Dupilumab Impact on Skin Resident Memory T Cells

Sponsor
Association pour la Recherche Clinique et Immunologique
Study ID
NCT03983460
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • 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.
  • Optimized TCS treatment — DRUG
    Application of betamethasone valerate 0.1% (Betneval 0.1% cream), a potent topical corticosteroid, and if not active, application of clobetasol propionate 0.05% (Dermoval 0.05% cream), a very potent topical corticosteroid. TCS treatment will be associated with a personal therapeutic education for treatment optimization.
  • Biopsies — PROCEDURE
    Four skin biopsies (5 mm diameter) and ten microbiopsies (2 \& 3 mm diameter) will be performed according the following schedule: * Day 0 * a 5 mm section biopsy from a non-lesional skin * a 5 mm section biopsy from an active lesion * a 3 mm section microbiopsies from a non-lesional skin * a 3 mm section microbiopsies from an active lesion * a 2 mm section microbiopsies from a non-lesional skin * a 2 mm section microbiopsies from an active lesion * Day 28 * a 5 mm section biopsy on improved/healed lesion * a 3 mm section microbiopsies on improved/healed lesion * a 2 mm section microbiopsies from non lesional skin identified at V1 * a 2 mm section microbiopsies on improved/healed lesion * Day 168 * a 5 mm section biopsy on improved/healed lesion * a 3 mm section microbiopsies on improved/healed lesion * a 2 mm section microbiopsies from non-lesional skin identified at V1 * a 2 mm section microbiopsies on improved/healed lesion
  • Skin prick-test — PROCEDURE
    Skin prick test is a method for medical diagnosis of allergy consisting in introducing a small amount of an allergen into the patient's skin. The allergen penetrates the epidermis by pricking the skin with a pin. Skin Prick test for Derp and Derf will be performed at Day 0, preferentially on the forearms, avoiding lesional areas. For the results interpretation, the two allergen Derp/Derf will be compared to 2 controls: * Negative control : saline solution * Positive control : histamine solution Positive criteria of prick tests results are: * Positive control's diameter ≥ 3mm * And negative control's diameter \< 3 mm * And tested allergen with wheal ≥ positive control, i.e. 3mm
  • Blood sample collection — PROCEDURE
    A 50ml blood sample will be collected by venipuncture at Day 0, Day 28 and Day 168. More specifically a 40 ml blood sample will be drawn on heparinized tubes for immunophenotyping and a 10 mL on serum blood collection tube for analysis of AD biomarkers by mass cytometry and ELISA.

Study Details

The main objective of the study consists in characterizing the immune cells that are present/persist in the skin and the blood of atopic dermatitis (AD) patients treated with Dupilumab, as well as with potent/very potent topical corticosteroids (TCS: betamethasone valerate cream 0.1% or clobetasol propionate cream 0.05%). A specific attention will be paid on the presence/persistence of skin Trm and ILCs. The study population will consist of 20 adult patients suffering from moderate to severe Atopic Dermatitis and eligible for Dupilumab treatment. (Patients should have inadequate response, intolerance or contraindication to systemic anti-inflammatory treatments). This is an exploratory, prospective, single-site, randomized, open labeled study. There is a treatment period of 168 days (24 weeks) and a post-treatment follow-up period of maximum 102 days.

Key Dates

Start date
Mar 9, 2020
Status verified
Mar 2020
Primary completion
Jun 30, 2021
Completion
Sep 30, 2021

Study Design

Enrollment
20 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Dupimulab arm
    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.
  • Active Comparator: Optimized TCS treatment arm
    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.

Primary Outcome Measure

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. [ Time Frame: At Day 0, Day 28 and Day 168. ]

Central Contacts

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