Upadacitinib is a novel selective Janus kinase (JAK) 1 inhibitor. JAK1 inhibition blocks the signaling of many important pro-inflammatory cytokines, including interleukin (IL)-2, IL-6, IL-7, and IL-15, which are known contributors to inflammatory disorders. This is a Phase 2b/3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and pharmacokinetics of upadacitinib as induction and maintenance therapy in adult subjects with moderately to severely active UC. The study comprises 3 substudies: a Phase 2b dose-ranging induction substudy (Substudy 1), a Phase 3 dose-confirming induction substudy (Substudy 2), and a Phase 3 maintenance substudy (Substudy 3). The study is designed to enroll approximately 844 subjects in Substudy 1 and Substudy 2 to meet scientific and regulatory objectives without enrolling an undue number of subjects in alignment with ethical considerations. Therefore, if the target number of subjects has been enrolled, there is a possibility that additional subjects in screening will not be enrolled. The study duration could be up to 77 weeks (excluding a possible washout period), including a Screening Period of up to 5 weeks, an 8-week double-blind Induction Period, an 8-week, open-label, Extended Treatment Period (for eligible subjects), a 52-week Maintenance Period, and a 30-day Follow-up Period. For subjects who meet criteria for loss of response during the Maintenance Period (Substudy 3), the Week 52/PD Visit should be conducted.