Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis
Condition: Dermatitis Atopic
MeSH terms: Dermatitis, Atopic; Dermatitis; Pruritus
Intervention: Dupilumab (SAR231893)
Intervention description: Pharmaceutical form: solution for injection Route of administration: subcutaneous
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Healthy participants served as control group providing normal skin reference for baseline skin biopsy derived outcome measure and were matched for gender, age, race and anatomical site of skin biopsy.
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Primary Objective:

      - Assess change in neuronal architecture following long term treatment with dupilumab in skin
      biopsies from atopic dermatitis (AD) participants with chronic pruritus.

      Secondary Objectives:

        -  Assess change in neuronal architecture following short term treatment with dupilumab and
           during follow-up in skin biopsies from AD participants with chronic pruritus.

        -  To evaluate the efficacy of dupilumab in AD participants with chronic pruritus.

        -  To evaluate the safety of dupilumab in adult participants with moderate-to-severe AD.
    

Eligibility criteria:

        Inclusion criteria:

        For AD participants

          -  Male or female of greater than or equal to (>=)18 years of age inclusive, at the time
             of signing the informed consent form (ICF).

          -  Diagnosed with moderate-to-severe chronic AD for at least 1 year before screening.

          -  Eligible to be treated with dupilumab according to product monograph.

          -  Pruritus lasting 6 or more weeks before baseline (Day 1).

          -  Eczema Area and Severity Index (EASI) score >=12 at baseline.

          -  Pruritus numerical rating scale (NRS) >=4 at baseline.

          -  Investigator global assessment (IGA) score of >=3 at screening (on the 0 to 4 scale)
             at baseline.

          -  Atopic dermatitis active lesions on the upper limbs or lower limbs suitable for a skin
             biopsy without oozing, bleeding, or infection on upper limbs or trunk.

          -  Participants with acute AD lesions as determined by Investigator's judgment.

          -  Stable treatment with non-prohibited medication or therapy during the study.

        For Healthy participants

          -  Male or female of >=18 years of age inclusive, at the time of signing the ICF.

          -  Certified as generally healthy by a comprehensive clinical assessment.

        Exclusion criteria:

        For AD participants

          -  Previous treatment with dupilumab stopped within 6 months of baseline due to
             inadequate response to dupilumab.

          -  Skin conditions other than AD that can confound assessments in the opinion of the
             investigator.

          -  Regular use (>2 visits per week) of a tanning booth/parlor within 4 weeks of the
             Screening Visit.

          -  Severe concomitant illness(es) that, in the Investigator's judgment, would adversely
             affect the participant's participation in the study.

          -  Participants with active tuberculosis (TB) or non-TB mycobacterial infection, or a
             history of incompletely treated TB unless it is well documented the participant has
             been adequately treated and can now start treatment with a biologic agent

          -  Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use
             of antiparasitic drug within 2 weeks before the Screening Visit (Visit 1) or during
             the Screening Period.

          -  Active chronic or acute infection requiring treatment with systemic antibiotics,
             antivirals, or antifungals within 2 weeks before the Screening Visit (Visit 1) or
             during the Screening Period.

          -  Known or suspected immunodeficiency, including history of invasive opportunistic
             infections.

          -  Active malignancy or history of malignancy within 5 years before the Baseline Visit,
             except completely treated in situ carcinoma of the cervix and completely treated and
             resolved non-metastatic squamous or basal cell carcinoma of the skin.

          -  Ocular disorder that in the opinion of the Investigator could adversely affect the
             individual's risk for study participation. Examples include, but are not limited to,
             individuals with a history of active cases of herpes keratitis, Sjogren's syndrome,
             keratoconjunctivitis sicca or dry eye syndrome that require daily use of supplemental
             lubrication or individuals with ocular conditions that require the use of ocular
             corticosteroids or cyclosporine.

          -  History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic
             therapy, including any excipient.

          -  Participant with any other medical or psychological condition including relevant
             laboratory or electrocardiogram abnormalities at screening.

        For healthy participants

          -  Regular use (>2 visits per week) of a tanning booth/ parlor within 4 weeks of the
             Screening Visit.

          -  Treatment with the following concomitant medications and procedures is prohibited
             within 4 weeks before the Screening Visit or 5 half-lives (whichever is longer) until
             End of Study Visit:

               -  Topical medication

               -  Analgesics

               -  Immunomodulators

               -  Antidepressants

               -  Anti-anxiety drugs

          -  Any Type 2 immune disorders uncontrolled Type 2 diabetes mellitus, Type 1 diabetes
             mellitus, neuropathy or any other neurological disease.

          -  Any concomitant illness(es) or conditions that, in the Investigator's judgment, would
             adversely affect the participant's participation in the study or potentially affect
             any skin biopsy related read out.

          -  Positive test for immunoglobulin E (IgE) antibodies.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.