Efficacy of Upadacitinib Re-induction Therapy in Patients With Ulcerative Colitis Who Lost Response to 30 mg Maintenance Dose

1. Subject with current diagnosis of Crohn's Disease or diagnosis of indeterminate colitis.

2. Current diagnosis of fulminant colitis and/or toxic megacolon.

3. History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.

4. Conditions that could interfere with drug absorption including but not limited to short bowel syndrome.

5. History of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy or is planning bowel surgery.

6. Subject has active TB or latent TB.

7. Subject who received fecal microbial transplantation within 30 days prior to Baseline.

8. Subject with new or chronic systemic use of known strong cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers while on UPA therapy should be evaluated by caring physician as to possibility of this medication being responsible for the loss of response to UPA. Herbal therapies and other traditional medicines are defined as any herbal formulation that is intended to treat or prevent health problems and may include supplements based on herbs which the subject is taking.

9. Subject currently receiving total parenteral nutrition (TPN) or plan to receive TPN at any time during study treatment.

10. Subject with positive C. difficile toxin stool assay during screening.

11. Infection(s) requiring treatment with intravenous anti-infectives within 30 days prior to the Baseline visit or oral/intramuscular anti-infectives within 14 days prior to the baseline visit.

12. 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

13. Subject has current or past history of recurrent or disseminated (even a single episode) herpes zoster

14. Subject has current or past history of disseminated (even a single episode) herpes simplex

15. Prior or current gastrointestinal (GI) dysplasia, other than completely removed dysplastic lesion in any biopsy performed during or before the screening endoscopy.

16. History of any malignancy, except for successfully treated nonmelanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.

17. History of gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk of GI perforation per investigator's judgment.

18. History of an allergic reaction or significant sensitivity to constituents of upadacitinib (and its excipients)

19. Subject who previously received stem cell transplantation

20. Subject has been a previous recipient of an organ transplant which requires continued immunosuppression.

21. History of cerebrovascular accident, myocardial infarction, coronary stenting, or aortocoronary bypass stenting or retinal vein occlusion; however, if the investigator determines there are no suitable treatment alternatives available for a subject who has experienced one of these events more than 6 months prior to the Baseline visit, the investigator must document a favorable benefit-risk assessment to justify the subject's inclusion in the study.

In patients with known VTE risk factors other than cardiovascular or alignancy risk factors, participation in this clinical trial is considered the most suitable treatment option among treatment alternatives and the risks and benefits have been discussed with the subject.

22. A serious AE or AE that is identified or a possible risk of UPA during prior treatment with upadacitinib that is deemed to have a causal relationship with upadacitinib by Investigator

23. Subjects who have been treated with any investigational drug of chemical or biologic nature within 30 days or five half-lives (whichever is longer) prior to the first dose of study treatment or who are currently enrolled in another interventional clinical study.

24. Received treatment with rectal aminosalicylates or corticosteroids, other enemas/suppositories (other than required for endoscopy), within 7 days prior to the Screening endoscopy and during the remainder of the Screening Period.

25. Received cyclosporine, tacrolimus, mycophenolate mofetil or thalidomide within 30 days prior to Baseline.

26. Subjects who received azathioprine or 6-mercaptopurine within 10 days of Baseline.

27. Subjects who received intravenous corticosteroids within 14 days prior to screening or during the screening period.

28. Subjects who require corticosteroids to remain in the study

29. Subject who received non-steroidal anti-inflammatory drugs (NSAIDs) (except topicalNSAIDs and the useof low dose aspirin for cardiovascular \[CV\] protection) within 7 days prior to baseline

What this study is about