Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease (NCT NCT03077412)

Last Updated: 2022-04-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

Week 24

Results posted on

2022-04-08

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Filgotinib 200 mg Participants received filgotinib 200 milligrams (mg) and placebo to match (PTM) filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.
Overall Study STARTED	17	25	15
Overall Study COMPLETED	14	12	6
Overall Study NOT COMPLETED	3	13	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Filgotinib 200 mg Participants received filgotinib 200 milligrams (mg) and placebo to match (PTM) filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.
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 Adverse Event	1	2	2
Overall Study Investigator's Discretion	0	1	1
Overall Study Withdrew Consent	0	2	0

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Filgotinib 200 mg n=17 Participants Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg n=25 Participants Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo n=15 Participants Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.	Total n=57 Participants Total of all reporting groups
Age, Continuous	39 years STANDARD_DEVIATION 11.2 • n=5 Participants	41 years STANDARD_DEVIATION 14.0 • n=7 Participants	39 years STANDARD_DEVIATION 11.8 • n=5 Participants	40 years STANDARD_DEVIATION 12.5 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	4 Participants n=5 Participants	23 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	15 Participants n=7 Participants	11 Participants n=5 Participants	34 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	15 Participants n=5 Participants	19 Participants n=7 Participants	14 Participants n=5 Participants	48 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Race · Not Permitted	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	17 Participants n=5 Participants	23 Participants n=7 Participants	15 Participants n=5 Participants	55 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Canada	1 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Austria	4 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Hungary	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment United States	4 participants n=5 Participants	15 participants n=7 Participants	8 participants n=5 Participants	27 participants n=4 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Italy	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment France	2 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Germany	3 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Filgotinib 200 mg n=17 Participants Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg n=24 Participants Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo n=12 Participants Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.
Percentage of Participants Who Achieved Combined Fistula Response at Week 24	47.1 percentage of participants Interval 26.0 to 68.9	29.2 percentage of participants Interval 14.6 to 47.9	25.0 percentage of participants Interval 7.2 to 52.7

SECONDARY outcome

Timeframe: Week 24

Population: Participants in the Full Analysis Set with at least 1 draining external perianal fistula opening at baseline were analyzed.

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.

Outcome measures

Outcome measures
Measure	Filgotinib 200 mg n=17 Participants Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg n=24 Participants Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo n=12 Participants Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.
Percentage of Participants Who Achieved Combined Fistula Remission at Week 24	47.1 percentage of participants Interval 26.0 to 68.9	25.0 percentage of participants Interval 11.5 to 43.5	16.7 percentage of participants Interval 3.0 to 43.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Filgotinib 200 mg n=17 Participants Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg n=24 Participants Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo n=12 Participants Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.
Time to Clinical Fistula Response up to Week 24	15 days Interval 15.0 to 28.0	16 days Interval 15.0 to 71.0	35.5 days Interval 15.0 to 71.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Filgotinib 200 mg n=17 Participants Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg n=24 Participants Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo n=12 Participants Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.
Time to Clinical Fistula Remission up to Week 24	15 days Interval 15.0 to 70.0	29 days Interval 16.0 to 74.0	71 days Interval 26.0 to Not enough participants achieved clinical fistula remission to calculate upper 90% CI.

SECONDARY outcome

Timeframe: Week 24

Population: Participants in the Full Analysis Set who had moderately to severely active proctitis at baseline were analyzed.

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.

Outcome measures

Outcome measures
Measure	Filgotinib 200 mg n=10 Participants Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.	Filgotinib 100 mg n=13 Participants Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for 24 weeks.	Placebo n=7 Participants Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for 24 weeks.
Percentage of Participants Who Achieved Proctitis Remission at Week 24	10.0 percentage of participants Interval 0.5 to 39.4	15.4 percentage of participants Interval 2.8 to 41.0	28.6 percentage of participants Interval 5.3 to 65.9

Adverse Events

Filgotinib 200 mg

Serious events: 5 serious events

Other events: 13 other events

Deaths: 0 deaths

Filgotinib 100 mg

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Filgotinib 200 mg n=17 participants at risk Participants received filgotinib 200 mg and PTM filgotinib 100 mg, once daily for up to Week 26.	Filgotinib 100 mg n=25 participants at risk Participants received filgotinib 100 mg and PTM filgotinib 200 mg, once daily for up to Week 29.3.	Placebo n=15 participants at risk Participants received PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily for up to Week 27.9.
Gastrointestinal disorders Crohn's disease	5.9% 1/17 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	8.0% 2/25 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/15 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal obstruction	5.9% 1/17 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/25 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/15 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Large intestinal stenosis	5.9% 1/17 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/25 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/15 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	5.9% 1/17 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/25 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/15 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.
Infections and infestations Suspected COVID-19	5.9% 1/17 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/25 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/15 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.
Infections and infestations Vulval abscess	0.00% 0/17 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	0.00% 0/25 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.	6.7% 1/15 • All-Cause Mortality: First dose date up to 24 weeks plus 30 days; Adverse Events: First dose date up to 24 weeks plus 30 days All-Cause Mortality: All Randomized Set included all participants who were randomized in the study; Adverse Events: Safety Analysis Set included all participants who received at least 1 dose of study drug.

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER