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A Study of EDP1066 in Healthy Participants and Participants With Mild to Moderate Psoriasis and Atopic Dermatitis

Phase 1
Completed
Conditions
Atopic Dermatitis
Psoriasis
Interventions
Other: EDP1066
Drug: Placebo oral capsule
Registration Number
NCT03542994
Lead Sponsor
Evelo Biosciences, Inc.
Brief Summary

Evelo will investigate the safety and tolerability of EDP1066 and its potential to be a medicinal product in healthy volunteers and individuals with mild to moderate psoriasis and atopic dermatitis.

Detailed Description

This will be a randomized, double-blind, placebo-controlled clinical study with dose escalations to assess safety, tolerability, and pharmacodynamic effect of EDP1066. 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 EDP1066 in this patient population provides an opportunity to gain pharmacodynamic information using a range of tissue biopsies and composite clinical endpoints.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
114
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:

  1. Participant has had a confirmed diagnosis of mild to moderate plaque-type psoriasis for at least 6 months involving ≤ 5% of body surface area (BSA) (excluding the scalp).
  2. Participant has a minimum of 2 psoriatic lesions with at least 1 plaque in a site suitable for biopsy.

Mild to moderate atopic dermatitis:

  1. Mild to moderate atopic dermatitis with a minimum of 3% to a maximum of 15% BSA involvement.
  2. Participant has had a confirmed diagnosis of mild to moderate atopic dermatitis for at least 6 months IGA score of 2 or 3.
  3. Participant has a minimum of 2 atopic dermatitis lesions with at least 1 in a site suitable for biopsy.
Exclusion Criteria
  1. 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.

  2. 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.

  3. Participant has received any investigational drug or experimental procedure within 90 days or 5 half-lives, whichever is longer, prior to study intervention administration.

  4. 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 2 grams/day in any 24 hour period).

  5. 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.

  6. Participant has renal or liver impairment, defined as:

    a. 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 b. 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Cohort 1EDP106612 healthy volunteers; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 66 mg, capsule, once daily, 15 days
Cohort 1Placebo oral capsule12 healthy volunteers; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 66 mg, capsule, once daily, 15 days
Cohort 2EDP106612 healthy volunteers; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 660 mg, capsule, once daily, 15 days
Cohort 2Placebo oral capsule12 healthy volunteers; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 660 mg, capsule, once daily, 15 days
Cohort 3EDP106612 healthy volunteers; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 15 days
Cohort 3Placebo oral capsule12 healthy volunteers; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 15 days
Cohort 4EDP106612 subjects with mild to moderate psoriasis; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 660 mg, capsule, once daily, 29 days
Cohort 4Placebo oral capsule12 subjects with mild to moderate psoriasis; 8 on EDP1066, 4 on placebo. Dose=up to a maximum of 660 mg, capsule, once daily, 29 days
Cohort 5EDP106624 subjects with mild to moderate psoriasis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 29 days
Cohort 5Placebo oral capsule24 subjects with mild to moderate psoriasis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 29 days
Cohort 6EDP1066up to 24 subjects with mild to moderate atopic dermatitis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 660 mg, capsule, once daily, 29 days
Cohort 6Placebo oral capsuleup to 24 subjects with mild to moderate atopic dermatitis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 660 mg, capsule, once daily, 29 days
Cohort 7EDP1066up to 24 subjects with mild to moderate atopic dermatitis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 29 days
Cohort 7Placebo oral capsuleup to 24 subjects with mild to moderate atopic dermatitis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 29 days
Cohort 8EDP1066up to 24 subjects with mild to moderate psoriasis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3g, capsule, once daily, 29 days
Cohort 8Placebo oral capsuleup to 24 subjects with mild to moderate psoriasis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3g, capsule, once daily, 29 days
Cohort 9EDP1066up to 24 subjects with mild to moderate atopic dermatitis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 29 days
Cohort 9Placebo oral capsuleup to 24 subjects with mild to moderate atopic dermatitis; 16 on EDP1066, 8 on placebo. Dose=up to a maximum of 3.3 g, capsule, once daily, 29 days
Primary Outcome Measures
NameTimeMethod
Safety and tolerability measured through Adverse Events (AEs)Day 1 to Day 60

Number of participants with AEs by seriousness and relationship to treatment

Safety and tolerability measured through lab measurementsDay 0 to Day 60

Number of participants with clinically significant change from baseline (Day 0) in laboratory values

Safety and tolerability measured through ECGDay 0 to Day 60

Number of participants with clinically relevant changes from baseline (Day 0) ECG parameters

Safety and tolerability measured through physical examinationDay 1 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 analysisDay 1 to Day 60

GI safety measurement through fecal calprotectin analysis

Secondary Outcome Measures
NameTimeMethod
Clinical improvement in subjects with mild to moderate psoriasisDay 0 to Day 60

Change from baseline (Day 0) Psoriasis-area-and-severity index score (PASI) in response to EDP1066, 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 dermatitisDay 0 to Day 60

Change from baseline (Day 0) Eczema-area-and-severity index score (EASI) in response to EDP1066, measured on a scale of 0 to 6 (where 0 is most favorable and 6 is least favorable).

Trial Locations

Locations (4)

MAC Clinical Research

🇬🇧

Stockton-on-Tees, United Kingdom

University of Surrey Clinical Research Center

🇬🇧

Guildford, Surrey, United Kingdom

Royal Liverpool Clinical Research Unit

🇬🇧

Liverpool, United Kingdom

Medicines Evaluation Unit Ltd., The Langley Building, Wythenshawe Hospital

🇬🇧

Manchester, United Kingdom

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