Clinical trial NCT03817190: Efficacy and Safety of Orally Administered DS107 in Adult Patients With Moderate to Severe Atopic Dermatitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: DS Biopharma
Sponsor class: INDUSTRY
First posted: 2019-01-25
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 220 subjects.

Detailed description: 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.

Primary outcomes:
measure: 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.
timeFrame: 16 Weeks
measure: Proportion of Patients Achieving EASI-75 in Treated Population Compared to Placebo Population at Week 16.
timeFrame: 16 Weeks
Secondary outcomes:
measure: 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.
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 18 and Week 20.
measure: 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
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 18 and Week 20.
measure: 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.
timeFrame: 20 Weeks
measure: Change From Baseline in EASI in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18 and 20.
timeFrame: Week 20
measure: Change From Baseline in Worst Itch NRS in Treated Population Compared to Placebo Population to Week 4, 8, 12, 16, 18.
timeFrame: Week 18
measure: 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.
timeFrame: Week 20
measure: Proportion of Patients Achieving a Decrease of at Least 4 Points in Worst Itch NRS in Treated Population Compared to Placebo Population From Baseline to Week 4, 8, 12, 16, 18 and 20,
timeFrame: Week 20
measure: 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.
timeFrame: Week 20
measure: 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.
timeFrame: Week 18
measure: Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score in Treated Population Compared to Placebo Population to Weeks 4, 8, 12, 16, 18.
timeFrame: 18 Weeks
measure: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).
timeFrame: 20 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: DS Investigational Site 524
state: Alabama
city: Huntington Beach
country: United States
facility: DS Investigational Site 528
state: California
city: Los Angeles
country: United States
facility: DS Investigational Site 502
state: California
city: San Diego
country: United States
facility: DS Investigational Site 504
state: California
city: San Diego
country: United States
facility: DS Investigational Site 505
state: California
city: Santa Ana
country: United States
facility: DS Investigational Site 516
state: California
city: Santa Monica
country: United States
facility: DS Investigational Site 501
state: California
city: Washington
country: United States
facility: DS Investigational Site 517
state: District of Columbia
city: Doral
country: United States
facility: DS Investigational Site 527
state: Florida
city: Sunrise
country: United States
facility: DS Investigational Site 510
state: Florida
city: Columbus
country: United States
facility: DS Investigational Site 512
state: Georgia
city: Skokie
country: United States
facility: DS Investigational Site 514
state: Illinois
city: Louisville
country: United States
facility: DS Investigational Site 513
state: Kentucky
city: Troy
country: United States
facility: DS Investigational Site 519
state: Michigan
city: Raleigh
country: United States
facility: DS Investigational Site 511
state: North Carolina
city: Grants Pass
country: United States
facility: DS Investigational Site 526
state: Oregon
city: Medford
country: United States
facility: DS Investigational Site 521
state: Oregon
city: Philadelphia
country: United States
facility: DS Investigational Site 525
state: Pennsylvania
city: Arlington
country: United States
facility: DS Investigational Site 509
state: Texas
city: Austin
country: United States
facility: DS Investigational Site 506
state: Texas
city: Cypress
country: United States
facility: DS Investigational Site 508
state: Texas
city: San Antonio
country: United States
facility: DS Investigational Site 507
state: Texas
city: Orem
country: United States
facility: DS Investigative Site 529
state: Utah
city: Salt Lake City
country: United States
facility: DS Investigative Site 530
state: Utah
city: Richmond
country: United States
facility: DS Investigational Site 523
state: Virginia
city: Kenosha
country: United States
facility: DS Investigational Site 518
state: Wisconsin
city: Graz
country: Austria
facility: DS Investigational Site 101
city: Augsburg
country: Germany
facility: DS Investigational Site 203
city: Berlin
country: Germany
facility: DS Investigational Site 202
city: Berlin
country: Germany
facility: DS Investigational Site 208
city: Dresden
country: Germany
facility: DS Investigational Site 204
city: Essen
country: Germany
facility: DS Investigational Site 206
city: Frankfurt
country: Germany
facility: DS Investigational Site 201
city: Gera
country: Germany
facility: DS Investigational Site 207
city: Leipzig
country: Germany
facility: DS Investigational Site 211
city: Luebeck
country: Germany
facility: DS Investigational Site 205
city: Mainz
country: Germany
facility: DS Investigational Site 210
city: Münster
country: Germany
facility: DS Investigational Site 214
city: Rostock
country: Germany
facility: DS Investigational Site 212
city: Jūrmala
country: Latvia
facility: DS Investigational Site 304
city: Riga
country: Latvia
facility: DS Investigational Site 301
city: Riga
country: Latvia
facility: DS Investigational Site 302
city: Riga
country: Latvia
facility: DS Investigational Site 303
city: Riga
country: Latvia
facility: DS Investigational Site 305
city: Gdańsk
country: Poland
facility: DS Investigational Site 406
city: Poznań
country: Poland
facility: DS Investigational Site 403
city: Warsaw
country: Poland
facility: DS Investigational Site 405
city: Warsaw
country: Poland
facility: DS Investigational Site 407
city: Wrocław
country: Poland
facility: DS Investigational Site 401
city: Łódź
country: Poland
facility: DS Investigational Site 402
Study officials:
affiliation: DS Biopharma
name: Markus Weissbach, MD
role: STUDY_CHAIR
References: