Dupilumab Impact on Skin Resident Memory T Cells | NCT03983460

NCT03983460

Protocol Section

Identification Module

Results Section

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Annotation Section

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Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dupimulab arm	Experimental	At Day 0, patients will receive Dupilumab treatment. The recommended dose of Dupilumab for adult patients is an initial dose of 600mg followed by 300mg given every two weeks administered as subcutaneous injection. Dupilumab could be self-administered by subcutaneous injection into thigh or abdomen or injected in the upper arm in case of administration by the patient's caregiver. It is recommended to rotate the injection site with each injection. At the end of treatment period, patient with AD IGA >1 will stop the study and patient with AD IGA≤1 will enter in a 3 months-follow-up period. During this period, they will stop treatment initiated at Day 0 and apply rescue TCS if appearance of AD lesion within 3 months. Patients will note in their diary the applications of rescue TCS. The relapse is defined as the necessity to apply TCS rescues.	Drug: Dupilumab Procedure: Biopsies Procedure: Skin prick-test Procedure: Blood sample collection
Optimized TCS treatment arm	Active Comparator	At Day 0, patients will receive topical corticosteroid treatment (TCS) adapted to the AD severity (potent and very potent TCS) with a personal therapeutic education for treatment optimization. It will be asked to perform, every day, an application of topical corticosteroid (TCS) (betamethasone valerate cream 0.1%, and if not active, clobetasol propionate cream 0.05%) on active lesions. Once the AD lesion is cleared, the patients will continue to apply TCS on healed lesions, twice a week until the end of the treatment period to prevent relapse. At the end of treatment period, patient with AD IGA >1 will stop the study and patient with AD IGA≤1 will enter in a 3 months-follow-up period. During this period, they will stop treatment initiated at Day 0 and apply rescue TCS if appearance of AD lesion within 3 months. Patients will note in their diary the applications of rescue TCS. The relapse is defined as the necessity to apply TCS rescues.	Drug: Optimized TCS treatment Procedure: Biopsies Procedure: Skin prick-test

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dupilumab	Drug	Each single used prefilled syringe contains 300 mg of Dupilumab in 2 mL solution (150mg/mL) Dupilumab is a fully human monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signaling, produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
To assess the change of the number (per biopsy or per mL of blood) and/or frequency (among live hematopoietic cells CD45+) of immune cells that are present in the skin and the blood of AD patients after Dupilumab or TCS treatment.	In this exploratory study, comprehensive immunophenotyping investigations will be conducted on the immune cells extracted from blood, and from the lesional, healed and non lesional skin biopsies of each patient. Capitalizing on the use of mass cytometry technology, which allows comprehensive analysis of 35-40 different markers on the same cell, we will establish a precise mapping of immune cells that circulate or infiltrate/persist the different lesions. A specific focus will determine the frequency/number of Trms and ILCs inside the skin, notably type-2 Trms (such as IL-4/IL-13 producing TH2) and ILC2.	At Day 0, Day 28 and Day 168.

Secondary Outcomes

Measure	Description	Time Frame
To investigate correlations between each immunological parameter and each clinical score as a continuous quantitative variable, as well as each immunological parameter and quality of life index as a continuous quantitative variable.	In order to determine the immunological parameters associated with the clinical state of patients (measured using IGA, EASI, SCORAD, lesional area score and life quality index), the following procedure will be done for each clinical score, and at each time. First, the correlation between the clinical score and each immunological parameter will be tested using linear regression models, including the type of treatment as a co-variable (one model for each immunological parameter). Then, a multiple linear regression model will be performed, where explanatory variables will include the treatment as well as some of the immunological parameters, based on statistical considerations as well as on clinical considerations. Immunological parameters with p-value<0.05 from the multiple linear regression model will be considered as significantly associated with the clinical state of patients.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject over 18 years of age
Subject able to read, understand and give documented informed consent
Subject willing and able to comply with the protocol requirements for the duration of the study
Subject with health insurance coverage according to local regulations
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 A highly effective method of birth controlled is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, combined oral contraceptives, intrauterine device, double barrier methods (e.g. condom with spermicide), sexual abstinence or vasectomized partner. Woman with no childbearing potential is defined as: woman with amenorrhea for at least 12 months (without an alternative medical cause); woman who had undergone a permanent sterilization method (eg bilateral tubal occlusion which includes tubal ligation procedures, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy.
Subject diagnosed with moderate-to-severe AD, defined as SCORAD≥20 and/or EASI≥7 (Eichenfield et al., 2014)
Subject with AD involvement of 10% (or more) Body Surface Area (BSA) according to component A of SCORAD
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)

Exclusion Criteria:

Pregnancy or breast-feeding women, or planning to become pregnant or breastfeed during the study
Women unwilling to use adequate birth control, if of reproductive potential and sexually active.
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 helminth infection
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 immunosuppressor/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
Subject having a planned surgery during the study
Subject presenting clinically significant medical disease that is uncontrolled despite treatment that is likely, in the opinion of the investigator, to impact patient's ability to participate in the study or to impact the study efficacy or safety assessments
Subject with any additional condition that, in the opinion of the investigator, may interfere with the assessment or put the subject at risk
Linguistic or mentally incapacity to sign the consent form
Subject protect by the law (adult under guardianship, or hospitalized in a public or private institution for a reason other than study, or incarcerated)
Subject in an exclusion period from a previous study or who is participating in another clinical trial

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis

ID	Term
C582203	dupilumab
D001624	Betamethasone Valerate
D001706	Biopsy
D010328	Patch Tests

ID	Term
D001623	Betamethasone
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes