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

Sponsor

Evelo Biosciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05121480

Collaborator

(none)

405

Enrollment

Locations

Arms

14.6

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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

Anticipated 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.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 :

Jan 31, 2022

Anticipated Primary Completion Date :

Mar 22, 2023

Anticipated Study Completion Date :

Apr 19, 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 Names: 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 Names: 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 Names: 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 Names: Prevotella histicola Drug: Placebo Placebo oral capsule

Outcome Measures

Primary Outcome Measures

Achievement of EASI-50 [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

Percentage of participants achieving EASI-50 [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
Percentage of participants achieving EASI-75 [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
Percentage of participants achieving EASI-90 [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
Mean absolute change in EASI [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
Mean percentage change in EASI [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
Percentage of Participants Achieving Investigator's Global Assessment (vIGA) of 0 or 1 with a ≥2 Point Improvement [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
Percentage of Participants Achieving vIGA of 0 or 1 [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
Percentage of Participants Achieving vIGA of 0 [16 weeks]
The efficacy of EDP1815 will be measured by the number of participants achieving a vIGA of 0 at Week16
Mean absolute change in vIGA*BSA (body surface area) [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
Mean percentage change in vIGA*BSA [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
Mean absolute change from baseline in BSA [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
Mean percentage change from baseline in BSA [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
Percentage of Participants Achieving BSA-50 [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
Percentage of Participants Achieving BSA-75 [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
Percentage of Participants Achieving BSA reduction to 3% BSA or less [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
Mean absolute change from baseline in SCORing Atopic Dermatitis (SCORAD) [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
Mean percentage change from baseline in SCORAD [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
Percentage of Participants Achieving SCORAD-50 [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
Percentage of Participants Achieving SCORAD-75 [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
Mean absolute change from baseline in the Dermatology Quality of Life Index (DLQI) [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
Mean percentage change from baseline in DLQI [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
Percentage of Participants achieving a reduction of ≥4 in the DLQI, of those with a score of ≥4 at baseline [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
Mean absolute change from baseline in worst Pruritus Numerical Rating Scale (PR-NRS) [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
Percentage of Participants achieving a reduction of ≥2 in the worst Pruritus-NRS, of those with a score of ≥2 at baseline [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
Percentage of Participants achieving a reduction of ≥4 in the worst PR-NRS, of those with a score of ≥4 at baseline [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
Mean absolute change from baseline in the Sleep Disturbance Numerical Rating Scale (SD-NRS) score [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
Percentage of Participants achieving a reduction of ≥2 in SD-NRS score, of those with a score of ≥2 at baseline [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
Mean absolute change from baseline in Patient Oriented Eczema Measure (POEM) [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
Mean percentage change from baseline in Patient Oriented Eczema Measure (POEM) [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
Percentage of Participants achieving a reduction of ≥4 in the POEM score, of those with a score of ≥4 at baseline [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
Number of courses of rescue therapy per Participant [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
Number of days of treatment with rescue therapy per Participant [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
Proportion of participants not requiring rescue therapy [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

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	USA-112	Fountain Valley	California	United States	92708
2	USA-123	Fremont	California	United States	94538
3	USA-114	Newport Beach	California	United States	92660
4	USA-101	Fort Lauderdale	Florida	United States	33308
5	USA-124	Jacksonville	Florida	United States	32216
6	USA-108	Miami	Florida	United States	33165
7	USA-120	Miami	Florida	United States	33175
8	USA-105	Miramar	Florida	United States	33027
9	USA-102	Orlando	Florida	United States	32801
10	USA-115	Sweetwater	Florida	United States	33172
11	USA-126	Tampa	Florida	United States	33613
12	USA-106	Tampa	Florida	United States	33624
13	USA-118	Sandy Springs	Georgia	United States	30328
14	USA-111	Clarksville	Indiana	United States	47129
15	USA-116	Louisville	Kentucky	United States	40241
16	USA-119	Baton Rouge	Louisiana	United States	70806
17	USA-109	Metairie	Louisiana	United States	70006
18	USA-125	Silver Spring	Maryland	United States	20902
19	USA-121	Columbus	Ohio	United States	43221
20	USA-128	Concord	Ohio	United States	44077
21	USA-104	Portland	Oregon	United States	97239
22	USA-127	Memphis	Tennessee	United States	38119
23	USA-117	Frisco	Texas	United States	75034
24	USA-110	Pflugerville	Texas	United States	78660
25	USA-113	Bellevue	Washington	United States	98004
26	AUS-102	Carlton		Australia
27	AUS-104	Kogarah		Australia
28	AUS-101	Melbourne		Australia
29	AUS-103	Parkville		Australia
30	AUS-106	Woolloongabba		Australia
31	BGR-105	Pleven		Bulgaria
32	BGR-104	Sevlievo		Bulgaria
33	BGR-101	Sofia		Bulgaria
34	BGR-102	Sofia		Bulgaria
35	BGR-103	Sofia		Bulgaria
36	CAN-109	Barrie		Canada
37	CAN-108	Edmonton		Canada
38	CAN-105	Markham		Canada
39	CAN-104	Mississauga		Canada
40	CAN-101	Ottawa		Canada
41	CAN-107	Richmond Hill		Canada
42	CAN-103	Surrey		Canada
43	CAN-106	Waterloo		Canada
44	CAN-111	Winnipeg		Canada
45	DEU-105	Berlin		Germany
46	DEU-107	Bochum		Germany
47	DEU-106	Erlangen		Germany
48	DEU-102	Frankfurt am Main		Germany
49	DEU-104	Gera		Germany
50	DEU-101	Hamburg		Germany
51	DEU-103	Heidelberg		Germany
52	POL-104	Gdańsk		Poland
53	POL-106	Gdynia		Poland
54	POL-107	Katowice		Poland
55	POL-101	Lublin		Poland
56	POL-102	Warszawa		Poland
57	POL-103	Wrocław		Poland
58	POL-105	Łódź		Poland