Dose-ranging Trial to Evaluate Delgocitinib Cream 1, 3, 8, and 20 mg/g Compared to Delgocitinib Cream Vehicle Over an 8-week Treatment Period in Adult Subjects With Atopic Dermatitis.

Study Overview
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Brief Summary
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This is a double-blind, multi-centre, randomised, 5-arm, vehicle-controlled, parallel-group trial. The trial is designed to establish a dose-response signal and investigate the efficacy and safety of delgocitinib cream in the treatment of adult subjects with mild to severe atopic dermatitis (AD).

Official Title
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A Phase 2b, Double-blind, Randomised, 5-arm, Vehicle-controlled, Dose Ranging Trial to Evaluate the Efficacy and Safety of Twice Daily Topical Applications of Delgocitinib Cream 1, 3, 8, 20 mg/g for 8 Weeks in Adult Subjects With Mild to Severe Atopic Dermatitis.

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Delgocitinib cream
* Drug: Delgocitinib cream vehicle


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age 18 years and above. Diagnosis of AD as defined by the Hanifin and Rajka 1980 criteria for AD. History of AD for ≥1 year. AD involvement of 5-50% treatable body surface area at screening and at baseline (excluding scalp). Disease severity graded as mild to severe according to vIGA-AD (i.e. vIGA-AD ≥2) at screening and baseline. Key Exclusion Criteria: AD lesion(s) on scalp at screening and/or baseline. Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, rosacea, urticaria, or psoriasis. Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD. Use of tanning beds or phototherapy within 4 weeks prior to baseline. Systemic treatment with immunosuppressive/modulating drugs or corticosteroids within 4 weeks prior to baseline or 3 or more bleach baths any week within 4 weeks prior to baseline. Treatment with topical corticosteroids, topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors, or oral antibiotics within 2 weeks prior to baseline. Change in systemic antihistamine therapy within 2 weeks prior to baseline i.e. the subjects must not start antihistamine treatment or change the current dosage regime within 2 weeks prior to baseline. Receipt of live attenuated vaccines within 4 weeks prior to baseline. Treatment with any marketed or investigational biologic agents within 6 months or 5 half-lives prior to baseline, or until cell counts return to normal, whichever is longer. History of any active skin infection within 1 week prior to baseline. Clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to baseline.

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 |
| --- | --- |
| Experimental: Delgocitinib cream 1 mg/g<br>Delgocitinib cream applied twice daily for 8 weeks | Drug: Delgocitinib cream<br>* Cream for topical application<br>* Other names: LEO 124249 cream;|
| Experimental: Delgocitinib cream 3 mg/g<br>Delgocitinib cream applied twice daily for 8 weeks | Drug: Delgocitinib cream<br>* Cream for topical application<br>* Other names: LEO 124249 cream;|
| Experimental: Delgocitinib cream 8 mg/g<br>Delgocitinib cream applied twice daily for 8 weeks | Drug: Delgocitinib cream<br>* Cream for topical application<br>* Other names: LEO 124249 cream;|
| Experimental: Delgocitinib cream 20 mg/g<br>Delgocitinib cream applied twice daily for 8 weeks | Drug: Delgocitinib cream<br>* Cream for topical application<br>* Other names: LEO 124249 cream;|
| Placebo Comparator: Delgocitinib cream vehicle<br>Delgocitinib cream vehicle applied twice daily for 8 weeks | Drug: Delgocitinib cream vehicle<br>* The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.<br>* Other names: LEO 124249 cream vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score. | EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe or more extensive condition. The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose selection. Mixed Model for Repeated Measurements (MMRM) analysis was used to determine the difference in the continuous endpoint between the active delgocitinib doses and delgocitinib cream vehicle. | Week 0 to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8. | vIGA-AD is an instrument used in clinical trials to assess the subject's global disease severity and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose-selection. Cochran-Mantel-Haenszel analysis was used to determine the difference in response rates between the active delgocitinib cream doses and the delgocitinib cream vehicle. | Week 0 to Week 8 | 
| EASI75 at Week 8 | EASI75 is defined as at least 75% reduction in EASI from baseline. | Week 0 to Week 8 | 
| Time to vIGA-AD TS | The time to vIGA-AD TS response is defined as the time from baseline to first assessment of a vIGA-AD score of 0 (Clear) or 1 (Almost Clear) with ≥2-step improvement | Week 0 to Week 8 |