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

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT03046056
Collaborator
Galapagos NV (Industry)
78
Enrollment
38
Locations
3
Arms
39.3
Actual Duration (Months)
2.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 2

Study Design

Study Type:
Interventional
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 :
Apr 11, 2017
Actual Primary Completion Date :
Jul 20, 2020
Actual Study Completion Date :
Jul 20, 2020

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Miami Crohn's and Colitis Center Miami Florida United States 33136
    2 Center for lnterventional Endoscopy- Florida Hospital Orlando Florida United States 32804
    3 University of South Florida South Tampa campus Tampa Florida United States 33606
    4 Indiana University Health University Hospital Indianapolis Indiana United States 46202
    5 University of Kansas Medical Center Kansas City Kansas United States 66160
    6 Gastro Center of Maryland Columbia Maryland United States 21045
    7 Meritus Center for Clinical Research Hagerstown Maryland United States 21742
    8 Clinical Research Institute of Michigan Chesterfield Michigan United States 48047
    9 Fargo Gastroenterology and Hepatology Clinic Fargo North Dakota United States 58103
    10 Gastro One Germantown Tennessee United States 38138
    11 Texas Clinical Research Institute Arlington Texas United States 76012
    12 Gastroenterology Research of San Antonio San Antonio Texas United States 78229
    13 TDDC San Marcos San Marcos Texas United States 78666
    14 Texas Digestive Disease Consultants Southlake Texas United States 76092
    15 McGuire DVAMC Richmond Virginia United States 23249
    16 Medical University of Innsbruck, Department of Internal Medicine I Innsbruck Austria 6020
    17 Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology Vienna Austria 1090
    18 Universitair Ziekenhuis Antwerpen Edegem Belgium 2650
    19 Centre Hospitalier Chretien Liège Belgium 4000
    20 Mount Sinai Hospital Toronto Canada M5T 3L9
    21 PerCuro Clinical Research Ltd. Victoria Canada V8V 3M9
    22 Hepato-Gastroenterologie HK, s.r.o. Hradec Kralove Czechia 500 12
    23 CHU de Toulouse -Hopital Rangueil (Main Office) Toulouse Cedex 9 Midi-Pyrenees France 31059
    24 Gastroenterologie, Hepatologie und Endokrinologie Hannover Germany 30625
    25 Universitatsklinikum Jena Jena Germany 07747
    26 Bugát Pál Kórház, Gasztroenterológiai osztály Gyöngyös Heves Hungary 3200
    27 Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórháza Békéscsaba Hungary 5600
    28 Azienda Ospedaliero - Universitaria Mater Domini Catanzaro Italy 88100
    29 Gastroenterologia, Policlinico Universitario Campus Bio-Medico di Roma Rome Italy 00128
    30 Hospital Universitario de Fuenlabrada Fuenlabrada Madrid Spain 28942
    31 Hospital Universitario Gran Canaria Dr. Negrin Las Palmas De Gran Canaria Spain 35016
    32 Ivano-Frankivsk Central City Clinical Hospital, Department of Therapy #1, SHEI Ivano-Frankivsk National Medical University Ivano-Frankivsk Ukraine 76018
    33 Communal Healthcare Institution Regional Hospital of War Veterans, Department of Therapy #1 Kharkiv Ukraine 61137
    34 Communal Institution of Ternopil Regional Council Ternopil University Hospital. Regional Center of Gastroenterology Ternopil Ukraine 46002
    35 Queen Elizabeth University Hospital Glasgow Scotland United Kingdom G51 4TF
    36 Royal Devon and Exeter Hospital, Department of Gastroenterology Exeter United Kingdom EX2 5DW
    37 St Georges Clinical Research Facility London United Kingdom SW17 0QT
    38 John Radcliffe Hospital Oxford United Kingdom OX3 9DU

    Sponsors and Collaborators

    • Gilead Sciences
    • Galapagos NV

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT03046056
    Other Study ID Numbers:
    • GS-US-419-4015
    • 2016-003179-23
    First Posted:
    Feb 8, 2017
    Last Update Posted:
    Aug 23, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    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:
    Crohn Disease

    Study Results

    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 Detail 198 participants were screened.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + placebo to match (PTM) filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Period Title: Overall Study
    STARTED 28 32 18
    COMPLETED 16 16 11
    NOT COMPLETED 12 16 7

    Baseline Characteristics

    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo Total
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks. Total of all reporting groups
    Overall Participants 28 32 18 78
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    46
    (16.3)
    42
    (12.9)
    45
    (12.9)
    44
    (14.2)
    Sex: Female, Male (Count of Participants)
    Female
    19
    67.9%
    23
    71.9%
    9
    50%
    51
    65.4%
    Male
    9
    32.1%
    9
    28.1%
    9
    50%
    27
    34.6%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    7.1%
    4
    12.5%
    2
    11.1%
    8
    10.3%
    Native Hawaiian or Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    25
    89.3%
    28
    87.5%
    16
    88.9%
    69
    88.5%
    Other
    1
    3.6%
    0
    0%
    0
    0%
    1
    1.3%
    Not Permitted
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    Not Hispanic or Latino
    26
    92.9%
    31
    96.9%
    17
    94.4%
    74
    94.9%
    Hispanic or Latino
    2
    7.1%
    1
    3.1%
    1
    5.6%
    4
    5.1%
    Not Permitted
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    15
    53.6%
    13
    40.6%
    10
    55.6%
    38
    48.7%
    Hungary
    0
    0%
    3
    9.4%
    1
    5.6%
    4
    5.1%
    Czechia
    0
    0%
    1
    3.1%
    0
    0%
    1
    1.3%
    Ukraine
    2
    7.1%
    0
    0%
    1
    5.6%
    3
    3.8%
    United Kingdom
    4
    14.3%
    1
    3.1%
    2
    11.1%
    7
    9%
    Spain
    1
    3.6%
    2
    6.3%
    0
    0%
    3
    3.8%
    Canada
    0
    0%
    4
    12.5%
    1
    5.6%
    5
    6.4%
    Austria
    1
    3.6%
    1
    3.1%
    0
    0%
    2
    2.6%
    Belgium
    0
    0%
    2
    6.3%
    0
    0%
    2
    2.6%
    Italy
    3
    10.7%
    1
    3.1%
    1
    5.6%
    5
    6.4%
    France
    2
    7.1%
    2
    6.3%
    1
    5.6%
    5
    6.4%
    Germany
    0
    0%
    2
    6.3%
    1
    5.6%
    3
    3.8%
    Crohn's Disease Activity Index Score (CDAI) (score on scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on scale]
    309
    (55.7)
    297
    (64.9)
    300
    (63.7)
    302
    (60.9)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Who Achieved Clinical Remission at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set included all the randomized participants who received at least one dose of the study drug.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 28 32 18
    Number (90% Confidence Interval) [percentage of participants]
    25.0
    89.3%
    25.0
    78.1%
    16.7
    92.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 8.3
    Confidence Interval (2-Sided) 90%
    -16.5 to 32.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 8.3
    Confidence Interval (2-Sided) 90%
    -15.9 to 32.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in Terminal Ileum Segmental Magnetic Resonance Index of Activity (MaRIA) Score at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 28 32 18
    Least Squares Mean (Standard Error) [score on scale]
    -1.8
    (1.51)
    0.7
    (1.39)
    0.5
    (1.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -2.3
    Confidence Interval (2-Sided) 90%
    -5.3 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.81
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value 0.2
    Confidence Interval (2-Sided) 90%
    -2.7 to 3.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.72
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in Distal Ileum Segmental MaRIA Score at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 28 32 18
    Least Squares Mean (Standard Error) [score on scale]
    -1.1
    (1.12)
    -0.5
    (1.08)
    0.5
    (1.26)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.6
    Confidence Interval (2-Sided) 90%
    -3.9 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.38
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 90%
    -3.2 to 1.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.32
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in Jejunum Segmental MaRIA Score at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 28 32 18
    Least Squares Mean (Standard Error) [score on scale]
    0.4
    (1.00)
    0.6
    (0.95)
    0.5
    (1.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 90%
    -2.2 to 2.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.24
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 90%
    -1.9 to 2.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.18
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants Who Achieved MaRIA Remission in Terminal Ileum Segment at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in terminal ileum segment at baseline, were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 22 30 16
    Number (90% Confidence Interval) [percentage of participants]
    4.5
    16.1%
    6.7
    20.9%
    6.3
    35%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value -1.7
    Confidence Interval (2-Sided) 90%
    -28.6 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 0.4
    Confidence Interval (2-Sided) 90%
    -24.5 to 26.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants Who Achieved MaRIA Remission in Distal Ileum Segment at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in distal ileum segment at baseline, were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 10 8 6
    Number (90% Confidence Interval) [percentage of participants]
    10.0
    35.7%
    0
    0%
    16.7
    92.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value -6.7
    Confidence Interval (2-Sided) 90%
    -47.3 to 37.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value -16.7
    Confidence Interval (2-Sided) 90%
    -58.2 to 30.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants Who Achieved MaRIA Remission in Jejunum Segment at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in jejunum segment at baseline, were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 6 8 3
    Number (90% Confidence Interval) [percentage of participants]
    33.3
    118.9%
    0
    0%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 33.3
    Confidence Interval (2-Sided) 90%
    -32.4 to 86.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Percentage of Participants Who Achieved MaRIA Response in Terminal Ileum Segment at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in terminal ileum segment at baseline, were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 22 30 16
    Number (90% Confidence Interval) [percentage of participants]
    22.7
    81.1%
    10.0
    31.3%
    25.0
    138.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value -2.3
    Confidence Interval (2-Sided) 90%
    -28.6 to 24.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value -15.0
    Confidence Interval (2-Sided) 90%
    -39.4 to 11.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Percentage of Participants Who Achieved MaRIA Response in Distal Ileum Segment at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in distal ileum segment at baseline, were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 10 8 6
    Number (90% Confidence Interval) [percentage of participants]
    20.0
    71.4%
    12.5
    39.1%
    16.7
    92.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 3.3
    Confidence Interval (2-Sided) 90%
    -38.9 to 45.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value -4.2
    Confidence Interval (2-Sided) 90%
    -47.5 to 40.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Percentage of Participants Who Achieved MaRIA Response in Jejunum Segment at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with active disease (segmental MaRIA score ≥ 7) in jejunum segment at baseline, were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 6 8 3
    Number (90% Confidence Interval) [percentage of participants]
    50.0
    178.6%
    12.5
    39.1%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 50.0
    Confidence Interval (2-Sided) 90%
    -16.8 to 89.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 12.5
    Confidence Interval (2-Sided) 90%
    -46.1 to 63.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Remission at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 25 32 18
    Number (90% Confidence Interval) [percentage of participants]
    8.0
    28.6%
    6.3
    19.7%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 8.0
    Confidence Interval (2-Sided) 90%
    -17.2 to 32.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 6.3
    Confidence Interval (2-Sided) 90%
    -18.1 to 30.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Percentage of Participants Who Achieved Participant Level Small Bowel MaRIA Response at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 25 32 18
    Number (90% Confidence Interval) [percentage of participants]
    20.0
    71.4%
    12.5
    39.1%
    16.7
    92.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 3.3
    Confidence Interval (2-Sided) 90%
    -22.1 to 28.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value -4.2
    Confidence Interval (2-Sided) 90%
    -28.1 to 20.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Percentage of Participants Who Achieved Early Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 28 32 18
    Number (90% Confidence Interval) [percentage of participants]
    39.3
    140.4%
    25.0
    78.1%
    22.2
    123.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 17.1
    Confidence Interval (2-Sided) 90%
    -7.6 to 40.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference in Proportions
    Estimated Value 2.8
    Confidence Interval (2-Sided) 90%
    -21.2 to 26.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Change From Baseline in CDAI Scores at Week 10
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 28 32 18
    Least Squares Mean (Standard Error) [score on scale]
    -105
    (23.6)
    -88
    (22.3)
    -57
    (26.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -48
    Confidence Interval (2-Sided) 90%
    -95 to -1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 28.1
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -31
    Confidence Interval (2-Sided) 90%
    -76 to 15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 27.4
    Estimation Comments
    15. Secondary Outcome
    Title Change From Baseline in CDAI Scores at Week 24
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    Measure Participants 28 32 18
    Least Squares Mean (Standard Error) [score on scale]
    -86
    (24.1)
    -71
    (22.8)
    -66
    (26.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Filgotinib 200 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -20
    Confidence Interval (2-Sided) 90%
    -68 to 28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 28.7
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Filgotinib 100 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -5
    Confidence Interval (2-Sided) 90%
    -52 to 42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 28.0
    Estimation Comments

    Adverse Events

    Time Frame All-Cause Mortality: First dose date up to last dose date (maximum: 28.7 weeks) plus 59 days; Adverse Events: First dose date up to last dose date (maximum: 28.7 weeks) plus 30 days
    Adverse Event Reporting Description All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.
    Arm/Group Title Filgotinib 200 mg Filgotinib 100 mg Placebo
    Arm/Group Description Filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 27 weeks. Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet orally once daily for up to 26.3 weeks. PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet orally once daily for up to 28.7 weeks.
    All Cause Mortality
    Filgotinib 200 mg Filgotinib 100 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/28 (3.6%) 0/32 (0%) 0/18 (0%)
    Serious Adverse Events
    Filgotinib 200 mg Filgotinib 100 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/28 (14.3%) 7/32 (21.9%) 0/18 (0%)
    Gastrointestinal disorders
    Crohn's disease 2/28 (7.1%) 4/32 (12.5%) 0/18 (0%)
    Ileus 0/28 (0%) 1/32 (3.1%) 0/18 (0%)
    Small intestinal obstruction 2/28 (7.1%) 0/32 (0%) 0/18 (0%)
    Infections and infestations
    Anal abscess 0/28 (0%) 1/32 (3.1%) 0/18 (0%)
    Pneumonia 0/28 (0%) 1/32 (3.1%) 0/18 (0%)
    Other (Not Including Serious) Adverse Events
    Filgotinib 200 mg Filgotinib 100 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/28 (71.4%) 24/32 (75%) 13/18 (72.2%)
    Blood and lymphatic system disorders
    Anaemia 1/28 (3.6%) 2/32 (6.3%) 1/18 (5.6%)
    Ear and labyrinth disorders
    Ear pain 0/28 (0%) 2/32 (6.3%) 0/18 (0%)
    Gastrointestinal disorders
    Abdominal distension 2/28 (7.1%) 1/32 (3.1%) 1/18 (5.6%)
    Abdominal pain 5/28 (17.9%) 6/32 (18.8%) 1/18 (5.6%)
    Anal incontinence 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Crohn's disease 4/28 (14.3%) 6/32 (18.8%) 2/18 (11.1%)
    Diarrhoea 0/28 (0%) 2/32 (6.3%) 0/18 (0%)
    Dyspepsia 0/28 (0%) 1/32 (3.1%) 1/18 (5.6%)
    Flatulence 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Gastrooesophageal reflux disease 1/28 (3.6%) 2/32 (6.3%) 1/18 (5.6%)
    Nausea 5/28 (17.9%) 3/32 (9.4%) 1/18 (5.6%)
    Proctalgia 1/28 (3.6%) 0/32 (0%) 1/18 (5.6%)
    Rectal haemorrhage 1/28 (3.6%) 0/32 (0%) 1/18 (5.6%)
    Vomiting 1/28 (3.6%) 2/32 (6.3%) 2/18 (11.1%)
    General disorders
    Asthenia 1/28 (3.6%) 0/32 (0%) 1/18 (5.6%)
    Fatigue 2/28 (7.1%) 1/32 (3.1%) 0/18 (0%)
    Influenza like illness 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Pyrexia 2/28 (7.1%) 0/32 (0%) 0/18 (0%)
    Infections and infestations
    Ear infection 1/28 (3.6%) 0/32 (0%) 1/18 (5.6%)
    Gastroenteritis viral 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Influenza 3/28 (10.7%) 1/32 (3.1%) 0/18 (0%)
    Nasopharyngitis 0/28 (0%) 4/32 (12.5%) 0/18 (0%)
    Sinusitis 4/28 (14.3%) 0/32 (0%) 1/18 (5.6%)
    Tooth abscess 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Upper respiratory tract infection 0/28 (0%) 2/32 (6.3%) 0/18 (0%)
    Urinary tract infection 1/28 (3.6%) 2/32 (6.3%) 0/18 (0%)
    Injury, poisoning and procedural complications
    Fall 2/28 (7.1%) 0/32 (0%) 0/18 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 2/28 (7.1%) 0/32 (0%) 0/18 (0%)
    Hypocalcaemia 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Hypomagnesaemia 0/28 (0%) 1/32 (3.1%) 1/18 (5.6%)
    Malnutrition 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/28 (0%) 1/32 (3.1%) 1/18 (5.6%)
    Back pain 1/28 (3.6%) 1/32 (3.1%) 1/18 (5.6%)
    Muscle spasms 0/28 (0%) 1/32 (3.1%) 2/18 (11.1%)
    Pain in extremity 0/28 (0%) 2/32 (6.3%) 1/18 (5.6%)
    Sacroiliitis 1/28 (3.6%) 0/32 (0%) 1/18 (5.6%)
    Nervous system disorders
    Dizziness 1/28 (3.6%) 2/32 (6.3%) 2/18 (11.1%)
    Headache 4/28 (14.3%) 4/32 (12.5%) 2/18 (11.1%)
    Paraesthesia 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Tremor 0/28 (0%) 1/32 (3.1%) 1/18 (5.6%)
    Psychiatric disorders
    Anxiety 1/28 (3.6%) 2/32 (6.3%) 0/18 (0%)
    Renal and urinary disorders
    Dysuria 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain 1/28 (3.6%) 2/32 (6.3%) 0/18 (0%)
    Sinus congestion 0/28 (0%) 1/32 (3.1%) 1/18 (5.6%)
    Skin and subcutaneous tissue disorders
    Dermatitis 0/28 (0%) 0/32 (0%) 1/18 (5.6%)
    Vascular disorders
    Hypertension 3/28 (10.7%) 1/32 (3.1%) 1/18 (5.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT03046056
    Other Study ID Numbers:
    • GS-US-419-4015
    • 2016-003179-23
    First Posted:
    Feb 8, 2017
    Last Update Posted:
    Aug 23, 2021
    Last Verified:
    Aug 1, 2021