Efficacy and Safety of Delgocitinib Cream in Adolescents 12-17 Years of Age With Moderate to Severe Chronic Hand Eczema

Study Overview
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Brief Summary
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The purpose of this trial is to test if delgocitinib cream is effective at treating chronic hand eczema (CHE) and what side effects it may have, in children aged 12-17. There will be a range of assessments that rate the severity and extent of CHE symptoms, general health and quality of life. Delgocitinib is a cream that suppresses specific processes in the body's response to diseases like CHE, such as inflammation. The trial will last up to 22 weeks and has a 1-4 week screening period, a 16 week treatment period and a 2 week follow up period. During the treatment period each child will use either delgocitinib cream or a cream vehicle twice a day. Which cream each child receives is chosen randomly by a computer. The cream vehicle is made of the same ingredients as the delgocitinib cream except for the active medical ingredient. There will be 8 visits with the trial doctor.

Official Title
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A Phase 3 Clinical Trial to Evaluate Efficacy and Safety of Twice-daily Applications of Delgocitinib Cream 20 mg/g Compared With Cream Vehicle for a 16-week Treatment Period in Adolescents 12-17 Years of Age With Moderate to Severe Chronic Hand Eczema

Conditions
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Chronic Hand Eczema

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CHE, defined as hand eczema that has persisted for more than 3 months or returned twice or more within the last 12 months. Disease severity graded as moderate to severe at screening and baseline according to IGA-CHE. Subjects who have a documented history of inadequate response to treatment with TCS or for whom TCS are documented to be otherwise medically inadvisable. Exclusion Criteria: Concurrent skin disease on the hands. Clinically significant infection on the hands. Systemic treatment with immunosuppressive drugs, immunomodulating drugs, retinoids, or corticosteroids within 28 days prior to baseline (steroid eyedrops and inhaled or intranasal steroids corresponding to up to 1 mg prednisolone for allergic conjunctivitis, asthma, or rhinitis are allowed). Use of tanning beds, phototherapy, or bleach baths on the hands within 28 days prior to baseline. Previous or current treatment with JAK inhibitors (including delgocitinib/LEO 124249), systemic or topical. Cutaneously applied treatment with immunomodulators or TCS on the hands within 14 days prior to baseline. Use of systemic antibiotics or cutaneously applied antibiotics on the hands within 14 days prior to baseline. Other cutaneously applied therapy on the hands (except for the use of subject's own emollients) within 7 days 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 7 days prior to baseline. Any disorder which is not stable and could: Affect the safety of the subject throughout the trial. Impede the subject's ability to complete the trial.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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<br>Delgocitinib cream 20 mg/g twice daily | Drug: Delgocitinib<br>* Cream for topical application<br>|
| Placebo Comparator: Cream vehicle<br>Cream vehicle twice daily | Drug: Cream vehicle<br>* The cream vehicle is similar to the delgocitinib cream except that it does not contain any active medical ingredient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IGA-CHE treatment success at Week 16 | The Investigator's Global Assessment for chronic hand eczema© (IGA-CHE) is a 5 point scale used in clinical trials to rate the severity of the subject's CHE from 0 (clear) to 4 (severe). Treatment success means a score of 0 (clear) or 1 (almost clear) with a ≥2 step improvement from baseline. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HECSI-90 at Week 16 | The Hand Eczema Severity Index (HECSI) is a scoring system to rate the severity of hand eczema. It gives a score from 0 (none) to 3 (severe) to 6 clinical signs of hand eczema: erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema over 5 regions of the hand - fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists. Each region is then assigned an area score from 0 (0%) to 4 (>75%) depending on how much is covered by lesions. For each region a region score is calculated by adding up the severity scores for the 6 clinical signs and multiplying with the area score. The HESCI score equals the sum of the 5 region scores and ranges from 0 to 360. HECSI-90 is at least 90% improvement in HECSI score from baseline | Week 16 | 
| Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 16 | The Hand Eczema Symptom Diary© (HESD) is an eDiary which patients use everyday to score the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours from 0 (none) to 10 (severe). This endpoint will only assess the 'itch' component for participants with a baseline HESD itch score (weekly average) of ≥4 points. | Week 16 | 
| Reduction of HESD pain score (weekly average) of ≥4 points from baseline at Week 16 | The Hand Eczema Symptom Diary© (HESD) is an eDiary which patients use everyday to score the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours from 0 (none) to 10 (severe). This endpoint will only assess the 'pain' component for participants with a baseline HESD pain score (weekly average) of ≥4 points. | Week 16 | 
| Reduction of HESD score (weekly average) of ≥4 points from baseline at Week 16 | The Hand Eczema Symptom Diary© (HESD) is an eDiary which patients use everyday to score the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours from 0 (none) to 10 (severe). The final HESD score is an average of these 6 individual scores. This endpoint will only assess the score for participants with a baseline HESD itch score (weekly average) of ≥4 points. | Week 16 | 
| IGA-CHE treatment success at Week 2 | The Investigator's Global Assessment for chronic hand eczema© (IGA-CHE) is a 5 point scale used in clinical trials to rate the severity of the subject's CHE from 0 (clear) to 4 (severe). Treatment success means a score of 0 (clear) or 1 (almost clear) with a ≥2 step improvement from baseline. | Week 2 | 
| IGA-CHE treatment success at Week 4 | The Investigator's Global Assessment for chronic hand eczema© (IGA-CHE) is a 5 point scale used in clinical trials to rate the severity of the subject's CHE from 0 (clear) to 4 (severe). Treatment success means a score of 0 (clear) or 1 (almost clear) with a ≥2 step improvement from baseline. | Week 4 | 
| IGA-CHE treatment success at Week 8 | The Investigator's Global Assessment for chronic hand eczema© (IGA-CHE) is a 5 point scale used in clinical trials to rate the severity of the subject's CHE from 0 (clear) to 4 (severe). Treatment success means a score of 0 (clear) or 1 (almost clear) with a ≥2 step improvement from baseline. | Week 8 | 
| IGA-CHE treatment success at Week 12 | The Investigator's Global Assessment for chronic hand eczema© (IGA-CHE) is a 5 point scale used in clinical trials to rate the severity of the subject's CHE from 0 (clear) to 4 (severe). Treatment success means a score of 0 (clear) or 1 (almost clear) with a ≥2 step improvement from baseline. | Week 12 | 
| Change in cDLQI score from baseline to Week 16 | The children's Dermatology Life Quality Index (cDLQI) is a validated questionnaire consisting of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week. Each question is scored from 0 (no impact) to 3 (high impact). The cDLQI score is the sum of the 10 items (score ranging from 0 to 30). | Week 16 | 
| Number of treatment emergent AEs from baseline up to Week 18 | An adverse event (AE) will be considered treatment emergent if started after the first application of treatment, or started before the first application of treatment and worsened in severity after treatment. | Week 18 |