KLH and Imiquimod Induced Skin Inflammation in Healthy Volunteers
Conditions
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.
Interventions
DRUGEDP1815
EDP1815 is an essentially non-viable, non-replicating pharmaceutical preparation of a single strain of Prevotella histicola, a naturally occurring human commensal microbe.
DRUGEDP2939
EDP2939 is a pharmaceutical preparation of extracellular vesicles.
DRUGPlacebo oral capsule
Placebo.
Sponsors
Evelo Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Intervention model description
This is a single-center, randomized, double-blind, placebo-controlled, platform trial to evaluate the effects of EDP1815 and EDP2939 on the systemic immune system, using intradermal KLH and topical IMQ skin challenges. A total of at least 72 healthy volunteers will be divided into 4 cohorts.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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 vital signs abnormalities. | Up to Day 74. | — |
| 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. |
| 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. | — |
| Number of participants with physical examination abnormalities. | Up to Day 74. | — |
| 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). |
Countries
Netherlands
Outcome results
None listed