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

Sponsor

Evelo Biosciences, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03733353

Collaborator

(none)

204

Enrollment

Locations

Arms

35.3

Actual Duration (Months)

22.7

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis Atopic Dermatitis	Drug: EDP1815 Drug: Placebo oral capsule Drug: Placebo oral tablet	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

204 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention 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.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 (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 19, 2018

Actual Primary Completion Date :

Oct 29, 2021

Actual Study Completion Date :

Oct 29, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Safety and tolerability measured through Adverse Events (AEs) [Day 1 to Day 70]
Number of participants with AEs by seriousness and relationship to treatment
Safety and tolerability measured through lab measurements [Day 0 to Day 70]
Number of participants with clinically significant change from baseline (Day 0) in laboratory values
Safety and tolerability measured through ECG [Day 0 to Day 70]
Number of participants with clinically relevant changes from baseline (Day 0) ECG parameters
Safety and tolerability measured through physical examination [Day 0 to Day 60]
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
GI safety measurement through biomarker analysis [Day 0 to Day 60]
GI safety measurement through fecal calprotectin analysis

Secondary Outcome Measures

Clinical improvement in subjects with mild to moderate psoriasis [Day 0 to Day 70]
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).
Clinical improvement in subjects with mild to moderate atopic dermatitis [Day 0 to Day 70]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	Country
1	UK-8	Barnsley	United Kingdom
2	UK-7	Blackpool	United Kingdom
3	UK-3	Cannock	United Kingdom
4	UK-4	Leeds	United Kingdom
5	UK-5	Liverpool	United Kingdom
6	UK-1	London	United Kingdom
7	UK-2	Manchester	United Kingdom
8	UK-6	Manchester	United Kingdom
9	UK-9	Stockton-on-Tees	United Kingdom

Sponsors and Collaborators

Evelo Biosciences, Inc.

Investigators

Study Director: Duncan McHale, MD, PhD, Evelo Biosciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Evelo Biosciences, Inc.

ClinicalTrials.gov Identifier:

NCT03733353

Other Study ID Numbers:

EDP1815-101
2018-002807-32

First Posted:

Nov 7, 2018

Last Update Posted:

Jan 10, 2022

Last Verified:

Jan 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 10, 2022