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)