A Study Investigating the Effect of EDP1815 in the Treatment of Mild, Moderate and Severe Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this research study is to determine whether the study drug, EDP1815, is safe and effective in the treatment of atopic dermatitis compared with placebo. The study will look at different doses of the study drug, and whether there are differences when the drug is given once daily or twice daily.

Detailed Description
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Atopic dermatitis (atopic eczema) is a very common type of skin disease. It typically causes red, dry, and itchy skin and may have a significant impact on quality of life. Rashes may appear on the arms and behind the knees, or anywhere else on the body. While there are existing therapies, there is currently no cure for atopic dermatitis. This is a randomized, double blind, placebo controlled, parallel group, Phase 2 study to evaluate the efficacy and safety of EDP1815 in adult participants 18 to ≤75 years of age with mild, moderate, and severe atopic dermatitis (AD). Participants will be screened within 28 days prior to the first dose of study intervention to confirm study eligibility. Subjects must have mild, moderate, or severe AD involving at least 5% Body Surface Area (BSA); an Investigator Global Assessment (IGA) score of 2, 3, or 4; and an Eczema Area Severity Index (EASI) of at least 6 at screening and Day 1. All participants must agree to use a background therapy (per protocol) twice daily for at least 14 days prior to Day 1 in order to be considered eligible for the study. Approximately 405 participants will be randomized to receive either EDP1815 or placebo (295 to EDP1815: 110 to placebo) and treated for 16 weeks. Participants in Cohorts 1, 2, & 3 will be randomized in a 3:1 ratio (225 to EDP1815: 75 to placebo). Participants in Cohort 4 will be randomized in a 2:1 ratio (70 to EDP1815: 35 to placebo). Cohorts 1, 2 & 3 will be run concurrently, and Cohort 4 recruitment will commence after enrollment for Cohorts 1, 2, & 3 are completed. Randomization will be stratified by baseline disease severity (mild [IGA = 2], moderate [IGA = 3] or severe [IGA = 4] AD). The investigational product will be administered either once or twice daily for 16 weeks. Background emollient (moisturizer) therapy must continue at least twice daily for the duration of the treatment and follow-up periods. Topical rescue therapy is allowed during the treatment period per protocol. The primary efficacy endpoint is achievement of an EASI-50 response at Week 16. Secondary efficacy endpoints will look at EASI, IGA, BSA, SCORAD, DLQI, Pruritus-NRS, Sleep Disturbance-NRS, POEM, and the need for rescue therapy at Weeks 4, 8, 12 and 16 (unless otherwise specified in the protocol). Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment. Scheduled clinic study visits for all subjects will occur at Screening, Day 1, Week 2, Week 4, Week 8, Week 12, Week 16 (end of treatment) and Week 20 (post-treatment follow-up). Participants discontinuing early from the study will undergo a 28-day follow-up period, where possible. At the end of the 16-week study treatment, qualified participants completing the study will have the option to enter an open label study.

Official Title
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A Phase 2, Multicenter, Double-Blind, Placebo-Controlled, Multiple-Cohort Study Investigating the Effect of EDP1815 in Participants for the Treatment of Mild, Moderate and Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: EDP1815
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent. Must meet age criteria. Must have a diagnosis of atopic dermatitis (AD)for at least 6 months. Must have severity of atopic dermatitis meeting the below criteria at both Screening and Day 1: An IGA of 2, 3 or 4 on the vIGA scale, and; A BSA of ≥5%, and; An EASI score of ≥6. Must agree to use emollients. Must meet contraception requirements. Exclusion Criteria: Have been in a clinical trial for EDP1815 prior to signing of ICF. Use of phototherapy or tanning beds; systemic medications/treatments that could affect AD or its symptoms including immunosuppressive therapy (e.g., oral or injectable corticosteroids, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, JAK inhibitors, tacrolimus, and/or leukotriene inhibitor) within 4 weeks of randomization. Treatment with topical agents that could affect atopic dermatitis, including topical corticosteroids, topical calcineurin inhibitors (e.g., tacrolimus or pimecrolimus), or topical PDE-4 inhibitor (e.g., crisaborole) within 14 days prior to randomization. Clinically significant abnormalities in screening laboratory values that in the opinion of the Investigator would make a participant unsuitable for inclusion in the study. One retest is permitted within the 28-day screening window. Hypersensitivity to P histicola or to any of the excipients. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator. Have any other conditions, which, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cohorts 1, 2 & 3 will be run concurrently, and Cohort 4 recruitment will commence after enrollment for Cohorts 1, 2, & 3 are completed. Randomization to Cohort 4 will not start before randomization to Cohorts 1, 2 & 3 have completed.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>100 participants with mild, moderate or severe Atopic Dermatitis 75 participants on EDP1815 and 25 participants on matching placebo administered as 2 capsules (1.6 x 10^11 total cells) once daily for 16 weeks | Drug: EDP1815<br>* EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria<br>* Other names: Prevotella histicola;Drug: Placebo<br>* Placebo oral capsule<br>|
| Experimental: Cohort 2<br>100 participants with mild, moderate or severe Atopic Dermatitis 75 participants on EDP1815 and 25 participants on matching placebo administered as 2 capsules (6.4 x 10^11 total cells) once daily for 16 weeks | Drug: EDP1815<br>* EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria<br>* Other names: Prevotella histicola;Drug: Placebo<br>* Placebo oral capsule<br>|
| Experimental: Cohort 3<br>100 participants with mild, moderate or severe Atopic Dermatitis 75 participants on EDP1815 and 25 participants on matching placebo administered as 1 capsule (3.2 x 10^11 cells) twice daily (6.4 x 10^11 total cells) for 16 weeks | Drug: EDP1815<br>* EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria<br>* Other names: Prevotella histicola;Drug: Placebo<br>* Placebo oral capsule<br>|
| Experimental: Cohort 4<br>105 participants with mild, moderate or severe Atopic Dermatitis 70 participants on EDP1815 and 35 participants on matching placebo administered at 1 capsule (8.0x10^10 total cells) once daily for 16 weeks | Drug: EDP1815<br>* EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria<br>* Other names: Prevotella histicola;Drug: Placebo<br>* Placebo oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of EASI-50 | The efficacy of EDP1815 will be measured by achieving a decrease of at least 50% from baseline in Eczema Area Severity Index (EASI) score of 50 (EASI-50) at Week 16. The EASI is a validated measure of eczema severity, which considers a combination of the disease severity and body surface area affected across 4 body regions. The EASI score ranges from 0 - 72. A lower score indicates a better outcome. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving EASI-50 | The efficacy of EDP1815 will be measured by the number of participants achieving an EASI-50 at Weeks 4, 8 and 12. The Eczema Area Severity Index (EASI) is a validated measure of eczema severity, which considers a combination of the disease severity and body surface area affected across 4 body regions (arms, legs, trunk, and head/neck). The EASI score ranges from 0 - 72, with a lower score indicating a better outcome. | 4, 8 and 12 weeks | 
| Percentage of Participants Achieving EASI-75 | The efficacy of EDP1815 will be measured by the number of participants achieving an EASI-75 at Weeks 4, 8, 12 and 16. The Eczema Area Severity Index (EASI) is a validated measure of eczema severity, which considers a combination of the disease severity and body surface area affected across 4 body regions (arms, legs, trunk, and head/neck). The EASI score ranges from 0 - 72, with a lower score indicating a better outcome. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving EASI-90 | The efficacy of EDP1815 will be measured by the number of participants achieving an EASI-90 at Weeks 4, 8, 12 and 16. The Eczema Area Severity Index (EASI) is a validated measure of eczema severity, which considers a combination of the disease severity and body surface area affected across 4 body regions (arms, legs, trunk, and head/neck). The EASI score ranges from 0 - 72, with a lower score indicating a better outcome. | 4, 8, 12, and 16 weeks | 
| Mean Absolute Change in EASI | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in EASI at weeks 4, 8, 12 and 16. The Eczema Area Severity Index (EASI) is a validated measure of eczema severity, which considers a combination of the disease severity and body surface area affected across 4 body regions (arms, legs, trunk, and head/neck). The EASI score ranges from 0 - 72, with a lower score indicating a better outcome. | 4, 8, 12, and 16 weeks | 
| Mean Percentage Change in EASI | The efficacy of EDP1815 will be measured using the mean percentage change from baseline in EASI from baseline at weeks 4, 8, 12 and 16. The Eczema Area Severity Index (EASI) is a validated measure of eczema severity, which considers a combination of the disease severity and body surface area affected across 4 body regions (arms, legs, trunk, and head/neck). The EASI score ranges from 0 - 72, with a lower score indicating a better outcome. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving Investigator's Global Assessment (vIGA) of 0 or 1 With a ≥2 Point Improvement | The efficacy of EDP1815 will be measured by the number of participants achieving a vIGA of 0 or 1 with a ≥2 Point Improvement from baseline at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving vIGA of 0 or 1 | The efficacy of EDP1815 will be measured by the number of participants achieving a vIGA of 0 or 1 at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving vIGA of 0 | The efficacy of EDP1815 will be measured by the number of participants achieving a vIGA of 0 at Week16 | 16 weeks | 
| Mean Absolute Change in vIGA*BSA | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in vIGA (Validated Investigator Global Assessment) multiplied by the BSA (body surface area) at weeks 4, 8, 12 and 16. | 4, 8, 12, and 16 weeks | 
| Mean Percentage Change in vIGA*BSA | The efficacy of EDP1815 will be measured using the mean percentage change from baseline in vIGA (Validated Investigator Global Assessment) multiplied by the BSA (body surface area) at weeks 4, 8, 12 and 16. | 4, 8, 12, and 16 weeks | 
| Mean Absolute Change From Baseline in BSA | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in BSA (body surface area) at weeks 4, 8, 12 and 16. The Body Surface Area (BSA) is a measure of the extent of atopic dermatitis at a given time. It is calculated by estimating the number of participant's handprints of active atopic dermatitis are present where one handprint represents 1% body surface area. This higher the BSA %, the more active atopic dermatitis is present. | 4, 8, 12, and 16 weeks | 
| Mean Percentage Change From Baseline in BSA | The efficacy of EDP1815 will be measured using the mean percentage change from baseline in BSA (body surface area) at weeks 4, 8, 12 and 16. The Body Surface Area (BSA) is a measure of the extent of atopic dermatitis at a given time. It is calculated by estimating the number of participant's handprints of active atopic dermatitis are present where one handprint represents 1% body surface area. This higher the BSA %, the more active atopic dermatitis is present. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving BSA-50 | The efficacy of EDP1815 will be measured by the number of participants achieving a BSA-50 at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving BSA-75 | The efficacy of EDP1815 will be measured by the number of participants achieving a BSA-75 at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving BSA Reduction to 3% BSA or Less | The efficacy of EDP1815 will be measured by the number of participants achieving a BSA reduction to 3% BSA or less at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Mean Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in SCORing Atopic Dermatitis (SCORAD) at weeks 4, 8, 12 and 16. The SCORAD is a clinical tool to assess the extent and severity of eczema, to assess treatment effects. There is both an investigator-rated area score using rule of nines to assess disease extent and a disease intensity score comprising erythema, swelling, oozing/crusting, exoriation, lichenification and dryness and a subjective symptoms component which considers itch and sleeplessness scored using a visual analog scale. These scores combine to give a SCORAD score between 0 - 103, with a higher score indicating worse atopic dermatitis. | 4, 8, 12, and 16 weeks | 
| Mean Percentage Change From Baseline in SCORAD | The efficacy of EDP1815 will be measured using the mean percentage change from baseline in SCORAD at weeks 4, 8, 12 and 16. The SCORAD is a clinical tool to assess the extent and severity of eczema, to assess treatment effects. There is both an investigator-rated area score using rule of nines to assess disease extent and a disease intensity score comprising erythema, swelling, oozing/crusting, exoriation, lichenification and dryness and a subjective symptoms component which considers itch and sleeplessness scored using a visual analog scale. These scores combine to give a SCORAD score between 0 - 103, with a higher score indicating worse atopic dermatitis. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving SCORAD-50 | The efficacy of EDP1815 will be measured by the number of participants achieving a SCORAD-50 at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving SCORAD-75 | The efficacy of EDP1815 will be measured by the number of participants achieving a SCORAD-75 at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Mean Absolute Change From Baseline in the Dermatology Quality of Life Index (DLQI) | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in the Dermatology Quality of Life Index (DLQI) at weeks 4, 8, 12 and 16. The DLQI is a validated patient reported outcomes instrument comprised of 10 questions to assess how a participant's skin disease has affected their quality of life over the past week. The score ranges from 0 - 30, with a higher score indicating greater impairment of quality of life. A 4-point change from baseline is considered the minimal clinically important difference threshold. | 4, 8, 12, and 16 weeks | 
| Mean Percentage Change From Baseline in DLQI | The efficacy of EDP1815 will be measured using the mean percentage change from baseline in the DLQI at weeks 4, 8, 12 and 16. The DLQI is a validated patient reported outcomes instrument comprised of 10 questions to assess how a participant's skin disease has affected their quality of life over the past week. The score ranges from 0 - 30, with a higher score indicating greater impairment of quality of life. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving a Reduction of ≥4 in the DLQI, of Those With a Score of ≥4 at Baseline | The efficacy of EDP1815 will be measured by the number of participants achieving a reduction of ≥4 in the DLQI, of those with a score of ≥4 at baseline at Week 16. The DLQI score ranges from 0 to 30, with higher scores indicating greater impairment of quality of life. | 16 weeks | 
| Mean Absolute Change From Baseline in Worst Pruritus Numerical Rating Scale (PR-NRS) | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in the worst Pruritus Numerical Rating Scale (PR-NRS) at weeks 4, 8, 12 and 16. The PP-NRS is a scale from 0 (no itch) to 10 (worse imaginable itch) for participants to rate their worst itch that they have experienced over the previous 24 hours. The value calculated for each visit is the mean of the daily values for the 7 days on and before the visit date as long as at least 4 non-missing scores are available. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving a Reduction of ≥2 in the Worst Pruritus-NRS, of Those With a Score of ≥2 at Baseline | The efficacy of EDP1815 will be measured by the number of participants achieving a reduction of ≥2 in the worst PR-NRS score, of those with a score of ≥2 at baseline at Weeks 4, 8, 12 and 16. The PP-NRS is a scale from 0 (no itch) to 10 (worse imaginable itch) for participants to rate their worst itch that they have experienced over the previous 24 hours. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving a Reduction of ≥4 in the Worst PR-NRS, of Those With a Score of ≥4 at Baseline | The efficacy of EDP1815 will be measured by the number of participants achieving a reduction of ≥4 in the worst PR-NRS score, of those with a score of ≥4 at baseline at Week 16. The PP-NRS is a scale from 0 (no itch) to 10 (worse imaginable itch) for participants to rate their worst itch that they have experienced over the previous 24 hours. | 16 weeks | 
| Mean Absolute Change From Baseline in the Sleep Disturbance Numerical Rating Scale (SD-NRS) Score | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in Sleep Disturbance Numerical Rating Scale (SD-NRS) score at weeks 4, 8, 12 and 16. The SD-NRS is a scale from 0 (best possible sleep) to 10 (worse possible sleep) for participants to rate their worst sleep that they have experienced over the previous 24 hours. The value calculated for each visit is the mean of the daily values for the 7 days on and before the visit date as long as at least 4 non-missing scores are available. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving a Reduction of ≥2 in SD-NRS Score, of Those With a Score of ≥2 at Baseline | The efficacy of EDP1815 will be measured by the number of participants achieving a reduction of ≥2 in the SD-NRS score, of those with a score of ≥2 at baseline at Week 16. The SD-NRS is a scale from 0 (best possible sleep) to 10 (worse possible sleep) for participants to rate their worst sleep that they have experienced over the previous 24 hours. | 16 weeks | 
| Mean Absolute Change From Baseline in Patient Oriented Eczema Measure (POEM) | The efficacy of EDP1815 will be measured using the mean absolute change from baseline in the Patient Oriented Eczema Measure (POEM) at weeks 4, 8, 12 and 16. There are 7 questions scored from 0 (no days) to 4 (every day), giving a POEM score range from 0 to 28, with higher scores representing higher disease severity. | 4, 8, 12, and 16 weeks | 
| Mean Percentage Change From Baseline in Patient Oriented Eczema Measure (POEM) | The efficacy of EDP1815 will be measured using the percentage change from baseline in the Patient Oriented Eczema Measure (POEM) at weeks 4, 8, 12 and 16. There are 7 questions scored from 0 (no days) to 4 (every day), giving a POEM score range from 0 to 28, with higher scores representing higher disease severity. | 4, 8, 12, and 16 weeks | 
| Percentage of Participants Achieving a Reduction of ≥4 in the POEM Score, of Those With a Score of ≥4 at Baseline | The efficacy of EDP1815 will be measured by the number of participants achieving a reduction of ≥4 in the POEM score, of those with a score of ≥4 at baseline at Week 16. There are 7 questions scored from 0 (no days) to 4 (every day), giving a POEM score range from 0 to 28, with higher scores representing higher disease severity. | 16 weeks | 
| Number of Courses of Rescue Therapy Per Participant | The efficacy of EDP1815 will be measured by the number of rescue therapy courses per participant at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 
| Number of Days of Treatment With Rescue Therapy Per Participant | The efficacy of EDP1815 will be measured by the number of rescue therapy treatment days per participant at Weeks 1-8 and 9-16 | 16 weeks | 
| Proportion of Participants Not Requiring Rescue Therapy | The efficacy of EDP1815 will be measured by the proportion of participants not requiring rescue therapy at Weeks 4, 8, 12 and 16 | 4, 8, 12, and 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild Atopic Dermatitis, Moderate Atopic Dermatitis, Severe Atopic Dermatitis, Mild Eczema, Moderate Eczema, Severe Eczema