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

Study sites Colombo North Teaching Hospital, Ragama Teaching Hospital Karapitiya, Galle Kandy Teaching Hospital, Kandy, Teaching Hospital, Kurunegala, National Hospital of Sri Lanka

This is a combined Phase 3 double-blind, randomized, placebo-controlled studies to evaluate the efficacy and safety of filgotinib in the induction and maintenance of remission in subjects with moderately to severely active CD. The study is divided into 2 parts (induction study and maintenance study). Based on protocol eligibility criteria, subjects will be screened for enrollment in either Cohort A (biologic naïve patients) or Cohort B (biologic experienced patients).

Subjects who meet protocol eligibility criteria will be assigned to the respective Cohort and subsequently randomized in a blinded fashion in a 1:1:1 ratio to 1 of 3 treatments to the induction study as follows:

Treatment 1 (n = 220): filgotinib 200 mg and placebo-to-match (PTM) filgotinib 100 mg, once daily Treatment 2 (n = 220): filgotinib 100 mg and PTM filgotinib 200 mg, once daily Treatment 3 (n = 220): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily

The study medication will consist of 200 mg and 100 mg filgotinib tablets for oral administration, and PTM 200 mg and 100 mg filgotinib tablets for oral administration.

Subjects in Cohort A and B who complete the Induction Study and achieve either clinical remission by PRO2 (patient reported outcomes consisting of 2 items: abdominal pain severity and liquid stool frequency) or endoscopic response by SES-CD (Simple Endoscopic Score for Crohn's Disease) at Week 10 will be re-randomized into the Maintenance Study at Week 11. Subjects who achieve neither clinical remission by PRO2 nor endoscopic response at Week 10 will have the option to enter a separate Long-Term Extension (LTE) study (Gilead Study GS-US-419-3896).

Standard management be offered to all arms given that the allowed concomitant medication(s) for Crohn’s Disease (CD) must be maintained at a stable dose for the noted time without dosing alteration or discontinuation. The allowed medications for CD are as follows:

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

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

• 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 the first 14 weeks after randomization

• Antibiotics for the treatment of CD (eg, metronidazole, ciprofloxacin) provided the dose prescribed has been stable for 2 weeks prior to randomization. Dose must remain stable for the first 10 weeks after randomization. Subjects who are on cyclic therapy must continue their standard low-dose regimen without change for the first 10 weeks after randomization.

1. Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit
2. Documented diagnosis of Crohn's disease (CD) with a minimum disease duration of 6 months with involvement of the ileum and/or colon at a minimum, as determined by histopathology and endoscopic assessment
3. Moderately to severely active Crohn's disease (CD) as determined by a) CDAI total score between 220 and 450 inclusive b) PRO2 score consisting of abdominal pain >2 (on CDAI scale of 0 to 3) OR daily stool frequency >4 c) Evidence of active disease as measured by SES-CD, (Total score >6, OR If disease is limited to the ileum and/or right colon, a combined score >4 in these two segments)
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. Current complications of Crohn's disease (CD) such as symptomatic strictures, severe rectal/anal stenosis, fistulae, short bowel syndrome, etc.
2. Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon
3. Active tuberculosis (TB) or history of latent TB that has not been treated
4. Use of any prohibited concomitant medications as described in the study protocol (details available at the SLCTR)