A Study to Assess Adverse Events and Change in Disease Activity Comparing Oral Upadacitinib to Subcutaneous Dupilumab in Children From 2 to Less Than 12 Years of Age With Moderate to Severe Atopic Dermatitis

Inclusion Criteria:

• A minimum weight of 10 kg and weight and height > 5th percentile for their ageaccording to local standard growth charts at the Baseline Visit.

• Atopic Dermatitis (AD), according to Hanifin and Rajka criteria, with onset ofsymptoms at least 6 months prior to Baseline.

• Eczema Area and Severity Index (EASI) score >= 16; vIGA-AD score >= 3 (Note: Incountries where dupilumab is only approved for severe AD, subjects to be included inthe Randomized Cohort should have severe AD [vIGA-AD = 4]); >= 10% Body Surface Areaof AD involvement at the Baseline Visit; and Baseline weekly average of daily WorstItch Scale (WIS) or Worst Scratch/Itch numerical rating scale (WSI-NRS) >= 4.

• Participant must satisfy at least one of the following criteria (Note: More than 1criterion may apply to an individual participant. All applicable criteria for eachindividual participant should be reported):

• To be included in the Randomized Cohort (Note: Participants must have severe AD [vIGA-AD = 4] in countries where dupilumab is approved only for severe AD.):

1. [For all countries except US] Documented history of inadequate response orintolerance to TCS and/or TCI OR for whom use of one or more of these topicaltreatments is medically inadvisable (e.g., high disease burden, Scoring AtopicDermatitis (SCORAD) > 50, EASI score > 21, or vIGA-AD > 3).

2. For dupilumab-naïve participants: History of inadequate response to a systemictherapy for AD other than dupilumab or oral corticosteroids or for whom theavailable systemic treatments are otherwise medically inadvisable (e.g.,because of important side effects or safety risks).

3. History of inadequate response to 2 or more courses of oral corticosteroidtherapy given for >= 14 days within 6 months prior to Screening or history oforal corticosteroid rebound, defined as recurrence of AD symptoms within 4months after its discontinuation.

4. For dupilumab-exposed participants: Prior exposure to dupilumab withoutdocumented history of inadequate response or intolerance (i.e., discontinuationof dupilumab for a non-medical reason, such as, but not limited to,non-coverage or loss of coverage for the drug by health insurance, or otherlogistic challenges [not safety- or efficacy-related] precluding theparticipants continued access to dupilumab).

• To be included in the Dupi-IR/Dupi-Medically Inadvisable Cohort:

• Previous inadequate response or intolerance to dupilumab OR

• Dupilumab is medically inadvisable (e.g., allergy to a component of dupilumab,etc.) AND a documented history of inadequate response or intolerance to TCSand/or TCI.

Exclusion Criteria:

• Current or past history of other active skin diseases (e.g., psoriasis or Nethertonsyndrome or lupus erythematosus) or skin infections (bacterial, fungal, or viral)requiring systemic treatment within 4 weeks of the Baseline Visit or which wouldinterfere with the appropriate assessment of AD lesions.

• Have used topical treatments for AD (except for topical emollient treatments)including but not limited to TCS, TCI, or topical phosphodiesterase type 4 (PDE-4)inhibitors, within 7 days of the Baseline Visit or any the following prohibitedconcomitant AD treatments within the specified timeframes below prior to theBaseline Visit:

• Systemic therapy for AD, including but not limited to corticosteroids,methotrexate, cyclosporine, azathioprine, PDE-4 inhibitors, interferon-γ, andmycophenolate mofetil within 4 weeks;

• Dupilumab within 8 weeks;

• Targeted biologic treatments (other than dupilumab) within 5 half-lives (ifknown) or within 12 weeks, whichever is longer;

• Phototherapy treatment, laser therapy, tanning booth, or extended sun exposurethat could affect disease severity or interfere with disease assessments within 4 weeks.

• Known history of retinal detachment, previous cataract surgery, previous significantocular trauma, or a known congenital ocular abnormality.

• For Randomized Cohort: diagnosed active parasitic infection; suspected or high riskof parasitic infection, unless clinical and (if necessary) laboratory assessmenthave ruled out active infection before randomization.