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

• Sponsor: DS Biopharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03817190
• Collaborator: (none)
• Enrollment: 219
• Locations: 50
• Arms: 2
• Actual Duration (Months): 11.5
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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 200 subjects.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: DS107; Drug: Placebo	Phase 2

Detailed Description

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

Patients will come to the clinic on 12 occasions: at Screening/Visit 1, Baseline/Visit 2, Week 2/Visit 3, Week 4/Visit 4, Week 6/Visit 5, Week 8/Visit 6, Week 10/Visit 7, Week 12/Visit 8, Week 14/ Visit 9, Week 16/Visit 10 (end of treatment), Week 18/ Visit 11 (follow up) and Week 20/Visit 12 (follow-up).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo-controlled, Study to Assess the Efficacy and Safety of Orally Administered DS107 in Adult Patients With Moderate to Severe Atopic Dermatitis
• Actual Study Start Date: Sep 19, 2019
• Actual Primary Completion Date: Sep 3, 2020
• Actual Study Completion Date: Sep 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2g Oral DS107 2g DS107 (4 DS107 capsules) administered once-daily for 16 weeks	Drug: DS107; DS107 Capsule; Other Names: DGLA
Placebo Comparator: Placebo Placebo (4 placebo capsules) orally administered once-daily for 16 weeks	Drug: Placebo; Placebo capsule

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Achieving a Validated Investigator Global Assessment Scale for Atopic Dermatitis Score of 0 or 1 and a Decrease of at Least 2 Points in vIGA-ADTM in Treated Population Compared to Placebo Population From Baseline at Week 16. [16 Weeks]

   Proportion of patients achieving a Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points in vIGA-ADTM in treated population compared to placebo population from Baseline at Week 16 using GLMM.

2. Proportion of Patients Achieving EASI-75 in Treated Population Compared to Placebo Population at Week 16. [16 Weeks]

   Proportion of patients achieving EASI-75 (≥75% improvement from Baseline) in treated population compared to placebo population at Week 16 using GLMM.

Secondary Outcome Measures

1. Proportion of Patients Achieving a vIGA-ADTM Score of 0 or 1 and a Decrease of at Least 2 Points in vIGA-ADTM in Treated Population Compared to Placebo Population From Baseline to Week 4, 8, 12, 18 and 20. [Baseline, Week 4, Week 8, Week 12, Week 18 and Week 20.]

   Proportion of patients achieving a vIGA-ADTM score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points in vIGA-ADTM in treated population compared to placebo population from Baseline to Week 4, 8, 12, 18 and 20 and the change in proportion of patients from Week 16 to Week 18 and 20.

2. Proportion of Patients Achieving EASI-75 in Treated Population Compared to Placebo Population at Weeks 4, 8, 12, 18 and 20. [Baseline, Week 4, Week 8, Week 12, Week 18 and Week 20.]

   Proportion of patients achieving EASI-75 (≥75% improvement from Baseline) in treated population compared to placebo population at Weeks 4, 8, 12, 18 and 20.

3. Change From Baseline in Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) Score in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20. [20 Weeks]

   The Validated Global Investigator Assessment scale for Atopic DermatitisTM (vIGA-AD) 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 vIGA indicates a positive outcome for the participant.

4. Change From Baseline in EASI in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20. [Week 20]

   Change from Baseline in Eczema Area and Severity Index (EASI) in treated population compared to placebo population to Weeks 4, 8, 12, 16, 18 and 20, and from Week 16 to Week 18 and 20. 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.

5. Proportion of Patients Achieving a Decrease of at Least 4 Points in Worst Itch Numeric Rating Scale (NRS) in Treated Population Compared to Placebo Population From Baseline to Week 4, 8, 12, 16, 18 and 20. [Week 20]

   Proportion of patients achieving a decrease of at least 4 points in worst itch numeric rating scale in treated population compared to placebo population from Baseline to Week 4, 8, 12, 16, 18 and 20.

6. Proportion of Patients Achieving a Decrease of at Least 3 Points in Worst Itch NRS in Treated Population Compared to Placebo Population From Baseline to Week 4, 8, 12, 16, 18 and 20. [Week 20]

   Proportion of patients achieving a decrease of at least 3 points in worst itch NRS in treated population compared to placebo population from Baseline to Week 4, 8, 12, 16, 18 and 20.

7. Change From Baseline in Worst Itch NRS in Treated Population Compared to Placebo Population to Week 4, 8, 12, 16 and 18. [Week 20]

   Change from Baseline in worst itch Numeric Rating Scale (NRS) in treated population compared to placebo population to Week 4, 8, 12, 16 and 18. 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 will 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.

8. Proportion of Patients Achieving EASI-50 in Treated Population Compared to Placebo Population at Week 4, 8, 12, 16, 18 and 20. [Week 20]

   Proportion of patients achieving EASI-50 (≥50% improvement from Baseline) in treated population compared to placebo population at Week 4, 8, 12, 16, 18 and 20.

9. Change From Baseline in the Body Surface Area Affected by AD in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20. [Week 20]

   Change from Baseline in the Body Surface Area (BSA) affected by AD in treated population compared to placebo population to Weeks 4, 8, 12, 16, 18 and 20, and from Week 16 to Week 18 and 20.

10. Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20. [20 Weeks]

    The SCORAD grading system was developed by the European Task Force on Atopic Dermatitis and has been a standard tool to assess atopic dermatitis (AD) severity in clinical studies. Six items (erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness) will be selected to evaluate the AD severity. The intensity of each item is graded using a 4-point scale: 0 = No symptoms 1 = Mild 2 = Moderate 3 = Severe The overall body surface area (BSA) affected by AD will be evaluated (from 0 to 100%) and included in the SCORAD scores. Loss of sleep and pruritus will be evaluated by patients on a visual analog scale (0-10). The SCORAD formula is A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The sum of these measures represents the SCORAD which can vary from 0 to 103. A decrease in SCORAD indicates a positive outcome for the participant.

11. Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs). [20 Weeks]

    Incidence of TEAEs and SAEs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. Patients with previous exposure to DS107.

2. 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.

3. Patients who used emollients containing urea, ceramides or hyaluronic acid less than 12 weeks prior to Baseline (Day 0).

4. 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.

5. Patients who had a history of hypersensitivity to any substance in DS107 or placebo capsules.

6. Patients who had a history of hypersensitivity to soy beans or soy lecithin.

7. Patients who had a white cell count or differential white cell count outside of the normal reference range at screening.

8. 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.

9. Patients who had a clinically significant impairment of renal or hepatic function.

10. 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.

11. Patients with active infectious diseases (e.g. hepatitis B, hepatitis C or advanced disease secondary to infection with human immunodeficiency virus).

12. 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).

13. 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.

14. 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.

1. Patients who were pregnant, planning pregnancy, breastfeeding and/or were unwilling to use adequate contraception (as specified in Inclusion Criterion 10) during the trial.

2. Patients, in the opinion of the investigator, not suitable to participate in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DS Investigational Site 524	Birmingham	Alabama	United States	35209
2	DS Investigational Site 528	Huntington Beach	California	United States	92647
3	DS Investigational Site 502	Los Angeles	California	United States	90045
4	DS Investigational Site 504	San Diego	California	United States	92108
5	DS Investigational Site 505	San Diego	California	United States	92123
6	DS Investigational Site 516	Santa Ana	California	United States	92705
7	DS Investigational Site 501	Santa Monica	California	United States	90404
8	DS Investigational Site 517	Washington	District of Columbia	United States	20037
9	DS Investigational Site 527	Doral	Florida	United States	33122
10	DS Investigational Site 510	Sunrise	Florida	United States	33351
11	DS Investigational Site 512	Columbus	Georgia	United States	31904
12	DS Investigational Site 514	Skokie	Illinois	United States	60077
13	DS Investigational Site 513	Louisville	Kentucky	United States	40241
14	DS Investigational Site 519	Troy	Michigan	United States	48084
15	DS Investigational Site 511	Raleigh	North Carolina	United States	27612
16	DS Investigational Site 526	Grants Pass	Oregon	United States	97527
17	DS Investigational Site 521	Medford	Oregon	United States	97504
18	DS Investigational Site 525	Philadelphia	Pennsylvania	United States	19046
19	DS Investigational Site 509	Arlington	Texas	United States	76011
20	DS Investigational Site 506	Austin	Texas	United States	78745
21	DS Investigational Site 508	Cypress	Texas	United States	77433
22	DS Investigational Site 507	San Antonio	Texas	United States	78213
23	DS Investigative Site 529	Orem	Utah	United States	84058
24	DS Investigative Site 530	Salt Lake City	Utah	United States	84117
25	DS Investigational Site 523	Richmond	Virginia	United States	23224
26	DS Investigational Site 518	Kenosha	Wisconsin	United States	53144
27	DS Investigational Site 101	Graz		Austria
28	DS Investigational Site 203	Augsburg		Germany
29	DS Investigational Site 202	Berlin		Germany
30	DS Investigational Site 208	Berlin		Germany
31	DS Investigational Site 204	Dresden		Germany
32	DS Investigational Site 206	Essen		Germany
33	DS Investigational Site 201	Frankfurt		Germany
34	DS Investigational Site 207	Gera		Germany
35	DS Investigational Site 211	Leipzig		Germany
36	DS Investigational Site 205	Luebeck		Germany
37	DS Investigational Site 210	Mainz		Germany
38	DS Investigational Site 214	Münster		Germany
39	DS Investigational Site 212	Rostock		Germany
40	DS Investigational Site 304	Jūrmala		Latvia
41	DS Investigational Site 301	Riga		Latvia
42	DS Investigational Site 302	Riga		Latvia
43	DS Investigational Site 303	Riga		Latvia
44	DS Investigational Site 305	Riga		Latvia
45	DS Investigational Site 406	Gdańsk		Poland
46	DS Investigational Site 403	Poznań		Poland
47	DS Investigational Site 405	Warsaw		Poland
48	DS Investigational Site 407	Warsaw		Poland
49	DS Investigational Site 401	Wrocław		Poland
50	DS Investigational Site 402	Łódź		Poland

Sponsors and Collaborators

• DS Biopharma

Investigators

• Study Chair: Markus Weissbach, MD, DS Biopharma

Study Documents (Full-Text)

• Study Protocol - Mar 18, 2020
• Statistical Analysis Plan - Sep 24, 2020

More Information

Publications

None provided.

• Responsible Party: DS Biopharma
• ClinicalTrials.gov Identifier: NCT03817190
• Other Study ID Numbers: DS107G-05-AD3
• First Posted: Jan 25, 2019
• Last Update Posted: May 6, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema

Study Results

Participant Flow

Pre-assignment Detail	A total of 219 patients were randomised in a 1:1 ratio.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Period Title: Overall Study
STARTED	110	109
COMPLETED	50	50
NOT COMPLETED	60	59

Baseline Characteristics

Arm/Group Title	Placebo	DS107 2000mg	Total
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.	Total of all reporting groups
Overall Participants	110	109	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.95 (14.90)	38.83 (15.45)	38.38 (15.15)
Sex: Female, Male (Count of Participants)
Female	60 54.5%	55 50.5%	115 52.5%
Male	50 45.5%	54 49.5%	104 47.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 1.8%	2 1.8%	4 1.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	17 15.5%	18 16.5%	35 16%
White	90 81.8%	87 79.8%	177 80.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.9%	2 1.8%	3 1.4%
Body Surface Area Affected (Percentage of body surface area) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of body surface area]	35.95 (17.69)	35.67 (18.08)	35.81 (17.85)

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Achieving a Validated Investigator Global Assessment Scale for Atopic Dermatitis Score of 0 or 1 and a Decrease of at Least 2 Points in vIGA-ADTM in Treated Population Compared to Placebo Population From Baseline at Week 16.
Description	Proportion of patients achieving a Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points in vIGA-ADTM in treated population compared to placebo population from Baseline at Week 16 using GLMM.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Full analysis set - consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Number [Number of participants]	15 13.6%	14 12.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DS107 2000mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6880
	Comments
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Proportion of participants
	Estimated Value	-0.2277
	Confidence Interval	(2-Sided) 95%; -1.0415 to 0.5860
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Proportion of Patients Achieving EASI-75 in Treated Population Compared to Placebo Population at Week 16.
Description	Proportion of patients achieving EASI-75 (≥75% improvement from Baseline) in treated population compared to placebo population at Week 16 using GLMM.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Full analysis set - consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Number [participants]	30 27.3%	27 24.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DS107 2000mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4321
	Comments
	Method	GLMM
	Comments
Method of Estimation	Estimation Parameter	Proportion of participants
	Estimated Value	-0.2760
	Confidence Interval	(2-Sided) 95%; -0.9185 to 0.3665
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Patients Achieving a vIGA-ADTM Score of 0 or 1 and a Decrease of at Least 2 Points in vIGA-ADTM in Treated Population Compared to Placebo Population From Baseline to Week 4, 8, 12, 18 and 20.
Description	Proportion of patients achieving a vIGA-ADTM score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points in vIGA-ADTM in treated population compared to placebo population from Baseline to Week 4, 8, 12, 18 and 20 and the change in proportion of patients from Week 16 to Week 18 and 20.
Time Frame	Baseline, Week 4, Week 8, Week 12, Week 18 and Week 20.

Outcome Measure Data

Analysis Population Description

Full analysis set - consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Baseline to Week 4	3 2.7%	2 1.8%
Baseline to Week 8	6 5.5%	6 5.5%
Baseline to Week 12	10 9.1%	7 6.4%
Baseline to Week 18	13 11.8%	7 6.4%
Baseline to Week 20	10 9.1%	13 11.9%
Week 16 to Week 18	1 0.9%	1 0.9%
Week 16 to Week 20	2 1.8%	1 0.9%

4. Secondary Outcome

Title	Proportion of Patients Achieving EASI-75 in Treated Population Compared to Placebo Population at Weeks 4, 8, 12, 18 and 20.
Description	Proportion of patients achieving EASI-75 (≥75% improvement from Baseline) in treated population compared to placebo population at Weeks 4, 8, 12, 18 and 20.
Time Frame	Baseline, Week 4, Week 8, Week 12, Week 18 and Week 20.

Outcome Measure Data

Analysis Population Description

Full analysis set - consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Baseline to Week 4	8 7.3%	8 7.3%
Baseline to Week 8	15 13.6%	7 6.4%
Baseline to Week 12	19 17.3%	10 9.2%
Baseline to Week 18	21 19.1%	20 18.3%
Baseline to Week 20	23 20.9%	22 20.2%

5. Secondary Outcome

Title	Change From Baseline in Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) Score in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20.
Description	The Validated Global Investigator Assessment scale for Atopic DermatitisTM (vIGA-AD) 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 vIGA indicates a positive outcome for the participant.
Time Frame	20 Weeks

Outcome Measure Data

Analysis Population Description

FAS consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4 vs Baseline	0.7843	-0.0454
Week 8 vs Baseline	0.3487	0.2577
Week 12 vs Baseline	0.1224	0.3091
Week 16 vs Baseline	0.2813	0.1394
Week 18 vs Baseline	0.0862	0.1283
Week 18 vs Last Visit ( Week 20)	0.0689	0.1024

6. Secondary Outcome

Title	Change From Baseline in EASI in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20.
Description	Change from Baseline in Eczema Area and Severity Index (EASI) in treated population compared to placebo population to Weeks 4, 8, 12, 16, 18 and 20, and from Week 16 to Week 18 and 20. 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.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4 vs Basline	31.4509	3.5453
Week 8 vs Baseline	14.4747	8.8565
Week 12 vs Baseline	6.4487	10.4186
Week 16 vs Baseline	18.4269	3.5470
Week 18 vs Baseline	4.1677	3.1252
Week 18 vs Last Visit (Week 20)	2.6189	10.1487

7. Secondary Outcome

Title	Proportion of Patients Achieving a Decrease of at Least 4 Points in Worst Itch Numeric Rating Scale (NRS) in Treated Population Compared to Placebo Population From Baseline to Week 4, 8, 12, 16, 18 and 20.
Description	Proportion of patients achieving a decrease of at least 4 points in worst itch numeric rating scale in treated population compared to placebo population from Baseline to Week 4, 8, 12, 16, 18 and 20.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

FAS consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4	6 5.5%	11 10.1%
Week 8	12 10.9%	12 11%
Week 12	10 9.1%	13 11.9%
Week 16	13 11.8%	12 11%
Week 18	12 10.9%	12 11%
Week 20	11 10%	10 9.2%

8. Secondary Outcome

Title	Proportion of Patients Achieving a Decrease of at Least 3 Points in Worst Itch NRS in Treated Population Compared to Placebo Population From Baseline to Week 4, 8, 12, 16, 18 and 20.
Description	Proportion of patients achieving a decrease of at least 3 points in worst itch NRS in treated population compared to placebo population from Baseline to Week 4, 8, 12, 16, 18 and 20.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4	12 10.9%	19 17.4%
Week 8	18 16.4%	22 20.2%
Week 12	21 19.1%	21 19.3%
Week 16	20 18.2%	22 20.2%
Week 18	17 15.5%	16 14.7%
Week 20	16 14.5%	16 14.7%

9. Secondary Outcome

Title	Change From Baseline in Worst Itch NRS in Treated Population Compared to Placebo Population to Week 4, 8, 12, 16 and 18.
Description	Change from Baseline in worst itch Numeric Rating Scale (NRS) in treated population compared to placebo population to Week 4, 8, 12, 16 and 18. 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 will 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.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4 vs Baseline	1.9916	-0.5094
Week 8 vs Baseline	1.2897	-0.2826
Week 12 vs Baseline	0.8685	-0.2133
Week 16 vs Baseline	0.2244	0.0258
Week 18 vs Baseline	0.0905	0.1468

10. Secondary Outcome

Title	Proportion of Patients Achieving EASI-50 in Treated Population Compared to Placebo Population at Week 4, 8, 12, 16, 18 and 20.
Description	Proportion of patients achieving EASI-50 (≥50% improvement from Baseline) in treated population compared to placebo population at Week 4, 8, 12, 16, 18 and 20.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4	21 19.1%	15 13.8%
Week 8	31 28.2%	26 23.9%
Week 12	28 25.5%	23 21.1%
Week 16	44 40%	45 41.3%
Week 18	29 26.4%	35 32.1%
Week 20	29 26.4%	33 30.3%

11. Secondary Outcome

Title	Change From Baseline in the Body Surface Area Affected by AD in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20.
Description	Change from Baseline in the Body Surface Area (BSA) affected by AD in treated population compared to placebo population to Weeks 4, 8, 12, 16, 18 and 20, and from Week 16 to Week 18 and 20.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4 vs Baseline	10.5575	-1.1911
Week 8 vs Baseline	7.0087	-0.2839
Week 12 vs Baseline	4.8296	-1.4232
Week 16 vs Baseline	6.5413	0.9244
Week 18 vs Baseline	1.4568	1.1470
Week 18 vs Last Visit (Week 20)	1.0590	0.7666

12. Secondary Outcome

Title	Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20, and From Week 16 to Week 18 and 20.
Description	The SCORAD grading system was developed by the European Task Force on Atopic Dermatitis and has been a standard tool to assess atopic dermatitis (AD) severity in clinical studies. Six items (erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness) will be selected to evaluate the AD severity. The intensity of each item is graded using a 4-point scale: 0 = No symptoms 1 = Mild 2 = Moderate 3 = Severe The overall body surface area (BSA) affected by AD will be evaluated (from 0 to 100%) and included in the SCORAD scores. Loss of sleep and pruritus will be evaluated by patients on a visual analog scale (0-10). The SCORAD formula is A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The sum of these measures represents the SCORAD which can vary from 0 to 103. A decrease in SCORAD indicates a positive outcome for the participant.
Time Frame	20 Weeks

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all patients who were randomised to the study and received at least one dose of study medication. FAS was the primary analysis population for efficacy endpoints. Analysis was done according to the treatment patients were randomised to.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	102	99
Week 4 vs Baseline	15.7003	-0.9182
Week 8 vs Baseline	12.6334	-0.0799
Week 12 vs Baseline	4.0487	5.2956
Week 16 vs Baseline	7.3626	1.8419
Week 18 vs Baseline	1.8556	4.3232
Week 18 vs Last Visit (Week 20)	2.5318	2.2924

13. Secondary Outcome

Title	Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).
Description	Incidence of TEAEs and SAEs.
Time Frame	20 Weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis set consists of all patients who received at least one dose of the medication. SAS was the analysis population for all safety endpoints. Analysis was done according to the actual treatment patients received.

Arm/Group Title	Placebo	DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.	2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
Measure Participants	110	109
All AEs	58	62
Serious AEs	5	5
AEs with relationship to study medication	23	42
AEs leading to death	0	0
AEs that led to withdrawal	12	17

Adverse Events

Time Frame	Up to 20 weeks.
Adverse Event Reporting Description	An adverse event is any undesirable experience occurring to a patient that has signed the ICF and who has taken their first dose of the study drug, whether or not considered related to the investigational IMP(s). All Adverse Events (AEs) must be recorded in the CRF, defining relationship to IMP and severity. AEs should also be recorded by the Investigator in the patient file/notes.
Arm/Group Title	Placebo		DS107 2000mg
Arm/Group Description	Placebo (4 placebo capsules) orally administered once daily for 16 weeks.		2g DS107 (4 DS107 capsules) orally administered once daily for 16 weeks.
All Cause Mortality
	Placebo		DS107 2000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/110 (0%)		0/109 (0%)
Serious Adverse Events
	Placebo		DS107 2000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/110 (4.5%)		5/109 (4.6%)
Gastrointestinal disorders
Colitis Ulcerative	1/110 (0.9%)	1	0/109 (0%)	0
Immune system disorders
Hypersensitivity	0/110 (0%)	0	1/109 (0.9%)	1
Infections and infestations
Coronavirus Infection	1/110 (0.9%)	1	0/109 (0%)	0
Influenza	0/110 (0%)	0	1/109 (0.9%)	1
Staphylococcal Skin Infection	1/110 (0.9%)	1	0/109 (0%)	0
Investigations
Blood Creatine Phosphokinase Increased	0/110 (0%)	0	1/109 (0.9%)	1
Skin and subcutaneous tissue disorders
Dermatitis Atopic	2/110 (1.8%)	2	2/109 (1.8%)	2
Other (Not Including Serious) Adverse Events
	Placebo		DS107 2000mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/110 (48.2%)		57/109 (52.3%)
Blood and lymphatic system disorders
Anemia	1/110 (0.9%)		1/109 (0.9%)
Cardiac disorders
Ventricular extrasystoles	1/110 (0.9%)		0/109 (0%)
Eye disorders
Conjunctivitis allergic	2/110 (1.8%)		1/109 (0.9%)
Eczema Eyelids	1/110 (0.9%)		0/109 (0%)
Eye Pain	1/110 (0.9%)		0/109 (0%)
Macular Oedema	0/110 (0%)		1/109 (0.9%)
Gastrointestinal disorders
Diarrhoea	4/110 (3.6%)		21/109 (19.3%)
Nausea	2/110 (1.8%)		6/109 (5.5%)
Abdominal discomfort	0/110 (0%)		1/109 (0.9%)
Abdominal distension	0/110 (0%)		1/109 (0.9%)
Abdominal pain	1/110 (0.9%)		3/109 (2.8%)
Abdominal pain upper	1/110 (0.9%)		4/109 (3.7%)
Constipation	1/110 (0.9%)		1/109 (0.9%)
Dyspepsia	0/110 (0%)		1/109 (0.9%)
Faeces soft	1/110 (0.9%)		0/109 (0%)
Functional gastrointestinal disorder	1/110 (0.9%)		0/109 (0%)
Gastrointestinal disorder	1/110 (0.9%)		0/109 (0%)
Gastroesophageal reflux disorder	0/110 (0%)		1/109 (0.9%)
Haematochezia	1/110 (0.9%)		0/109 (0%)
Haemorrhoids thrombosed	0/110 (0%)		1/109 (0.9%)
Lip swelling	0/110 (0%)		1/109 (0.9%)
Toothache	0/110 (0%)		1/109 (0.9%)
Vomiting	1/110 (0.9%)		1/109 (0.9%)
General disorders
Chest Pain	1/110 (0.9%)		0/109 (0%)
Fatigue	0/110 (0%)		1/109 (0.9%)
Feeling abnormal	1/110 (0.9%)		0/109 (0%)
General physical health deterioration	0/110 (0%)		1/109 (0.9%)
Peripheral swelling	0/110 (0%)		1/109 (0.9%)
Pyrexia	0/110 (0%)		1/109 (0.9%)
Sluggishness	1/110 (0.9%)		0/109 (0%)
Immune system disorders
Hypersensitivity	2/110 (1.8%)		0/109 (0%)
Infections and infestations
Breast abscess	0/110 (0%)		1/109 (0.9%)
Bronchitis	0/110 (0%)		1/109 (0.9%)
Folliculitis	1/110 (0.9%)		1/109 (0.9%)
Gastroenteritis	1/110 (0.9%)		0/109 (0%)
Herpes simplex	0/110 (0%)		1/109 (0.9%)
Herpes virus infection	1/110 (0.9%)		0/109 (0%)
Hordeolum	0/110 (0%)		1/109 (0.9%)
Influenza	0/110 (0%)		1/109 (0.9%)
Nasal herpes	0/110 (0%)		1/109 (0.9%)
Nasopharyngitis	3/110 (2.7%)		3/109 (2.8%)
Oral herpes	0/110 (0%)		1/109 (0.9%)
Otitis media	1/110 (0.9%)		0/109 (0%)
Pharyngitis	1/110 (0.9%)		0/109 (0%)
Pulpitis dental	1/110 (0.9%)		0/109 (0%)
Pyoderma	1/110 (0.9%)		0/109 (0%)
Respiratory tract infection	0/110 (0%)		1/109 (0.9%)
Respiratory tract infection viral	1/110 (0.9%)		0/109 (0%)
Rhinitis	1/110 (0.9%)		1/109 (0.9%)
Skin infection	1/110 (0.9%)		0/109 (0%)
Superinfection bacterial	1/110 (0.9%)		0/109 (0%)
Upper respiratory tract infection	1/110 (0.9%)		0/109 (0%)
Injury, poisoning and procedural complications
Arthropod bite	1/110 (0.9%)		0/109 (0%)
Foot fracture	1/110 (0.9%)		0/109 (0%)
Heat stroke	1/110 (0.9%)		0/109 (0%)
Sunburn	1/110 (0.9%)		0/109 (0%)
Tooth injury	1/110 (0.9%)		0/109 (0%)
Investigations
Alanine aminotransferase increased	1/110 (0.9%)		0/109 (0%)
Aspartate aminotransferase increased	1/110 (0.9%)		1/109 (0.9%)
Blood creatine phosphokinase increased	1/110 (0.9%)		3/109 (2.8%)
Blood creatinine increased	0/110 (0%)		1/109 (0.9%)
Blood glucose increased	1/110 (0.9%)		0/109 (0%)
Blood pressure increased	0/110 (0%)		1/109 (0.9%)
Blood triglycerides increased	3/110 (2.7%)		1/109 (0.9%)
White blood cell count increased	1/110 (0.9%)		0/109 (0%)
Metabolism and nutrition disorders
Gout	0/110 (0%)		2/109 (1.8%)
Hypertriglyceridaemia	1/110 (0.9%)		0/109 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/110 (0%)		1/109 (0.9%)
Joint hyperextension	1/110 (0.9%)		0/109 (0%)
Muscle spasms	1/110 (0.9%)		0/109 (0%)
Pain in extremity	1/110 (0.9%)		0/109 (0%)
Nervous system disorders
Headache	10/110 (9.1%)		3/109 (2.8%)
Dizziness	0/110 (0%)		1/109 (0.9%)
Dysgeusia	0/110 (0%)		1/109 (0.9%)
Hypoesthesia	1/110 (0.9%)		0/109 (0%)
Psychiatric disorders
Emotional distress	0/110 (0%)		1/109 (0.9%)
Insomnia	1/110 (0.9%)		2/109 (1.8%)
Sleep disorder	2/110 (1.8%)		1/109 (0.9%)
Urinary tract inflammation	1/110 (0.9%)		0/109 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	3/110 (2.7%)		0/109 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/110 (0.9%)		1/109 (0.9%)
Cough	1/110 (0.9%)		2/109 (1.8%)
Rhinitis allergic	2/110 (1.8%)		2/109 (1.8%)
Throat tightness	1/110 (0.9%)		0/109 (0%)
Skin and subcutaneous tissue disorders
Dermatitis Atopic	26/110 (23.6%)		13/109 (11.9%)
Acne	0/110 (0%)		1/109 (0.9%)
Alopecia areata	1/110 (0.9%)		0/109 (0%)
Diffuse alopecia	2/110 (1.8%)		0/109 (0%)
Eczema	2/110 (1.8%)		1/109 (0.9%)
Erythrodermic atopic dermatitis	1/110 (0.9%)		0/109 (0%)
Intertrigo	0/110 (0%)		1/109 (0.9%)
Pruritus	2/110 (1.8%)		2/109 (1.8%)
Skin exfoliation	1/110 (0.9%)		0/109 (0%)
Skin ulcer	0/110 (0%)		1/109 (0.9%)
Solar dermatitis	0/110 (0%)		1/109 (0.9%)
Vascular disorders
Hypertension	0/110 (0%)		1/109 (0.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.