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

• ClinicalTrials.gov Identifier: NCT05121480
• Recruitment Status: Active, not recruiting
• First Posted: November 16, 2021
• Last Update Posted: November 4, 2022
• Sponsor: Evelo Biosciences, Inc.
• Information provided by (Responsible Party): Evelo Biosciences, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Atopic Dermatitis	Drug: EDP1815; Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 405 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 31, 2022
• Estimated Primary Completion Date: March 9, 2023
• Estimated Study Completion Date: April 6, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; 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; EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria; Other Name: Prevotella histicola; Drug: Placebo; Placebo oral capsule
Experimental: Cohort 2; 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; EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria; Other Name: Prevotella histicola; Drug: Placebo; Placebo oral capsule
Experimental: Cohort 3; 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; EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria; Other Name: Prevotella histicola; Drug: Placebo; Placebo oral capsule
Experimental: Cohort 4; 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; EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria; Other Name: Prevotella histicola; Drug: Placebo; Placebo oral capsule

Outcome Measures

Primary Outcome Measures :

1. Achievement of EASI-50 [ Time Frame: 16 weeks ]
   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

Secondary Outcome Measures :

1. Percentage of participants achieving EASI-50 [ Time Frame: 4, 8 and 12 weeks ]
   The efficacy of EDP1815 will be measured by the number of participants achieving an EASI-50 at Weeks 4, 8 and 12
2. Percentage of participants achieving EASI-75 [ Time Frame: 4, 8, 12, and 16 weeks ]
   The efficacy of EDP1815 will be measured by the number of participants achieving an EASI-75 at Weeks 4, 8, 12 and 16
3. Percentage of participants achieving EASI-90 [ Time Frame: 4, 8, 12, and 16 weeks ]
   The efficacy of EDP1815 will be measured by the number of participants achieving an EASI-90 at Weeks 4, 8, 12 and 16
4. Mean absolute change in EASI [ Time Frame: 4, 8, 12, and 16 weeks ]
   The efficacy of EDP1815 will be measured using the mean absolute change from baseline in EASI at weeks 4, 8, 12 and 16
5. Mean percentage change in EASI [ Time Frame: 4, 8, 12, and 16 weeks ]
   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
6. Percentage of Participants Achieving Investigator's Global Assessment (vIGA) of 0 or 1 with a ≥2 Point Improvement [ Time Frame: 4, 8, 12, and 16 weeks ]
   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
7. Percentage of Participants Achieving vIGA of 0 or 1 [ Time Frame: 4, 8, 12, and 16 weeks ]
   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
8. Percentage of Participants Achieving vIGA of 0 [ Time Frame: 16 weeks ]
   The efficacy of EDP1815 will be measured by the number of participants achieving a vIGA of 0 at Week16
9. Mean absolute change in vIGA*BSA (body surface area) [ Time Frame: 4, 8, 12, and 16 weeks ]
   The efficacy of EDP1815 will be measured using the mean absolute change from baseline in vIGA*BSA (body surface area) at weeks 4, 8, 12 and 16
10. Mean percentage change in vIGA*BSA [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured using the mean percentage change from baseline in vIGA*BSA at weeks 4, 8, 12 and 16
11. Mean absolute change from baseline in BSA [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured using the mean absolute change from baseline in BSA at weeks 4, 8, 12 and 16
12. Mean percentage change from baseline in BSA [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured using the mean percentage change from baseline in BSA at weeks 4, 8, 12 and 16
13. Percentage of Participants Achieving BSA-50 [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured by the number of participants achieving a BSA-50 at Weeks 4, 8, 12 and 16
14. Percentage of Participants Achieving BSA-75 [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured by the number of participants achieving a BSA-75 at Weeks 4, 8, 12 and 16
15. Percentage of Participants Achieving BSA reduction to 3% BSA or less [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
16. Mean absolute change from baseline in SCORing Atopic Dermatitis (SCORAD) [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
17. Mean percentage change from baseline in SCORAD [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured using the mean percentage change from baseline in SCORAD at weeks 4, 8, 12 and 16
18. Percentage of Participants Achieving SCORAD-50 [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured by the number of participants achieving a SCORAD-50 at Weeks 4, 8, 12 and 16
19. Percentage of Participants Achieving SCORAD-75 [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured by the number of participants achieving a SCORAD-75 at Weeks 4, 8, 12 and 16
20. Mean absolute change from baseline in the Dermatology Quality of Life Index (DLQI) [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
21. Mean percentage change from baseline in DLQI [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured using the mean percentage change from baseline in the DLQI at weeks 4, 8, 12 and 16
22. Percentage of Participants achieving a reduction of ≥4 in the DLQI, of those with a score of ≥4 at baseline [ Time Frame: 16 weeks ]
    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
23. Mean absolute change from baseline in worst Pruritus Numerical Rating Scale (PR-NRS) [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
24. Percentage of Participants achieving a reduction of ≥2 in the worst Pruritus-NRS, of those with a score of ≥2 at baseline [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
25. Percentage of Participants achieving a reduction of ≥4 in the worst PR-NRS, of those with a score of ≥4 at baseline [ Time Frame: 16 weeks ]
    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
26. Mean absolute change from baseline in the Sleep Disturbance Numerical Rating Scale (SD-NRS) score [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
27. Percentage of Participants achieving a reduction of ≥2 in SD-NRS score, of those with a score of ≥2 at baseline [ Time Frame: 16 weeks ]
    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
28. Mean absolute change from baseline in Patient Oriented Eczema Measure (POEM) [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
29. Mean percentage change from baseline in Patient Oriented Eczema Measure (POEM) [ Time Frame: 4, 8, 12, and 16 weeks ]
    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
30. Percentage of Participants achieving a reduction of ≥4 in the POEM score, of those with a score of ≥4 at baseline [ Time Frame: 16 weeks ]
    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
31. Number of courses of rescue therapy per Participant [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured by the number of rescue therapy courses per participant at Weeks 4, 8, 12 and 16
32. Number of days of treatment with rescue therapy per Participant [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured by the number of rescue therapy treatment days per participant at Weeks 4, 8, 12 and 16
33. Proportion of participants not requiring rescue therapy [ Time Frame: 4, 8, 12, and 16 weeks ]
    The efficacy of EDP1815 will be measured by the proportion of participants not requiring rescue therapy at Weeks 4, 8, 12 and 16

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

USA-131

Birmingham, Alabama, United States, 35244

United States, California

USA-112

Fountain Valley, California, United States, 92708

USA-123

Fremont, California, United States, 94538

USA-114

Newport Beach, California, United States, 92660

United States, Florida

USA-101

Fort Lauderdale, Florida, United States, 33308

USA-124

Jacksonville, Florida, United States, 32216

USA-108

Miami, Florida, United States, 33165

USA-120

Miami, Florida, United States, 33175

USA-105

Miramar, Florida, United States, 33027

USA-102

Orlando, Florida, United States, 32801

USA-115

Sweetwater, Florida, United States, 33172

USA-126

Tampa, Florida, United States, 33613

USA-106

Tampa, Florida, United States, 33624

United States, Georgia

USA-118

Sandy Springs, Georgia, United States, 30328

United States, Indiana

USA-111

Clarksville, Indiana, United States, 47129

United States, Kentucky

USA-116

Louisville, Kentucky, United States, 40241

United States, Louisiana

USA-119

Baton Rouge, Louisiana, United States, 70806

USA-109

Metairie, Louisiana, United States, 70006

United States, Maryland

USA-125

Silver Spring, Maryland, United States, 20902

United States, Michigan

USA-130

Ann Arbor, Michigan, United States, 48103

United States, Ohio

USA-121

Columbus, Ohio, United States, 43221

USA-128

Concord, Ohio, United States, 44077

United States, Oregon

USA-104

Portland, Oregon, United States, 97239

United States, Tennessee

USA-127

Memphis, Tennessee, United States, 38119

United States, Texas

USA-117

Frisco, Texas, United States, 75034

USA-110

Pflugerville, Texas, United States, 78660

United States, Washington

USA-113

Bellevue, Washington, United States, 98004

Australia

AUS-102

Carlton, Australia

AUS-104

Kogarah, Australia

AUS-101

Melbourne, Australia

AUS-106

Woolloongabba, Australia

Bulgaria

BGR-105

Pleven, Bulgaria

BGR-104

Sevlievo, Bulgaria

BGR-101

Sofia, Bulgaria

BGR-102

Sofia, Bulgaria

BGR-103

Sofia, Bulgaria

Canada

CAN-109

Barrie, Canada

CAN-108

Edmonton, Canada

CAN-105

Markham, Canada

CAN-104

Mississauga, Canada

CAN-101

Ottawa, Canada

CAN-107

Richmond Hill, Canada

CAN-103

Surrey, Canada

CAN-106

Waterloo, Canada

CAN-111

Winnipeg, Canada

Germany

DEU-105

Berlin, Germany

DEU-107

Bochum, Germany

DEU-106

Erlangen, Germany

DEU-102

Frankfurt am Main, Germany

DEU-104

Gera, Germany

DEU-101

Hamburg, Germany

DEU-103

Heidelberg, Germany

Poland

POL-104

Gdańsk, Poland

POL-106

Gdynia, Poland

POL-107

Katowice, Poland

POL-101

Lublin, Poland

POL-102

Warszawa, Poland

POL-103

Wrocław, Poland

POL-105

Łódź, Poland

Sponsors and Collaborators

Evelo Biosciences, Inc.

Investigators

• Principal Investigator: Benjamin Ehst, MD, PhD; Oregon Medical Research Center
• Study Director: Yanislav Mihaylov, MD; Evelo Biosciences, Inc.

More Information

• Responsible Party: Evelo Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT05121480
• Other Study ID Numbers: EDP1815-207; 2021-001805-63 ( EudraCT Number )
• First Posted: November 16, 2021
• Last Update Posted: November 4, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Evelo Biosciences, Inc.:

Mild Atopic Dermatitis; Moderate Atopic Dermatitis; Severe Atopic Dermatitis; Mild Eczema; Moderate Eczema; Severe Eczema

Additional relevant MeSH terms:

Dermatitis, Atopic; Dermatitis; Eczema; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases