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Study to Evaluate the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Ulcerative Colitis (SELECTION)

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ClinicalTrials.gov Identifier: NCT02914522
Recruitment Status : Completed
First Posted : September 26, 2016
Results First Posted : April 21, 2021
Last Update Posted : April 21, 2021
Sponsor:
Collaborator:
Galapagos NV
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE September 22, 2016
First Posted Date  ICMJE September 26, 2016
Results First Submitted Date  ICMJE March 23, 2021
Results First Posted Date  ICMJE April 21, 2021
Last Update Posted Date April 21, 2021
Actual Study Start Date  ICMJE November 14, 2016
Actual Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2021)
  • Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10 [ Time Frame: Week 10 ]
    EBS remission was defined as an endoscopic subscore of 0 or 1; rectal bleeding subscore of 0; and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration); rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes; stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal. Total score for EBS ranged from 0 to 9 (sum of all subscores), with higher scores indicating more severe disease.
  • Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58 [ Time Frame: Week 58 ]
    EBS remission was defined as an endoscopic subscore of 0 or 1; rectal bleeding subscore of 0; and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration); rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes; stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal. Total score for EBS ranged from 0 to 9 (sum of all subscores), with higher scores indicating more severe disease.
Original Primary Outcome Measures  ICMJE
 (submitted: September 22, 2016)
  • Induction Study: Proportion of Participants Achieving Remission Based on Components of Mayo Clinic Score (MCS) at Week 10 [ Time Frame: Week 10 ]
  • Maintenance Study: Proportion of Participants Achieving Remission Based on Components of MCS at Week 58 [ Time Frame: Week 58 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2021)
  • Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10 [ Time Frame: Week 10 ]
    MCS remission was defined as having a MCS of 2 or less and no single subscore higher than 1. The MCS was composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and physician's global assessment (PGA). The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating more severe disease.
  • Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10 [ Time Frame: Week 10 ]
    Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
  • Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10 [ Time Frame: Week 10 ]
    Geboes histologic remission was assessed using the Geboes histologic scores for evaluation of disease severity in ulcerative colitis and classifies histologic changes. Remission was defined as having Grade 0 of <= 0.3, Grade 1 of <= 1.1, Grade 2A of <= 2A.3, Grade 2B of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0. Possible scores are Grade 0: Architectural changes (0.0=No abnormality to 0.3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (1.0=No increase to 1.3=Marked increase); Grade 2A: Eosinophils in lamina propria (2A.0=No increase to 2A.3-=Marked increase; Grade 2B: Neutrophils in lamina propria (2B.0= No increase to 2B.3=Marked increase); Grade 3: Neutrophils in epithelium (3.0=None to 3.3=>50% crypts involved); Grade 4: Crypt destruction (4.0=none to 4.3=Unequivocal crypt destruction), and Grade 5: Erosions and ulcerations: (5.0=No erosion, ulceration or granulation to 5.4=Ulcer or granulation tissue).
  • Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10 [ Time Frame: Week 10 ]
    MCS remission (alternative definition) was defined as having rectal bleeding, stool frequency, and PGA subscores of 0 and an endoscopic subscore of 0 or 1; overall MCS of ≤ 1. MCS possible subscores: rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), PGA subscore (range: 0 to 3 with higher score indicating the severe disease), and an endoscopic subscore (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating more severe disease.
  • Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 [ Time Frame: Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10 ]
    Cmax is defined as the maximum observed concentration of drug.
  • Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 [ Time Frame: Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10 ]
    Tmax is defined as the time to reach maximum observed concentration of drug.
  • Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 [ Time Frame: Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
  • Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 [ Time Frame: Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10 ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.
  • Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 [ Time Frame: Predose and at 0.5, 1, 2, 3, 4 and 6 hours postdose at a single visit between Week 2 and Week 10 ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.
  • Maintenance Study: Percentage of Participants Who Achieved MCS Remission at Week 58 [ Time Frame: Week 58 ]
    MCS remission was defined as having a MCS of 2 or less and no single subscore higher than 1. The MCS was composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and PGA. The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating more severe disease.
  • Maintenance Study: Percentage of Participants Who Achieved Sustained EBS Remission at Week 58 [ Time Frame: Week 58 ]
    Sustained EBS remission was defined as having achieved EBS remission at both Weeks 10 and 58.
  • Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at Week 58 [ Time Frame: Week 58 ]
    Six-month corticosteroid-free EBS remission at Week 58 was defined as achieving EBS remission with no corticosteroid use for the indication of ulcerative colitis for at least 6 months prior to Week 58.
  • Maintenance Study: Percentage of Participants Who Achieved Endoscopic Subscore of 0 at Weeks 58 [ Time Frame: Week 58 ]
    Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
  • Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 58 [ Time Frame: Week 58 ]
    Geboes histologic remission was assessed using the Geboes histologic scores for evaluation of disease severity in ulcerative colitis and classifies histologic changes. Remission was defined as having Grade 0 of <= 0.3, Grade 1 of <= 1.1, Grade 2A of <= 2A.3, Grade 2B of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0. Possible scores are Grade 0: Architectural changes (0.0=No abnormality to 0.3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (1.0=No increase to 1.3=Marked increase); Grade 2A: Eosinophils in lamina propria (2A.0=No increase to 2A.3-=Marked increase; Grade 2B: Neutrophils in lamina propria (2B.0= No increase to 2B.3=Marked increase); Grade 3: Neutrophils in epithelium (3.0=None to 3.3=>50% crypts involved); Grade 4: Crypt destruction (4.0=none to 4.3=Unequivocal crypt destruction), and Grade 5: Erosions and ulcerations: (5.0=No erosion, ulceration or granulation to 5.4=Ulcer or granulation tissue).
  • Maintenance Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 58 [ Time Frame: Week 58 ]
    MCS remission (alternative definition) was defined as having rectal bleeding, stool frequency, and PGA subscores of 0 and an endoscopic subscore of 0 or 1; overall MCS of ≤ 1. MCS possible subscores: rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), PGA subscore (range: 0 to 3 with higher score indicating the severe disease), and an endoscopic subscore (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating more severe disease.
  • Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 [ Time Frame: Week 26 (any Time) and Week 58 (predose) ]
    Plasma concentration is defined as the measured drug concentration of filgotinib and its metabolite GS-829845. Lower limit of quantitation (LLOQ) was defined as 1 ng/mL for analyte filgotinib and 2 ng/mL for analyte GS-829845.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2016)
  • Induction Study: Proportion of Participants Achieving MCS Remission at Week 10 [ Time Frame: Week 10 ]
  • Induction Study: Proportion of Participants Achieving Endoscopic Subscore of 0 at Week 10 [ Time Frame: Week 10 ]
  • Induction Study: Proportion of Participants Achieving Histologic Remission at Week 10 [ Time Frame: Week 10 ]
  • Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Week 4 postdose and Week 10 predose ]
  • Maintenance Study: Proportion of Participants Achieving MCS Remission at Week 58 [ Time Frame: Week 58 ]
  • Maintenance Study: Proportion of Participants Achieving Remission Based on Components of MCS at Weeks 10 and 58 [ Time Frame: Weeks 10 and 58 ]
  • Maintenance Study: Proportion of Participants Achieving 6-Month Corticosteroid-Free Remission Based on Components of MCS at Week 58 [ Time Frame: Week 58 ]
  • Maintenance Study: Proportion of Participants Achieving Endoscopic Subscore of 0 at Week 58 [ Time Frame: Week 58 ]
  • Maintenance Study: Proportion of Participants Achieving Histologic Remission at Week 58 [ Time Frame: Week 58 ]
  • Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Week 26 (predose or postdose) and Week 58 predose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Adults With Moderately to Severely Active Ulcerative Colitis
Official Title  ICMJE Combined Phase 2b/3, Double-Blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Brief Summary

The primary objectives of this study are to evaluate the efficacy of filgotinib in the induction and maintenance treatment of moderately to severely active ulcerative colitis (UC) in participants who are biologic-naive and biologic-experienced.

Participants who complete the study, or met protocol specified efficacy discontinuation criteria will have the option to enter a separate, long-term extension (LTE) study (Gilead Study GS-US-418-3899: NCT02914535).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Drug: Filgotinib
    Tablet(s) administered orally once daily
    Other Names:
    • GS-6034
    • GLPG0634
  • Drug: PTM filgotinib
    Tablet(s) administered orally once daily
Study Arms  ICMJE
  • Experimental: Induction Study (Cohort A): Filgotinib 200 mg
    Participants in Cohort A (biologic-naive) received filgotinib 200 milligrams (mg) and placebo-to-match (PTM) filgotinib 100 mg orally once daily for 10 weeks.
    Interventions:
    • Drug: Filgotinib
    • Drug: PTM filgotinib
  • Experimental: Induction Study (Cohort A): Filgotinib 100 mg
    Participants in Cohort A (biologic-naive) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
    Interventions:
    • Drug: Filgotinib
    • Drug: PTM filgotinib
  • Placebo Comparator: Induction Study (Cohort A): Placebo
    Participants in Cohort A (biologic-naive) received PTM filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
    Intervention: Drug: PTM filgotinib
  • Experimental: Induction Study (Cohort B): Filgotinib 200 mg
    Participants in Cohort B (biologic-experienced) received filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
    Interventions:
    • Drug: Filgotinib
    • Drug: PTM filgotinib
  • Experimental: Induction Study (Cohort B): Filgotinib 100 mg
    Participants in Cohort B (biologic-experienced) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
    Interventions:
    • Drug: Filgotinib
    • Drug: PTM filgotinib
  • Placebo Comparator: Induction Study (Cohort B): Placebo
    Participants in Cohort B (biologic-experienced) received PTM filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
    Intervention: Drug: PTM filgotinib
  • Experimental: Maintenance Study: Filgotinib 200 mg From Induction Filgotinib 200 mg
    Participants in the Filgotinib 200 mg arm who completed the Induction Study and achieved either Endoscopy/Bleeding/Stool Frequency (EBS) remission or Mayo Clinic Score (MCS) response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive filgotinib 200 mg and PTM filgotinib 100 mg for an additional 47 weeks (up to Week 58).
    Interventions:
    • Drug: Filgotinib
    • Drug: PTM filgotinib
  • Placebo Comparator: Maintenance Study: Placebo From Induction Filgotinib 200 mg
    Participants in the Filgotinib 200 mg arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive PTM filgotinib orally once daily for an additional 47 weeks (up to Week 58).
    Intervention: Drug: PTM filgotinib
  • Experimental: Maintenance Study: Filgotinib 100 mg From Induction Filgotinib 100 mg
    Participants in the Filgotinib 100 mg arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive filgotinib 100 mg and PTM filgotinib 200 mg for an additional 47 weeks (up to Week 58).
    Interventions:
    • Drug: Filgotinib
    • Drug: PTM filgotinib
  • Placebo Comparator: Maintenance Study: Placebo From Induction Filgotinib 100 mg
    Participants in the Filgotinib 100 mg arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were rerandomized at Week 11 into the Maintenance Study to receive PTM filgotinib orally once daily for an additional 47 weeks (up to Week 58).
    Intervention: Drug: PTM filgotinib
  • Placebo Comparator: Maintenance Study: Placebo From Induction Placebo
    Participants in the Placebo arm who completed the Induction Study and achieved either EBS remission or MCS response at Week 10 were re-randomized at Week 11 into the Maintenance Study to receive PTM filgotinib for an additional 47 weeks (up to Week 58).
    Intervention: Drug: PTM filgotinib
Publications * Feagan BG, Danese S, Loftus EV Jr, Vermeire S, Schreiber S, Ritter T, Fogel R, Mehta R, Nijhawan S, Kempiński R, Filip R, Hospodarskyy I, Seidler U, Seibold F, Beales ILP, Kim HJ, McNally J, Yun C, Zhao S, Liu X, Hsueh CH, Tasset C, Besuyen R, Watanabe M, Sandborn WJ, Rogler G, Hibi T, Peyrin-Biroulet L. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet. 2021 Jun 19;397(10292):2372-2384. doi: 10.1016/S0140-6736(21)00666-8. Epub 2021 Jun 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
1351
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2016)
1300
Actual Study Completion Date  ICMJE March 31, 2020
Actual Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit
  • Documented diagnosis of UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge. Documentation should include endoscopic and histopathologic evidence of UC.
  • A surveillance colonoscopy is required at screening in individuals with a history of UC for 8 or more years, if one was not performed in the prior 24 months
  • Moderately to severely active UC
  • 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 (TNFa) antagonists, or vedolizumab

Key Exclusion Criteria:

  • Presence of Crohn's disease, indeterminate colitis, ischemic colitis, fulminant colitis, ulcerative proctitis, or toxic mega-colon
  • Active tuberculosis (TB) or history of latent TB that has not been treated
  • Use of any concomitant prohibited medications as described in the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Croatia,   Czechia,   France,   Georgia,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Norway,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Iceland
 
Administrative Information
NCT Number  ICMJE NCT02914522
Other Study ID Numbers  ICMJE GS-US-418-3898
2016-001392-78 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Galapagos NV
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP