Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula response at Week 24. Participants will have the option to enter a separate Long-Term Extension (LTE) study (GS-US-419-3896; NCT02914600) if they meet eligibility requirements.

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease

Conditions
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Fistulizing Crohn's Disease

Intervention / Treatment
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* Drug: Filgotinib
* Drug: Placebo to match filgotinib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of screening visit Diagnosis of Crohn's disease (CD) with a minimum duration of CD of at least 3 months Has draining perianal fistulae as a complication of CD, confirmed by magnetic resonance imaging (MRI) at screening Previously demonstrated an inadequate clinical response, loss of response to, or intolerance of at least 1 of the following agents (depending on current country treatment recommendations/guidelines): Antibiotics AND/OR Immunomodulators AND/OR Tumor necrosis factor α (TNFα) Antagonist Is willing and able to undergo MRI per protocol requirements Is willing and able to undergo flexible sigmoidoscopy per protocol requirements Key Exclusion Criteria: Presence of current rectovaginal anovaginal or enterovesicular fistulae Presence of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon History of total proctocolectomy, total colectomy, presence of ileostomy or colostomy, or likely requirement for surgery during the study Use of any prohibited concomitant medications as described in the study protocol Active tuberculosis (TB) or history of latent TB that has not been treated Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Filgotinib 200 mg<br>Filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks | Drug: Filgotinib<br>* Tablet(s) administered orally once daily<br>* Other names: GLPG0634;Drug: Placebo to match filgotinib<br>* Tablet(s) administered orally once daily<br>|
| Experimental: Filgotinib 100 mg<br>Filgotinib 100 mg + placebo to match filgotinib 200 mg for 24 weeks | Drug: Filgotinib<br>* Tablet(s) administered orally once daily<br>* Other names: GLPG0634;Drug: Placebo to match filgotinib<br>* Tablet(s) administered orally once daily<br>|
| Experimental: Placebo<br>Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks | Drug: Placebo to match filgotinib<br>* Tablet(s) administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Combined Fistula Response at Week 24 | Combined fistula response at Week 24 was defined as reduction of greater than or equal to (≥) 1 from baseline in the number of draining external perianal fistula openings that were present at baseline, and absence of fluid collections > 1 centimeter (cm) on magnetic resonance imaging (MRI) pelvis at Week 24, among participants with at least 1 draining external perianal fistula opening at baseline. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Combined Fistula Remission at Week 24 | Combined fistula remission at Week 24 was defined as perianal fistula closure of all external openings that were draining at baseline, and absence of fluid collections > 1 cm on MRI of pelvis at Week 24, among participants with at least 1 draining external perianal fistula opening at baseline. | Week 24 | 
| Time to Clinical Fistula Response up to Week 24 | Time to clinical fistula response was defined as the time interval in days from date of first dosing of study drug to the first observation (during scheduled or unscheduled clinical visits) when ≥ 1 of the draining external perianal fistula openings that were present at baseline achieves perianal fistula closure, among participants with at least 1 draining external perianal fistula opening at baseline. Participants not known to had a clinical fistula response were to have their clinical fistula response time censored at the last time that lack of clinical fistula response was documented. | Time from treatment start to first visit when ≥ 1 of the draining external perianal fistula openings that were present at baseline achieved perianal fistula closure up to Week 24 | 
| Time to Clinical Fistula Remission up to Week 24 | Time to clinical fistula remission was defined as the time interval in days from date of first dosing of study drug to the first observation (during schedule or unscheduled clinical visits) of perianal fistula closure of all external openings that were draining at baseline, among participants with at least 1 draining external perianal fistula opening at baseline. Participants not known to had a clinical fistula remission were have their clinical fistula remission time censored at the last time that lack of clinical fistula remission was documented. | Time from treatment start to first visit when perianal fistula closure takes place of all external openings that were draining at baseline up to Week 24 | 
| Percentage of Participants Who Achieved Proctitis Remission at Week 24 | The simple endoscopic score for Crohn's disease (SES-CD) score evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and presence of narrowings). The total SES-CD is calculated as the sum of the 4 variables for the required bowel segment. Values are given to each variable and for every examined bowel segment. The SES-CD size of ulcer subscore ranges from 0 (none) to 3 (very large) and for ulcerated surface subscore ranges from 0 (none) to 3 (>30 % of affected area). Higher value of the subscore indicates disease worsening. Proctitis remission at Week 24 was defined as a proctitis SES-CD score (sum of ulcer size and ulcerated surface SES-CD endoscopy subscores for the rectum and anal canal) of 0 assessed by centrally read flexible sigmoidoscopy at Week 24, in participants that had moderately to severely active proctitis at baseline. Moderately to Severely Active Proctitis defined as proctitis SES-CD Score > 2. | Week 24 |