What is the efficacy and safety of Filgotinib in the induction and maintenance treatment of moderately to severely active Ulcerative Colitis in participants who are biologic-naive and biologic-experienced?

Study sites: Colombo North Teaching Hospital, Ragama Teaching Hospital Karapitiya, Galle, Kandy Teaching Hospital, Kandy

The study is divided into 2 parts (induction study and maintenance study). Based on protocol eligibility criteria, subjects will be screened for enrolment in either Cohort A (biologic naïve patients) or Cohort B (biologic experienced patients)

Induction study

Subjects who meet protocol eligibility criteria will be assigned to the respective Cohort and subsequently randomized using an interactive system (Interactive Web Response System [IWRS] in a blinded fashion in a 2:2:1 ratio to 1 of 3 treatments as follows;

Treatment 1 (n = 260): filgotinib 200 mg and placebo-to-match (PTM) filgotinib 100 mg, once daily Treatment 2 (n = 260): filgotinib 100 mg and PTM filgotinib 200 mg, once daily Treatment 3 (n = 130): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily

Study medication will be administered orally, for a total duration of 10 weeks.

Maintenance study

Subjects in Cohort A and B who complete the Induction Study and achieve either MCS (Mayo Clinic Score response) or EBS (establishing endoscopy/bleeding/stool) remission criteria at Week 10 will be re-randomized in a blinded fashion in a 2:1 ratio to either the same dose of filgotinib or placebo into the Maintenance Study at week 11 and will continue in blinded treatment till week 58 (total of 48 weeks). Subjects who complete all procedures per protocol, will have the option to continue study drug in a blinded fashion in the long term extension study.

Subjects who are non-responders based on the results of the Week 10 assessments will be offered the option to receive open-label filgotinib by entering into the LTE study (GS-US-419-3899). Subjects meeting disease worsening criteria after week 11 or later must be discontinued from blinded treatment and will be offered the option to receive open-label filgotinib 200 mg by entering into the LTE study.

Standard management will be offered to the subjects given that subjects on following therapies must be willing to remain on stable doses for the noted times;

a) Oral 5-aminosalicylate (5-ASA) compounds provided the dose prescribed has been stable for at least 4 weeks prior to randomization; dose must be stable for first 10 weeks after randomization

b) Azathioprine, 6-MP or MTX provided the dose prescribed has been stable for 4 weeks prior to randomization; dose must be stable for first 10 weeks after randomization

c) Oral corticosteroid therapy (prednisone prescribed at a stable dose <30 mg/day or budesonide prescribed at a stable dose of <9 mg/day) provided the dose prescribed has been stable for 2 weeks prior to randomization; dose must be stable for first 14 weeks after randomization.

Blinding will be maintained by Interactive Web Responsive System (IWRS), all the blinded Investigational product will be having the similar labels of “Filgotinib & Matching Placebo”

Participants, Healthcare providers and data collectors will be blinded to the intervention status.

1. Males and non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit

2. Documented diagnosis of ulcerative colitis of at least 6 months and with a minimum disease extent of 15 cm from the anal verge. Documentation should include endoscopic and histopathologic evidence of UC. (note: a surveillance colonoscopy is required at screening in individuals with a history of ulcerative colitis for 8 or more years, if one was not performed in the prior 24 months.

3. Moderately to severely active ulcerative colitis Severity index will be evaluated using a centrally read endoscopy score > 2, arectal bleeding score > 1, a stool frequency score > 1 and PGA (physician global assessment) of > 2 as determined by the Mayo clinic scoring system with endoscopy occurring within 14 days to first dose of study drug; total score must be between 6 and 12, inclusive.

4. Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least 1 of the following agents: corticosteroids, immunomodulators, tumor necrosis factor alpha (TNFa) antagonists, or vedolizumab

1. Presence of Crohn's disease, indeterminate colitis, ischemic colitis, fulminant colitis, ulcerative proctitis, or toxic mega-colon 2.Active tuberculosis (TB) or history of latent TB that has not been treated
2. Use of any concomitant prohibited medications as described in the protocol (details are available at the SLCTR)