Crohn's Disease
Conditions
Brief summary
The primary objectives of this study are to evaluate the safety and efficacy of filgotinib during induction and maintenance treatment of moderately to severely active Crohn's disease (CD) in participants who are biologic-naive and biologic-experienced. Participants who complete the study, or do not meet protocol response or remission criteria at Week 10 will have the option to enter a separate long-term extension (LTE) study (Study GS-US-419-3896).
Interventions
DRUGFilgotinib
Filgotinib tablets administered orally once daily.
OTHERPlacebo
Placebo administered orally once daily.
Sponsors
Gilead Sciences
Galapagos NV
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: * Documented diagnosis of CD with a minimum disease duration of 3 months with involvement of the ileum and/or colon at a minimum, as determined by histopathology and endoscopic assessment * Moderately to severely active CD * Cohort A (Biologic Naïve): 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 and immunomodulators * Cohort A (Biologic Experienced): 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) or discontinuation of use of at least one of the following agents for reasons other than inadequate clinical response, loss of response or intolerance: tumor necrosis factor alpha (TNFa) antagonists, vedolizumab, and ustekinumab * Cohort B (Biologic Experienced): 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): TNFa antagonists, vedolizumab, and ustekinumab Key
Exclusion criteria
* Current complications of CD such as symptomatic strictures, severe rectal/anal stenosis, fistulae other than perianal fistulae, short bowel syndrome, etc. * Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon * Active tuberculosis (TB) or history of latent TB that has not been treated * Use of any prohibited concomitant medications as described in the study protocol NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | Week 10 | The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points. |
| Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10 | Week 10 | The Simple Endoscopic Score for Crohn's Disease (SES-CD) assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score. |
| Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58 | Week 58 | The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points. |
| Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58 | Week 58 | The SES-CD assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by CDAI at Both Weeks 10 and 58 | Weeks 10 and 58 | The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Sustained Clinical Remission by CDAI: CDAI \<150 combined at both Week 10 and Week 58. |
| Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by CDAI at Week 58 | Week 58 | The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. 6-Month Corticosteroid-Free Clinical remission by CDAI: CDAI \<150 with no corticosteroid use for indication of Crohn's disease for at least 6 months prior to Week 58. |
| Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58 | Weeks 10 and 58 | The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Sustained Clinical Remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1 combined at both Week 10 and Week 58. |
| Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58 | Week 58 | The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. 6-month Corticosteroid-Free Clinical Remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1 with no corticosteroid use for at least 6 months prior to Week 58. |
| Induction Study:Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4 | Week 4: 0.5, 1, 2, and 3 hours (hrs) post dose | Plasma concentrations of filgotinib \[nanogram/milliliters (ng/mL)\]. |
| Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10 | Week 10: Predose | Plasma concentrations of filgotinib (ng/mL). |
| Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10 | Week 10 | The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Clinical Remission was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. |
| Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 58 | Week 58: Pre-dose | Plasma concentrations of filgotinib (ng/mL). |
| Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4 | Week 4: 0.5, 1, 2, and 3 hrs post dose | Plasma concentrations of GS-829845 (ng/mL). |
| Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10 | Week 10: Predose | Plasma concentrations of GS-829845 (ng/mL). |
| Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 26 | Week 26: At any timepoint | Plasma concentrations of GS-829845 (ng/mL). |
| Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 58 | Week 58: Pre-dose | Plasma concentrations of GS-829845 (ng/mL). |
| Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 26 | Week 26: At any timepoint | Plasma concentrations of filgotinib (ng/mL). |
| Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10 | Week 10 | The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical response was defined as reduction in CDAI score from Induction baseline by at least 100 points or CDAI score \< 150 points. |
| Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58 | Week 58 | The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Clinical Remission was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. |
| Maintenance Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 58 | Week 58 | The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical response was defined as reduction in CDAI score from Induction baseline by at least 100 points or CDAI score \< 150 points. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czechia, France, Georgia, Germany, Greece, Hong Kong, Hungary, Iceland, India, Ireland, Israel, Italy, Japan, Malaysia, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Sri Lanka, Sweden, Switzerland, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants with diagnosis of moderately to severely Active Crohn's disease (CD) were enrolled in the study. Participants who were biologic-naïve or biologic-experienced were enrolled in Cohort A and participants who were biologic-experienced were enrolled in Cohort B, respectively.
Pre-assignment details
Participants who met protocol eligibility criteria were assigned to the respective Cohort and subsequently randomized in a blinded fashion in a 1:1:1 ratio to 1 of 3 treatments: filgotinib 200 milligram (mg), filgotinib 100 mg and placebo.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) Biologic naïve and biologic experienced participants received filgotinib 200 mg with placebo-to-match (PTM) filgotinib 100 mg tablet orally once daily, for a period of 10 weeks. | 223 |
| Cohort A: Filgotinib 100 mg (Induction Study) Biologic naïve and biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks. | 245 |
| Cohort A: Placebo (Induction Study) Biologic naïve and biologic experienced participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks. | 239 |
| Cohort B: Filgotinib 200 mg (Induction Study) Biologic experienced participants received filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks. | 204 |
| Cohort B: Filgotinib 100 mg (Induction Study) Biologic experienced participants received filgotinib 100 mg with PTM filgotinib 200 mg tablet orally once daily, for a period of 10 weeks. | 230 |
| Cohort B: Placebo (Induction Study) Biologic experienced participants received PTM filgotinib 200 mg with PTM filgotinib 100 mg tablet orally once daily, for a period of 10 weeks. | 231 |
| Total | 1,372 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Induction Study (Day 1 to Week 10) | Adverse Event | 15 | 14 | 14 | 24 | 31 | 19 | 0 | 0 | 0 | 0 | 0 |
| Induction Study (Day 1 to Week 10) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Study (Day 1 to Week 10) | Non-Compliance with Study Drug | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Induction Study (Day 1 to Week 10) | Physician Decision | 1 | 5 | 2 | 0 | 4 | 4 | 0 | 0 | 0 | 0 | 0 |
| Induction Study (Day 1 to Week 10) | Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Study (Day 1 to Week 10) | Protocol Violation | 0 | 4 | 1 | 1 | 3 | 1 | 0 | 0 | 0 | 0 | 0 |
| Induction Study (Day 1 to Week 10) | Randomized but not treated | 1 | 0 | 2 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
| Induction Study (Day 1 to Week 10) | Withdrawal by Subject | 1 | 9 | 6 | 0 | 7 | 12 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Study (Weeks 11 to 58) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 2 | 11 | 2 | 12 |
| Maintenance Study (Weeks 11 to 58) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 0 | 0 |
| Maintenance Study (Weeks 11 to 58) | Non-Compliance with Study Drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Maintenance Study (Weeks 11 to 58) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 1 | 3 |
| Maintenance Study (Weeks 11 to 58) | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Maintenance Study (Weeks 11 to 58) | Protocol-Specified Disease Worsening | 0 | 0 | 0 | 0 | 0 | 0 | 31 | 32 | 40 | 25 | 43 |
| Maintenance Study (Weeks 11 to 58) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 2 | 0 | 4 |
| Maintenance Study (Weeks 11 to 58) | Randomized but not treated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Maintenance Study (Weeks 11 to 58) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 1 | 2 | 1 | 9 |
Baseline characteristics
| Characteristic | Cohort A: Filgotinib 200 mg (Induction Study) | Cohort A: Filgotinib 100 mg (Induction Study) | Cohort A: Placebo (Induction Study) | Cohort B: Filgotinib 200 mg (Induction Study) | Cohort B: Filgotinib 100 mg (Induction Study) | Cohort B: Placebo (Induction Study) | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 12 Participants | 10 Participants | 13 Participants | 10 Participants | 4 Participants | 59 Participants |
| Age, Categorical Between 18 and 65 years | 213 Participants | 233 Participants | 229 Participants | 191 Participants | 220 Participants | 227 Participants | 1313 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 4 Participants | 2 Participants | 8 Participants | 4 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 214 Participants | 237 Participants | 232 Participants | 193 Participants | 217 Participants | 220 Participants | 1313 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 3 Participants | 9 Participants | 5 Participants | 7 Participants | 32 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 45 Participants | 52 Participants | 44 Participants | 24 Participants | 25 Participants | 31 Participants | 221 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 6 Participants | 4 Participants | 6 Participants | 9 Participants | 6 Participants | 34 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 11 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 7 Participants | 5 Participants | 4 Participants | 13 Participants | 12 Participants | 13 Participants | 54 Participants |
| Race/Ethnicity, Customized White | 166 Participants | 179 Participants | 185 Participants | 158 Participants | 182 Participants | 178 Participants | 1048 Participants |
| Region of Enrollment Australia | 11 participants | 6 participants | 8 participants | 4 participants | 9 participants | 11 participants | 49 participants |
| Region of Enrollment Austria | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants | 0 participants | 3 participants |
| Region of Enrollment Belgium | 6 participants | 11 participants | 7 participants | 15 participants | 12 participants | 11 participants | 62 participants |
| Region of Enrollment Canada | 9 participants | 6 participants | 7 participants | 7 participants | 4 participants | 4 participants | 37 participants |
| Region of Enrollment Croatia | 0 participants | 1 participants | 1 participants | 0 participants | 1 participants | 1 participants | 4 participants |
| Region of Enrollment Czechia | 2 participants | 9 participants | 9 participants | 1 participants | 2 participants | 5 participants | 28 participants |
| Region of Enrollment France | 19 participants | 15 participants | 16 participants | 28 participants | 21 participants | 31 participants | 130 participants |
| Region of Enrollment Georgia | 2 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment Germany | 8 participants | 10 participants | 9 participants | 19 participants | 18 participants | 19 participants | 83 participants |
| Region of Enrollment Greece | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Hong Kong | 1 participants | 0 participants | 3 participants | 0 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment Hungary | 6 participants | 6 participants | 2 participants | 1 participants | 0 participants | 1 participants | 16 participants |
| Region of Enrollment Iceland | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment India | 23 participants | 30 participants | 20 participants | 7 participants | 6 participants | 5 participants | 91 participants |
| Region of Enrollment Ireland | 1 participants | 1 participants | 0 participants | 4 participants | 0 participants | 1 participants | 7 participants |
| Region of Enrollment Israel | 2 participants | 9 participants | 2 participants | 6 participants | 3 participants | 7 participants | 29 participants |
| Region of Enrollment Italy | 3 participants | 8 participants | 3 participants | 7 participants | 6 participants | 5 participants | 32 participants |
| Region of Enrollment Japan | 8 participants | 10 participants | 8 participants | 12 participants | 10 participants | 13 participants | 61 participants |
| Region of Enrollment Malaysia | 4 participants | 3 participants | 0 participants | 1 participants | 0 participants | 0 participants | 8 participants |
| Region of Enrollment Netherlands | 6 participants | 3 participants | 5 participants | 6 participants | 7 participants | 9 participants | 36 participants |
| Region of Enrollment New Zealand | 2 participants | 1 participants | 3 participants | 0 participants | 3 participants | 2 participants | 11 participants |
| Region of Enrollment Norway | 0 participants | 1 participants | 1 participants | 1 participants | 1 participants | 0 participants | 4 participants |
| Region of Enrollment Poland | 35 participants | 25 participants | 34 participants | 12 participants | 7 participants | 12 participants | 125 participants |
| Region of Enrollment Portugal | 1 participants | 3 participants | 1 participants | 0 participants | 2 participants | 2 participants | 9 participants |
| Region of Enrollment Romania | 2 participants | 1 participants | 3 participants | 1 participants | 2 participants | 0 participants | 9 participants |
| Region of Enrollment Russia | 7 participants | 4 participants | 5 participants | 3 participants | 3 participants | 2 participants | 24 participants |
| Region of Enrollment Serbia | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 1 participants | 3 participants |
| Region of Enrollment Singapore | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Slovakia | 0 participants | 3 participants | 2 participants | 3 participants | 3 participants | 4 participants | 15 participants |
| Region of Enrollment South Africa | 6 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 9 participants |
| Region of Enrollment South Korea | 0 participants | 2 participants | 7 participants | 0 participants | 4 participants | 5 participants | 18 participants |
| Region of Enrollment Spain | 5 participants | 5 participants | 1 participants | 5 participants | 8 participants | 3 participants | 27 participants |
| Region of Enrollment Sri Lanka | 4 participants | 4 participants | 3 participants | 0 participants | 0 participants | 1 participants | 12 participants |
| Region of Enrollment Sweden | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants |
| Region of Enrollment Switzerland | 1 participants | 0 participants | 6 participants | 0 participants | 2 participants | 4 participants | 13 participants |
| Region of Enrollment Taiwan | 4 participants | 1 participants | 1 participants | 1 participants | 0 participants | 3 participants | 10 participants |
| Region of Enrollment Ukraine | 18 participants | 16 participants | 20 participants | 0 participants | 0 participants | 0 participants | 54 participants |
| Region of Enrollment United Kingdom | 5 participants | 5 participants | 4 participants | 6 participants | 7 participants | 6 participants | 33 participants |
| Region of Enrollment United States | 22 participants | 41 participants | 45 participants | 51 participants | 84 participants | 60 participants | 303 participants |
| Sex: Female, Male Female | 110 Participants | 106 Participants | 130 Participants | 115 Participants | 129 Participants | 116 Participants | 706 Participants |
| Sex: Female, Male Male | 113 Participants | 139 Participants | 109 Participants | 89 Participants | 101 Participants | 115 Participants | 666 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 / 222 | 0 / 245 | 0 / 237 | 0 / 202 | 0 / 228 | 0 / 229 | 0 / 118 | 0 / 56 | 0 / 104 | 0 / 55 | 0 / 145 |
| other Total, other adverse events | 87 / 222 | 90 / 245 | 90 / 237 | 106 / 202 | 107 / 228 | 109 / 229 | 59 / 118 | 28 / 56 | 59 / 104 | 25 / 55 | 77 / 145 |
| serious Total, serious adverse events | 18 / 222 | 16 / 245 | 15 / 237 | 19 / 202 | 36 / 228 | 26 / 229 | 13 / 118 | 5 / 56 | 14 / 104 | 3 / 55 | 14 / 145 |
Outcome results
Primary
Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points.
Time frame: Week 10
Population: The Full Analysis Set (FAS) for each 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) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 32.9 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 25.7 percentage of participants |
| Cohort A: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 19.8 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 26.7 percentage of participants |
| Cohort B: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 16.7 percentage of participants |
| Cohort B: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by Crohn's Disease Activity Index (CDAI) at Week 10 | 14.8 percentage of participants |
Comparison: Cochran-Mantel-Haenszel (CMH) test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, \>=1).p-value: 0.001795% CI: [4.7, 20.7]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, \>=1).p-value: 0.17395% CI: [-2.4, 12.7]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.002395% CI: [4.1, 19.9]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.603895% CI: [-5.2, 8.7]Cochran-Mantel-Haenszel
Primary
Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10
The Simple Endoscopic Score for Crohn's Disease (SES-CD) assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score.
Time frame: Week 10
Population: FAS for induction study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10 | 23.9 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10 | 20.8 percentage of participants |
| Cohort A: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10 | 18.1 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10 | 11.9 percentage of participants |
| Cohort B: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10 | 13.6 percentage of participants |
| Cohort B: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Endoscopic Response at Week 10 | 11.4 percentage of participants |
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, \>=1).p-value: 0.136595% CI: [-2, 12.9]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, \>=1).p-value: 0.510395% CI: [-4.8, 9.5]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.979795% CI: [-6.5, 6.6]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.426495% CI: [-3.9, 8.8]Cochran-Mantel-Haenszel
Primary
Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI of \< 150 points.
Time frame: Week 58
Population: The FAS for the Maintenance Study included all participants randomized to either the filgotinib 200 mg or filgotinib 100 mg treatment groups in the Induction Studies who were re-randomized in the Maintenance Study and took at least 1 dose of study drug in the Maintenance Study and achieved clinical remission by PRO2 or endoscopic response at Week 10.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58 | 42.9 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58 | 23.5 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58 | 28.3 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by CDAI at Week 58 | 22.6 percentage of participants |
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.083995% CI: [-1, 28.4]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.828895% CI: [-12.1, 15]Cochran-Mantel-Haenszel
Primary
Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58
The SES-CD assessed the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease. Endoscopic response was defined as ≥ 50% reduction from baseline in total SES-CD score.
Time frame: Week 58
Population: The FAS for the Maintenance Study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58 | 30.4 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58 | 18.4 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58 | 9.4 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Endoscopic Response at Week 58 | 13.2 percentage of participants |
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.003895% CI: [8.2, 33.1]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.346695% CI: [-6.6, 18.3]Cochran-Mantel-Haenszel
Secondary
Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10
The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Clinical Remission was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point.
Time frame: Week 10
Population: FAS for induction study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10 | 32.9 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10 | 30.6 percentage of participants |
| Cohort A: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10 | 25.7 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10 | 29.7 percentage of participants |
| Cohort B: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10 | 18.9 percentage of participants |
| Cohort B: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 10 | 17.9 percentage of participants |
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, \>=1).p-value: 0.096395% CI: [-1.4, 15.2]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, \>=1).p-value: 0.30595% CI: [-3.9, 12.2]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.003995% CI: [3.7, 20.2]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.755695% CI: [-6.2, 8.5]Cochran-Mantel-Haenszel
Secondary
Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical response was defined as reduction in CDAI score from Induction baseline by at least 100 points or CDAI score \< 150 points.
Time frame: Week 10
Population: FAS for induction study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10 | 52.3 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10 | 46.1 percentage of participants |
| Cohort A: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10 | 39.7 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10 | 38.6 percentage of participants |
| Cohort B: Filgotinib 100 mg (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10 | 35.5 percentage of participants |
| Cohort B: Placebo (Induction Study) | Induction Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 10 | 27.5 percentage of participants |
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, ≥1).p-value: 0.007495% CI: [3.2, 20.8]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (0, ≥1).p-value: 0.215995% CI: [-3.2, 14.1]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.01195% CI: [2.6, 20.6]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of oral, systemic corticosteroids (Yes/No) and of immunomodulators (Yes/No) at Day 1, and number of prior exposures to biologic agent (\<=1, \>1).p-value: 0.059395% CI: [-0.4, 16.7]Cochran-Mantel-Haenszel
Secondary
Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10
Plasma concentrations of filgotinib (ng/mL).
Time frame: Week 10: Predose
Population: PK Analysis Set for Induction study was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10 | 46.8 ng/mL | Standard Deviation 180 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10 | 21.3 ng/mL | Standard Deviation 79.5 |
| Cohort A: Placebo (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10 | 47.9 ng/mL | Standard Deviation 215 |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 10 | 40.8 ng/mL | Standard Deviation 139 |
Secondary
Induction Study:Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4
Plasma concentrations of filgotinib \[nanogram/milliliters (ng/mL)\].
Time frame: Week 4: 0.5, 1, 2, and 3 hours (hrs) post dose
Population: Pharmacokinetic (PK) Analysis Set (included all randomized participants who took at least 1 dose of filgotinib and had at least 1 non-missing concentration value for filgotinib and/or its metabolite GS-829845 reported by the PK laboratory) for Induction study was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study:Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4 | 1170 ng/mL | Standard Deviation 1270 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study:Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4 | 611 ng/mL | Standard Deviation 634 |
| Cohort A: Placebo (Induction Study) | Induction Study:Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4 | 1140 ng/mL | Standard Deviation 1070 |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study:Pharmacokinetic Plasma Concentrations of Filgotinib at Week 4 | 604 ng/mL | Standard Deviation 634 |
Secondary
Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10
Plasma concentrations of GS-829845 (ng/mL).
Time frame: Week 10: Predose
Population: PK Analysis Set for Induction study was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10 | 2550 ng/mL | Standard Deviation 1390 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10 | 1290 ng/mL | Standard Deviation 801 |
| Cohort A: Placebo (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10 | 2640 ng/mL | Standard Deviation 1470 |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 10 | 1480 ng/mL | Standard Deviation 917 |
Secondary
Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4
Plasma concentrations of GS-829845 (ng/mL).
Time frame: Week 4: 0.5, 1, 2, and 3 hrs post dose
Population: PK Analysis Set for Induction study was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4 | 3100 ng/mL | Standard Deviation 1530 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4 | 1800 ng/mL | Standard Deviation 936 |
| Cohort A: Placebo (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4 | 3140 ng/mL | Standard Deviation 1450 |
| Cohort B: Filgotinib 200 mg (Induction Study) | Induction Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 4 | 1870 ng/mL | Standard Deviation 776 |
Secondary
Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by CDAI at Week 58
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. 6-Month Corticosteroid-Free Clinical remission by CDAI: CDAI \<150 with no corticosteroid use for indication of Crohn's disease for at least 6 months prior to Week 58.
Time frame: Week 58
Population: The FAS for the Maintenance Study with available data was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by CDAI at Week 58 | 34.0 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by CDAI at Week 58 | 4.9 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by CDAI at Week 58 | 20.0 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by CDAI at Week 58 | 12.0 percentage of participants |
Comparison: CMH test was stratified by immunomodulators (Yes) at Maintenance baseline, immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (Yes), and immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (No).p-value: 0.1995% CI: [-5.1, 33.1]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by immunomodulators (Yes) at Maintenance baseline, immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (Yes), and immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (No).p-value: 0.424895% CI: [-22.6, 11.6]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58
The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. 6-month Corticosteroid-Free Clinical Remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1 with no corticosteroid use for at least 6 months prior to Week 58.
Time frame: Week 58
Population: The FAS for the Maintenance Study with available data was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58 | 32.0 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58 | 7.3 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58 | 20.0 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved 6 Month Corticosteroid-Free Remission by PRO2 at Week 58 | 12.0 percentage of participants |
Comparison: CMH test was stratified by immunomodulators (Yes) at Maintenance baseline, immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (Yes), and immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (No).p-value: 0.263195% CI: [-8.3, 32.3]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by immunomodulators (Yes) at Maintenance baseline, immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (Yes), and immunomodulators (No) at Maintenance baseline and history of exposure to biologic agent (No).p-value: 0.644495% CI: [-20.9, 14]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58
The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Clinical Remission was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point.
Time frame: Week 58
Population: The FAS for the Maintenance Study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58 | 43.8 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58 | 29.6 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58 | 26.4 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Remission by PRO2 at Week 58 | 24.5 percentage of participants |
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.038295% CI: [2, 31.6]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.426395% CI: [-8.5, 20]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 58
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Clinical response was defined as reduction in CDAI score from Induction baseline by at least 100 points or CDAI score \< 150 points.
Time frame: Week 58
Population: The FAS for the Maintenance Study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 58 | 45.5 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 58 | 33.7 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 58 | 34.0 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Clinical Response by CDAI at Week 58 | 30.2 percentage of participants |
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.182795% CI: [-4.7, 26.4]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.594495% CI: [-11.1, 19.2]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by CDAI at Both Weeks 10 and 58
The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The sub scores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Sustained Clinical Remission by CDAI: CDAI \<150 combined at both Week 10 and Week 58.
Time frame: Weeks 10 and 58
Population: The FAS for the Maintenance Study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by CDAI at Both Weeks 10 and 58 | 38.4 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by CDAI at Both Weeks 10 and 58 | 19.4 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by CDAI at Both Weeks 10 and 58 | 22.6 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by CDAI at Both Weeks 10 and 58 | 20.8 percentage of participants |
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.051295% CI: [1, 29.3]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use of immunomodulators (Yes/No) at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.980195% CI: [-13.3, 13]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58
The PRO2 was a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency and abdominal pain (rated on a scale of 0-3) assessed for 7 days. Sustained Clinical Remission by PRO2: liquid or very soft stool ≤3 and abdominal pain ≤1 combined at both Week 10 and Week 58.
Time frame: Weeks 10 and 58
Population: The FAS for the Maintenance Study was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58 | 41.1 percentage of participants |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58 | 25.5 percentage of participants |
| Cohort A: Placebo (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58 | 20.8 percentage of participants |
| Cohort B: Filgotinib 200 mg (Induction Study) | Maintenance Study: Percentage of Participants Who Achieved Sustained Clinical Remission by PRO2 at Both Weeks 10 and 58 | 24.5 percentage of participants |
Comparison: CMH test was stratified by concomitant use immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.012295% CI: [5.7, 34]Cochran-Mantel-Haenszel
Comparison: CMH test was stratified by concomitant use immunomodulators (Yes/No), at Maintenance baseline, and history of exposure to a biologic agent (Yes/No).p-value: 0.770895% CI: [-12, 16.1]Cochran-Mantel-Haenszel
Secondary
Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 26
Plasma concentrations of filgotinib (ng/mL).
Time frame: Week 26: At any timepoint
Population: PK Analysis Set for Maintenance study was analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 26 | 284 ng/mL | Standard Deviation 623 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 26 | 58.5 ng/mL | Standard Deviation 150 |
Secondary
Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 58
Plasma concentrations of filgotinib (ng/mL).
Time frame: Week 58: Pre-dose
Population: PK Analysis Set for Maintenance study was analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 58 | 75.8 ng/mL | Standard Deviation 238 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib at Week 58 | 16.9 ng/mL | Standard Deviation 55.5 |
Secondary
Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 26
Plasma concentrations of GS-829845 (ng/mL).
Time frame: Week 26: At any timepoint
Population: PK Analysis Set for Maintenance study was analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 26 | 3090 ng/mL | Standard Deviation 1500 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 26 | 1460 ng/mL | Standard Deviation 814 |
Secondary
Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 58
Plasma concentrations of GS-829845 (ng/mL).
Time frame: Week 58: Pre-dose
Population: PK Analysis Set for Maintenance study was analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Filgotinib 200 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 58 | 2430 ng/mL | Standard Deviation 1430 |
| Cohort A: Filgotinib 100 mg (Induction Study) | Maintenance Study: Pharmacokinetic Plasma Concentrations of Filgotinib's Metabolite GS-829845 at Week 58 | 1220 ng/mL | Standard Deviation 551 |