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

Inclusion 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% ofthe 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 7consecutive days immediately preceding the Baseline Visit. A minimum of 4 dailyscores 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 emollientmoisturizer) twice daily for at least 7 days before the Baseline Visit and for theduration of the study. Note: Subject may use prescription moisturizers ormoisturizers containing ceramide, urea, filaggrin degradation products or hyaluronicacid 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 wouldinterfere with assessment of AD lesions;

• Two or more past episodes of herpes zoster, or one or more episodes ofdisseminated herpes zoster;

• One or more past episodes of disseminated herpes simplex (including eczemaherpeticum);

• HIV infection defined as confirmed positive anti- HIV Ab test;

• Active TB or meet TB exclusionary parameters (specific requirements for TBtesting are provided in the operations manual);

• For Japan: Positive result of beta-D-glucan (screening for Pneumocystisjirovecii infection) or two consecutive indeterminate results of beta-D-glucanduring 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 theBaseline Visit;

• Chronic recurring infection and/or active viral infection that, based on theinvestigator's clinical assessment, makes the subject an unsuitable candidatefor the study;

• COVID-19 infection: In subjects who tested positive for COVID-19, at least 5days must have passed between a COVID-19 positive test result and the Baselinevisit of asymptomatic subjects. Subjects with mild/moderate COVID-19 infectioncan be enrolled if fever is resolved without use of antipyretics for 24 hoursand other symptoms improved, or if 5 days have passed since the COVID-19positive test result (whichever comes last). Subjects may be rescreened ifdeemed appropriate by the investigator based upon the subject's health status.

• Chronic AD with onset of symptoms at least 3 years prior to Baseline and subjectmeets Hanifin and Rajka criteria.- Participants with current or past history ofinfection including, Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV)

• At Baseline any of the following medical diseases or disorders:

• Recent (within past 6 months) cerebrovascular accident, myocardial infarction,coronary stenting, (note: include the following only for new protocols) andaorto-coronary bypass surgery or venous thromboembolism;

• Any unstable clinical condition which, in the opinion of the investigator wouldput the subject at risk by participating in the protocol;

• Diagnosed active parasitic infection, suspected or high risk of parasiticinfection unless clinical (and if necessary) laboratory assessment have ruledout active infection before randomization;

• History of an organ transplant which requires continued immunosuppression;

• History of an allergic reaction or significant sensitivity to constituents ofthe study drug (and its excipients) and/or other products in the same class;

• History of GI perforation (other than due to appendicitis or mechanicalinjury), diverticulitis, or significantly increased risk for GI perforation perinvestigator judgment;

• Conditions that could interfere with drug absorption including but not limitedto short bowel syndrome or gastric bypass surgery; subjects with a history ofgastric banding/segmentation are not excluded;

• History of malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix;