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

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: Filgotinib
Drug: PTM filgotinib

Registration Number: NCT02914522

Lead Sponsor: Gilead Sciences

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1351

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Induction Study (Cohort B): Filgotinib 200 mg	Filgotinib	Participants in Cohort B (biologic-experienced) received filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
Induction Study (Cohort B): Filgotinib 100 mg	Filgotinib	Participants in Cohort B (biologic-experienced) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
Maintenance Study: Filgotinib 200 mg From Induction Filgotinib 200 mg	Filgotinib	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).
Maintenance Study: Placebo From Induction Filgotinib 100 mg	PTM filgotinib	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).
Maintenance Study: Filgotinib 200 mg From Induction Filgotinib 200 mg	PTM filgotinib	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).
Induction Study (Cohort A): Filgotinib 200 mg	PTM filgotinib	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.
Induction Study (Cohort A): Placebo	PTM filgotinib	Participants in Cohort A (biologic-naive) received PTM filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
Induction Study (Cohort B): Placebo	PTM filgotinib	Participants in Cohort B (biologic-experienced) received PTM filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
Maintenance Study: Filgotinib 100 mg From Induction Filgotinib 100 mg	PTM filgotinib	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).
Maintenance Study: Placebo From Induction Placebo	PTM filgotinib	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).
Induction Study (Cohort B): Filgotinib 100 mg	PTM filgotinib	Participants in Cohort B (biologic-experienced) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
Maintenance Study: Placebo From Induction Filgotinib 200 mg	PTM filgotinib	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).
Induction Study (Cohort A): Filgotinib 100 mg	PTM filgotinib	Participants in Cohort A (biologic-naive) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
Induction Study (Cohort B): Filgotinib 200 mg	PTM filgotinib	Participants in Cohort B (biologic-experienced) received filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks.
Induction Study (Cohort A): Filgotinib 200 mg	Filgotinib	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.
Induction Study (Cohort A): Filgotinib 100 mg	Filgotinib	Participants in Cohort A (biologic-naive) received filgotinib 100 mg and PTM filgotinib 200 mg orally once daily for 10 weeks.
Maintenance Study: Filgotinib 100 mg From Induction Filgotinib 100 mg	Filgotinib	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).

Primary Outcome Measures

Name	Time	Method
Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58	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.
Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10	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.

Secondary Outcome Measures

Name	Time	Method
Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10	Week 10	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 Endoscopic Subscore of 0 at Weeks 58	Week 58	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	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: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984	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: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845	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	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: Ctau of Filgotinib and Its Metabolite GS-82984	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.
Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10	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.
Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at Week 58	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 MCS Remission (Alternative Definition) at Week 58	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.
Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10	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.
Maintenance Study: Percentage of Participants Who Achieved MCS Remission at Week 58	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	Week 58	Sustained EBS remission was defined as having achieved EBS remission at both Weeks 10 and 58.
Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845	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.
Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984	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.
Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 58	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).

Trial Locations

Locations (342): Digestive Health Specialists of the Southeast
🇺🇸
Dothan, Alabama, United States
Mayo Clinic Arizona
🇺🇸
Scottsdale, Arizona, United States
VA Long Beach Healthcare System
🇺🇸
Long Beach, California, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
South Denver Gastroenterology, PC
🇺🇸
Lone Tree, Colorado, United States
Connecticut GI PC-Research Division
🇺🇸
Farmington, Connecticut, United States
UF Health at Shands Hospital
🇺🇸
Gainesville, Florida, United States
Florida Research Institute
🇺🇸
Lakewood Ranch, Florida, United States
University of Miami Crohn's and Colitis Center
🇺🇸
Miami, Florida, United States
Cordova Research Institute
🇺🇸
Miami, Florida, United States
Scroll for more (332 remaining)
Digestive Health Specialists of the Southeast
🇺🇸Dothan, Alabama, United States