The purpose of this amendment is to correct minor clerical errors for consistency throughout the protocol in addition to the following: - Add pharmacodynamic assessment and palatability evaluation of upadacitinib oral solution to Part 1 objectives in Section 1 (Synopsis) and Section 3.1 (Objectives). - Add statistical analyses of palatability evaluation to Section 7.5 - Add minimum enrollment of 4 subjects to each bodyweight category to Section 1 (Synopsis) and Section 4.1 (Investigational Plan). - Add additional details regarding limiting subject discomfort in Section 4.2 (Discussion of Study Design), on discontinuation of subjects in Section 5.6 (Withdrawal of Subjects and Discontinuation of Study), on QTc criterion in Section 6.2 (Toxicity Management and on end of study in Section 11 (Completion of Study). - Section 5.2 Contraception Requirements for Females. Additional description for females of childbearing potential. - Section 6.1 (Complaints and Adverse Events). Updated information on CTCAE and pregnancy. - Removed "in a blinded manner" from cardiovascular paragraph. Section 6.2 (Toxicity Management). - Added Section 6.3 (Data Monitoring Committee and Cardiovascular Adjudication Committee)" to Section 6.4. - Update abbreviations in Appendix A (Study Specific Abbreviations and Terms). - Update Appendix D (Study Activities Table) to clarify study activities including addition of a ± 7 day window to study visits in Part 2 - Operations Manual. Section 3.16, Follow-Up. Remove telephone follow-up. - Operations Manual. Section 3.18, Dispense Study Drug. Move section and add additional details. - Operations Manual. Section 5.2, Packaging and Labeling. Specified that upadacitinib oral solution should be protected from freezing and add temperature excursion information. - Operations Manual. Section 5.3, Method of Assigning Subjects to Treatment Groups. Update the subject identification number from 6 to 8 digits.

(continued) - Operations Manual. Section 5, Study Drug, Subsections 5.4, 5.5 and 5.6. Provide additional information regarding study drug procedures. - Operations Manual. Replace TB RISK ASSESSMENT FORM EXAMPLE and TANNER STAGES. - Operations Manual. Update the definitions in ECZEMA AREA AND SEVERITY INDEX (EASI) SCORING EXAMPLE. - Added two appendices to Operations Manual ORAL SOLUTION DOSING INFORMATION WITH REQUIRED SYRINGE SIZE and INSTRUCTIONS FOR USE: ORAL SOLUTION. - Operations Manual. Added to appendices of protocol.

The purpose of this amendment is to correct minor clerical errors for consistency throughout the protocol in addition to the following: - Update the study design to include an additional group of subjects 6 months to less than 2 years of age. - Add a new oral upadacitinib formulation of 0.5 mg/mL. - Update the safety related language throughout the protocol. - Update language for moderate/strong inhibitors. - Update Section 5.6: Treatment Compliance in the Operations Manual.

The purpose of this amendment is to correct minor clerical errors for consistency throughout the protocol in addition to the following: - Updated sponsor/emergency medical contact. - Updated dose levels and body weight categories in Table 2 for subjects 2 to < 12 years of age and added dosing recommendations for subjects 6 months to < 2 years in cohorts 5 and 6 in Table 3. - Added citation to selection of doses discussion. - Added summary of conclusions on efficacy and safety from the available Phase 3 AD studies in Section 2.1, Benefits and Risks to Subjects. - Updated Eligibility Criterion 3 to have separate weight limits based on age. - Added information regarding development of oral solutions. - Added information regarding COVID-19 procedures throughout the document. - Replace PF 04965842 with abrocitinib in JAK inhibitor list in Prior/Concomitant Therapy - Added information regarding adjudication committee used to assess potential gastrointestinal perforation AEs. - Updated language regarding study drug withdrawal criterion and toxicity management related to gastrointestinal perforation. - Added a study stopping criteria related to elevations in creatinine phosphokinase: Two or more subjects administered study drug experience a confirmed symptomatic creatinine phosphokinase (CPK) elevation ≥ 4x upper limit of normal considered related to study drug. - Updated sample size estimation. - Added additional text regarding dose adjustment for subjects in Part 1 of the study. - Updated text for re-screening procedure in Appendix F, Section 3.2 - Added text to collect full date of birth to Appendix F, Section 3.3. - Removed home urine pregnancy test paragraph from Appendix F, Section 3.13, Clinical Laboratory Tests. - Added information regarding at self-scoring of Tanner stage in Appendix F, Section 3.12. - Updated table in Operations Manual Appendix G with new weight categories.

The purpose of this amendment is to correct minor clerical errors for consistency throughout the protocol in addition to the following: - Clarified that for the calculation of the EASI score, the age at the respective visit is used (Appendix E of the Operations Manual). - Changed the contact information for reporting protocol deviations and product complaints in the operations manual.

The purpose of this amendment is to correct minor clerical errors for consistency throughout the protocol in addition to the following: - SPONSOR/EMERGENCY MEDICAL CONTACT updated. - Updated the safety team's email address. - Changed central laboratory to Labcorp Central Laboratory Services Limited Partnership. - In Eligibility criterion number 3, updated minimum age to 3 years of age starting with protocol version 6.0. - In Eligibility criteria number 12, added "history of retinopathy of prematurity, congenital structural abnormalities of the eye (e.g., Marfan's Syndrome), inherited vitreoretinal degenerations or vitreoretinopathies (e.g., Stickler syndrome) or prior history of retinal detachment" as exclusionary conditions. - Throughout the document updated minimum age of subjects in study to 2 years of age - Removed Cohorts 5 and 6 from the study design and all language related to these cohorts throughout the document. - Added ophthalmology assessment every 3 months to check visual acuity of subjects that are < 3 years old until they reach their third year of age, or as needed for subjects ≥ 3 years of age.