NMF-CsA-Dupi Trial

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

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.

Study Overview

• Status: Recruiting
• Conditions: Dermatitis, Atopic
• Intervention / Treatment: Drug: Topical corticosteroids; Drug: Systemic cyclosporine; Drug: Systemic dupilumab

• Study Type: Interventional
• Enrollment (Anticipated): 318
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Suzanne G.M.A. Pasmans, Prof; Phone Number: +31 6 53524299; Email: s.pasmans@erasmusmc.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands
      • Recruiting
      • Erasmus MC - Sophia Children's Hospital
      • Contact: prof. S.G.M.A. Pasmans, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / 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: Neoral
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: DUPIXENT

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CDLQI ≥4 years	Children's Dermatology Life Quality Index, in the context of a cost-effectiveness analysis	t = 0, 3 months and 6 months
IDQoL <4 years	Infants' Dermatitis Quality of Life Index, in the context of a cost-effectiveness analysis	t = 0, 3 months and 6 months
Emollients and steroid use in frequency and tubes used	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.	t = 0, 1 month, 2 months, 3 months, 4 months, 5 months and 6 months
Healthcare costs related to the treatment of AD	In context of a cost-effectiveness analysis: To assess medical specialist care, hospitalization, medication, and other costs directly associated with the treatment and recurrence.	Over the course of 6 months
Adverse events	Adverse events related to therapy as reported at any time during treatment by patient, custodian or investigator.	Over the course of 6 months
NMF measured via Raman spectroscopy	Natural Moisturizing Factor, to acquire more knowledge about external and internal factors that influence the NMF biomarker	t = - 2 weeks, 0, 3 months and 6 months
Microbiome profile	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.	t = 0, 3 months and 6 months
Humoral blood panel (systemic arms)	Changes in IgE during systemic treatment over the course of 6 months.	t = 0, 1 month, 3 months and 6 months
Humoral blood panel (topical arm)	Changes in IgE during topical treatment over the course of 6 months.	t = 0 and 6 months
Cellular blood panel (systemic arm)	Changes in leucocyte differentiation during systemic treatment over the course of 6 months.	t = 0, 1 month, 3 months and 6 months
FLG null mutations	Genotyping on skin barrier proteins, to acquire more knowledge about external and internal factors that influence atopic dermatitis and the NMF biomarker	t = 0
Activity of atopy	The activity of rhinoconjunctivitis, asthma and food allergy examined by a pediatric allergist and pediatric pulmonologist.	t = 0, 3 months and 6 months
Psychosocial factors (CBCL)	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.	t = 0
Psychosocial factors (OBVL)	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	t = 0

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: April 29, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: systemic treatment; natural moisturizing factor
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: MEC-2019-0568; 2019-003247-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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