Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Small Bowel Crohn's Disease (SBCD) (DIVERGENCE 1)
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| ClinicalTrials.gov Identifier: NCT03046056 |
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Recruitment Status :
Completed
First Posted : February 8, 2017
Results First Posted : August 9, 2021
Last Update Posted : August 23, 2021
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Sponsor:
Gilead Sciences
Collaborator:
Galapagos NV
Information provided by (Responsible Party):
Gilead Sciences
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Small Bowel Crohn's Disease | Drug: Filgotinib Drug: Placebo to match filgotinib | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 78 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | April 11, 2017 |
| Actual Primary Completion Date : | July 20, 2020 |
| Actual Study Completion Date : | July 20, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Crohn disease
MedlinePlus related topics:
Crohn's Disease
| Arm | Intervention/treatment |
|---|---|
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Experimental: Filgotinib 200 mg
Filgotinib 200 mg tablet + placebo to match (PTM) filgotinib 100 mg tablet for up to 27 weeks.
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Drug: Filgotinib
Tablet(s) administered orally once daily
Other Names:
Drug: Placebo to match filgotinib Tablet(s) administered orally once daily |
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Experimental: Filgotinib 100 mg
Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet for up to 26.3 weeks.
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Drug: Filgotinib
Tablet(s) administered orally once daily
Other Names:
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 |
Primary Outcome Measures :
- Percentage of Participants Who Achieved Clinical Remission at Week 24 [ Time Frame: 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 :
- Change From Baseline in Terminal Ileum Segmental Magnetic Resonance Index of Activity (MaRIA) Score at Week 24 [ Time Frame: 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.
- Change From Baseline in Distal Ileum Segmental MaRIA Score at Week 24 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 MaRIA Response in Jejunum Segment at Week 24 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03046056
Locations
Show 38 study locations
Sponsors and Collaborators
Gilead Sciences
Galapagos NV
Investigators
| Study Director: | Gilead Study Director | Gilead Sciences |
Study Documents (Full-Text)
Documents provided by Gilead Sciences:
Documents provided by Gilead Sciences:
Study Protocol [PDF] February 4, 2020
Statistical Analysis Plan [PDF] October 1, 2020
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT03046056 |
| Other Study ID Numbers: |
GS-US-419-4015 2016-003179-23 ( EudraCT Number ) |
| First Posted: | February 8, 2017 Key Record Dates |
| Results First Posted: | August 9, 2021 |
| Last Update Posted: | August 23, 2021 |
| Last Verified: | August 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Crohn Disease Inflammatory Bowel Diseases Gastroenteritis |
Gastrointestinal Diseases Digestive System Diseases Intestinal Diseases |