Back to resultsNMF-CsA-Dupi Trial
Primary Purpose
Dermatitis, Atopic
Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Topical corticosteroids
Systemic cyclosporine
Systemic dupilumab
Sponsored by
About this trial
This is an interventional treatment trial for Dermatitis, Atopic focused on measuring natural moisturizing factor, systemic treatment
Eligibility Criteria
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
Sites / Locations
- Erasmus MC - Sophia Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Topical corticosteroids (control)
Systemic cyclosporine
Systemic dupilumab
Arm Description
This group will receive topical corticosteroids.
This group will receive topical corticosteroids and systemic cyclosporin.
his group will receive topical corticosteroids and systemic dupilumab.
Outcomes
Primary Outcome Measures
EASI
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
Relative reduction of 75% from baseline EASI without the use of rescue medication
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.
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.
POEM
Change from baseline in Patient-Oriented Eczema Measure questionnaire (0-28) over the course of 6 months, with higher scores meaning worse outcomes.
SCORAD
Change from baseline in Scoring Atopic Dermatitis scale (0-103) over the course of 6 months, with higher scores meaning worse outcomes.
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.
Full Information
NCT ID
NCT04878770
First Posted
April 29, 2021
Last Updated
August 17, 2021
Sponsor
Erasmus Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT04878770
Brief Title
NMF-CsA-Dupi Trial
Official Title
Use of the NMF Biomarker as Predictive Diagnostic for Effective Use of Cyclosporine and Dupilumab in the Treatment of Atopic Dermatitis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 16, 2021 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dermatitis, Atopic
Keywords
natural moisturizing factor, systemic treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Outcomes Assessor
Masking Description
Personnel involved assessing disease severity are blinded for the NMF biomarker result.
Allocation
Randomized
Enrollment
318 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Topical corticosteroids (control)
Arm Type
Active Comparator
Arm Description
This group will receive topical corticosteroids.
Arm Title
Systemic cyclosporine
Arm Type
Active Comparator
Arm Description
This group will receive topical corticosteroids and systemic cyclosporin.
Arm Title
Systemic dupilumab
Arm Type
Active Comparator
Arm Description
his group will receive topical corticosteroids and systemic dupilumab.
Intervention Type
Drug
Intervention Name(s)
Topical corticosteroids
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Systemic cyclosporine
Other Intervention Name(s)
Neoral
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Systemic dupilumab
Other Intervention Name(s)
DUPIXENT
Intervention Description
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.
Primary Outcome Measure Information:
Title
EASI
Description
Change from baseline Eczema Area and Severity Index (0-72) over the course of 6 months, with higher scores meaning worse outcomes.
Time Frame
t = 0, 1 month, 2 months, 3 months and 6 months
Secondary Outcome Measure Information:
Title
EASI75
Description
Relative reduction of 75% from baseline EASI without the use of rescue medication
Time Frame
t = 1 month, 2 months, 3 months and 6 months
Title
IGA 0 or IGA 1
Description
Proportion of patients that achieved IGA 0 or IGA 1 (Investigator's Global Assessment) without the use of rescue medication.
Time Frame
t = 0, 1 month, 2 months, 3 months and 6 months
Title
NRS-11 reduction for itch ≥ 4 points
Description
Proportion of patients that achieved a reduction ≥4 points on the Numeric Rating Scale-11 (0-10) for itch intensity.
Time Frame
t = 0, 1 month, 2 months, 3 months and 6 months
Title
POEM
Description
Change from baseline in Patient-Oriented Eczema Measure questionnaire (0-28) over the course of 6 months, with higher scores meaning worse outcomes.
Time Frame
t = 0, 1 month, 2 months, 3 months and 6 months
Title
SCORAD
Description
Change from baseline in Scoring Atopic Dermatitis scale (0-103) over the course of 6 months, with higher scores meaning worse outcomes.
Time Frame
t = 0, 1 month, 2 months, 3 months and 6 months
Title
RECAP
Description
Change from baseline in the Recap of Atopic Eczema questionnaire (0-28) over the course of 6 months, with higher scores meaning worse outcomes.
Time Frame
t = 0, 1 month, 2 months, 3 months and 6 months
Other Pre-specified Outcome Measures:
Title
CDLQI ≥4 years
Description
Children's Dermatology Life Quality Index, in the context of a cost-effectiveness analysis
Time Frame
t = 0, 3 months and 6 months
Title
IDQoL <4 years
Description
Infants' Dermatitis Quality of Life Index, in the context of a cost-effectiveness analysis
Time Frame
t = 0, 3 months and 6 months
Title
Emollients and steroid use in frequency and tubes used
Description
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.
Time Frame
t = 0, 1 month, 2 months, 3 months, 4 months, 5 months and 6 months
Title
Healthcare costs related to the treatment of AD
Description
In context of a cost-effectiveness analysis: To assess medical specialist care, hospitalization, medication, and other costs directly associated with the treatment and recurrence.
Time Frame
Over the course of 6 months
Title
Adverse events
Description
Adverse events related to therapy as reported at any time during treatment by patient, custodian or investigator.
Time Frame
Over the course of 6 months
Title
NMF measured via Raman spectroscopy
Description
Natural Moisturizing Factor, to acquire more knowledge about external and internal factors that influence the NMF biomarker
Time Frame
t = - 2 weeks, 0, 3 months and 6 months
Title
Microbiome profile
Description
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.
Time Frame
t = 0, 3 months and 6 months
Title
Humoral blood panel (systemic arms)
Description
Changes in IgE during systemic treatment over the course of 6 months.
Time Frame
t = 0, 1 month, 3 months and 6 months
Title
Humoral blood panel (topical arm)
Description
Changes in IgE during topical treatment over the course of 6 months.
Time Frame
t = 0 and 6 months
Title
Cellular blood panel (systemic arm)
Description
Changes in leucocyte differentiation during systemic treatment over the course of 6 months.
Time Frame
t = 0, 1 month, 3 months and 6 months
Title
FLG null mutations
Description
Genotyping on skin barrier proteins, to acquire more knowledge about external and internal factors that influence atopic dermatitis and the NMF biomarker
Time Frame
t = 0
Title
Activity of atopy
Description
The activity of rhinoconjunctivitis, asthma and food allergy examined by a pediatric allergist and pediatric pulmonologist.
Time Frame
t = 0, 3 months and 6 months
Title
Psychosocial factors (CBCL)
Description
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.
Time Frame
t = 0
Title
Psychosocial factors (OBVL)
Description
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
Time Frame
t = 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Suzanne G.M.A. Pasmans, Prof
Phone
+31 6 53524299
Email
s.pasmans@erasmusmc.nl
Facility Information:
Facility Name
Erasmus MC - Sophia Children's Hospital
City
Rotterdam
State/Province
Zuid-Holland
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
prof. S.G.M.A. Pasmans, MD PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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NMF-CsA-Dupi Trial
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