Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease (Divergence2)

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

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.

Study Overview

• Status: Completed
• Conditions: Fistulizing Crohn's Disease
• Intervention / Treatment: Drug: Filgotinib; Drug: Placebo to match filgotinib

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt am Wörthersee
  • Vienna, Austria, 1090
    • Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology
• Belgium
  • Leuven, Belgium, B-3000
    • Universitaire Ziekenhuizen Leuven
• Canada
  • Toronto, Canada, M5T 3L9
    • Mount Sinai Hospital
  • Toronto, Canada, M9V 4B8
    • Toronto Digestive Disease Associates Inc.
• France
  • La Tronche, France, 38700
    • CHU Grenoble Alpes - Hopital Michallon (main office)
  • RENNES Cedex 9, France, 85809
    • CHU de Rennes - Hôpital Pontchaillou (main office)
  • Vandœuvre-lès-Nancy, France, 54511
    • CHU Nancy - Hôpital de Brabois
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus an der TU Dresden
  • Jena, Germany, 07747
    • Universitatsklinkum Jena
• Hungary
  • Bekes
    • Bekescsaba, Bekes, Hungary, 5600
      • Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
  • Heves
    • Gyöngyös, Heves, Hungary, 3200
      • Bugát Pál Kórház, Gasztroenterológiai osztály
• Italy
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas
• United Kingdom
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital, Department of Gastroenterology
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Crohn's and Colitis Center
    • Orlando, Florida, United States, 32804
      • Center for Interventional Endoscopy - Florida Hospital
    • Tampa, Florida, United States, 33606
      • University of South Florida South Tampa Campus
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Clinical Trials Unit
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • John Hopkins Gastroenterology and Hepatology Services at the Green Spring Station Clinic
    • Columbia, Maryland, United States, 21045
      • Gastro Center of Maryland
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37212-2702
      • Vanderbilt University Medical Center - IBD Clinic
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Garland, Texas, United States, 75044
      • DHAT Research Institute
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire DVAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Filgotinib 200 mg; Filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks	Drug: Filgotinib; Tablet(s) administered orally once daily; Other Names: GS-6034; GLPG0634; Drug: Placebo to match filgotinib; Tablet(s) administered orally once daily
Experimental: Filgotinib 100 mg; Filgotinib 100 mg + placebo to match filgotinib 200 mg for 24 weeks	Drug: Filgotinib; Tablet(s) administered orally once daily; Other Names: GS-6034; GLPG0634; Drug: Placebo to match filgotinib; Tablet(s) administered orally once daily
Experimental: Placebo; Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks	Drug: Placebo to match filgotinib; Tablet(s) administered orally once daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Galapagos NV

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2017
• Primary Completion (Actual): January 20, 2021
• Study Completion (Actual): February 17, 2021

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: GS-US-419-4016; 2016-003153-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No