Additional Study Information: The Takeda study drug used in this study is vedolizumab, a monoclonal antibody. Monoclonal antibodies are proteins made in laboratories that act like proteins in our bodies called antibodies. Vedolizumab acts specifically in the gut and works by preventing certain immune cells from going to the gut and helps reduce inflammation that can cause the symptoms (frequent bowel movements, and bleeding from the rectum) of CD. Vedolizumab will be given through IV, lasting approximately 30 minutes. The other drugs used in this study are upadacitinib and/or upadacitinib placebo. Upadacitinib works by blocking the action of enzymes called Janus kinases (JAK), which help control inflammation by reducing the activity of the immune system. Upadacitinib and the upadacitinib placebo are in capsule form and are oral medications. Both vedolizumab and upadacitinib are medications that have been approved separately for treatment of patients with moderately to severely active CD who have had an inadequate response, lost response, or were intolerant to other treatments. However, in this study these two medications will be combined and this combination, called dual targeted therapy, is investigational. The study will enroll up to 396 participants at up to 120 sites in regions including North and South America, Europe, Middle East and Asia. The study consists of 4 parts: Screening (Day 0), Induction (Week 0 -12), Maintenance (Week 13-52), and Follow-Up (Week 53- 70). Eligibility: Age 18 to 65 years; Moderately to severely active CD, who have not failed more than 2 classes of either biological or small molecule.