Effect of Dupilumab (Anti-IL4Rα) on the Host-Microbe Interface in Atopic Dermatitis

Inclusion Criteria:

   - Must be able to understand and provide informed consent

   - Chronic AD, (according to the Atopic Dermatitis Research Network [ADRN] Standard
   Diagnostic Criteria), that has been present for at least 3 years before the Screening
   Visit

   - EASI score ≥12 at the Screening Visit and ≥16 at the Treatment Initiation Visit

   - Investigator Global Assessment (IGA) score ≥3 (on the 0-4 IGA scale) at the Screening
   and Treatment Initiation Visits

   - ≥10% body surface area of AD involvement at the Screening and Treatment Initiation
   Visits

   - Must have active lesions (minimum of 3 of at least 4x4 cm^2 each on the upper or lower
   extremities, excluding the palms of the hands and soles of the feet) at the Screening
   and Treatment Initiation Visits

   - Documented recent history (within 6 months before the Screening Visit) of inadequate
   response to outpatient treatment with topical corticosteroids of medium to high
   potency (± topical calcineurin inhibitors as appropriate), or for whom topical
   treatments are otherwise inadvisable

   - Must agree to apply a stable dose of a topical emollient (moisturizer) at least twice
   daily for at least 7 days before the Treatment Initiation Visit, and must confirm
   application at the Treatment Initiation Visit

   - Individuals with asthma must adhere to asthma controller medication(s) for the
   duration of the study including the open-label and follow-up portions

   - Females of childbearing potential must have a negative pregnancy test at the Screening
   and Treatment Initiation Visits

   - Females with reproductive potential* and sexually active must agree to use FDA
   approved methods of birth control for the duration of the study, including during the
   open-label and follow-up portions of the study:

   --FDA approved methods of birth control include hormonal contraceptives, intrauterine
   device, double barrier contraception (i.e., condom plus diaphragm), or male partner
   with documented vasectomy.

   ---*Menopause is defined as at least 12 consecutive months without menses; if in
   question, a follicle stimulating hormone of ≥25 U/mL must be documented. Hysterectomy,
   bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable;
   if documented, women with these conditions are not required to use additional
   contraception.

   - Males who are sexually active must agree to use an acceptable method of birth control
   (e.g. barrier methods with vaginal spermicide, surgical sterilization or surgically
   sterilized partner), or have a female partner practicing an approved birth control
   method for females as described in Inclusion Criterion above.

   - Willing and able to comply with all clinic visits and study-related procedures

   - Able to understand and complete study-related questionnaires

Exclusion Criteria:

   - Inability or unwillingness of an individual to give written informed consent or comply
   with study protocol

   - Known systemic hypersensitivity to any of the excipients of the dupilumab or placebo
   study products

   - Known or suspected immunosuppression, including history of invasive opportunistic
   infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis,
   pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent
   immune-compromised status, as judged by the investigator

   - Known history of human immunodeficiency virus (HIV) infection

   - 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 or active case of:

      - herpes keratitis,

      - Sjogren's Syndrome,

      - keratoconjunctivitis sicca or Dry Eye Syndrome that requires daily use of
      supplemental lubrication, or

      - ocular condition(s) requiring the regular use of ocular corticosteroids or
      cyclosporine.

   - Parasitic infection, except for vaginal trichomoniasis, within 12 months of the
   Treatment Initiation Visit, or high risk for contracting parasitic infections (e.g.,
   living in or traveling to endemic areas)

   - Presence of skin comorbidities that may interfere with study assessments

   - History of malignancy within 5 years before the Treatment Initiation 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 or melanoma in
   situ

   - History of non-malignant lymphoproliferative disorders

   - History of alcohol or drug abuse within 2 years before the Screening Visit

   - Severe concomitant illness(es) that, in the investigator's judgment, would adversely
   affect the individual's participation in the study. Examples include, but are not
   limited to, individuals with short life expectancy, uncontrolled diabetes (HbA1c ≥9%),
   cardiovascular conditions (e.g., stage III or IV cardiac failure according to the New
   York Heart Association classification), severe renal conditions (e.g., individuals on
   dialysis), hepato-biliary conditions (e.g., Child-Pugh class B or C), neurological
   conditions (e.g., demyelinating diseases), active major autoimmune diseases (e.g.,
   lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), other severe
   endocrinological, gastrointestinal, metabolic, pulmonary, or lymphatic diseases.

   - Any other medical or psychological condition including relevant laboratory
   abnormalities at screening that, in the opinion of the investigator, suggests a new
   and/or insufficiently understood disease, may present an unreasonable risk to the
   study participant as a result of his/her participation in this clinical trial, may
   make individual's participation unreliable, or may interfere with study assessments.
   This includes hypersensitivity to local anesthetics (e.g., lidocaine or Novocain),
   bleeding disorders, treatment with anticoagulants or other conditions that make the
   biopsy procedure inadvisable.

   - Planned major surgical procedure during the screening period or study treatment (i.e.
   Screening through Day 112)

   - Member of the investigational team or his/her immediate family

   - Pregnant or breast-feeding women, or women planning to become pregnant or breastfeed
   during the study including the open-label and follow up portions of the study

   - Individuals unwilling to use adequate birth control, if of reproductive potential and
   sexually active. Adequate birth control is defined as agreement to consistently
   practice an approved method of contraception for the duration of the study, including
   the open-label and follow up portions of the study.

   - History of keloid formation

   - History of serious life-threatening reaction to latex, tape, or adhesives

   - Prior treatment with dupilumab

   - Individuals with asthma who have required use of a systemic corticosteroid within 3
   months prior to the Treatment Initiation Visit or who require a dose greater than 880
   mcg/day of fluticasone propionate or equivalent inhaled corticosteroid to maintain
   asthma control

   - Treatment with biologics as follows:

      - Any cell-depleting agents, including but not limited to rituximab, within 6
      months before the Treatment Initiation Visit, or until lymphocyte and CD 19+
      lymphocyte count returns to normal, whichever is longer

      - Infliximab, adalimumab, golimumab, certolizumab pegol, abatacept, etanercept,
      anakinra within 16 weeks before the Treatment Initiation Visit for any
      indication, or

      - Other biologics within 5 half-lives (if known) or 16 weeks before the Treatment
      Initiation Visit, whichever is longer

   - Treatment with a live (attenuated) vaccine within 12 weeks before the Treatment
   Initiation Visit or planning to receive a live vaccine during the study (through Day
   182)

   - Use of an investigational drug within 8 weeks or within 5 half-lives (if known),
   whichever is longer, before the Treatment Initiation Visit

   - Chronic or acute infection requiring treatment with systemic antibiotics, antivirals,
   antiparasitics, antiprotozoals, or antifungals within 4 weeks before the Treatment
   Initiation Visit, or superficial skin infections within 1 week before the Treatment
   Initiation Visit

   - The following treatments within 4 weeks before the Treatment Initiation Visit, or any
   condition that, in the opinion of the investigator, will likely require such
   treatment(s) during the screening period and study treatment (i.e., Screening through
   Day 112):

      - Systemic corticosteroids

      - Immunosuppressive/immunomodulating drugs (e.g., cyclosporine,
      mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, or
      methotrexate)

   - Use of phototherapy (such as narrow band ultraviolet B [NBUVB], ultraviolet B [UVB],
   ultraviolet A1 [UVA1], psoralen + UVA [PUVA]) or a tanning booth/parlor within 4 weeks
   of the Treatment Initiation Visit

   - Treatment with bleach bath within 3 weeks before the Treatment Initiation Visit

   - Use of a chlorinated hot tub within 3 weeks before the Treatment Initiation Visit

   - Treatment with topical corticosteroids, phosphodiesterase inhibitors (crisaborole), or
   calcineurin inhibitors (tacrolimus or pimecrolimus) within 1 week before the Treatment
   Initiation Visit

   - Initiation of treatment of AD with prescription moisturizers or moisturizers
   containing ceramide, hyaluronic acid, urea, or filaggrin during the screening period
   (participants may continue using stable doses of such moisturizers if initiated before
   the Screening Visit)

   - Planned or anticipated use of any prohibited medications or procedures during the
   screening period and study treatment (i.e., Screening through Day 112)