Efficacy and Safety Study of Orally Administered DS107 in Moderate to Severe Atopic Dermatitis Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether orally administered DS107 (1g and 2g doses) is effective in the treatment of moderate to severe atopic dermatitis. Oral DS107 capsules will be administered for 8 weeks and will be compared against placebo. The study will enroll approximately 300 subjects.

Detailed Description
-----------------
The study will consist of 3 treatment arms, each consisting of approximately 100 subjects. Treatment Arm 1 will receive 1g Oral DS107 daily. Treatment Arm 2 will receive 2g Oral DS107 daily. Treatment Arm 3 will receive placebo daily. The primary objective of the study is to assess the efficacy and safety of daily 1g and 2g doses of Oral DS107 versus placebo. Subjects will come to the clinic on 7 occasions: Screening, Baseline, Week 2, Week 4, Week 6, Week 8 (end of treatment/early termination) and Week 10 (follow-up). The primary efficacy variable will be the IGA (Investigator's Global Assessment). Secondary efficacy variables will include IGA, EASI (Eczema Area and Severity Index), and NRS (Numeric Rating Scale),

Official Title
-----------------
A Randomised, Double-blind, Placebo-controlled, Phase 2b Study to Assess the Efficacy and Safety of Orally Administered DS107 in Patients With Moderate to Severe Atopic Dermatitis

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: DS107
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with a clinically confirmed diagnosis of active Atopic Dermatitis according to Hanafin and Rajka criteria Subjects with moderate to severe Atopic Dermatitis at baseline as defined by an IGA of minimum 3 at baseline Subjects with Atopic Dermatitis covering a minimum 10% of the body surface area at baseline Male or female subjects who are aged 18 years and older on the day of signing the informed consent form (ICF) Exclusion Criteria: Subjects with other skin conditions that might interfere with Atopic Dermatitis diagnosis and/or evaluation (such as psoriasis or current active viral, bacterial and fungal skin infections) as assessed by the Investigator Subjects who have used systemic treatments (other than biologics) that could affect Atopic Dermatitis less than 4 weeks prior to baseline visit (Day 0), e.g. retinoids, methotrexate, cyclosporine, hydroxycarbamide (hydroxyurea), azathioprine and oral/injectable corticosteroids. Intranasal corticosteroids and inhaled corticosteroids for stable medical conditions are allowed Subjects who have used any topical medicated treatment for Atopic Dermatitis two weeks prior to start of treatment/Baseline (Day 0), including but not limited to, topical corticosteroids, tars and bleach Subjects who use topical products containing urea, ceramides or hyaluronic acid two weeks prior to Baseline Subjects who have a history of hypersensitivity to any substance in Oral DS107 or placebo capsules Subjects who have any clinically significant controlled or uncontrolled medical condition or laboratory abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with the interpretation of study results Subjects with significant uncontrolled cardiovascular, neurologic, malignant, psychiatric, respiratory or hypertensive disease, as well as diabetes and arthritis or any other illness that, in the opinion of the investigator, is likely to interfere with completion of the study Subjects with chronic infectious disease (e.g. hepatitis B, hepatitis C or infection with human immunodeficiency virus)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1g DS107<br>1g DS107 (2 DS107 capsules and 2 placebo capsules) orally administered once-daily for 8 weeks. | Drug: DS107<br> <br> |
| Experimental: 2g DS107<br>2g DS107 (4 DS107 capsules) orally administered once-daily for 8 weeks. | Drug: DS107<br> <br> |
| Placebo Comparator: Placebo<br>Placebo (4 placebo capsules) orally administered once-daily for 8 weeks. | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving an Investigators Global Assessment (IGA) of 0 (Clear) or 1 (Almost Clear) and a Decrease of at Least 2 Points in IGA in Treated Population Compared to Placebo Population at Week 8. | Proportion of patients achieving an IGA of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points in IGA in treated population compared to placebo population at Week 8. The IGA scale awards a score of 0-4 based on a 5-point severity scale from clear to severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease). IGA uses clinical characteristics of erythema, infiltration, papulation and oozing/crusting as scoring guidelines for the overall severity assessment. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving an IGA Score of 0 (Clear) or 1 (Almost Clear) and a Decrease of at Least 2 Points in IGA in Treated Population Compared to Placebo Population From Baseline to Weeks 2, 4, 6, and 10. | Proportion of patients achieving an IGA score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points in IGA in treated population compared to placebo population from Baseline to Weeks 2, 4, 6, and 10. The IGA scale awards a score of 0-4 based on a 5-point severity scale from clear to severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease). IGA uses clinical characteristics of erythema, infiltration, papulation and oozing/crusting as scoring guidelines for the overall severity assessment. | Baseline, Week 2, Week 4, Week 6 and Week 10 | 
| Proportion of Patients Achieving a Decrease of at Least 2 Points in IGA in Treated Population Compared to Placebo Population From Baseline to Weeks 2, 4, 6, 8, and 10 | Proportion of patients achieving a decrease of at least 2 points in IGA in treated population compared to placebo population from Baseline to Weeks 2, 4, 6, 8, and 10. The IGA scale awards a score of 0-4 based on a 5-point severity scale from clear to severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease). IGA uses clinical characteristics of erythema, infiltration, papulation and oozing/crusting as scoring guidelines for the overall severity assessment. | Baseline, Week 2, Week 4, Week 6, Week 8 and Week 10 | 
| Change From Baseline in Eczema Area and Severity Index (EASI) in Treated Population Compared to Placebo Population at Weeks 2, 4, 6, 8, and 10 | Change from Baseline in EASI in treated population compared to placebo population at Weeks 2, 4, 6, 8, and 10. It quantifies the severity of a patient's AD based on both lesion severity and the percent of Body Surface Area (BSA) affected. The EASI is a composite score ranging from 0-72 that takes into account the degree of erythema, induration/papulation, excoriation, and lichenification (each scored from 0 to 3 separately, half points are permitted) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The subscales used are summed in order to give a final EASI score. A decrease in EASI score represents a positive outcome for the patient. | Baseline, Week 2, Week 4, Week 6, Week 8 and Week 10 | 
| Change From Baseline in Numeric Rating Scale (NRS) for Pruritus in Treated Population Compared to Placebo Population at Weeks 2, 4, 6, 8, and 10 | Change from Baseline in Numeric Rating Scale (NRS) for pruritus in treated population compared to placebo population at Weeks 2, 4, 6, 8, and 10. Severity of pruritus related to AD will be self-assessed by patients daily using the NRS. Patients were asked to estimate the intensity of pruritus at its worst over the previous 24 hours. The Pruritus NRS is a single-question assessment tool that will be used to assess the patient's worst itch as a result of AD in the previous 24 hours. Patients scored their pruritus due to AD on a scale of 0 - 10, with 0 (no itch) and 10 (worst itch imaginable). Patients will complete the rating scale at screening and then daily starting at baseline through to the last study visit. A decrease in NRS represents a positive outcome for the patient. | Baseline, Week 2, Week 4, Week 6, Week 8 and Week 10 |