Dupilumab Skin Barrier Function Study in Atopic Dermatitis
Condition: Atopic Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: Dupilumab SAR231893
Intervention description: Pharmaceutical form:solution for injection Route of administration: subcutaneous
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Primary Objective:

      - Evaluate changes in skin barrier function with transepidermal water loss (TEWL) assessed
      after skin tape stripping (STS) in pre-defined lesional skin in participants with moderate to
      severe atopic dermatitis (AD) treated with dupilumab.

      Secondary Objectives:

        -  Evaluate changes in skin barrier function with TEWL assessed after STS in pre-defined
           lesional and non-lesional skin in participants with moderate to severe AD treated with
           dupilumab in reference to normal skin of healthy volunteers.

        -  Evaluate time course of skin barrier function with TEWL assessed before and after STS in
           pre-defined lesional and non-lesional skin in participants with moderate to severe AD
           treated with dupilumab in reference to normal skin of healthy volunteers.
    

Eligibility criteria:

        Inclusion criteria :

        - Participant must be between 12 to 65 years of age (inclusive), at the time of signing the
        informed consent.

        Atopic dermatitis participants:

          -  Male or female participants.

          -  Participants with AD diagnosis according to Hanifin and Rajka criteria at least 1 year
             before screening.

          -  Investigator Global Assessment score of >=3 at screening (on the 0-4 scale).

          -  Participants with moderate to severe atopic dermatitis that were eligible to be
             treated with dupilumab according to product monograph.

          -  Participants with AD must have had active lesions on the upper limbs or lower limbs,
             with severity for lesion erythema or edema/papulation >=2 at screening on the 0-3
             scale of the individual signs score.

          -  Patients must have had a non-lesional (normal looking) skin area 4 centimeters from
             the edge of the lesional area.

          -  Were willing to refrain from applying any topical medication products on the target
             assessment areas (including lesional and non-lesional) throughout the study unless
             necessary to alleviate intolerable symptoms.

          -  Were willing to refrain taking showers or soaking in a bathtub with soaps and body
             washes within 6 hours before TEWL assessments.

          -  Were willing to apply Cetaphil or Vanicream moisturizer up to twice a day with an
             exception of moisturizer application on the targeted assessment areas (lesional and
             non-lesional areas) during the entire study from Day -7 to end of treatment.

          -  Were willing and able to comply with all clinic visits and study-related procedures.

        Healthy volunteers:

          -  Age and gender matched to a selected AD participant. Adolescents aged 12 to 17 years
             matched by post puberty status, and adults aged 18 to 65 years were matched by age as
             close as possible within 10 years of age.

          -  No current dermatologic or systemic condition that could interfere with the
             assessments.

          -  Contraceptive use by women should be consistent with local regulations regarding the
             methods of contraception for those participating in clinical studies.

          -  Capable of understanding and giving signed informed consent/assent as were described
             in the protocol, which included compliance with the requirements and restrictions
             listed in the informed consent form (ICF) and in this protocol. For adolescents >=12
             and <18 years of age a specific ICF must also be signed by the participant's legally
             authorized representative.

        Exclusion criteria:

          -  Skin conditions other than AD that can confound assessments in the area of TEWL
             assessments in the opinion of the investigator (i.e., skin atrophy, ichthyosis,
             Netherton syndrome, severe photo damage).

          -  Cracked, crusted, oozing, or bleeding AD lesions in the designated lesional assessment
             area leaving insufficient skin that was adequate for TEWL assessments.

          -  Hypersensitivity to the active substance or to any of the excipients of dupilumab.

          -  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 required daily use of supplemental
             lubrication; or individuals with ocular conditions that required the use of ocular
             corticosteroids or cyclosporine.

          -  Systemic AD treatment or phototherapy within 4 weeks of Baseline.

          -  Topical AD treatment within 1 week of Baseline. Face and neck may be treated with
             topical steroids during the washout period if approved by the investigator.

          -  Severe concomitant illness(es) that, in the investigator's judgment, would adversely
             affect the participant's participation in the study. Examples included, but were not
             limited to participants with short life expectancy, participants with uncontrolled
             diabetes (hemoglobin A1c >=9%), participants with cardiovascular conditions (eg, Class
             III or IV cardiac failure according to the New York Heart Association classification),
             severe renal conditions (eg, participants on dialysis), hepato-biliary conditions (eg,
             Child-Pugh class B or C), neurological conditions (eg, demyelinating diseases), active
             major autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid
             arthritis, etc.), other severe endocrinological, gastrointestinal, metabolic,
             pulmonary, psychiatric (known suicidal intentions) or lymphatic diseases. The specific
             justification for participants excluded under this criterion were noted in study
             documents (chart notes, electronic case report forms, screening logs, etc.).

          -  History of hypersensitivity reaction to tape or adhesives.

          -  Treatment with an investigational drug within 8 weeks or within 5 half-lives (if
             known) prior to Day 1, whichever was longer.

          -  Current participation in another investigational clinical study.

          -  Individuals accommodated in an institution because of regulatory or legal order;
             prisoners or participants who were legally institutionalized.

          -  Participants were dependent on the Sponsor or Investigator (in conjunction with
             section 1.61 of the ICH-GCP Ordinance E6).

          -  Individuals directly involved in the conduct of the study, or immediate family members
             of such individuals.

          -  Any specific situation during study implementation/course that might rise ethics
             considerations.

          -  Planned or anticipated major surgical procedure during the participant's participation
             in this study.

          -  Pregnant or breast feeding women, or were planning to become pregnant or breastfeed
             during the participant's participation in this study.

          -  Women unwilling to use adequate birth control, if of reproductive potential* and
             sexually active. Adequate birth control was defined as agreement to consistently
             practice an effective and accepted method of contraception throughout the duration of
             the study and for 12 weeks after last dose of study drug. These included condom,
             spermicide, hormonal contraceptives, intrauterine device, or double barrier
             contraception (i.e., condom + diaphragm) or a male partner with documented vasectomy.
             Additional requirements for acceptable contraception might apply in certain countries,
             based on local regulations. Investigators in these countries were notified accordingly
             in a protocol clarification letter.

             *For females, menopause was defined as at least 12 consecutive months without menses;
             if in question, a follicle stimulating hormone level of >=25 milliunits per milliliter
             must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation
             must be documented, as applicable; if documented, women with these conditions were not
             required to use additional contraception.

          -  Healthy volunteers with a personal history of an atopic condition.

          -  Healthy volunteers with use of any topical treatment anywhere except Cetaphil or
             Vanicream moisturizer on non-targeted skin areas.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.