Efficacy and Safety of Delgocitinib Cream in Adults With Moderate to Severe Chronic Hand Eczema (DELTA 2)

Study Overview
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Brief Summary
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This is a 16-week study in adult participants with chronic hand eczema (CHE). The participants will visit the clinic regularly to have the study doctor assess their CHE and to answer questions about itch, pain, CHE symptoms, and quality of life. The purpose is to assess how delgocitinib cream works to treat CHE when compared to a placebo cream with no active substance.

Official Title
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A Phase 3 Clinical Trial to Confirm Efficacy and Evaluate Safety of Twice-daily Delgocitinib Cream 20 mg/g Compared With Cream Vehicle for a 16-week Treatment Period in Adult Subjects With Moderate to Severe Chronic Hand Eczema (DELTA 2)

Conditions
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Chronic Hand Eczema

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


Participation Criteria
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Eligibility Criteria
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Main 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 (i.e. an IGA-CHE score of 3 or 4). HESD itch score (weekly average) of ≥4 points at baseline. Participants who have a documented recent history of inadequate response to treatment with topical corticosteroids (TCS) or for whom TCS are documented to be otherwise medically inadvisable (e.g. due to important side effects or safety risks). Participants adherent to standard non-medicated skin care including avoidance of known and relevant irritants and allergens. Main exclusion criteria: Concurrent skin diseases on the hands, e.g. tinea manuum. Active atopic dermatitis requiring medical treatment in regions other than the hands and feet. Active psoriasis on any part of the body. Hyperkeratotic hand eczema in combination with a history of psoriasis on any part of the body. Clinically significant infection on the hands. Systemic treatment with immunosuppressive drugs, immunomodulating drugs, retinoids, or corticosteroids within 28 days prior to baseline. Use of tanning beds, phototherapy, or bleach baths on the hands within 28 days prior to baseline. Previous or current treatment with Janus kinase (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 transdermal or 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. Treatment with any marketed biological therapy or investigational biologic agents: Any cell-depleting agents: within 6 months prior to baseline, or until lymphocyte count returns to normal, whichever is longer. Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to baseline. Clinically significant infection within 28 days prior to baseline which, in the opinion of the investigator, may compromise the safety of the participant in the trial, interfere with evaluation of the IMP, or reduce the participant's ability to participate in the trial. History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the participant taking antiretroviral medications as determined by medical history and/or participant's verbal report. Any disorder which is not stable and could: Affect the safety of the participant throughout the trial. Impede the participant's ability to complete the trial. Positive hepatitis B surface antigen or hepatitis C virus antibody serology at screening.

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 20 mg/g<br>Twice-daily topical application for 16 weeks | Drug: Delgocitinib cream<br>* Cream for topical application<br>* Other names: LEO 124249 cream;|
| Placebo Comparator: Cream vehicle<br>Twice-daily topical application for 16 weeks | Drug: Cream vehicle<br>* The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IGA-CHE TS at Week 16 | The Investigator's Global Assessment for chronic hand eczema (IGA-CHE) is an instrument used in clinical trials to rate the severity of the participant's global chronic hand eczema (CHE) and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). IGA-CHE treatment success (IGA-CHE TS) is defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-step improvement from baseline. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 16 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. | 16 weeks | 
| Reduction of HESD score (weekly average) of ≥4 points from baseline at Week 16 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. The HESD score is derived as the average of the 6 signs and symptoms. This endpoint will be evaluated among participants with a baseline HESD score (weekly average) ≥4 points. | 16 weeks | 
| IGA-CHE TS at Week 8 | The Investigator's Global Assessment for chronic hand eczema (IGA-CHE) is an instrument used in clinical trials to rate the severity of the participant's global CHE and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). IGA-CHE treatment success (IGA-CHE TS) is defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-step improvement from baseline. | 8 weeks | 
| IGA-CHE TS at Week 4 | The Investigator's Global Assessment for chronic hand eczema (IGA-CHE) is an instrument used in clinical trials to rate the severity of the participant's global CHE and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). IGA-CHE treatment success (IGA-CHE TS) is defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-step improvement from baseline. | 4 weeks | 
| Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 8 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. | 8 weeks | 
| Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 4 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. | 4 weeks | 
| Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 2 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. | 2 weeks | 
| Reduction of HESD score (weekly average) of ≥4 points from baseline at Week 8 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. The HESD score is derived as the average of the 6 signs and symptoms. This endpoint will be evaluated among participants with a baseline HESD score (weekly average) ≥4 points. | 8 weeks | 
| Reduction of HESD score (weekly average) of ≥4 points from baseline at Week 4 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. The HESD score is derived as the average of the 6 signs and symptoms. This endpoint will be evaluated among participants with a baseline HESD score (weekly average) ≥4 points. | 4 weeks | 
| Reduction of HESD pain score (weekly average) of ≥4 points from baseline at Week 16 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'pain' component and will be evaluated among participants with a baseline HESD pain score (weekly average) ≥4 points. | 16 weeks | 
| Reduction of HESD pain score (weekly average) of ≥4 points from baseline at Week 8 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'pain' component and will be evaluated among participants with a baseline HESD pain score (weekly average) ≥4 points. | 8 weeks | 
| Reduction of HESD pain score (weekly average) of ≥4 points from baseline at Week 4 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'pain' component and will be evaluated among participants with a baseline HESD pain score (weekly average) ≥4 points. | 4 weeks | 
| HECSI-90 at Week 16 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score). HECSI-90 is defined as at least 90% improvement in HECSI score from baseline. | 16 weeks | 
| HECSI-75 at Week 16 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score). HECSI-75 is defined as at least 75% improvement in HECSI score from baseline. | 16 weeks | 
| HECSI-75 at Week 8 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score). HECSI-75 is defined as at least 75% improvement in HECSI score from baseline. | 8 weeks | 
| Percentage change in HECSI score from baseline to Week 16 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score). | 16 weeks | 
| Change in DLQI score from baseline to Week 16 | The Dermatology Life Quality Index (DLQI) 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. The DLQI score is the sum of the 10 items (score ranging from 0 to 30). | 16 weeks | 
| Change in HESD score (weekly average) from baseline to Week 16 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. The HESD score is derived as the average of the 6 signs and symptoms. | 16 weeks | 
| Change in HESD itch score (weekly average) from baseline to Week 16 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'itch' component. | 16 weeks | 
| Change in HESD pain score (weekly average) from baseline to Week 16 | The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'pain' component. | 16 weeks | 
| Change in HEIS score from baseline to Week 16 | The Hand Eczema Impact Scale (HEIS) addresses 9 items within the following domains: Proximal Daily Activity Limitations (PDAL), embarrassment with the appearance of the hands, frustration with CHE, sleep, work, and physical functioning. Each item is scored on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The HEIS score is the average of the 9 items. | 16 weeks | 
| Change in HEIS PDAL score from baseline to Week 16 | Proximal Daily Activity Limitations (PDAL) is one of the items addressed in the Hand Eczema Impact Scale (HEIS) and is scored on a 5-point scale ranging from 0 (not at all) to 4 (extremely). | 16 weeks | 
| Reduction of DLQI score of ≥4 points from baseline at Week 16 | The Dermatology Life Quality Index (DLQI) 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. The DLQI score is the sum of the 10 items (score ranging from 0 to 30). This endpoint will be evaluated among participants with a baseline DLQI score ≥4 points. | 16 weeks | 
| Number of treatment-emergent AEs from baseline up to end of trial per participant | An adverse event (AE) will be considered treatment emergent if started after the first application of investigational medicinal product (IMP), or if started before the first application of IMP and worsened in severity after first dose of IMP. End of trial is defined as Week 16 for participants who roll over to the long-term extension trial and as Week 18 for participants who do not roll over. | 16 weeks (18 weeks for participants not participating in the long-term extension trial [LP0133-1403]) |