Dupilumab Impact on Skin Resident Memory T Cells

NCT ID: NCT03983460

Last Updated: 2020-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-09

Study Completion Date

2021-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Atopic Dermatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Dupilumab

Intervention Type 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.

Biopsies

Intervention Type 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

Intervention Type 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

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

Optimized TCS treatment

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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.

Interventions

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Dupilumab

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.

Intervention Type DRUG

Optimized TCS treatment

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.

Intervention Type DRUG

Biopsies

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

Intervention Type PROCEDURE

Skin prick-test

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

Intervention Type PROCEDURE

Blood sample collection

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.

Intervention Type PROCEDURE

Other Intervention Names

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Betamethasone valerate 0.1% and Clobetasol propionate 0.05%

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Association pour la Recherche Clinique et Immunologique

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Service d'Allergologie et Immunologie Clinique - Hôpital Lyon Sud

Pierre-Bénite, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Sophie Gilibert, Ph.D.

Role: CONTACT

+33478861859

Facility Contacts

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Audrey Nosbaum, MD PhD

Role: primary

+33478861859

Other Identifiers

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18082A0002

Identifier Type: -

Identifier Source: org_study_id

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