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

Primary Purpose

Fistulizing Crohn's Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Filgotinib
Placebo to match filgotinib
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fistulizing Crohn's Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Miami Crohn's and Colitis Center
  • Center for Interventional Endoscopy - Florida Hospital
  • University of South Florida South Tampa Campus
  • Northwestern University Feinberg School of Medicine
  • University of Louisville Clinical Trials Unit
  • John Hopkins Gastroenterology and Hepatology Services at the Green Spring Station Clinic
  • Gastro Center of Maryland
  • Gastro One
  • Vanderbilt University Medical Center - IBD Clinic
  • Texas Clinical Research Institute
  • DHAT Research Institute
  • Texas Digestive Disease Consultants
  • McGuire DVAMC
  • Klinikum Klagenfurt am Wörthersee
  • Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology
  • Universitaire Ziekenhuizen Leuven
  • Mount Sinai Hospital
  • Toronto Digestive Disease Associates Inc.
  • CHU Grenoble Alpes - Hopital Michallon (main office)
  • CHU de Rennes - Hôpital Pontchaillou (main office)
  • CHU Nancy - Hopital de Brabois
  • Universitätsklinikum Carl Gustav Carus an der TU Dresden
  • Universitatsklinkum Jena
  • Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórháza
  • Bugát Pál Kórház, Gasztroenterológiai osztály
  • Istituto Clinico Humanitas
  • Royal Devon and Exeter Hospital, Department of Gastroenterology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Filgotinib 200 mg

Filgotinib 100 mg

Placebo

Arm Description

Filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks

Filgotinib 100 mg + placebo to match filgotinib 200 mg for 24 weeks

Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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 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.
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.

Full Information

First Posted
March 8, 2017
Last Updated
April 7, 2022
Sponsor
Gilead Sciences
Collaborators
Galapagos NV
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1. Study Identification

Unique Protocol Identification Number
NCT03077412
Brief Title
Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease
Acronym
Divergence2
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
April 6, 2017 (Actual)
Primary Completion Date
January 20, 2021 (Actual)
Study Completion Date
February 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
Collaborators
Galapagos NV

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fistulizing Crohn's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Filgotinib 200 mg
Arm Type
Experimental
Arm Description
Filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks
Arm Title
Filgotinib 100 mg
Arm Type
Experimental
Arm Description
Filgotinib 100 mg + placebo to match filgotinib 200 mg for 24 weeks
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Filgotinib
Other Intervention Name(s)
GS-6034, GLPG0634
Intervention Description
Tablet(s) administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo to match filgotinib
Intervention Description
Tablet(s) administered orally once daily
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Combined Fistula Response at Week 24
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Combined Fistula Remission at Week 24
Description
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.
Time Frame
Week 24
Title
Time to Clinical Fistula Response up to Week 24
Description
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 Frame
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
Title
Time to Clinical Fistula Remission up to Week 24
Description
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 Frame
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
Title
Percentage of Participants Who Achieved Proctitis Remission at Week 24
Description
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.
Time Frame
Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Miami Crohn's and Colitis Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Center for Interventional Endoscopy - Florida Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
University of South Florida South Tampa Campus
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Louisville Clinical Trials Unit
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
John Hopkins Gastroenterology and Hepatology Services at the Green Spring Station Clinic
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Gastro Center of Maryland
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21045
Country
United States
Facility Name
Gastro One
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Vanderbilt University Medical Center - IBD Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212-2702
Country
United States
Facility Name
Texas Clinical Research Institute
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
DHAT Research Institute
City
Garland
State/Province
Texas
ZIP/Postal Code
75044
Country
United States
Facility Name
Texas Digestive Disease Consultants
City
Southlake
State/Province
Texas
ZIP/Postal Code
76092
Country
United States
Facility Name
McGuire DVAMC
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Klinikum Klagenfurt am Wörthersee
City
Klagenfurt
ZIP/Postal Code
9020
Country
Austria
Facility Name
Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Universitaire Ziekenhuizen Leuven
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Mount Sinai Hospital
City
Toronto
ZIP/Postal Code
M5T 3L9
Country
Canada
Facility Name
Toronto Digestive Disease Associates Inc.
City
Toronto
ZIP/Postal Code
M9V 4B8
Country
Canada
Facility Name
CHU Grenoble Alpes - Hopital Michallon (main office)
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
CHU de Rennes - Hôpital Pontchaillou (main office)
City
RENNES Cedex 9
ZIP/Postal Code
85809
Country
France
Facility Name
CHU Nancy - Hopital de Brabois
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Universitätsklinikum Carl Gustav Carus an der TU Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitatsklinkum Jena
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórháza
City
Bekescsaba
State/Province
Bekes
ZIP/Postal Code
5600
Country
Hungary
Facility Name
Bugát Pál Kórház, Gasztroenterológiai osztály
City
Gyöngyös
State/Province
Heves
ZIP/Postal Code
3200
Country
Hungary
Facility Name
Istituto Clinico Humanitas
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
Facility Name
Royal Devon and Exeter Hospital, Department of Gastroenterology
City
Exeter
ZIP/Postal Code
EX2 5DW
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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