NMF-CsA-Dupi Trial

Dermatitis, Atopic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04878770
• Other study ID #: MEC-2019-0568
• Secondary ID: 2019-003247-30
• Status: Recruiting
• Phase: N/A
• Start date: August 16, 2021
• Est. completion date: January 1, 2025

Study information

• Verified date: August 2021
• Source: Erasmus Medical Center
• Contact: Suzanne G.M.A. Pasmans, Prof
• Phone: +31 6 53524299
• Email: s.pasmans[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 318
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis, Atopic

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Netherlands	Erasmus MC - Sophia Children's Hospital	Rotterdam	Zuid-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CDLQI =4 years	Children's Dermatology Life Quality Index, in the context of a cost-effectiveness analysis	t = 0, 3 months and 6 months
Other	IDQoL <4 years	Infants' Dermatitis Quality of Life Index, in the context of a cost-effectiveness analysis	t = 0, 3 months and 6 months
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Humoral blood panel (topical arm)	Changes in IgE during topical treatment over the course of 6 months.	t = 0 and 6 months
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	EASI75	Relative reduction of 75% from baseline EASI without the use of rescue medication	t = 1 month, 2 months, 3 months and 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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