Ulcerative Colitis
Conditions
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).
Interventions
DRUGFilgotinib
Tablet(s) administered orally once daily
DRUGPTM filgotinib
Tablet(s) administered orally once daily
Sponsors
Galapagos NV
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Males or non-pregnant, 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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. |
| 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: 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: 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. |
| 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 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: 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 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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). |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czechia, France, Georgia, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Australia, New Zealand, North America, South America, Asia and Europe. The first participant was screened on 14 November 2016. The last study visit occurred on 31 March 2020.
Pre-assignment details
2040 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg Participants in Cohort A (biologic-naive) received filgotinib 200 mg and PTM filgotinib 100 mg orally once daily for 10 weeks. | 245 |
| 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. | 277 |
| 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. | 137 |
| 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. | 262 |
| 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. | 285 |
| 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. | 142 |
| Total | 1,348 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Induction Study: Up to Week 11 | Adverse Event | 5 | 6 | 4 | 18 | 14 | 10 | 0 | 0 | 0 | 0 | 0 |
| Induction Study: Up to Week 11 | Did not Receive Study Drug | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Induction Study: Up to Week 11 | Investigator's Discretion | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Study: Up to Week 11 | Lost to Follow-up | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Study: Up to Week 11 | Non-compliance With Study Drug | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Study: Up to Week 11 | Pregnancy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Study: Up to Week 11 | Protocol Violation | 0 | 2 | 1 | 3 | 4 | 2 | 0 | 0 | 0 | 0 | 0 |
| Induction Study: Up to Week 11 | Withdrew Consent | 4 | 11 | 4 | 6 | 3 | 3 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Study: Week 11 to Week 58 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 2 | 10 | 4 | 3 |
| Maintenance Study: Week 11 to Week 58 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Maintenance Study: Week 11 to Week 58 | Investigator's Discretion | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 |
| Maintenance Study: Week 11 to Week 58 | Non-compliance With Study Drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Maintenance Study: Week 11 to Week 58 | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Maintenance Study: Week 11 to Week 58 | Protocol-specified Disease Worsening | 0 | 0 | 0 | 0 | 0 | 0 | 34 | 49 | 53 | 39 | 21 |
| Maintenance Study: Week 11 to Week 58 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 | 3 | 0 | 1 |
| Maintenance Study: Week 11 to Week 58 | Withdrew Consent | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 6 | 3 | 4 |
Baseline characteristics
| Characteristic | Induction Study (Cohort A): Filgotinib 200 mg | Induction Study (Cohort A): Filgotinib 100 mg | Induction Study (Cohort B): Placebo | Induction Study (Cohort B): Filgotinib 100 mg | Induction Study (Cohort B): Filgotinib 200 mg | Total | Induction Study (Cohort A): Placebo |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 16 Participants | 14 Participants | 21 Participants | 19 Participants | 89 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 234 Participants | 261 Participants | 128 Participants | 264 Participants | 243 Participants | 1259 Participants | 129 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 6 Participants | 6 Participants | 4 Participants | 8 Participants | 8 Participants | 35 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 238 Participants | 269 Participants | 134 Participants | 273 Participants | 249 Participants | 1297 Participants | 134 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 1 Participants | 2 Participants | 4 Participants | 4 Participants | 5 Participants | 16 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 77 Participants | 79 Participants | 27 Participants | 51 Participants | 50 Participants | 322 Participants | 38 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 19 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 0 Participants | 1 Participants | 13 Participants | 16 Participants | 18 Participants | 49 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 165 Participants | 192 Participants | 98 Participants | 212 Participants | 190 Participants | 952 Participants | 95 Participants |
| Region of Enrollment Argentina | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants |
| Region of Enrollment Australia | 6 Participants | 3 Participants | 2 Participants | 8 Participants | 10 Participants | 30 Participants | 1 Participants |
| Region of Enrollment Austria | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 7 Participants | 0 Participants |
| Region of Enrollment Belgium | 0 Participants | 0 Participants | 6 Participants | 14 Participants | 16 Participants | 36 Participants | 0 Participants |
| Region of Enrollment Bulgaria | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants |
| Region of Enrollment Canada | 2 Participants | 2 Participants | 4 Participants | 5 Participants | 3 Participants | 17 Participants | 1 Participants |
| Region of Enrollment Croatia | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants | 0 Participants |
| Region of Enrollment Czechia | 3 Participants | 4 Participants | 0 Participants | 2 Participants | 4 Participants | 17 Participants | 4 Participants |
| Region of Enrollment France | 1 Participants | 1 Participants | 19 Participants | 26 Participants | 32 Participants | 80 Participants | 1 Participants |
| Region of Enrollment Georgia | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants |
| Region of Enrollment Germany | 1 Participants | 3 Participants | 9 Participants | 26 Participants | 31 Participants | 70 Participants | 0 Participants |
| Region of Enrollment Greece | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 5 Participants | 0 Participants |
| Region of Enrollment Hong Kong | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants |
| Region of Enrollment Hungary | 9 Participants | 8 Participants | 2 Participants | 5 Participants | 0 Participants | 27 Participants | 3 Participants |
| Region of Enrollment India | 55 Participants | 49 Participants | 3 Participants | 3 Participants | 8 Participants | 145 Participants | 27 Participants |
| Region of Enrollment Ireland | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Israel | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 5 Participants | 11 Participants | 0 Participants |
| Region of Enrollment Italy | 4 Participants | 6 Participants | 12 Participants | 19 Participants | 15 Participants | 57 Participants | 1 Participants |
| Region of Enrollment Japan | 15 Participants | 16 Participants | 14 Participants | 29 Participants | 29 Participants | 109 Participants | 6 Participants |
| Region of Enrollment Malaysia | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants |
| Region of Enrollment Mexico | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Netherlands | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants | 0 Participants |
| Region of Enrollment New Zealand | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 10 Participants | 0 Participants |
| Region of Enrollment Norway | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants | 2 Participants |
| Region of Enrollment Poland | 57 Participants | 56 Participants | 11 Participants | 22 Participants | 17 Participants | 188 Participants | 25 Participants |
| Region of Enrollment Portugal | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Romania | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants | 19 Participants | 2 Participants |
| Region of Enrollment Russia | 21 Participants | 10 Participants | 1 Participants | 9 Participants | 6 Participants | 59 Participants | 12 Participants |
| Region of Enrollment Serbia | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants |
| Region of Enrollment Singapore | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Slovakia | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants |
| Region of Enrollment South Africa | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 8 Participants | 2 Participants |
| Region of Enrollment South Korea | 1 Participants | 7 Participants | 5 Participants | 12 Participants | 5 Participants | 32 Participants | 2 Participants |
| Region of Enrollment Spain | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 8 Participants | 0 Participants |
| Region of Enrollment Sweden | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 6 Participants | 1 Participants |
| Region of Enrollment Switzerland | 0 Participants | 0 Participants | 7 Participants | 5 Participants | 7 Participants | 19 Participants | 0 Participants |
| Region of Enrollment Taiwan | 1 Participants | 3 Participants | 0 Participants | 4 Participants | 4 Participants | 12 Participants | 0 Participants |
| Region of Enrollment Ukraine | 33 Participants | 46 Participants | 0 Participants | 2 Participants | 1 Participants | 106 Participants | 24 Participants |
| Region of Enrollment United Kingdom | 7 Participants | 3 Participants | 7 Participants | 11 Participants | 12 Participants | 40 Participants | 0 Participants |
| Region of Enrollment United States | 14 Participants | 33 Participants | 21 Participants | 58 Participants | 36 Participants | 181 Participants | 19 Participants |
| Sex: Female, Male Female | 122 Participants | 120 Participants | 56 Participants | 99 Participants | 114 Participants | 561 Participants | 50 Participants |
| Sex: Female, Male Male | 123 Participants | 157 Participants | 86 Participants | 186 Participants | 148 Participants | 787 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 245 | 0 / 278 | 0 / 137 | 0 / 262 | 0 / 286 | 0 / 143 | 2 / 202 | 0 / 99 | 0 / 179 | 0 / 91 | 0 / 93 |
| other Total, other adverse events | 40 / 245 | 43 / 277 | 20 / 137 | 83 / 262 | 77 / 285 | 55 / 142 | 67 / 202 | 33 / 99 | 53 / 179 | 33 / 91 | 26 / 93 |
| serious Total, serious adverse events | 3 / 245 | 13 / 277 | 4 / 137 | 19 / 262 | 15 / 285 | 9 / 142 | 9 / 202 | 0 / 99 | 8 / 179 | 7 / 91 | 4 / 93 |
Outcome results
Primary
Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at 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.
Time frame: Week 10
Population: Full Analysis Set for the Induction study (Cohorts A and B) included all randomized participants who took at least 1 dose of study drug in the corresponding Induction study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10 | 26.1 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10 | 19.1 percentage of participants |
| Induction Study (Cohort A): Placebo | Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10 | 15.3 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10 | 11.5 percentage of participants |
| Induction Study (Cohort B): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10 | 9.5 percentage of participants |
| Induction Study (Cohort B): Placebo | Induction Study: Percentage of Participants Who Achieved Endoscopy/Bleeding/Stool Frequency (EBS) Remission at Week 10 | 4.2 percentage of participants |
p-value: 0.015795% CI: [2.1, 19.5]Cochran-Mantel-Haenszel
p-value: 0.337995% CI: [-4.3, 12]Cochran-Mantel-Haenszel
p-value: 0.010395% CI: [1.6, 12.8]Cochran-Mantel-Haenszel
p-value: 0.064595% CI: [0, 10.5]Cochran-Mantel-Haenszel
Primary
Maintenance Study: Percentage of Participants Who Achieved EBS Remission at 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.
Time frame: Week 58
Population: Full Analysis Set for the Maintenance Study included all participants randomized to either the filgotinib 200 mg or filgotinib 100 mg treatment groups in the Induction Study (Cohorts A and B) who achieved EBS remission or MCS response at Week 10, were rerandomized, and took at least 1 dose of study drug in the Maintenance Study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58 | 37.2 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58 | 11.2 percentage of participants |
| Induction Study (Cohort A): Placebo | Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58 | 23.8 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved EBS Remission at Week 58 | 13.5 percentage of participants |
p-value: <0.000195% CI: [16, 35.9]Cochran-Mantel-Haenszel
p-value: 0.04295% CI: [0, 20.7]Cochran-Mantel-Haenszel
Secondary
Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10
Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
Time frame: Week 10
Population: Participants in the Full Analysis Set for the Induction Study (Cohorts A and B) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10 | 12.2 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10 | 5.8 percentage of participants |
| Induction Study (Cohort A): Placebo | Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10 | 3.6 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10 | 3.4 percentage of participants |
| Induction Study (Cohort B): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10 | 2.1 percentage of participants |
| Induction Study (Cohort B): Placebo | Induction Study: Percentage of Participants Who Achieved an Endoscopic Subscore of 0 at Week 10 | 2.1 percentage of participants |
p-value: 0.004795% CI: [2.9, 14.3]Cochran-Mantel-Haenszel
p-value: 0.349595% CI: [-2.6, 6.8]Cochran-Mantel-Haenszel
p-value: 0.426995% CI: [-2.5, 5.1]Cochran-Mantel-Haenszel
p-value: 0.998795% CI: [-3.4, 3.4]Cochran-Mantel-Haenszel
Secondary
Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at 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).
Time frame: Week 10
Population: Participants in the Full Analysis Set for the Induction study (Cohorts A and B) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10 | 35.1 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10 | 23.8 percentage of participants |
| Induction Study (Cohort A): Placebo | Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10 | 16.1 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10 | 19.8 percentage of participants |
| Induction Study (Cohort B): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10 | 13.7 percentage of participants |
| Induction Study (Cohort B): Placebo | Induction Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 10 | 8.5 percentage of participants |
p-value: <0.000195% CI: [9.9, 28.2]Cochran-Mantel-Haenszel
p-value: 0.067295% CI: [-0.7, 16.2]Cochran-Mantel-Haenszel
p-value: 0.001995% CI: [4.2, 18.6]Cochran-Mantel-Haenszel
p-value: 0.128695% CI: [-1.4, 11.8]Cochran-Mantel-Haenszel
Secondary
Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at 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.
Time frame: Week 10
Population: Participants in the Full Analysis Set for the Induction Study (Cohorts A and B) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10 | 12.2 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10 | 8.7 percentage of participants |
| Induction Study (Cohort A): Placebo | Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10 | 4.4 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10 | 3.8 percentage of participants |
| Induction Study (Cohort B): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10 | 2.1 percentage of participants |
| Induction Study (Cohort B): Placebo | Induction Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 10 | 2.1 percentage of participants |
p-value: 0.010595% CI: [1.9, 13.8]Cochran-Mantel-Haenszel
p-value: 0.106295% CI: [-1, 9.6]Cochran-Mantel-Haenszel
p-value: 0.308495% CI: [-2.2, 5.6]Cochran-Mantel-Haenszel
p-value: 0.910995% CI: [-3.4, 3.4]Cochran-Mantel-Haenszel
Secondary
Induction Study: Percentage of Participants Who Achieved MCS Remission at 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.
Time frame: Week 10
Population: Participants in the Full Analysis Set for the Induction Study (Cohorts A and B) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10 | 24.5 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10 | 17.0 percentage of participants |
| Induction Study (Cohort A): Placebo | Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10 | 12.4 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10 | 9.5 percentage of participants |
| Induction Study (Cohort B): Filgotinib 100 mg | Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10 | 6.0 percentage of participants |
| Induction Study (Cohort B): Placebo | Induction Study: Percentage of Participants Who Achieved MCS Remission at Week 10 | 4.2 percentage of participants |
p-value: 0.005395% CI: [3.8, 20.4]Cochran-Mantel-Haenszel
p-value: 0.229595% CI: [-3.1, 12.2]Cochran-Mantel-Haenszel
p-value: 0.039395% CI: [-0.1, 10.7]Cochran-Mantel-Haenszel
p-value: 0.530895% CI: [-3.1, 6.6]Cochran-Mantel-Haenszel
Secondary
Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845
Cmax is defined as the maximum observed concentration of drug.
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
Population: PK Substudy Analysis Set included all randomized participants who took at least 1 dose of filgotinib, participated in the PK substudy, and had at least 1 nonmissing intensive concentration value for filgotinib and/or GS-829845 with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 1746.3 nanograms per milliliter (ng/mL) | Standard Deviation 1244.05 |
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 3227.5 nanograms per milliliter (ng/mL) | Standard Deviation 1204.5 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 1812.2 nanograms per milliliter (ng/mL) | Standard Deviation 701.46 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 725.1 nanograms per milliliter (ng/mL) | Standard Deviation 313.36 |
| Induction Study (Cohort A): Placebo | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 2283.3 nanograms per milliliter (ng/mL) | Standard Deviation 1012.03 |
| Induction Study (Cohort A): Placebo | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 4373.3 nanograms per milliliter (ng/mL) | Standard Deviation 1121.58 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 977.9 nanograms per milliliter (ng/mL) | Standard Deviation 403.51 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: Pharmacokinetic (PK) Parameter: Cmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 2002.9 nanograms per milliliter (ng/mL) | Standard Deviation 598.73 |
Secondary
Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
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
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 5537.3 h*ng/mL | Standard Deviation 1900.93 |
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 60938.4 h*ng/mL | Standard Deviation 6961.77 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 30643.2 h*ng/mL | Standard Deviation 12935.37 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 1881.9 h*ng/mL | Standard Deviation 797.51 |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 6743.1 h*ng/mL | Standard Deviation 1743.68 |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 79286.3 h*ng/mL | Standard Deviation 27968.49 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 2420.3 h*ng/mL | Standard Deviation 837.26 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: AUClast of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 34385.6 h*ng/mL | Standard Deviation 15160.15 |
Secondary
Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
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
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 57982.0 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 17767.52 |
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 5501.3 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 1956.39 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 31187.9 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 11858.78 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 1909.3 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 788.13 |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 6475.6 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 1643 |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 80208.6 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 25096.57 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 36075.6 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 13396.86 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: AUCtau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 2492.3 hour*nanograms per milliliter (h*ng/mL) | Standard Deviation 852.52 |
Secondary
Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984
Ctau is defined as the observed drug concentration at the end of the dosing interval.
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
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 12.0 ng/mL | Standard Deviation 4.74 |
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 2050.0 ng/mL | Standard Deviation 493.66 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 934.8 ng/mL | Standard Deviation 372.68 |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 4.5 ng/mL | Standard Deviation 3.61 |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 36.6 ng/mL | Standard Deviation 79.06 |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 2581.3 ng/mL | Standard Deviation 777.07 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Filgotinib | 4.1 ng/mL | Standard Deviation 3.05 |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: Ctau of Filgotinib and Its Metabolite GS-82984 | Metabolite GS-829845 | 1062.8 ng/mL | Standard Deviation 463.67 |
Secondary
Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845
Tmax is defined as the time to reach maximum observed concentration of drug.
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
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 1.50 hour (h) |
| Induction Study (Cohort A): Filgotinib 200 mg | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 3.76 hour (h) |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 3.00 hour (h) |
| Induction Study (Cohort A): Filgotinib 100 mg | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 0.75 hour (h) |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 1.00 hour (h) |
| Induction Study (Cohort A): Placebo | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 3.02 hour (h) |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Filgotinib | 0.57 hour (h) |
| Induction Study (Cohort B): Filgotinib 200 mg | Induction Study: PK Parameter: Tmax of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845 | 3.00 hour (h) |
Secondary
Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at 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.
Time frame: Week 58
Population: Participants in the Full Analysis Set who were on corticosteroids at Maintenance Study baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at Week 58 | 27.2 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at Week 58 | 6.4 percentage of participants |
| Induction Study (Cohort A): Placebo | Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at Week 58 | 13.6 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved 6-Month Corticosteroid-Free EBS Remission at Week 58 | 5.4 percentage of participants |
p-value: 0.005595% CI: [7.7, 33.9]Cochran-Mantel-Haenszel
p-value: 0.126595% CI: [-4.2, 20.6]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved Endoscopic Subscore of 0 at Weeks 58
Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
Time frame: Week 58
Population: Participants in the Full Analysis Set for the Maintenance Study were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Subscore of 0 at Weeks 58 | 15.6 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Subscore of 0 at Weeks 58 | 6.1 percentage of participants |
| Induction Study (Cohort A): Placebo | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Subscore of 0 at Weeks 58 | 13.4 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Subscore of 0 at Weeks 58 | 7.9 percentage of participants |
p-value: 0.015795% CI: [1.8, 17.1]Cochran-Mantel-Haenszel
p-value: 0.180895% CI: [-2.9, 13.9]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at 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).
Time frame: Week 58
Population: Participants in the Full Analysis Set for the Maintenance Study were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 58 | 38.2 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 58 | 13.3 percentage of participants |
| Induction Study (Cohort A): Placebo | Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 58 | 27.9 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved Geboes Histologic Remission at Week 58 | 18.0 percentage of participants |
p-value: <0.000195% CI: [14.6, 35.2]Cochran-Mantel-Haenszel
p-value: 0.052195% CI: [-1.3, 21.2]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at 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.
Time frame: Week 58
Population: Participants in the Full Analysis Set for the Maintenance Study were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 58 | 22.1 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 58 | 6.1 percentage of participants |
| Induction Study (Cohort A): Placebo | Maintenance Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 58 | 12.2 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved MCS Remission (Alternative Definition) at Week 58 | 7.9 percentage of participants |
p-value: 0.000595% CI: [7.8, 24.2]Cochran-Mantel-Haenszel
p-value: 0.294695% CI: [-3.9, 12.6]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved MCS Remission at 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.
Time frame: Week 58
Population: Participants in the Full Analysis Set for the Maintenance Study were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved MCS Remission at Week 58 | 34.7 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Percentage of Participants Who Achieved MCS Remission at Week 58 | 9.2 percentage of participants |
| Induction Study (Cohort A): Placebo | Maintenance Study: Percentage of Participants Who Achieved MCS Remission at Week 58 | 22.7 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved MCS Remission at Week 58 | 13.5 percentage of participants |
p-value: <0.000195% CI: [16, 35]Cochran-Mantel-Haenszel
p-value: 0.065895% CI: [-1.1, 19.5]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved Sustained EBS Remission at Week 58
Sustained EBS remission was defined as having achieved EBS remission at both Weeks 10 and 58.
Time frame: Week 58
Population: Participants in the Full Analysis Set for the Maintenance Study were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved Sustained EBS Remission at Week 58 | 18.1 percentage of participants |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Percentage of Participants Who Achieved Sustained EBS Remission at Week 58 | 5.1 percentage of participants |
| Induction Study (Cohort A): Placebo | Maintenance Study: Percentage of Participants Who Achieved Sustained EBS Remission at Week 58 | 8.7 percentage of participants |
| Induction Study (Cohort B): Filgotinib 200 mg | Maintenance Study: Percentage of Participants Who Achieved Sustained EBS Remission at Week 58 | 7.9 percentage of participants |
p-value: 0.002495% CI: [5.3, 20.6]Cochran-Mantel-Haenszel
p-value: 0.795195% CI: [-7, 8.7]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845
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.
Time frame: Week 26 (any Time) and Week 58 (predose)
Population: PK Analysis Set included all participants in the Safety Analysis Set who who took at least 1 dose of filgotinib and had at least 1 nonmissing plasma concentration value for filgotinib and/or its metabolite GS-829845 with available data were analyzed. Data was not collected for the Maintenance Study Placebo arms.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Filgotinib: Week 26 | 8.5 ng/mL |
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Filgotinib: Week 58 | 3.9 ng/mL |
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845: Week 26 | 2495.0 ng/mL |
| Induction Study (Cohort A): Filgotinib 200 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845: Week 58 | 1930.0 ng/mL |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845: Week 58 | 973.5 ng/mL |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Filgotinib: Week 26 | 4.4 ng/mL |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Metabolite GS-829845: Week 26 | 1180.0 ng/mL |
| Induction Study (Cohort A): Filgotinib 100 mg | Maintenance Study: Plasma Concentration of Filgotinib and Its Metabolite GS-829845 | Filgotinib: Week 58 | 4.1 ng/mL |