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

The objective of this study is to compare the efficacy and safety of orally administered DS107 (2g) versus placebo in the treatment of moderate to severe Atopic Dermatitis (AD).

Oral DS107/Placebo capsules will be administered for 16 weeks. The study will enrol approximately 220 subjects.

This study involves a comparison of 2g DS107 with placebo, administered orally once daily for a total of 16 weeks. Patients will be randomized to one of the two treatment arms in a 1:1 ratio.

The primary endpoint will be the vIGA (Validated Investigator's Global Assessment) and EASI (Eczema Area and Severity Index). Other endpoints include vIGA, EASI, SCORAD, BSA (Body Surface Area) and NRS (Numeric Rating Scale).

Eligibility Criteria:
Inclusion Criteria:

1. Patients with a clinically confirmed diagnosis of active AD according to the American Academy of Dermatology Consensus Criteria that had been present for at least 6 months before the screening visit.
2. Patients with moderate to severe AD at baseline as defined by a Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) score of 3 Or 4 at baseline.
3. Patients with an Eczema Area and Severity Index (EASI) score of ≥16 at screening and baseline.
4. Patients with AD covering a minimum 10% of the Body Surface Area (BSA) at baseline.
5. Patients with a worst itch Numeric Rating Scale (NRS) score in a day of ≥4 (on 11-point NRS) at the screening and baseline visits.
6. Patients whose pre-study clinical laboratory findings did not interfere with their participation in the study, in the opinion of the investigator.
7. Patients who were able and willing to stop all current treatments for AD throughout the study (except for allowed emollients).
8. Patients who were on a stable dose of a bland emollient for at least 7 days prior to baseline.
9. Male or female patients aged 18 years and older on the day of signing the informed consent form (ICF).
10. Female patients and male patients with female partners of child bearing potential had to use highly effective birth control methods or have a sterilised partner for the duration of the study.
11. Recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments were otherwise medically inadvisable (e.g. because of important side effects or safety risks).
12. Patients who were able to communicate well with the investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent prior to initiation of any study specific activities or procedures.

Exclusion Criteria:

1. Patients with other skin conditions that might interfere with AD diagnosis and/or evaluation (such as psoriasis or current active viral, bacterial and fungal topical skin infections) as assessed by the investigator.
2. Patients who had used systemic treatments that could affect AD 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 were allowed.
3. Patients with previous exposure to DS107.
4. Patients who had used any topical medicated treatment for AD (except for emollients) two weeks prior to start of treatment/Baseline (Day 0) including but not limited to, topical corticosteroids, calcineurin inhibitors, tars, bleach, antimicrobials and bleach baths.
5. Patients who used emollients containing urea, ceramides or hyaluronic acid less than 12 weeks prior to Baseline (Day 0).
6. Patients who have had excessive sun exposure, have used tanning booths or other ultraviolet (UV) light sources four weeks prior to Baseline (Day 0) and/or were planning a trip to a sunny climate or to use tanning booths or other UV sources between screening and follow-up visits.
7. Patients who had a history of hypersensitivity to any substance in DS107 or placebo capsules.
8. Patients who had a history of hypersensitivity to soy beans or soy lecithin.
9. Patients who had a white cell count or differential white cell count outside of the normal reference range at screening.
10. Patients who had 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 interpretation of study results.
11. Patients who had a clinically significant impairment of renal or hepatic function.
12. Patients with significant uncontrolled cardiovascular, neurologic, malignant, psychiatric, respiratory or hypertensive disease, as well as uncontrolled diabetes and fluoride arthritis or any other illness that, in the opinion of the investigator, was likely to interfere with completion of the study.
13. Patients with active infectious diseases (e.g. hepatitis B, hepatitis C or advanced disease secondary to infection with human immunodeficiency virus).
14. Patients with a history of clinically significant drug or alcohol abuse in the opinion of the investigator in the last year prior to Baseline (Day 0).
15. Patients who had participated in any other clinical study with an investigational drug within 3 months before the first day of administration of study treatment.
16. Patients who have had treatment with biologics as follows:

    Any cell-depleting agents including but not limited to rituximab: within 6 months before the screening visit, or until lymphocyte count returned to normal, whichever was longer. b. Other biologics influencing cell proliferation: within 6 months before the screening visit. c. Dupilumab or other monoclonal antibodies within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever was longer.
17. Patients who were pregnant, planning pregnancy, breastfeeding and/or were unwilling to use adequate contraception (as specified in Inclusion Criterion 10) during the trial.
18. Patients, in the opinion of the investigator, not suitable to participate in the study.