Evaluation of the Immunopharmacology of EDP1815 and EDP2939
Study Details
Study Description
Brief Summary
A single-center, randomized, double-blind, placebo-controlled, multiple dose platform trial.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Cohort 1 EDP1815 or placebo in capsule A, dosed for 60 days. Randomization is 2:1 active:placebo. |
Drug: EDP1815
EDP1815 is an essentially non-viable, non-replicating pharmaceutical preparation of a single strain of Prevotella histicola, a naturally occurring human commensal microbe.
Drug: Placebo oral capsule
Placebo.
|
| Other: Cohort 2 EDP1815 or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. |
Drug: EDP1815
EDP1815 is an essentially non-viable, non-replicating pharmaceutical preparation of a single strain of Prevotella histicola, a naturally occurring human commensal microbe.
Drug: Placebo oral capsule
Placebo.
|
| Other: Cohort 3 EDP2939 lower dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. |
Drug: EDP2939
EDP2939 is a pharmaceutical preparation of extracellular vesicles.
Drug: Placebo oral capsule
Placebo.
|
| Other: Cohort 4 EDP2939 higher dose or placebo in capsule B, dosed for 60 days. Randomization is 2:1 active:placebo. |
Drug: EDP2939
EDP2939 is a pharmaceutical preparation of extracellular vesicles.
Drug: Placebo oral capsule
Placebo.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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).
- 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 vital signs abnormalities. [Up to Day 74.]
- Number of participants with physical examination abnormalities. [Up to Day 74.]
Eligibility Criteria
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.
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Body mass index of 18 to 35 kg/m2, inclusive.
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Caucasian.
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Healthy based on medical history, physical examination, blood pressure, ECG and blood and urine laboratory tests.
Key Exclusion Criteria:
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Use of Aldara® (imiquimod cream) within 3 weeks prior to the study.
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Has previously received Immucothel® or KLH.
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Allergy to Alhydrogel® or Aldara® (imiquimod cream).
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Current or recurrent skin diseases affecting the arms or back, or extensive tattoos in these areas.
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Previous diagnosis of psoriasis.
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History of pathological scar formation (e.g. keloid scar).
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History of skin cancer (basal cell carcinoma, squamous cell carcinoma, melanoma).
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Significant bowel disease (e.g. inflammatory bowel disease, coeliac disease)
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Currently has an infection or has needed antibiotics within 6 weeks before the study.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre for Human Drug Research | Leiden | Netherlands | 2333 CL |
Sponsors and Collaborators
- Evelo Biosciences, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EDP1815-105