Safety and Efficacy Study of Topically Applied DS107 Cream in Mild to Moderate Atopic Dermatitis Patients (AD)

Study Overview
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Brief Summary
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The purpose of this randomized, double blind, placebo controlled, parallel group study is to compare the safety and efficacy of topically applied DS107 cream (1% and 5%) versus vehicle cream, in the treatment of adult patients with mild to moderate Atopic Dermatitis (AD).

Detailed Description
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This was a randomized, vehicle-controlled, double-blind, parallel-group, multicenter, Phase 2b study to investigate the safety and efficacy of topically administered DS107 cream and the dose-response relationship between DS107 cream and vehicle cream in patients 18 years and older with mild to moderate AD. Approximately 300 patients (100 per treatment group), with mild to moderate AD were to be included in this study. All patients signed the patient information sheet (PIS)/informed consent form (ICF) and underwent screening for study eligibility. Eligible patients were randomized (1:1:1) to receive 1% DS107 cream, 5% DS107 cream or, vehicle cream: Treatment Group A: 1% DS107 cream Treatment Group B: 5% DS107 cream Treatment Group C: Vehicle cream Study cream was to be applied topically to all affected or commonly affected areas twice daily (BID) for 8 weeks. To maintain the double-blind conditions, the DS107 and vehicle creams were identical in appearance. During their participation, patients were to come to the clinic on 7 occasions: Screening, Baseline, and at Weeks 2, 4, 6, 8 (end of treatment), and 10 (follow-up). At the start of the study, areas for treatment were defined, DS107 or vehicle cream was then applied to those areas (and any newly affected areas) throughout the 8-week treatment period. Patients were instructed to apply the study cream liberally to the affected area in the morning and the evening. Emollients could be applied to other areas of dry skin that were not in the defined treatment area. On the days of clinic visits, patients were instructed to abstain from applying study cream for 6 hours prior to the visit and then to apply study cream as soon as possible after the clinic visit. Once enrolled, patients were restricted from using any other treatment for AD. Any medication (prescription and over-the-counter [OTC] drugs) or therapeutic intervention deemed necessary for the patient, and which in the opinion of the investigator did not interfere with the safety and efficacy evaluations, could be continued unless they were included in the prohibited list of medications and therapeutic regimens.

Official Title
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A Randomised, Double-blind, Vehicle-Controlled, Phase IIb Study to Assess the Efficacy and Safety of Topically Applied DS107 Cream to Adults With Mild to Moderate Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: DS107
* Other: Vehicle cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a clinically confirmed diagnosis of active Atopic Dermatitis according to Hanifin and Rajka criteria Patients with mild to moderate Atopic Dermatitis at baseline as defined by an Investigator's Global Assessment (IGA) score of 3 or 2 at baseline visit Patients with Atopic Dermatitis covering a minimum 5% of the body surface area at baseline Male or female patients aged 18 years and older on the day of signing the informed consent form (ICF) Exclusion Criteria: Patients with other skin conditions that might interfere with Atopic Dermatitis diagnosis and/or evaluation (such as psoriasis or current active viral, bacterial and fungal topical skin infections) as assessed by the Investigator Patients who have used systemic treatments (other than biologics) that could affect Atopic Dermatitis less that 4 weeks prior to baseline visit (Day 0), e.g. retinoids, methotrexate, cyclosporine, hydroxycarbamide (hydroxyurea), azathioprine and oral/injectable corticosteroids. Intranasal corticosteroids for stable medical conditions are allowed Patients who have used any topical medicated treatment for Atopic Dermatitis two weeks prior to the start of treatment/baseline (Day 0) including but not limited to, topical corticosteroids, calcineurin inhibitors, tars, bleach, antimicrobials, and bleach baths Patients who use topical products containing urea, ceramides or hyaluronic acid two weeks prior to Day 0 Patients who have a history of hypersensitivity to any substance in DS107 cream or vehicle cream Patients who have any clinically significant controlled or uncontrolled medical condition or laboratory abnormality that would, in the opinion of the Investigator, put the patient at undue risk or interfere with the interpretation of study results Patients with significant uncontrolled cardiovascular, neurologic, malignant, psychiatric, respiratory or hypertensive disease, as well as uncontrolled diabetes and floride arthritis or any other illness that, in the opinion of the Investigator, is likely to interfere with completion of the study Patients with chronic infectious diseases (e.g. hepatitis B, hepatitis C, or infection with human immunodeficiency virus)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle Cream<br>Vehicle cream applied topically to all affected or commonly affected areas twice-daily for 8 weeks | Other: Vehicle cream<br> <br> * Other names: DS107 Placebo Cream;|
| Experimental: 1% DS107 Cream<br>1% DS107 cream applied topically to all affected or commonly affected areas twice-daily for 8 weeks | Drug: DS107<br> <br> * Other names: 1%w/w DS107 DGLA Cream & 5%w/w DS107 DGLA Cream;|
| Experimental: 5% DS107 Cream<br>5% DS107 cream applied topically to all affected or commonly affected areas twice-daily for 8 weeks | Drug: DS107<br> <br> * Other names: 1%w/w DS107 DGLA Cream & 5%w/w DS107 DGLA Cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Numeric Rating Scale (NRS) for Pruritus in Treated Population Compared to Vehicle Population at Week 8 | Change from baseline in Numeric Rating Scale (NRS) for Pruritus in treated population compared to vehicle population at Week 8. Severity of pruritus related to atopic dermatitis (AD) was 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 was 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 indicating no itch and 10 indicating the worst itch imaginable. Patients were required to complete the rating scale daily starting at screening through to the last study visit. A decrease in worst itch NRS indicates a positive outcome for the participant. | Baseline and Week 8 | 
| Change From Baseline in Eczema Area and Severity Index (EASI) in Treated Population Compared to Vehicle Population at Week 8 | Change from baseline in EASI in treated population compared to vehicle population at Week 8. EASI quantifies the severity of a patient's atopic dermatitis (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 severity of each sign is assessed using a 4-point scale (half points are permitted): 0 = none 1 = mild 2 = moderate 3 = severe A decrease in EASI indicates a positive outcome for the participant. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in NRS for Pruritus Intreated Populations Compared to Vehicle Population at Week 2, 4, 6, 10 | Change from baseline in NRS for Pruritus in the treated populations compared to vehicle population at Weeks 2, 4, 6, 10. Severity of pruritus related to atopic dermatitis (AD) was 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 was used to assess the patient's worst itch as a result of AD in the previous 24 hours. Patients will score their pruritus due to AD on a scale of 0 - 10, with 0 indicating no itch and 10 indicating the worst itch imaginable. Patients were asked to complete the rating scale daily starting at screening through to the last study visit. A decrease in worst itch NRS indicates a positive outcome for the participant. | Baseline, Week 2, Week 6 and Week 10 | 
| Proportion of Patients Achieving a Decrease of at Least 2.7 Points in NRS in the Treated Populations Compared to Vehicle Population From Baseline to Weeks 2, 4, 6, 8, and 10. | • Proportion of Patients Achieving a Decrease of at Least 2.7 Points in Numeric Rating Scale (NRS) in Treated Population Compared to Vehicle Population from Baseline to Week 2, 4, 6, 8 and 10. The NRS for Pruritus is a single-question assessment tool that was used to assess the patient's worst itch as a result of AD in the previous 24 hours. Patients were asked to estimate the intensity of pruritus at its worst over the previous 24 hours. Patients were to score their pruritus due to AD on a scale of 0-10, with 0 (no itch) and 10 (worst itch imaginable) | 10 weeks | 
| Change From Baseline in EASI in Treated Population Compared to Vehicle Population at Weeks 2, 4, 6, 10. | Change from baseline in EASI in the treated populations compared to vehicle population at Weeks 2, 4, 6, 10. EASI quantifies the severity of a patient's atopic dermatitis (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 severity of each sign is assessed using a 4-point scale (half points are permitted): 0 = none 1 = mild 2 = moderate 3 = severe A decrease in EASI indicates a positive outcome for the participant. | Baseline, Week 2, Week 4, Week 6 and Week 10 | 
| Proportion of Patients Achieving an Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) and a Decrease of at Least 2 Points in IGA in Treated Population Compared to Vehicle Population From Baseline to Week 2, 4, 6, 8, 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 vehicle population from baseline to Week 2, 4, 6, 8, 10. EASI quantifies the severity of a patient's atopic dermatitis (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 severity of each sign is assessed using a 4-point scale (half points are permitted): 0 = none 1 = mild 2 = moderate 3 = severe A decrease in EASI indicates a positive outcome for the participant. | 10 weeks | 
| Proportion of Patients Achieving a Decrease of at Least 2 Points in IGA in the Treated Populations Compared to Vehicle Population From Baseline to Week 2, 4, 6, 8, 10. | Proportion of Patients Achieving a Decrease of at Least 2 Points in Investigator Global Assessment (IGA) in the Treated Populations Compared to Vehicle Population From Baseline to Week 2, 4, 6, 8, 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. | 10 weeks | 
| Change From Baseline in IGA Score in the Treated Populations Compared to Vehicle Population at Weeks 2, 4, 6, 8, 10. | The Global Investigator Assessment scale (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). The scale uses clinical characteristics of erythema, infiltration, papulation and oozing/crusting as scoring guidelines for the overall severity assessment. A decrease in IGA indicates a positive outcome for the participant. | Baseline, Week 2, Week 4, Week 6, Week 8 and Week 10 |