Clinical trial NCT05121480: A Study Investigating the Effect of EDP1815 in the Treatment of Mild, Moderate and Severe Atopic Dermatitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: Mild Atopic Dermatitis
Moderate Atopic Dermatitis
Severe Atopic Dermatitis
Mild Eczema
Moderate Eczema
Severe Eczema
Lead sponsor: Evelo Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-16
Enrollment: 421
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Achievement of EASI-50
timeFrame: 16 weeks
Secondary outcomes:
measure: Percentage of Participants Achieving EASI-50
timeFrame: 4, 8 and 12 weeks
measure: Percentage of Participants Achieving EASI-75
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving EASI-90
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Absolute Change in EASI
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Percentage Change in EASI
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving Investigator's Global Assessment (vIGA) of 0 or 1 With a ≥2 Point Improvement
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving vIGA of 0 or 1
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving vIGA of 0
timeFrame: 16 weeks
measure: Mean Absolute Change in vIGA*BSA
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Percentage Change in vIGA*BSA
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Absolute Change From Baseline in BSA
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Percentage Change From Baseline in BSA
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving BSA-50
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving BSA-75
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving BSA Reduction to 3% BSA or Less
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD)
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Percentage Change From Baseline in SCORAD
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving SCORAD-50
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving SCORAD-75
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Absolute Change From Baseline in the Dermatology Quality of Life Index (DLQI)
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Percentage Change From Baseline in DLQI
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving a Reduction of ≥4 in the DLQI, of Those With a Score of ≥4 at Baseline
timeFrame: 16 weeks
measure: Mean Absolute Change From Baseline in Worst Pruritus Numerical Rating Scale (PR-NRS)
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving a Reduction of ≥2 in the Worst Pruritus-NRS, of Those With a Score of ≥2 at Baseline
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving a Reduction of ≥4 in the Worst PR-NRS, of Those With a Score of ≥4 at Baseline
timeFrame: 16 weeks
measure: Mean Absolute Change From Baseline in the Sleep Disturbance Numerical Rating Scale (SD-NRS) Score
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving a Reduction of ≥2 in SD-NRS Score, of Those With a Score of ≥2 at Baseline
timeFrame: 16 weeks
measure: Mean Absolute Change From Baseline in Patient Oriented Eczema Measure (POEM)
timeFrame: 4, 8, 12, and 16 weeks
measure: Mean Percentage Change From Baseline in Patient Oriented Eczema Measure (POEM)
timeFrame: 4, 8, 12, and 16 weeks
measure: Percentage of Participants Achieving a Reduction of ≥4 in the POEM Score, of Those With a Score of ≥4 at Baseline
timeFrame: 16 weeks
measure: Number of Courses of Rescue Therapy Per Participant
timeFrame: 4, 8, 12, and 16 weeks
measure: Number of Days of Treatment With Rescue Therapy Per Participant
timeFrame: 16 weeks
measure: Proportion of Participants Not Requiring Rescue Therapy
timeFrame: 4, 8, 12, and 16 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: USA-131
state: Alabama
city: Fountain Valley
country: United States
facility: USA-112
state: California
city: Fremont
country: United States
facility: USA-123
state: California
city: Newport Beach
country: United States
facility: USA-114
state: California
city: Fort Lauderdale
country: United States
facility: USA-101
state: Florida
city: Jacksonville
country: United States
facility: USA-124
state: Florida
city: Miami
country: United States
facility: USA-108
state: Florida
city: Miami
country: United States
facility: USA-120
state: Florida
city: Miramar
country: United States
facility: USA-105
state: Florida
city: Orlando
country: United States
facility: USA-102
state: Florida
city: Sweetwater
country: United States
facility: USA-115
state: Florida
city: Tampa
country: United States
facility: USA-126
state: Florida
city: Tampa
country: United States
facility: USA-106
state: Florida
city: Sandy Springs
country: United States
facility: USA-118
state: Georgia
city: Clarksville
country: United States
facility: USA-111
state: Indiana
city: Louisville
country: United States
facility: USA-116
state: Kentucky
city: Baton Rouge
country: United States
facility: USA-119
state: Louisiana
city: Metairie
country: United States
facility: USA-109
state: Louisiana
city: Silver Spring
country: United States
facility: USA-125
state: Maryland
city: Ann Arbor
country: United States
facility: USA-130
state: Michigan
city: Columbus
country: United States
facility: USA-121
state: Ohio
city: Concord
country: United States
facility: USA-128
state: Ohio
city: Portland
country: United States
facility: USA-104
state: Oregon
city: Memphis
country: United States
facility: USA-127
state: Tennessee
city: Frisco
country: United States
facility: USA-117
state: Texas
city: Pflugerville
country: United States
facility: USA-110
state: Texas
city: Bellevue
country: United States
facility: USA-113
state: Washington
city: Carlton
country: Australia
facility: AUS-102
city: Kogarah
country: Australia
facility: AUS-104
city: Melbourne
country: Australia
facility: AUS-101
city: Woolloongabba
country: Australia
facility: AUS-106
city: Pleven
country: Bulgaria
facility: BGR-105
city: Sevlievo
country: Bulgaria
facility: BGR-104
city: Sofia
country: Bulgaria
facility: BGR-101
city: Sofia
country: Bulgaria
facility: BGR-102
city: Sofia
country: Bulgaria
facility: BGR-103
city: Barrie
country: Canada
facility: CAN-109
city: Edmonton
country: Canada
facility: CAN-108
city: Markham
country: Canada
facility: CAN-105
city: Mississauga
country: Canada
facility: CAN-104
city: Ottawa
country: Canada
facility: CAN-101
city: Richmond Hill
country: Canada
facility: CAN-107
city: Surrey
country: Canada
facility: CAN-103
city: Waterloo
country: Canada
facility: CAN-106
city: Winnipeg
country: Canada
facility: CAN-111
city: Berlin
country: Germany
facility: DEU-105
city: Bochum
country: Germany
facility: DEU-107
city: Erlangen
country: Germany
facility: DEU-106
city: Frankfurt am Main
country: Germany
facility: DEU-102
city: Gera
country: Germany
facility: DEU-104
city: Hamburg
country: Germany
facility: DEU-101
city: Heidelberg
country: Germany
facility: DEU-103
city: Gdańsk
country: Poland
facility: POL-104
city: Gdynia
country: Poland
facility: POL-106
city: Katowice
country: Poland
facility: POL-107
city: Lublin
country: Poland
facility: POL-101
city: Warszawa
country: Poland
facility: POL-102
city: Wrocław
country: Poland
facility: POL-103
city: Łódź
country: Poland
facility: POL-105
Study officials:
affiliation: Oregon Medical Research Center
name: Benjamin Ehst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Evelo Biosciences, Inc.
name: Yanislav Mihaylov, MD
role: STUDY_DIRECTOR
References: