Fistulizing Crohn's Disease
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula response at Week 24. Participants will have the option to enter a separate Long-Term Extension (LTE) study (GS-US-419-3896; NCT02914600) if they meet eligibility requirements.
Interventions
DRUGFilgotinib
Tablet(s) administered orally once daily
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 screening visit * Diagnosis of Crohn's disease (CD) with a minimum duration of CD of at least 3 months * Has draining perianal fistulae as a complication of CD, confirmed by magnetic resonance imaging (MRI) at screening * Previously demonstrated an inadequate clinical response, loss of response to, or intolerance of at least 1 of the following agents (depending on current country treatment recommendations/guidelines): * Antibiotics AND/OR * Immunomodulators AND/OR * Tumor necrosis factor α (TNFα) Antagonist * Is willing and able to undergo MRI per protocol requirements * Is willing and able to undergo flexible sigmoidoscopy per protocol requirements Key
Exclusion criteria
* Presence of current rectovaginal anovaginal or enterovesicular fistulae * Presence of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon * History of total proctocolectomy, total colectomy, presence of ileostomy or colostomy, or likely requirement for surgery during the study * Use of any prohibited concomitant medications as described in the study protocol * Active tuberculosis (TB) or history of latent TB that has not been treated Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Combined Fistula Response at Week 24 | Week 24 | Combined fistula response at Week 24 was defined as reduction of greater than or equal to (≥) 1 from baseline in the number of draining external perianal fistula openings that were present at baseline, and absence of fluid collections \> 1 centimeter (cm) on magnetic resonance imaging (MRI) pelvis at Week 24, among participants with at least 1 draining external perianal fistula opening at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Combined Fistula Remission at Week 24 | Week 24 | Combined fistula remission at Week 24 was defined as perianal fistula closure of all external openings that were draining at baseline, and absence of fluid collections \> 1 cm on MRI of pelvis at Week 24, among participants with at least 1 draining external perianal fistula opening at baseline. |
| Time to Clinical Fistula Response up to Week 24 | Time from treatment start to first visit when ≥ 1 of the draining external perianal fistula openings that were present at baseline achieved perianal fistula closure up to Week 24 | Time to clinical fistula response was defined as the time interval in days from date of first dosing of study drug to the first observation (during scheduled or unscheduled clinical visits) when ≥ 1 of the draining external perianal fistula openings that were present at baseline achieves perianal fistula closure, among participants with at least 1 draining external perianal fistula opening at baseline. Participants not known to had a clinical fistula response were to have their clinical fistula response time censored at the last time that lack of clinical fistula response was documented. |
| Time to Clinical Fistula Remission up to Week 24 | Time from treatment start to first visit when perianal fistula closure takes place of all external openings that were draining at baseline up to Week 24 | Time to clinical fistula remission was defined as the time interval in days from date of first dosing of study drug to the first observation (during schedule or unscheduled clinical visits) of perianal fistula closure of all external openings that were draining at baseline, among participants with at least 1 draining external perianal fistula opening at baseline. Participants not known to had a clinical fistula remission were have their clinical fistula remission time censored at the last time that lack of clinical fistula remission was documented. |
| Percentage of Participants Who Achieved Proctitis Remission at Week 24 | Week 24 | The simple endoscopic score for Crohn's disease (SES-CD) score evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and presence of narrowings). The total SES-CD is calculated as the sum of the 4 variables for the required bowel segment. Values are given to each variable and for every examined bowel segment. The SES-CD size of ulcer subscore ranges from 0 (none) to 3 (very large) and for ulcerated surface subscore ranges from 0 (none) to 3 (\>30 % of affected area). Higher value of the subscore indicates disease worsening. Proctitis remission at Week 24 was defined as a proctitis SES-CD score (sum of ulcer size and ulcerated surface SES-CD endoscopy subscores for the rectum and anal canal) of 0 assessed by centrally read flexible sigmoidoscopy at Week 24, in participants that had moderately to severely active proctitis at baseline. Moderately to Severely Active Proctitis defined as proctitis SES-CD Score \> 2. |
Countries
Austria, Belgium, Canada, France, Germany, Hungary, Italy, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe and the United States. The first participant was screened on 06 April 2017. The last study visit occurred on 17 February 2021.
Pre-assignment details
106 participants were screened. Participants who were non-responders, met disease worsening criteria or completed all procedures per protocol, were offered the option to continue into a separate Long Term Extension (LTE) study (GS-US-419-3896; NCT02914600), if deemed appropriate by the investigator.
Participants by arm
| Arm | Count |
|---|---|
| Filgotinib 200 mg Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks. | 17 |
| Filgotinib 100 mg Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks. | 25 |
| Placebo Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks. | 15 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 |
| Overall Study | Investigator's Discretion | 0 | 1 | 1 |
| Overall Study | Non-Responder [Crohn's Disease Activity Index (CDAI) and Perianal CDAI non-response] at Week 10 | 1 | 5 | 3 |
| Overall Study | Protocol-Specified Disease Worsening | 1 | 3 | 3 |
| Overall Study | Withdrew Consent | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Filgotinib 200 mg | Filgotinib 100 mg | Placebo |
|---|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 12.5 | 39 years STANDARD_DEVIATION 11.2 | 41 years STANDARD_DEVIATION 14 | 39 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 55 Participants | 17 Participants | 23 Participants | 15 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 4 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 48 Participants | 15 Participants | 19 Participants | 14 Participants |
| Region of Enrollment Austria | 8 participants | 4 participants | 2 participants | 2 participants |
| Region of Enrollment Belgium | 3 participants | 1 participants | 1 participants | 1 participants |
| Region of Enrollment Canada | 5 participants | 1 participants | 3 participants | 1 participants |
| Region of Enrollment France | 5 participants | 2 participants | 3 participants | 0 participants |
| Region of Enrollment Germany | 4 participants | 3 participants | 0 participants | 1 participants |
| Region of Enrollment Hungary | 3 participants | 1 participants | 1 participants | 1 participants |
| Region of Enrollment Italy | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment United Kingdom | 1 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment United States | 27 participants | 4 participants | 15 participants | 8 participants |
| Sex: Female, Male Female | 23 Participants | 9 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Male | 34 Participants | 8 Participants | 15 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 25 | 0 / 15 |
| other Total, other adverse events | 13 / 17 | 14 / 25 | 11 / 15 |
| serious Total, serious adverse events | 5 / 17 | 2 / 25 | 1 / 15 |
Outcome results
Primary
Percentage of Participants Who Achieved Combined Fistula Response at Week 24
Combined fistula response at Week 24 was defined as reduction of greater than or equal to (≥) 1 from baseline in the number of draining external perianal fistula openings that were present at baseline, and absence of fluid collections \> 1 centimeter (cm) on magnetic resonance imaging (MRI) pelvis at Week 24, among participants with at least 1 draining external perianal fistula opening at baseline.
Time frame: Week 24
Population: Participants in Full Analysis Set (all the randomized participants who received at least 1 dose of the study drug) with at least 1 draining external perianal fistula opening at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved Combined Fistula Response at Week 24 | 47.1 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved Combined Fistula Response at Week 24 | 29.2 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Combined Fistula Response at Week 24 | 25.0 percentage of participants |
90% CI: [-9.9, 50]
90% CI: [-26.5, 34.3]
Secondary
Percentage of Participants Who Achieved Combined Fistula Remission at Week 24
Combined fistula remission at Week 24 was defined as perianal fistula closure of all external openings that were draining at baseline, and absence of fluid collections \> 1 cm on MRI of pelvis at Week 24, among participants with at least 1 draining external perianal fistula opening at baseline.
Time frame: Week 24
Population: Participants in the Full Analysis Set with at least 1 draining external perianal fistula opening at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved Combined Fistula Remission at Week 24 | 47.1 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved Combined Fistula Remission at Week 24 | 25.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Combined Fistula Remission at Week 24 | 16.7 percentage of participants |
90% CI: [-1.3, 57.3]
90% CI: [-22.5, 38.1]
Secondary
Percentage of Participants Who Achieved Proctitis Remission at Week 24
The simple endoscopic score for Crohn's disease (SES-CD) score evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and presence of narrowings). The total SES-CD is calculated as the sum of the 4 variables for the required bowel segment. Values are given to each variable and for every examined bowel segment. The SES-CD size of ulcer subscore ranges from 0 (none) to 3 (very large) and for ulcerated surface subscore ranges from 0 (none) to 3 (\>30 % of affected area). Higher value of the subscore indicates disease worsening. Proctitis remission at Week 24 was defined as a proctitis SES-CD score (sum of ulcer size and ulcerated surface SES-CD endoscopy subscores for the rectum and anal canal) of 0 assessed by centrally read flexible sigmoidoscopy at Week 24, in participants that had moderately to severely active proctitis at baseline. Moderately to Severely Active Proctitis defined as proctitis SES-CD Score \> 2.
Time frame: Week 24
Population: Participants in the Full Analysis Set who had moderately to severely active proctitis at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Filgotinib 200 mg | Percentage of Participants Who Achieved Proctitis Remission at Week 24 | 10.0 percentage of participants |
| Filgotinib 100 mg | Percentage of Participants Who Achieved Proctitis Remission at Week 24 | 15.4 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Proctitis Remission at Week 24 | 28.6 percentage of participants |
90% CI: [-55.6, 21.3]
90% CI: [-51, 24.1]
Secondary
Time to Clinical Fistula Remission up to Week 24
Time to clinical fistula remission was defined as the time interval in days from date of first dosing of study drug to the first observation (during schedule or unscheduled clinical visits) of perianal fistula closure of all external openings that were draining at baseline, among participants with at least 1 draining external perianal fistula opening at baseline. Participants not known to had a clinical fistula remission were have their clinical fistula remission time censored at the last time that lack of clinical fistula remission was documented.
Time frame: Time from treatment start to first visit when perianal fistula closure takes place of all external openings that were draining at baseline up to Week 24
Population: Participants in the Full Analysis Set with at least 1 draining external perianal fistula opening at baseline were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib 200 mg | Time to Clinical Fistula Remission up to Week 24 | 15 days |
| Filgotinib 100 mg | Time to Clinical Fistula Remission up to Week 24 | 29 days |
| Placebo | Time to Clinical Fistula Remission up to Week 24 | 71 days |
90% CI: [0.87, 4.01]
90% CI: [0.65, 2.92]
Secondary
Time to Clinical Fistula Response up to Week 24
Time to clinical fistula response was defined as the time interval in days from date of first dosing of study drug to the first observation (during scheduled or unscheduled clinical visits) when ≥ 1 of the draining external perianal fistula openings that were present at baseline achieves perianal fistula closure, among participants with at least 1 draining external perianal fistula opening at baseline. Participants not known to had a clinical fistula response were to have their clinical fistula response time censored at the last time that lack of clinical fistula response was documented.
Time frame: Time from treatment start to first visit when ≥ 1 of the draining external perianal fistula openings that were present at baseline achieved perianal fistula closure up to Week 24
Population: Participants in the Full Analysis Set with at least 1 draining external perianal fistula opening at baseline were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Filgotinib 200 mg | Time to Clinical Fistula Response up to Week 24 | 15 days |
| Filgotinib 100 mg | Time to Clinical Fistula Response up to Week 24 | 16 days |
| Placebo | Time to Clinical Fistula Response up to Week 24 | 35.5 days |
90% CI: [0.64, 2.49]
90% CI: [0.47, 1.75]