815 is an essentially non-live, specific strain of Prevotella histicola, a natural human commensal organism. EDP2939 is a pharmaceutical preparation of microbial extracellular vesicles.
Four cohorts of volunteers (n=18 per cohort) will be studied using different capsule formulations and doses, administered for 60 days. Volunteers will be immunised with intramuscular KLH. Intradermal KLH re-challenge and topical IMQ challenge will commence on Day 57 with serial pharmacodynamic assessments to Day 60. Responses will be evaluated using dermal imaging (laser speckled contrast imaging; LSCI, and multi-spectral photography), as well as dermal and systemic immunological biomarkers.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
- Capable of giving signed informed consent, and willing to comply with requirements of the study.
- Age 18 years to 45 years, inclusive.
- Body mass index of 18 to 35 kg/m2, inclusive.
- Caucasian.
- Healthy based on medical history, physical examination, blood pressure, ECG and blood and urine laboratory tests.
Key
- Use of Aldara® (imiquimod cream) within 3 weeks prior to the study.
- Has previously received Immucothel® or KLH.
- Allergy to Alhydrogel® or Aldara® (imiquimod cream).
- Current or recurrent skin diseases affecting the arms or back, or extensive tattoos in these areas.
- Previous diagnosis of psoriasis.
- History of pathological scar formation (e.g. keloid scar).
- History of skin cancer (basal cell carcinoma, squamous cell carcinoma, melanoma).
- Significant bowel disease (e.g. inflammatory bowel disease, coeliac disease)
- Currently has an infection or has needed antibiotics within 6 weeks before the study.
- Current smoker of more than 5 cigarettes per day
- Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks before start of the study
- History of Schistosomiasis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 3 Placebo oral capsule EDP2939 lower dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. Cohort 4 EDP2939 EDP2939 higher dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. Cohort 2 Placebo oral capsule EDP1815 or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. Cohort 3 EDP2939 EDP2939 lower dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. Cohort 4 Placebo oral capsule EDP2939 higher dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. Cohort 1 Placebo oral capsule EDP1815 or placebo in capsule A, dosed for 60 days. Randomization is 2:1 active:placebo. Cohort 1 EDP1815 EDP1815 or placebo in capsule A, dosed for 60 days. Randomization is 2:1 active:placebo. Cohort 2 EDP1815 EDP1815 or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo.
- Primary Outcome Measures
Name Time Method KLH-induced immune reaction. At 24 hours after Day 57 intradermal re-challenge. This will be measured as basal flow (arbitrary units, AU) by LSCI.
- Secondary Outcome Measures
Name Time Method IMQ-induced immune reaction - erythema. At 24 hours, 48 hours and 72 hours after Day 57 initiation of IMQ challenge. This will be measured as erythema (AU) by multispectral imaging.
Number of participants with blood laboratory safety abnormalities. Up to Day 74. Number of participants with urinary laboratory safety abnormalities. Up to Day 74. Number of participants with electrocardiogram (ECG) abnormalities. Up to Day 74. KLH-induced immune reaction - erythema. At 4 hours, 24 hours, 48 hours and 72 hours after Day 57 intradermal re-challenge. This will be measured as erythema (AU) by multispectral imaging.
IMQ-induced immune reaction - basal flow. At 24 hours, 48 hours and 72 hours after Day 57 initiation of IMQ challenge. This will be measured as basal flow (AU) by LSCI.
Specific B-cell response to KLH. After Day 57 intradermal re-challenge. This will be measured as anti-KLH IgM and IgG (% of baseline concentration).
KLH-induced immune reaction - basal flow. At 4 hours, 48 hours and 72 hours after Day 57 intradermal re-challenge. This will be measured as basal flow (AU) by LSCI.
Serious adverse event (SAE) and adverse event (AE) incidents. Up to Day 74. SAEs and AEs assessed by: type, frequency, severity and treatment-relatedness of the event.
KLH-induced immune reaction - flare. At 4 hours, 24 hours, 48 hours and 72 hours after Day 57 intradermal re-challenge. This will be measured as flare (AU) by LSCI.
IMQ-induced immune reaction - flare. At 24 hours, 48 hours and 72 hours after Day 57 initiation of IMQ challenge. This will be measured as flare (AU) by LSCI.
Number of participants with vital signs abnormalities. Up to Day 74. Number of participants with physical examination abnormalities. Up to Day 74.
Trial Locations
- Locations (1)
Centre for Human Drug Research
🇳🇱Leiden, Netherlands