Atopic Dermatitis MedDRA version: 20.0 Level: LLT Classification code 10003639 Term: Atopic dermatitis System Organ Class: 100000004858
Conditions
Interventions
Product Name: dupilumab
Pharmaceutical Form: Injection
Trade Name: Betneval 0.1% cream
Pharmaceutical Form: Cream
Trade Name: Dermoval
Sponsors
ARCI (trade name LYON RECHERCHE CLINIQUE : LyREC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subject over 18 years of age • For woman with childbearing potential ; • Use of a highly effective method of birth control from at least 1 month prior to study enrollment until the last visit • Negative urine pregnancy test at inclusion visit • Subject diagnosed with moderate-to-severe AD, defined as SCORAD=20 and/or EASI=7 (Eichenfield et al., 2014) • Subject with I, II, III or IV skin phototype (according to Fitzpatrick scale) • Subject accepting skin prick-tests and skin biopsies • Subject having a least one non lesional area on the body (off head and neck, feet and hands) • Subject eligible for systemic treatment • Failure, intolerance or contraindication to available systemic treatments (i.e. cyclosporine/ methotrexate) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • Pregnancy or breast-feeding women, or planning to become pregnant or breastfeed during the study • Subject currently experiencing or having a history of other concomitant skin conditions that would interfere with evaluation of AD • History of allergic reaction to local anesthetic product • History of wound healing disorders (e.g. hypertrophic scars, keloids) • Subject with known active infection to HBV, HCV or HIV • Subject with known blood dyscrasia • Subject having an allergen immunotherapy within 3 months before study • Subject treated by antihistamine 5 days before study. Please note, antihistamine administered to treat allergic rhino conjunctivitis is allowed after V1. • Subject treated with an investigational drug within 8 weeks or within 5 half-life (if known), whichever is longer, before the baseline visit • Subject treated with cyclosporine, methotrexate oral corticosteroids, azathioprine, mycophenolate-mofetil, and/or any other systemic immunosupperessor/immunomodulator within 4 weeks before the study • Subject treated by a biologic therapy within 5 half-life before the study • Subject treated with ultraviolet therapy within 4 weeks before study • Subject treated with a live (attenuated) vaccine within 12 weeks before baseline visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To phenotype the immune cells that are present in the skin and the blood of AD patients (D0) and persist one and six months after dupilumab or TCS treatment (D28 and D168).; Secondary Objective: - To correlate the phenotype of immune cells present in the skin and the blood at D0, D28 and D168, and the magnitude of clinical symptoms (as measured using IGA, EASI, SCORAD, lesional area score and life quality index (DLQI)) - To correlate the phenotype of immune cells present in the skin and the blood, and the clinical efficacy of dupilumab and TCS treatments (together and individually) at D28 and D168. - To correlate the phenotype of immune cells present in the skin and the blood at D0, D28 and D168, and the frequency of AD relapse during the 3 months follow-up period. ; Primary end point(s): We will follow the evolution of the number (per biopsy or per mL of blood) and/or frequency (among live hematopoietic cells CD45+) of the following populations: - CD8+ T cells (TCRab+ CD8b+), - CD4+FoxP3- T cells (TCRab+ CD4+ FoxP3-), - Tregs (TCRab+ CD4+ FoxP3+), - B cells (CD19+ HLADR+), - gd T cells (TCRgd+), - iNKT (TCRabint CD161+ TCRVa24+ CD56+), - NK cells (CD56+ NKP46+ CD14- CD16+ CD7+), - ILC (Lineage- CD94- CD34- CD127+ CRTH2+/- NKP44+/- CD103+/-), - Neutrophils (CD16+ CD66a+ CD66b+ CRTH2-), - Eosinophils (CD16low CD66b+ CRTH2+), - Basophils (CD19- HLADR- Fc?RI+ CD123+ CRTH2+), - Mast cells (HLADR- CD123- Fc?RI+ CD117+), - Langerhans cells (CD207+ HLADR+ CD11clow), - plasmacytoid DCs (HLADR+ CD123+ CRTH2+ BDCA2+), - cDC1 (HLADR+ CD11c+ XCR1+ CD14- CD16-), - cDC2 (HLADR+ CD11c+ SIRPa+ CD14- CD16-), - Monocytes (HLAD | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Endpoints for secondary objective 1: Correlations will be searched between each immunological parameter and: - each clinical score (IGA, EASI, SCORAD, lesional area score) and their evolution as a continuous quantitative variable, - quality of life index as a continuous quantitative variable. Then, correlations will also be searched between a cluster of relevant immunological parameters and clinical parameters cited above. Endpoints for secondary objective 2: Correlations will be searched between each immunological parameter and: - change in clinical score (IGA, EASI, SCORAD), as a qualitative variable with 2 modalities (good responders vs bad responders) - quality of life index, as a qualitative variable with 2 modalities (good responders vs bad responders) Then, correlations will also be searched between a cluster of relevant immunological parameters and clinical parameters cited above. During this study, all patients reaching the following criteria will be considered as good responders: - 1st criteria: IGA =1 or a 2-point change from the baseline IGA - 2nd criteria: EASI75 (75% improvement from the baseline EASI) - 3rd criteria: SCORAD75 (75% improvement from the baseline SCORAD) - 4th criteria: 4-point decrease from the baseline DLQI. Correlations will be searched between each immunological parameter and: - the development of new AD lesions in the 3 following months, as qualitative variable with 2 modalities (relapse vs not relapse), - the interval of time between the end of treatment and AD relapse, as a continuous variable. Then, correlations will be also searched between a cluster of relevant immunological parameters and clinical parameters cited above. | — |
Countries
France
Contacts
Public ContactClinical Research Unit
ARCI (trade name LYON RECHERCHE CLINIQUE : LyREC)
Outcome results
None listed