NMF-CsA-Dupi Trial
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Topical corticosteroids (control) This group will receive topical corticosteroids. |
Drug: Topical corticosteroids
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.
|
| Active Comparator: Systemic cyclosporine This group will receive topical corticosteroids and systemic cyclosporin. |
Drug: Topical corticosteroids
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.
Drug: Systemic cyclosporine
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.
Other Names:
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| Active Comparator: Systemic dupilumab his group will receive topical corticosteroids and systemic dupilumab. |
Drug: Topical corticosteroids
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.
Drug: Systemic dupilumab
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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- EASI [t = 0, 1 month, 2 months, 3 months and 6 months]
Change from baseline Eczema Area and Severity Index (0-72) over the course of 6 months, with higher scores meaning worse outcomes.
Secondary Outcome Measures
- EASI75 [t = 1 month, 2 months, 3 months and 6 months]
Relative reduction of 75% from baseline EASI without the use of rescue medication
- IGA 0 or IGA 1 [t = 0, 1 month, 2 months, 3 months and 6 months]
Proportion of patients that achieved IGA 0 or IGA 1 (Investigator's Global Assessment) without the use of rescue medication.
- NRS-11 reduction for itch ≥ 4 points [t = 0, 1 month, 2 months, 3 months and 6 months]
Proportion of patients that achieved a reduction ≥4 points on the Numeric Rating Scale-11 (0-10) for itch intensity.
- POEM [t = 0, 1 month, 2 months, 3 months and 6 months]
Change from baseline in Patient-Oriented Eczema Measure questionnaire (0-28) over the course of 6 months, with higher scores meaning worse outcomes.
- SCORAD [t = 0, 1 month, 2 months, 3 months and 6 months]
Change from baseline in Scoring Atopic Dermatitis scale (0-103) over the course of 6 months, with higher scores meaning worse outcomes.
- RECAP [t = 0, 1 month, 2 months, 3 months and 6 months]
Change from baseline in the Recap of Atopic Eczema questionnaire (0-28) over the course of 6 months, with higher scores meaning worse outcomes.
Other Outcome Measures
- CDLQI ≥4 years [t = 0, 3 months and 6 months]
Children's Dermatology Life Quality Index, in the context of a cost-effectiveness analysis
- IDQoL <4 years [t = 0, 3 months and 6 months]
Infants' Dermatitis Quality of Life Index, in the context of a cost-effectiveness analysis
- Emollients and steroid use in frequency and tubes used [t = 0, 1 month, 2 months, 3 months, 4 months, 5 months and 6 months]
In context of a cost-effectiveness analysis: To assess the use of topical medication, including emollients, expressed in number of grams and/or used tubes, and changes therein during systemic treatment.
- Healthcare costs related to the treatment of AD [Over the course of 6 months]
In context of a cost-effectiveness analysis: To assess medical specialist care, hospitalization, medication, and other costs directly associated with the treatment and recurrence.
- Adverse events [Over the course of 6 months]
Adverse events related to therapy as reported at any time during treatment by patient, custodian or investigator.
- NMF measured via Raman spectroscopy [t = - 2 weeks, 0, 3 months and 6 months]
Natural Moisturizing Factor, to acquire more knowledge about external and internal factors that influence the NMF biomarker
- Microbiome profile [t = 0, 3 months and 6 months]
To investigate differences in microbiome profiles between patients with normal vs low NMF, and to investigate changes from baseline in microbiome profile during treatment, periodic swabs of nose, lesional skin, non-lesional skin and faeces will be obtained from patients.
- Humoral blood panel (systemic arms) [t = 0, 1 month, 3 months and 6 months]
Changes in IgE during systemic treatment over the course of 6 months.
- Humoral blood panel (topical arm) [t = 0 and 6 months]
Changes in IgE during topical treatment over the course of 6 months.
- Cellular blood panel (systemic arm) [t = 0, 1 month, 3 months and 6 months]
Changes in leucocyte differentiation during systemic treatment over the course of 6 months.
- FLG null mutations [t = 0]
Genotyping on skin barrier proteins, to acquire more knowledge about external and internal factors that influence atopic dermatitis and the NMF biomarker
- Activity of atopy [t = 0, 3 months and 6 months]
The activity of rhinoconjunctivitis, asthma and food allergy examined by a pediatric allergist and pediatric pulmonologist.
- Psychosocial factors (CBCL) [t = 0]
To investigate the influence of psychosocial factors in the patient on pediatric atopic dermatitis as assessed by the CBCL (Child Behaviour Checklist). Patients are assessed by questions grouped in empirically based syndrome scales: Aggressive Behavior, Anxious/Depressed, Attention Problems, Rule-Breaking Behavior, Somatic Complaints, Social Problems, Thought Problems, Withdrawn/Depressed. Higher percentile scores per scale indicate worse outcomes.
- Psychosocial factors (OBVL) [t = 0]
To investigate the influence of psychosocial factors in the family on pediatric atopic dermatitis as assessed by the OBVL (OpvoedingsBelastingVragenLijst / Parenting Stress Questionnaire), with higher percentile scores indicating worse outcomes
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Children and adolescents, aged 2-18 years, with moderate-to-severe atopic dermatitis (diagnosed according to the UK working party criteria)
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Patient and parents/guardians able to participate in the study and willing to give written informed consent
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EASI (Eczema Area Severity Index) ≥ 6 at screening and baseline (corresponding with moderate-to-severe disease)
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IGA (Investigator Global Assessment) ≥ 3 at screening and baseline (corresponding with moderate-to-severe disease)
Exclusion Criteria:
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Children under the age of 2 years and patients older than 18 years
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Contraindication for ciclosporin
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Contraindication for dupilumab
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Patient (or one of the parents/guardians) not willing to be randomized
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Children with a history of any known primary immunodeficiency disorder
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Children with a history of cancer
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EASI < 6 at screening or baseline
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IGA < 3 at screening or baseline
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Erasmus MC - Sophia Children's Hospital | Rotterdam | Zuid-Holland | Netherlands |
Sponsors and Collaborators
- Erasmus Medical Center
- ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MEC-2019-0568
- 2019-003247-30