A Study of Upadacitinib in Adult Participants With Moderate-to-Severe Atopic Dermatitis and Inadequate Response to Dupilumab

Inclusion Criteria:

* Chronic AD with onset of symptoms at least 3 years prior to Baseline and subject meets Hanifin and Rajka criteria.
* Participant meets all the following disease activity criteria at Baseline Visit:

  * Eczema Area and Severity Index (EASI) score \>= 12;
  * validated Investigator´s Global Assessment for AD (vIGA-AD) score \>= 3;
  * Body surface area (BSA) involvement of \>= 10% in a majority of subjects (\>= 50% of the overall study population)
  * Baseline weekly average of daily Worst Pruritus-Numerical Rating Scale (WP-NRS) \>= 4. Note: The Baseline weekly average of daily WP-NRS will be calculated from the 7 consecutive days immediately preceding the Baseline Visit. A minimum of 4 daily scores out of the 7 days is needed.
  * Inadequate response to dupilumab treatment after at least 4 months of current use.
  * Particpant has applied a topical emollient (an additive-free, bland emollient moisturizer) twice daily for at least 7 days before the Baseline Visit and for the duration of the study. Note: Subject may use prescription moisturizers or moisturizers containing ceramide, urea, filaggrin degradation products or hyaluronic acid if such moisturizers were initiated before the Screening visit.

Exclusion Criteria:

* Meeting any of the following conditions at Baseline:

  * Other active skin diseases or skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline Visit or would interfere with assessment of AD lesions;
  * Two or more past episodes of herpes zoster, or one or more episodes of disseminated herpes zoster;
  * One or more past episodes of disseminated herpes simplex (including eczema herpeticum);
  * HIV infection defined as confirmed positive anti- HIV Ab test;
  * Participants with current or past history of infection including, Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV);
  * Active TB or meet TB exclusionary parameters (specific requirements for TB testing are provided in the operations manual);
  * For Japan: Positive result of beta-D-glucan (screening for Pneumocystis jirovecii infection) or two consecutive indeterminate results of beta-D-glucan during the Screening Period;
  * Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit;
  * Chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, makes the subject an unsuitable candidate for the study;
  * COVID-19 infection: In subjects who tested positive for COVID-19, at least 5 days must have passed between a COVID-19 positive test result and the Baseline visit of asymptomatic subjects. Subjects with mild/moderate COVID-19 infection can be enrolled if fever is resolved without use of antipyretics for 24 hours and other symptoms improved, or if 5 days have passed since the COVID-19 positive test result (whichever comes last). Subjects may be rescreened if deemed appropriate by the investigator based upon the subject's health status.
* At Baseline any of the following medical diseases or disorders:

  * Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery or venous thromboembolism;
  * Any unstable clinical condition which, in the opinion of the investigator would put the subject at risk by participating in the protocol;
  * Diagnosed active parasitic infection, suspected or high risk of parasitic infection unless clinical (and if necessary) laboratory assessment have ruled out active infection before randomization;
  * History of an organ transplant which requires continued immunosuppression;
  * History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class;
  * History of GI perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment;
  * Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery including sleeve gastrectomy; subjects with a history of gastric banding/segmentation are not excluded;
  * History of malignancy except for successfully treated NMSC or localized carcinoma in situ of the cervix.