Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Small Bowel Crohn's Disease (SBCD)
- Conditions
- Small Bowel Crohn's Disease
- Interventions
- Registration Number
- NCT03046056
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 78
-
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Filgotinib 200 mg Placebo to match filgotinib Filgotinib 200 mg tablet + placebo to match (PTM) filgotinib 100 mg tablet for up to 27 weeks. Placebo Placebo to match filgotinib PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet for up to 28.7 weeks. Filgotinib 100 mg Placebo to match filgotinib Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet for up to 26.3 weeks. Filgotinib 200 mg Filgotinib Filgotinib 200 mg tablet + placebo to match (PTM) filgotinib 100 mg tablet for up to 27 weeks. Filgotinib 100 mg Filgotinib Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet for up to 26.3 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved Clinical Remission at Week 24 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Terminal Ileum Segmental Magnetic Resonance Index of Activity (MaRIA) Score at Week 24 Baseline; 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.
Percentage of Participants Who Achieved MaRIA Remission in Terminal Ileum Segment at Week 24 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.
Percentage of Participants Who Achieved MaRIA Response in Terminal Ileum Segment at Week 24 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.
Percentage of Participants Who Achieved MaRIA Response in Distal Ileum Segment at Week 24 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.
Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Remission at Week 24 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.
Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Response at Week 24 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.
Percentage of Participants Who Achieved Early Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 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.
Change From Baseline in CDAI Scores at Week 10 Baseline; 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.
Change From Baseline in Distal Ileum Segmental MaRIA Score at Week 24 Baseline; 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.
Change From Baseline in Jejunum Segmental MaRIA Score at Week 24 Baseline; 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.
Percentage of Participants Who Achieved MaRIA Remission in Distal Ileum Segment at Week 24 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.
Percentage of Participants Who Achieved MaRIA Remission in Jejunum Segment at Week 24 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.
Percentage of Participants Who Achieved MaRIA Response in Jejunum Segment at Week 24 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.
Change From Baseline in CDAI Scores at Week 24 Baseline; 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.
Trial Locations
- Locations (38)
Gastro One
🇺🇸Germantown, Tennessee, United States
Medical University of Innsbruck, Department of Internal Medicine I
🇦🇹Innsbruck, Austria
University of Miami Crohn's and Colitis Center
🇺🇸Miami, Florida, United States
Indiana University Health University Hospital
🇺🇸Indianapolis, Indiana, United States
Gastro Center of Maryland
🇺🇸Columbia, Maryland, United States
Fargo Gastroenterology and Hepatology Clinic
🇺🇸Fargo, North Dakota, United States
Center for lnterventional Endoscopy- Florida Hospital
🇺🇸Orlando, Florida, United States
University of South Florida South Tampa campus
🇺🇸Tampa, Florida, United States
Clinical Research Institute of Michigan
🇺🇸Chesterfield, Michigan, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
Meritus Center for Clinical Research
🇺🇸Hagerstown, Maryland, United States
Gastroenterology Research of San Antonio
🇺🇸San Antonio, Texas, United States
McGuire DVAMC
🇺🇸Richmond, Virginia, United States
TDDC San Marcos
🇺🇸San Marcos, Texas, United States
Texas Digestive Disease Consultants
🇺🇸Southlake, Texas, United States
Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology
🇦🇹Vienna, Austria
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Mount Sinai Hospital
🇨🇦Toronto, Canada
Centre Hospitalier Chretien
🇧🇪Liège, Belgium
PerCuro Clinical Research Ltd.
🇨🇦Victoria, Canada
CHU de Toulouse -Hopital Rangueil (Main Office)
🇫🇷Toulouse Cedex 9, Midi-Pyrenees, France
Hepato-Gastroenterologie HK, s.r.o.
🇨🇿Hradec Kralove, Czechia
Universitatsklinikum Jena
🇩🇪Jena, Germany
Gastroenterologie, Hepatologie und Endokrinologie
🇩🇪Hannover, Germany
Bugát Pál Kórház, Gasztroenterológiai osztály
🇭🇺Gyöngyös, Heves, Hungary
Azienda Ospedaliero - Universitaria Mater Domini
🇮🇹Catanzaro, Italy
Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórháza
🇭🇺Békéscsaba, Hungary
Hospital Universitario de Fuenlabrada
🇪🇸Fuenlabrada, Madrid, Spain
Gastroenterologia, Policlinico Universitario Campus Bio-Medico di Roma
🇮🇹Rome, Italy
Communal Institution of Ternopil Regional Council Ternopil University Hospital. Regional Center of Gastroenterology
🇺🇦Ternopil, Ukraine
Communal Healthcare Institution Regional Hospital of War Veterans, Department of Therapy #1
🇺🇦Kharkiv, Ukraine
Hospital Universitario Gran Canaria Dr. Negrin
🇪🇸Las Palmas De Gran Canaria, Spain
Ivano-Frankivsk Central City Clinical Hospital, Department of Therapy #1, SHEI Ivano-Frankivsk National Medical University
🇺🇦Ivano-Frankivsk, Ukraine
Queen Elizabeth University Hospital
🇬🇧Glasgow, Scotland, United Kingdom
St Georges Clinical Research Facility
🇬🇧London, United Kingdom
Royal Devon and Exeter Hospital, Department of Gastroenterology
🇬🇧Exeter, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States