A Study of EDP1815 in Healthy Participants and Participants With Mild to Moderate Psoriasis and Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
Evelo will investigate the safety and tolerability of EDP1815 and its potential to be a medicinal product in healthy volunteers and individuals with mild to moderate psoriasis and atopic dermatitis.

Detailed Description
-----------------
This will be a randomized, double-blind, placebo-controlled clinical study with dose escalations to assess safety, tolerability, and pharmacodynamic effect of EDP1815. Since this clinical study is the first study in humans, the participants will be healthy volunteers or subjects with mild to moderate psoriasis or atopic dermatitis who are otherwise well. Investigation of EDP1815 in this patient population provides an opportunity to gain pharmacodynamic information using a range of tissue biopsies and composite clinical endpoints.

Official Title
-----------------
A Phase 1 Randomized Double-Blind Placebo-controlled Single and Multiple Ascending Dose Study of EDP1815 in Healthy Participants and Participants With Mild to Moderate Psoriasis or Atopic Dermatitis

Conditions
-----------------
Psoriasis, Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: EDP1815
* Drug: Placebo oral capsule
* Drug: Placebo oral tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: General: Participant has a body mass index of ≥ 18 kg/m2 to ≤ 35 kg/m2 at Screening. Healthy Volunteers: Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. Mild to moderate psoriasis: Participant has had a confirmed diagnosis of mild to moderate plaque-type psoriasis for at least 6 months involving ≤ 10% of body surface area (BSA) (excluding the scalp). Participant has a minimum of 2 psoriatic lesions with at least 1 plaque in a site suitable for biopsy. Mild to moderate atopic dermatitis: Mild to moderate atopic dermatitis with a minimum of 3% to a maximum of 15% BSA involvement. Participant has had a confirmed diagnosis of mild to moderate atopic dermatitis for at least 6 months (IGA score of 2 or 3). Participant has a minimum of 2 atopic dermatitis lesions with at least 1 in a site suitable for biopsy. Exclusion Criteria: Female participant who is pregnant, or plans to become pregnant during the study, or breastfeeding, or sexually active with childbearing potential who is not using a medically accepted birth control method. Participant has received live attenuated vaccination within 6 weeks prior to Screening or intends to have such a vaccination during the course of the study. Participant has received any investigational drug or experimental procedure within 90 days or 5 half-lives, whichever is longer, prior to study intervention administration. Participant requires treatment with an anti-inflammatory drug during the study period. Paracetamol will be permitted for use as an antipyretic and/or analgesic (maximum of 4 grams/day in any 24 hour period). Participant has an active infection (e.g. sepsis, pneumonia, abscess) or has had an infection requiring antibiotic treatment within 6 weeks prior to Investigational Medicinal Product (IMP) administration. When in doubt, the investigator should confer with the Sponsor study physician. Participant has renal or liver impairment, defined as: For healthy volunteers: i. For women, serum creatinine level ≥ 125 μmol/L; for men, ≥ 135 μmol/L, or ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 1.5 x upper limit of normal (ULN), or iii. Alkaline phosphatase (ALP) and/or bilirubin > 1.5 x ULN For participants with mild to moderate atopic dermatitis or psoriasis: i. For women, serum creatinine level ≥ 125 μmol/L; for men, ≥ 135 μmol/L, or ii. ALT or AST > 2 x ULN and/or bilirubin > 1.5 x ULN

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study is a double-blind dose escalation cohort study in healthy volunteers and participants with either mild to moderate psoriasis or mild to moderate atopic dermatitis. The study consists of 10 cohorts and will test doses of EDP1815 versus placebo. The safety and tolerability of EDP1815 will be tested in participants with psoriasis and atopic dermatitis alongside pharmacodynamic effects on the systemic immune system and observation of any clinical effects.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>12 healthy volunteers; 8 on EDP1815, 4 on placebo. Dose=1/10th of HED, capsule, once daily, 15 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 2<br>12 healthy volunteers; 8 on EDP1815, 4 on placebo. Dose= 1 x HED, capsule, once daily, 15 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 3<br>12 subjects with mild to moderate psoriasis; 8 on EDP1815, 4 on placebo. Dose= 1 x HED, capsule, once daily, 29 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 4<br>24 subjects with mild to moderate psoriasis; 16 on EDP1815, 8 on placebo. Dose= 5 x HED capsule, once daily, 29 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 5<br>24 subjects with mild to moderate atopic dermatitis; 16 on EDP1815, 8 on placebo. Dose= 5 x HED, mini-tablets in capsule, once daily, 29 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 6<br>24 subjects with mild to moderate psoriasis; 16 on EDP1815, 8 on placebo. Dose=5 x HED, mini-tablets in capsule, once daily, 29 days. | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 7<br>24 subjects with mild to moderate atopic dermatitis; 16 on EDP1815, 8 on placebo. Dose= 5 x HED, capsule, once daily, 56 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 8<br>24 subjects with mild to moderate psoriasis; 16 on EDP1815, 8 on placebo. Dose= 8 x HED, tablet, once daily, 56 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral tablet<br>* Placebo<br>|
| Other: Cohort 9<br>24 subjects with mild to moderate psoriasis; 16 on EDP1815, 8 on placebo. Dose= 2 x HED, capsule, once daily, 56 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|
| Other: Cohort 10<br>24 subjects with mild to moderate atopic dermatitis; 16 on EDP1815, 8 on placebo. Dose= 4 x HED, capsule, once daily, 56 days | Drug: EDP1815<br>* EDP1815 is an orally administered monoclonal microbial<br>Drug: Placebo oral capsule<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability measured through Adverse Events (AEs) | Number of participants with AEs by seriousness and relationship to treatment | Day 1 to Day 70 | 
| Safety and tolerability measured through lab measurements | Number of participants with clinically significant change from baseline (Day 0) in laboratory values | Day 0 to Day 70 | 
| Safety and tolerability measured through ECG | Number of participants with clinically relevant changes from baseline (Day 0) ECG parameters | Day 0 to Day 70 | 
| Safety and tolerability measured through physical examination | Physical examination of stool samples based on the Bristol Stool Scale (Types 3 and 4 are ideal stool): Type 1: Separate hard lumps, like nuts (hard to pass); Type 2: Sausage-shaped, but lumpy; Type 3: Like a sausage but with cracks on its surface; Type 4: Like a sausage or snake, smooth and soft; Type 5: Soft blobs with clear cut edges (easy to pass); Type 6: Fluffy pieces with ragged edges, a mushy stool; Type 7: Watery, no solid pieces, entirely liquid | Day 0 to Day 60 | 
| GI safety measurement through biomarker analysis | GI safety measurement through fecal calprotectin analysis | Day 0 to Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement in subjects with mild to moderate psoriasis | Change from baseline (Day 0) Psoriasis-area-and-severity index score (PASI) in response to EDP1815, measured on a scale of 0 to 6 (where 0 is most favorable and 6 is least favorable). | Day 0 to Day 70 | 
| Clinical improvement in subjects with mild to moderate atopic dermatitis | Change from baseline (Day 0) Eczema-area-and-severity index score (EASI) in response to EDP1815, measured on a scale of 0 to 6 (where 0 is most favorable and 6 is least favorable). | Day 0 to Day 70 |