Evaluation of the Immunopharmacology of EDP1815 and EDP2939

Study Overview
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Brief Summary
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A single-center, randomized, double-blind, placebo-controlled, multiple dose platform trial.

Detailed Description
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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.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Dose Platform Study Investigating the Immunopharmacology of EDP1815 and EDP2939.

Conditions
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KLH and Imiquimod Induced Skin Inflammation in Healthy Volunteers

Intervention / Treatment
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* Drug: EDP1815
* Drug: EDP2939
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>EDP1815 or placebo in capsule A, dosed for 60 days. Randomization is 2:1 active:placebo. | Drug: EDP1815<br>* EDP1815 is an essentially non-viable, non-replicating pharmaceutical preparation of a single strain of Prevotella histicola, a naturally occurring human commensal microbe.<br>Drug: Placebo oral capsule<br>* Placebo.<br>|
| Other: Cohort 2<br>EDP1815 or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. | Drug: EDP1815<br>* EDP1815 is an essentially non-viable, non-replicating pharmaceutical preparation of a single strain of Prevotella histicola, a naturally occurring human commensal microbe.<br>Drug: Placebo oral capsule<br>* Placebo.<br>|
| Other: Cohort 3<br>EDP2939 lower dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. | Drug: EDP2939<br>* EDP2939 is a pharmaceutical preparation of extracellular vesicles.<br>Drug: Placebo oral capsule<br>* Placebo.<br>|
| Other: Cohort 4<br>EDP2939 higher dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. | Drug: EDP2939<br>* EDP2939 is a pharmaceutical preparation of extracellular vesicles.<br>Drug: Placebo oral capsule<br>* Placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| KLH-induced immune reaction. | This will be measured as basal flow (arbitrary units, AU) by LSCI. | At 24 hours after Day 57 intradermal re-challenge. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| KLH-induced immune reaction - basal flow. | This will be measured as basal flow (AU) by LSCI. | At 4 hours, 48 hours and 72 hours after Day 57 intradermal re-challenge. | 
| KLH-induced immune reaction - flare. | This will be measured as flare (AU) by LSCI. | At 4 hours, 24 hours, 48 hours and 72 hours after Day 57 intradermal re-challenge. | 
| KLH-induced immune reaction - erythema. | This will be measured as erythema (AU) by multispectral imaging. | At 4 hours, 24 hours, 48 hours and 72 hours after Day 57 intradermal re-challenge. | 
| IMQ-induced immune reaction - basal flow. | This will be measured as basal flow (AU) by LSCI. | At 24 hours, 48 hours and 72 hours after Day 57 initiation of IMQ challenge. | 
| IMQ-induced immune reaction - flare. | This will be measured as flare (AU) by LSCI. | At 24 hours, 48 hours and 72 hours after Day 57 initiation of IMQ challenge. | 
| IMQ-induced immune reaction - erythema. | This will be measured as erythema (AU) by multispectral imaging. | At 24 hours, 48 hours and 72 hours after Day 57 initiation of IMQ challenge. | 
| Specific B-cell response to KLH. | This will be measured as anti-KLH IgM and IgG (% of baseline concentration). | After Day 57 intradermal re-challenge. | 
| Serious adverse event (SAE) and adverse event (AE) incidents. | SAEs and AEs assessed by: type, frequency, severity and treatment-relatedness of the event. | Up to Day 74. | 
| 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 vital signs abnormalities. |  | Up to Day 74. | 
| Number of participants with physical examination abnormalities. |  | Up to Day 74. |