NMF-CsA-Dupi Trial

Study Overview
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Brief Summary
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The goal of this study is to investigate whether stratification of children with atopic dermatitis on the NMF biomarkers results in an improvement of effectiveness and efficiency in the use of systemic treatment (ciclosporin and dupilumab) in moderate-to-severe atopic dermatitis.

Official Title
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Use of the NMF Biomarker as Predictive Diagnostic for Effective Use of Cyclosporine and Dupilumab in the Treatment of Atopic Dermatitis

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: Topical corticosteroids
* Drug: Systemic cyclosporine
* Drug: Systemic dupilumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children and adolescents, aged 2-18 years, with moderate-to-severe atopic dermatitis (diagnosed according to the UK working party criteria) Patient and parents/guardians able to participate in the study and willing to give written informed consent EASI (Eczema Area Severity Index) ≥ 6 at screening and baseline (corresponding with moderate-to-severe disease) IGA (Investigator Global Assessment) ≥ 3 at screening and baseline (corresponding with moderate-to-severe disease) Exclusion Criteria: Children under the age of 2 years and patients older than 18 years Contraindication for ciclosporin Contraindication for dupilumab Patient (or one of the parents/guardians) not willing to be randomized Children with a history of any known primary immunodeficiency disorder Children with a history of cancer EASI < 6 at screening or baseline IGA < 3 at screening or baseline

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum 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
Interventional Model Description: This is a partially-blinded randomized controlled trial that investigates if NMF-biomarker status has an effect on the effectiveness of systemic treatment with CsA in children with moderate-to-severe AD. It also investigates whether stratification on the NMF biomarker results in an improvement of efficiency in the use of systemic treatment with CsA in the treatment of moderate-to-severe AD.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Topical corticosteroids (control)<br>This group will receive topical corticosteroids. | Drug: Topical corticosteroids<br>* Topical corticosteroids (TCS) are registered for patients of all ages, and are together with emollients, the pillars in the basic treatment of atopic dermatitis. In this study, patients in both the intervention groups and control group are treated with daily emollients and a TCS of moderate to high potency if needed. Rescue medication with TCS of higher potency may be prescribed if basic therapy is inadequate in controlling AD symptoms.<br>|
| Active Comparator: Systemic cyclosporine<br>This group will receive topical corticosteroids and systemic cyclosporin. | Drug: Topical corticosteroids<br>* Topical corticosteroids (TCS) are registered for patients of all ages, and are together with emollients, the pillars in the basic treatment of atopic dermatitis. In this study, patients in both the intervention groups and control group are treated with daily emollients and a TCS of moderate to high potency if needed. Rescue medication with TCS of higher potency may be prescribed if basic therapy is inadequate in controlling AD symptoms.<br>Drug: Systemic cyclosporine<br>* Systemic cyclosporine A (CsA) is an immunosuppressive therapy and is a registered treatment for AD in adults. According to national guidelines, CsA is the first choice for systemic treatment in children with moderate-to-severe AD. For CsA a starting dose of 4-5mg/kg/day is administered orally and then tapered down to 2-3mg/kg/day depending on clinical effect. Two doses will be taken at two fixed times per day. Treatment with systemic CsA will be continued for a total of 6 months.<br>* Other names: Neoral;|
| Active Comparator: Systemic dupilumab<br>his group will receive topical corticosteroids and systemic dupilumab. | Drug: Topical corticosteroids<br>* Topical corticosteroids (TCS) are registered for patients of all ages, and are together with emollients, the pillars in the basic treatment of atopic dermatitis. In this study, patients in both the intervention groups and control group are treated with daily emollients and a TCS of moderate to high potency if needed. Rescue medication with TCS of higher potency may be prescribed if basic therapy is inadequate in controlling AD symptoms.<br>Drug: Systemic dupilumab<br>* Dupilumab (DUPIXENT) is indicated for the treatment of children of 6 years and older with moderate-to-sever atopic dermatitis whos disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids. rm: Active Comparator: Systemic dupilumab Dupilumab (DUPIXENT) is administered as a solution by subdermal injection according to national guidelines, based on age and body weight.<br>* Other names: DUPIXENT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EASI | Change from baseline Eczema Area and Severity Index (0-72) over the course of 6 months, with higher scores meaning worse outcomes. | t = 0, 1 month, 2 months, 3 months and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EASI75 | Relative reduction of 75% from baseline EASI without the use of rescue medication | t = 1 month, 2 months, 3 months and 6 months | 
| IGA 0 or IGA 1 | Proportion of patients that achieved IGA 0 or IGA 1 (Investigator's Global Assessment) without the use of rescue medication. | t = 0, 1 month, 2 months, 3 months and 6 months | 
| NRS-11 reduction for itch ≥ 4 points | Proportion of patients that achieved a reduction ≥4 points on the Numeric Rating Scale-11 (0-10) for itch intensity. | t = 0, 1 month, 2 months, 3 months and 6 months | 
| POEM | Change from baseline in Patient-Oriented Eczema Measure questionnaire (0-28) over the course of 6 months, with higher scores meaning worse outcomes. | t = 0, 1 month, 2 months, 3 months and 6 months | 
| SCORAD | Change from baseline in Scoring Atopic Dermatitis scale (0-103) over the course of 6 months, with higher scores meaning worse outcomes. | t = 0, 1 month, 2 months, 3 months and 6 months | 
| RECAP | Change from baseline in the Recap of Atopic Eczema questionnaire (0-28) over the course of 6 months, with higher scores meaning worse outcomes. | t = 0, 1 month, 2 months, 3 months and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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natural moisturizing factor, systemic treatment