E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Atopic Dermatitis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy Objective: - To compare the efficacy of orally administered DS107 (2g) versus placebo, in the treatment of adult patients with moderate to severe AD. Safety Objective: - To assess the safety of orally administered DS107 (2g) versus placebo, in adult patients with moderate to severe AD. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with a clinically confirmed diagnosis of active AD according to the American Academy of Dermatology Consensus Criteria that has been present for at least 6 months before the screening visit. 2. Patients with moderate to severe AD at baseline as defined by a vIGA-ADTM score of 3 or 4 at baseline. 3. Patients with an 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 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 do not interfere with their participation in the study, in the opinion of the Investigator. 7. Patients who are able and willing to stop all current treatments for AD throughout the study (except for allowed emollients). 8. Patients who are on a stable dose of a bland emollient for at least 7 days prior to baseline. Note: Patients who have been on a stable emollient with an active ingredient (for example urea, ceramide and hyaluronic acid) for at least 12 weeks prior to screening and are otherwise eligible may continue using their pre-existing emollients, if deemed appropriate by the investigator and if they are willing and able to continue using the same stable emollient for the duration of the study. 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 must use highly effective birth control methods or have a sterilised partner for the duration of the study. Note: - Highly effective birth control methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include systemic hormonal contraceptives, intrauterine device or sexual abstinence. - Hormonal contraceptives must be on a stable dose for at least one month before baseline. - Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. 11. Recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks). Note: - Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to vIGA-ADTM 0=clear to 2=mild) despite treatment with a daily regimen of Topical corticosteroids (TCS) of medium to higher potency (± Topical calcineurin inhibitors (TCI) as appropriate), applied for at least 28 days or for the maximum duration recommended by the product prescribing information (e.g., 14 days for super-potent TCS), whichever is shorter. - Patients with documented systemic treatment for AD (for example systemic corticosteroids, cyclosporin) in the past 6 months are also considered as inadequate responders to topical treatments and are potentially eligible for treatment with DS107 after appropriate washout. - Important side effects or safety risks are those that outweigh the potential treatment benefits and include intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects, as assessed by the Investigator or by the patient’s treating physician. 12. Patients who are 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. |
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E.4 | Principal 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 skin infections) as assessed by the Investigator. 2. Patients who have 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 are allowed. 3. Patient with previous exposure to DS107. 4. Patients who have 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 use 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 are 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 have a history of hypersensitivity to any substance in DS107 capsules or placebo capsules. 8. Patients who have a history of hypersensitivity to soy beans or soy lecithin. 9. Patients who have a white cell count or differential white cell count outside of the normal reference range at screening. Note: For patients with a mild leucocytosis or leucopenia and otherwise a normal white cell blood count may be enrolled following consultation with the medical monitor by the investigator. 10. 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 interpretation of study results. 11. Patients who have 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 floride arthritis or any other illness that, in the opinion of the Investigator, is likely to interfere with completion of the study. 13. Patients with active infectious disease (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 have 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: a. Any cell-depleting agents including but not limited to rituximab: within 6 months before the screening visit, or until lymphocyte count returns to normal, whichever is 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 is longer 17. Patients who are pregnant, planning pregnancy, breastfeeding and/or are 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- 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 at Week 16. - Proportion of patients achieving EASI-75 (≥75% improvement from baseline) in treated population compared to placebo population at Week 16.
Note: Each of the independent primary endpoints will be assessed separately. Success in either of the primary endpoints denotes treatment success. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline at Week 16. |
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E.5.2 | Secondary end point(s) |
- 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. - 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 and the change in proportion of patients from Week 16 to Week 18 and 20. - Change from baseline in 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. - 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. - 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 and the change in proportion of patients from Week 16 to Week 18 and 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 and the change in proportion of patients from Week 16 to Week 18 and 20. - Change from baseline in worst itch NRS in treated population compared to placebo population to Week 4, 8, 12, 16, 18 and 20 and from Week 16 to Week 18 and 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 and the change in proportion of patients from Week 16 to Week 18 and 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. - 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. - Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs).
Exploratory Endpoints - Proportion of patients achieving a decrease of at least 2 points in vIGA-ADTM in treated population compared to placebo population from baseline to Week 4, 8, 12, 16, 18 and 20 and the change in proportion of patients from Week 16 to Week 18 and 20. - Change from baseline in the Dermatology Life Quality Index (DLQI) 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. - Change from baseline in the Patient Orientated Eczema Measure (POEM) 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. - Change in sleep quality assessment (Athens Insomnia Scale) in treated population compared to placebo population from baseline to Week 4, 8, 12, 16, 18 and 20 and from Week 16 to Week 18 and 20. - Change from baseline in the Patient-Oriented SCORAD (PO-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. - Trough plasma levels in treated population compared to placebo population at Baseline/Day 0, Week 4, Week 8 and Week 16. - Determination of AD biomarkers in treated population compared to placebo population at Baseline/Day 0 and Week 16. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, Week 4, 8, 12, 16, 18, 20 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Germany |
Latvia |
Poland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of Trial is defined as Last Subject Last Visit (LSLV). LSLV is defined as the date the Investigator reviews the last subject’s safety data and determines that no further evaluation is required for the subject to complete the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 12 |