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

Gilead Sciences78 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Small Bowel Crohn's Disease

Interventions

FilgotinibDRUG

Tablet(s) administered orally once daily

Placebo to match filgotinibDRUG

Tablet(s) administered orally once daily

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (38)

Outcomes

Primary Outcomes

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.

Time frame: Week 24

Secondary Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

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University of Miami Crohn's and Colitis Center

Miami, Florida, United States

Center for lnterventional Endoscopy- Florida Hospital

Orlando, Florida, United States

University of South Florida South Tampa campus

Tampa, Florida, United States

Indiana University Health University Hospital

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Gastro Center of Maryland

Columbia, Maryland, United States

Meritus Center for Clinical Research

Hagerstown, Maryland, United States

Clinical Research Institute of Michigan

Chesterfield, Michigan, United States

Fargo Gastroenterology and Hepatology Clinic

Fargo, North Dakota, United States

Gastro One

Germantown, Tennessee, United States

...and 28 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline; Week 24