The current study has two main objectives:- To investigate if the effectiveness of CsA differs for NMF low vs. NMF normal (corresponding with FLG mutation vs. FLG wild type) in children with moderate-to-severe AD. - To investigate if the…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- EASI (Eczema Area and Severity Index, EASI) at t = 1, 3 and 6 months
Secondary outcome
- Proportion of patients that achieved EASI75 (relative reduction of 75% from
baseline EASI) without the use of rescue medication, at t = 1, 3 and 6 months -
Proportion of patients that achieved IGA 0 or IGA 1 (Investigator*s Global
Assessment) without the use of rescue medication at t = 1, 3 and 6 months -
Proportion of patients that achieved a reduction >=4 points on the NRS-11 for
itch intensity (Numeric Rating Scale) at t = 1, 3, and 6 months - POEM
(Patient-Oriented Eczema Measure) at t = 1, 3, and 6 months - SCORAD (Scoring
Atopic Dermatitis) at t = 1, 3 and 6 months - RECAP (Recap of Atopic Eczema) at
t = 1, 3 and 6 months Cost-effectiveness Analysis: - EASI at t = 1, 3, 6 months
- CDLQI (Children*s Dermatology Life Quality Index) >=4 years; IDQoL (Infants*
Dermatitis Quality of Life Index) <4 years, at t = 0, 3 and 6 months - EQ-5D-Y
at t = 0, 3 and 6 months - Emollients and steroid use in frequency and tubes
used (per patient) over the course of 6 months - Healthcare costs related to
the treatment of AD (medical specialist care, hospitalization, and costs
directly associated with complications and recurrence) over the course of 6
months.
Background summary
If topical therapy fails, the next step for treatment of moderate-to-severe
atopic dermatitis (AD) in children is systemic therapy (cyclosporine A (CsA) or
dupilumab). Prognostic tools for effective use of CsA and dupilumab are
currently lacking, resulting in over- and under treatment.
The strongest genetic risk factor for AD is a null mutation in the filaggrin
gene (FLG). Stratification of patients based on the FLG null endotype could
enable more targeted treatment. In current clinical practice FLG-null mutations
are not determined for AD, since genotyping is costly, slow and requires a high
level of expertise. The Natural Moisturizing Factor (NMF) biomarker, measured
by Raman spectroscopy, is an accurate surrogate marker for the presence of
FLG-null mutations.
Study objective
The current study has two main objectives:
- To investigate if the effectiveness of CsA differs for NMF low vs. NMF normal
(corresponding with FLG mutation vs. FLG wild type) in children with
moderate-to-severe AD.
- To investigate if the effectiveness of dupilumab differs for NMF low vs. NMF
normal in children with moderate-to-severe AD.
Study design
This is a stratified biomarker study that investigates whether the
NMF-biomarker status has an effect on the effectiveness of systemic treatment
with respectively CsA or dupilumab in children with moderate-to-severe AD.
Intervention
After NMF measurement, patients are randomized to CsA treatment, to dupilumab
treatment, or to no CsA and dupilumab treatment (control group). The duration
of systemic treatment is 6 months. All groups will be treated with emollients
and topical corticosteroids as topical therapy.
Study burden and risks
Risks: Patients may experience an exacerbation of their AD during the washout
period, which may result in discomfort, necessitating escape medication.
Patients may experience adverse effects from either CsA or dupilumab treatment,
as can also occur during regular clinical care. Possible side-effects will be
closely monitored throughout the study.
A risk associated with this study is that some children who are treated gain no
improvement of their AD. Step up therapy will be provided according to usual
care.
Benefit: The majority of patients with CsA or dupilumab treatment will acquire
improvement of clinical symptoms and achieve better disease control.
Burden: Patients may experience discomfort during additional study measurements
such as drawing blood. Study visits and answering surveys will cost the patient
and caretaker additional time.
Wytemaweg 80
Rotterdam 3015CN
NL
Wytemaweg 80
Rotterdam 3015CN
NL
Listed location countries
Age
Inclusion criteria
children and adolescents, aged between 2 - 18 years, with moderate to severe
atopic dermatitis
(AD 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
(Investigators Global Assessment) >= 3 at screening and baseline (corresponding
with moderate-to-severe
disease)
Exclusion criteria
children under the age of 2 years (due to the prescribe conditions of CsA) and
patients older
than 18 years - contraindication for CsA - 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 at baseline -
IGA - Pregnancy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-003247-30-NL |
| CCMO | NL71053.078.19 |