Phase 2b Dose-ranging Trial to Evaluate Delgocitinib Cream 1, 3, 8, and 20 mg/g Compared to Delgocitinib Cream Vehicle Over a 16-week Treatment Period in Adult Subjects With Chronic Hand Eczema

Study Overview
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Brief Summary
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The purpose of this research trial was to test different strengths of a new trial medication, delgocitinib cream 1, 3, 8, and 20 mg/g, and to investigate how treatment with delgocitinib cream affects chronic hand eczema. This was judged by a range of assessments that rate the severity and extent of chronic hand eczema and its symptoms, as well as general health status and quality of life.

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 Application of Delgocitinib Cream 1, 3, 8, and 20 mg/g for 16 Weeks in Adult Subjects With Mild to Severe Chronic Hand Eczema

Conditions
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Chronic Hand Eczema

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 or above. Diagnosis of chronic hand eczema defined as hand eczema, which has persisted for more than 3 months or returned twice or more within the last 12 months. Disease severity graded as mild to severe according to IGA (i.e., IGA ≥2). Recent history (within 1 year before the screening visit) of inadequate response to topical corticosteroid treatment or topical corticosteroid treatment being medically inadvisable. Diagnostic patch testing performed within 3 years prior to the screening visit. Key Exclusion Criteria: Concurrent skin diseases on the hands e.g tinnea manuum. Active atopic dermatitis in regions other than the hands or psoriasis requiring medical treatment. Clinically significant infection (e.g., impetiginised hand eczema) on the hands. Systemic treatment with immunosuppressive drugs, immunomodulating drugs, retinoids, or corticosteroids within 4 weeks prior to baseline. Psoralen ultraviolet A (PUVA) or ultraviolet B (UVB) therapy on the hands within 4 weeks prior to baseline. Receipt of live attenuated vaccines 4 weeks prior to baseline. Cutaneously applied treatment with immunomodulators (e.g., phosphodiesterase-4 (PDE-4) inhibitors, pimecrolimus, tacrolimus) or topical corticosteroids on the hands within 2 weeks prior to baseline. Use of systemic antibiotics or cutaneously applied antibiotics on the hands within 2 weeks prior to baseline. Change in systemic antihistamine therapy within 2 weeks prior to baseline i.e., subjects must not start antihistamine treatment or change the current dosage regime within 2 weeks prior to baseline. Other cutaneously applied therapy on the hands (except for the use of subject's own emollients) within 1 week prior to baseline. Cutaneously applied treatments in regions other than the hands, which could interfere with clinical trial evaluations or pose a safety concern within 1 week prior to baseline. Receipt of any marketed or investigational biologic agents within 6 months or 5 half-lives prior to baseline or until cells count returns to normal, whichever is longer. Clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to baseline. Tuberculosis requiring treatment within 12 months prior to screening and/or subjects with a positive blood test for tuberculosis at screening. History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications. Any disorder which is not stable and in the investigator's opinion could affect the safety of the subject, influence the findings of the trial, or impede the subject's ability to complete the trial. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (anti-HCV) serology at screening. Subjects with positive HBsAb may be randomised provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb.

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 16 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 16 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 16 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 16 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 16 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 |
| --- | --- | --- |
| Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) Score of 0 (Clear) or 1 (Almost Clear) With at Least a 2-step Improvement (IGA-CHE Treatment Success) From Baseline to Week 16. | IGA-CHE is an instrument used in clinical trials to rate the severity of subject's global disease stage 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 delgocitinib cream vehicle. | Week 0 to Week 16. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hand Eczema Severity Index (HECSI) From Baseline to Week 16. | HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). The lowest HECSI score is 0 and the highest possible is 360. A higher HECSI score is indicating more severe hand eczema. The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose selection. A mixed model for repeated measurements (MMRM) analysis was used to determine the difference in the continuous endpoint between the active delgocitinib cream doses and delgocitinib cream vehicle. | Week 0 to Week 16. | 
| Time to IGA-CHE Treatment Success. | Time to IGA-CHE treatment success response is defined as the time from baseline to first assessment of an IGA-CHE score of 0 (clear) or 1 (almost clear) with at least a 2-step improvement. | Week 0 to Week 16. |