Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Small Bowel Crohn's Disease (SBCD) (DIVERGENCE 1)

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of Filgotinib in the Treatment of Small Bowel Crohn's Disease (SBCD)

The primary objective of this study is to evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical remission defined as Crohn's disease activity index (CDAI) < 150, at Week 24 in participants with small bowel Crohn's disease (CD). Participants will have the option to enter a separate long-term extension study if they meet eligibility requirements.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medical University of Innsbruck, Department of Internal Medicine I
  • Vienna, Austria, 1090
    • Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology
• Belgium
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Liège, Belgium, 4000
    • Centre Hospitalier Chretien
• Canada
  • Toronto, Canada, M5T 3L9
    • Mount Sinai Hospital
  • Victoria, Canada, V8V 3M9
    • PerCuro Clinical Research Ltd.
• Czechia
  • Hradec Kralove, Czechia, 500 12
    • Hepato-Gastroenterologie HK, s.r.o.
• France
  • Midi-Pyrenees
    • Toulouse Cedex 9, Midi-Pyrenees, France, 31059
      • CHU de Toulouse -Hopital Rangueil (Main Office)
• Germany
  • Hannover, Germany, 30625
    • Gastroenterologie, Hepatologie und Endokrinologie
  • Jena, Germany, 07747
    • Universitätsklinikum Jena
• Hungary
  • Békéscsaba, Hungary, 5600
    • Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaza
  • Heves
    • Gyöngyös, Heves, Hungary, 3200
      • Bugát Pál Kórház, Gasztroenterológiai osztály
• Italy
  • Catanzaro, Italy, 88100
    • Azienda Ospedaliero - Universitaria Mater Domini
  • Rome, Italy, 00128
    • Gastroenterologia, Policlinico Universitario Campus Bio-Medico di Roma
• Spain
  • Las Palmas De Gran Canaria, Spain, 35016
    • Hospital Universitario Gran Canaria Dr. Negrin
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital Universitario de Fuenlabrada
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Central City Clinical Hospital, Department of Therapy #1, SHEI Ivano-Frankivsk National Medical University
  • Kharkiv, Ukraine, 61137
    • Communal Healthcare Institution Regional Hospital of War Veterans, Department of Therapy #1
  • Ternopil, Ukraine, 46002
    • Communal Institution of Ternopil Regional Council Ternopil University Hospital. Regional Center of Gastroenterology
• United Kingdom
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital, Department of Gastroenterology
  • London, United Kingdom, SW17 0QT
    • St Georges Clinical Research Facility
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Queen Elizabeth University Hospital
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Crohn's and Colitis Center
    • Orlando, Florida, United States, 32804
      • Center for lnterventional Endoscopy- Florida Hospital
    • Tampa, Florida, United States, 33606
      • University of South Florida South Tampa Campus
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health University Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Gastro Center of Maryland
    • Hagerstown, Maryland, United States, 21742
      • Meritus Center for Clinical Research
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Fargo Gastroenterology and Hepatology Clinic
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • San Antonio, Texas, United States, 78229
      • Gastroenterology Research of San Antonio
    • San Marcos, Texas, United States, 78666
      • TDDC San Marcos
    • 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: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Males or non-pregnant, nonlactating females, ages 18 to 75 years, inclusive based on the date of screening visit
• Moderately or severely active CD
• Minimum duration of CD of at least 6 months
• Presence of diseased small bowel (SB) segments in at least 1 of the following segments: terminal ileum, distal ileum, or jejunum
• Patients with additional colonic involvement of CD are permitted in study as long as SBCD is present

• Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least 1 of the following agents (depending on current country treatment recommendations/guidelines):

  • Corticosteroids
  • Immunomodulators
  • Tumor necrosis factor-alpha (TNFα) antagonists
  • Vedolizumab
  • Ustekinumab
• Willing and able to undergo magnetic resonance enterography (MRE) per protocol requirements

Key Exclusion Criteria:

• Presence of symptomatic or clinically significant (eg, obstructive or symptomatic) strictures or stenosis.
• Presence of fistulae
• Evidence of short bowel syndrome
• Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon
• History of total colectomy, subtotal-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 tablet + placebo to match (PTM) filgotinib 100 mg tablet for up to 27 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 tablet + PTM filgotinib 200 mg tablet for up to 26.3 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
Placebo Comparator: Placebo; PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet for up to 28.7 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 Clinical Remission at Week 24	The CDAI score is used to quantify the symptoms of participants with Crohn's Disease (CD). The score ranges from 0 to 600. Clinical remission by CDAI was defined as a score of < 150. A higher score indicates more severe disease.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Terminal Ileum Segmental Magnetic Resonance Index of Activity (MaRIA) Score at Week 24	Magnetic resonance enterography (MRE) is an imaging technique to evaluate disease activity in CD. MaRIA is an MRE-based scoring system. The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and relative contrast enhancement (RCE). A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these components for the terminal ileum segment of the small bowel. A segmental score of ≥ 7 indicates active inflammation and a score of ≥ 11 indicates the presence of an ulcer. Segmental scores less than 7 indicate remission. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. Difference in least squared means (Diff in LSM) were from analysis of covariance (ANCOVA) model. A negative change from baseline indicates improvement and a positive change from baseline indicates disease worsening.	Baseline; Week 24
Change From Baseline in Distal Ileum Segmental MaRIA Score at Week 24	MRE is an imaging technique to evaluate disease activity in CD. MaRIA is an MRE-based scoring system. The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at Screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the distal ileum segment of the small bowel. A segmental score of ≥ 7 indicates active inflammation and a score of ≥ 11 indicates the presence of an ulcer. Segmental scores less than 7 indicate remission in that segment. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. Diff in LSM were from ANCOVA model. A negative change from baseline indicates improvement and a positive change from baseline indicates disease worsening.	Baseline; Week 24
Change From Baseline in Jejunum Segmental MaRIA Score at Week 24	MRE is an imaging technique to evaluate disease activity in CD. MaRIA is an MRE-based scoring system.The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at Screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the jejunum segment of the small bowel. A segmental score of ≥ 7 indicates active inflammation and a score of ≥ 11 indicates the presence of an ulcer. Segmental scores less than 7 indicate remission in that segment. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. Diff in LSM were from ANCOVA model. A positive change from baseline indicates disease worsening.	Baseline; Week 24
Percentage of Participants Who Achieved MaRIA Remission in Terminal Ileum Segment at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the terminal ileum segment of the small bowel. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. MaRIA remission was defined as a segmental MaRIA score < 7 in terminal ileum segment at Week 24 among participants with MaRIA score ≥ 7 in the same segment at baseline. A segmental score of ≥ 7 indicates active inflammation and a score of ≥ 11 indicates the presence of an ulcer.	Week 24
Percentage of Participants Who Achieved MaRIA Remission in Distal Ileum Segment at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the distal ileum segment of the small bowel. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. MaRIA remission was defined as a segmental MaRIA score < 7 in distal ileum segment at Week 24 among participants with MaRIA score ≥ 7 in the same segment at baseline. A segmental score of ≥ 7 indicates active inflammation and a score of ≥ 11 indicates the presence of an ulcer.	Week 24
Percentage of Participants Who Achieved MaRIA Remission in Jejunum Segment at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the jejunum segment of the small bowel. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. MaRIA remission was defined as a segmental MaRIA score < 7 in jejunum segment at Week 24 among participants with MaRIA score ≥ 7 in the same segment at baseline. A segmental score of ≥ 7 indicates active inflammation and a score of ≥ 11 indicates the presence of an ulcer.	Week 24
Percentage of Participants Who Achieved MaRIA Response in Terminal Ileum Segment at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the terminal ileum segment of the small bowel. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. MaRIA response was defined as a segmental MaRIA score < 11 with baseline score ≥ 11, or a segmental MaRIA score < 7 with baseline score < 11, or ≥ minimum detectable difference (MDD) units decrease from baseline score for segments with baseline MaRIA score ≥ 7 in the terminal ileum. For segments with baseline MaRIA score ≥ 15, the MDD is 6.5 units and for baseline MaRIA score < 15, the MDD is 4.0 units.	Week 24
Percentage of Participants Who Achieved MaRIA Response in Distal Ileum Segment at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the distal ileum segment of the small bowel. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. MaRIA response was defined as a segmental MaRIA score < 11 with baseline score ≥ 11, or a segmental MaRIA score < 7 with baseline score < 11, or ≥ MDD units decrease from baseline score for segments with baseline MaRIA score≥ 7 in the distal ileum. For segments with baseline MaRIA score ≥ 15, the minimum detectable difference (MDD) is 6.5 units and for baseline MaRIA score < 15, the MDD is 4.0 units.	Week 24
Percentage of Participants Who Achieved MaRIA Response in Jejunum Segment at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for the jejunum segment of the small bowel. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. MaRIA response was defined as a segmental MaRIA score < 11 with baseline score ≥ 11, or a segmental MaRIA score < 7 with baseline score < 11, or ≥ MDD units decrease from baseline score for segments with baseline MaRIA score ≥ 7 in the jejunum. For segments with baseline MaRIA score ≥ 15, the MDD is 6.5 units and for baseline MaRIA score < 15, the MDD is 4.0 units.	Week 24
Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Remission at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for each of the 3 small bowel segments. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. Small bowel MaRIA remission was defined as MaRIA score < 7 at Week 24 in each of the 3 small bowel segments, among participants with MaRIA score ≥ 7 in at least 1 small bowel segment at baseline.	Week 24
Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Response at Week 24	The MaRIA scoring system is a composite index of 4 components. These components are edema, ulcers, gut wall thickness, and RCE. A segmental MaRIA score can be calculated at screening (used as the baseline) and Week 24 as a weighted sum of these 4 components for each of the 3 small bowel segments. The MaRIA score ranges from approximately 0 to 31, for any given segment. A higher score indicates more severe disease. Participant level small bowel MaRIA response was defined as all small bowel segments with baseline MaRIA score ≥7 achieve segment level MaRIA response, with no segment level disease worsening in any other segment(s) at Week 24, among participants with MaRIA score ≥ 7 in at least 1 small bowel segment at baseline.	Week 24
Percentage of Participants Who Achieved Early Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10	The CDAI score is used to quantify the symptoms of participants with CD. The score ranges from 0 to 600. Clinical remission by CDAI was defined as a score of < 150. A higher score indicates more severe disease.	Week 10
Change From Baseline in CDAI Scores at Week 10	The CDAI score is used to quantify the symptoms of participants with CD. The score ranges from 0 to 600. A score of < 150 indicates remission. A higher score indicates more severe disease. Difference in least squared means (Diff in LSM) were from analysis of covariance (ANCOVA) model. A negative change from baseline indicates improvement.	Baseline; Week 10
Change From Baseline in CDAI Scores at Week 24	The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. The score ranges from 0 to 600. A score of < 150 indicates remission. A higher score indicates more severe disease. Diff in LSM were from ANCOVA model. A negative change from baseline indicates improvement.	Baseline; Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Galapagos NV

Publications and helpful links

General Publications

• Riviere P, D'Haens G, Peyrin-Biroulet L, Baert F, Lambrecht G, Pariente B, Bossuyt P, Buisson A, Oldenburg B, Vermeire S, Laharie D. Location but Not Severity of Endoscopic Lesions Influences Endoscopic Remission Rates in Crohn's Disease: A Post Hoc Analysis of TAILORIX. Am J Gastroenterol. 2021 Jan 1;116(1):134-141. doi: 10.14309/ajg.0000000000000834.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2017
• Primary Completion (Actual): July 20, 2020
• Study Completion (Actual): July 20, 2020

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 6, 2017
• First Posted (Estimate): February 8, 2017

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: August 1, 2021

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-419-4015; 2016-003179-23 (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