Small Bowel Crohn's Disease
Conditions
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.
Interventions
DRUGFilgotinib
Tablet(s) administered orally once daily
Tablet(s) administered orally once daily
Sponsors
Galapagos NV
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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. |
| 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 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. |
| 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 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. |
| 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. |
Countries
Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Canada, and Europe. The first participant was screened on 11 April 2017. The last study visit occurred on 20 July 2020.
Pre-assignment details
198 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Filgotinib 200 mg Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. | 28 |
| Filgotinib 100 mg Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. | 32 |
| Placebo PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks. | 18 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 | 0 |
| Overall Study | Investigator's Discretion | 0 | 1 | 0 |
| Overall Study | Non-compliance With Study Drug | 0 | 0 | 2 |
| Overall Study | Non-responder at Week 10 | 6 | 6 | 4 |
| Overall Study | Protocol-specified Disease Worsening | 3 | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Withdrew Consent | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Filgotinib 200 mg | Filgotinib 100 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 16.3 | 42 years STANDARD_DEVIATION 12.9 | 45 years STANDARD_DEVIATION 12.9 | 44 years STANDARD_DEVIATION 14.2 |
| Crohn's Disease Activity Index Score (CDAI) | 309 score on scale STANDARD_DEVIATION 55.7 | 297 score on scale STANDARD_DEVIATION 64.9 | 300 score on scale STANDARD_DEVIATION 63.7 | 302 score on scale STANDARD_DEVIATION 60.9 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 26 Participants | 31 Participants | 17 Participants | 74 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 25 Participants | 28 Participants | 16 Participants | 69 Participants |
| Region of Enrollment Austria | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Belgium | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Canada | 0 participants | 4 participants | 1 participants | 5 participants |
| Region of Enrollment Czechia | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment France | 2 participants | 2 participants | 1 participants | 5 participants |
| Region of Enrollment Germany | 0 participants | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Hungary | 0 participants | 3 participants | 1 participants | 4 participants |
| Region of Enrollment Italy | 3 participants | 1 participants | 1 participants | 5 participants |
| Region of Enrollment Spain | 1 participants | 2 participants | 0 participants | 3 participants |
| Region of Enrollment Ukraine | 2 participants | 0 participants | 1 participants | 3 participants |
| Region of Enrollment United Kingdom | 4 participants | 1 participants | 2 participants | 7 participants |
| Region of Enrollment United States | 15 participants | 13 participants | 10 participants | 38 participants |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 9 Participants | 51 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 28 | 0 / 32 | 0 / 18 |
| other Total, other adverse events | 20 / 28 | 24 / 32 | 13 / 18 |
| serious Total, serious adverse events | 4 / 28 | 7 / 32 | 0 / 18 |
Outcome results
Primary
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
Population: Full Analysis Set included all the randomized participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved Clinical Remission at Week 24 | 25.0 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved Clinical Remission at Week 24 | 25.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Clinical Remission at Week 24 | 16.7 percentage of participants |
90% CI: [-16.5, 32.1]
90% CI: [-15.9, 32]
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Filgotinib 200 mg | Change From Baseline in CDAI Scores at Week 10 | -105 score on scale | Standard Error 23.6 |
| Filgotinib 100 mg | Change From Baseline in CDAI Scores at Week 10 | -88 score on scale | Standard Error 22.3 |
| Placebo | Change From Baseline in CDAI Scores at Week 10 | -57 score on scale | Standard Error 26.2 |
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-95, -1]
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-76, 15]
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Filgotinib 200 mg | Change From Baseline in CDAI Scores at Week 24 | -86 score on scale | Standard Error 24.1 |
| Filgotinib 100 mg | Change From Baseline in CDAI Scores at Week 24 | -71 score on scale | Standard Error 22.8 |
| Placebo | Change From Baseline in CDAI Scores at Week 24 | -66 score on scale | Standard Error 26.7 |
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-68, 28]
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-52, 42]
Secondary
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.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Filgotinib 200 mg | Change From Baseline in Distal Ileum Segmental MaRIA Score at Week 24 | -1.1 score on scale | Standard Error 1.12 |
| Filgotinib 100 mg | Change From Baseline in Distal Ileum Segmental MaRIA Score at Week 24 | -0.5 score on scale | Standard Error 1.08 |
| Placebo | Change From Baseline in Distal Ileum Segmental MaRIA Score at Week 24 | 0.5 score on scale | Standard Error 1.26 |
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-3.9, 0.7]
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-3.2, 1.2]
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Filgotinib 200 mg | Change From Baseline in Jejunum Segmental MaRIA Score at Week 24 | 0.4 score on scale | Standard Error 1 |
| Filgotinib 100 mg | Change From Baseline in Jejunum Segmental MaRIA Score at Week 24 | 0.6 score on scale | Standard Error 0.95 |
| Placebo | Change From Baseline in Jejunum Segmental MaRIA Score at Week 24 | 0.5 score on scale | Standard Error 1.12 |
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-2.2, 2]
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-1.9, 2]
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Filgotinib 200 mg | Change From Baseline in Terminal Ileum Segmental Magnetic Resonance Index of Activity (MaRIA) Score at Week 24 | -1.8 score on scale | Standard Error 1.51 |
| Filgotinib 100 mg | Change From Baseline in Terminal Ileum Segmental Magnetic Resonance Index of Activity (MaRIA) Score at Week 24 | 0.7 score on scale | Standard Error 1.39 |
| Placebo | Change From Baseline in Terminal Ileum Segmental Magnetic Resonance Index of Activity (MaRIA) Score at Week 24 | 0.5 score on scale | Standard Error 1.64 |
Comparison: Difference in least squared means (Diff in LSM), and its 90% confidence interval (CI) were from analysis of covariance (ANCOVA) model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-5.3, 0.7]
Comparison: Diff in LSM, and its 90% CI were from ANCOVA model adjusted by baseline segmental MaRIA score, concomitant use of oral, systemically absorbed corticosteroids at baseline, concomitant use of immunomodulators at baseline, prior exposure to biologics, and treatment group.90% CI: [-2.7, 3.1]
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved Early Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 39.3 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved Early Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 25.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Early Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 22.2 percentage of participants |
90% CI: [-7.6, 40.4]
90% CI: [-21.2, 26.5]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in distal ileum segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved MaRIA Remission in Distal Ileum Segment at Week 24 | 10.0 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved MaRIA Remission in Distal Ileum Segment at Week 24 | 0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved MaRIA Remission in Distal Ileum Segment at Week 24 | 16.7 percentage of participants |
90% CI: [-47.3, 37]
90% CI: [-58.2, 30]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in jejunum segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved MaRIA Remission in Jejunum Segment at Week 24 | 33.3 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved MaRIA Remission in Jejunum Segment at Week 24 | 0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved MaRIA Remission in Jejunum Segment at Week 24 | 0 percentage of participants |
90% CI: [-32.4, 86.5]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in terminal ileum segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved MaRIA Remission in Terminal Ileum Segment at Week 24 | 4.5 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved MaRIA Remission in Terminal Ileum Segment at Week 24 | 6.7 percentage of participants |
| Placebo | Percentage of Participants Who Achieved MaRIA Remission in Terminal Ileum Segment at Week 24 | 6.3 percentage of participants |
90% CI: [-28.6, 25.5]
90% CI: [-24.5, 26.2]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in distal ileum segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved MaRIA Response in Distal Ileum Segment at Week 24 | 20.0 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved MaRIA Response in Distal Ileum Segment at Week 24 | 12.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved MaRIA Response in Distal Ileum Segment at Week 24 | 16.7 percentage of participants |
90% CI: [-38.9, 45.7]
90% CI: [-47.5, 40.8]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in jejunum segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved MaRIA Response in Jejunum Segment at Week 24 | 50.0 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved MaRIA Response in Jejunum Segment at Week 24 | 12.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved MaRIA Response in Jejunum Segment at Week 24 | 0 percentage of participants |
90% CI: [-16.8, 89.5]
90% CI: [-46.1, 63.3]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in terminal ileum segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved MaRIA Response in Terminal Ileum Segment at Week 24 | 22.7 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved MaRIA Response in Terminal Ileum Segment at Week 24 | 10.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved MaRIA Response in Terminal Ileum Segment at Week 24 | 25.0 percentage of participants |
90% CI: [-28.6, 24.3]
90% CI: [-39.4, 11.3]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in at least 1 small bowel segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Remission at Week 24 | 8.0 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Remission at Week 24 | 6.3 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Remission at Week 24 | 0 percentage of participants |
90% CI: [-17.2, 32.6]
90% CI: [-18.1, 30.2]
Secondary
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
Population: Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in at least 1 small bowel segment at baseline, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Response at Week 24 | 20.0 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Response at Week 24 | 12.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Response at Week 24 | 16.7 percentage of participants |
90% CI: [-22.1, 28.1]
90% CI: [-28.1, 20.3]