Fistulizing Crohn's DiseasePhase 2Divergence2NCT03077412
Study to Evaluate the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease
A Phase 2 study testing Filgotinib in people with Fistulizing Crohn's Disease, run by Gilead Sciences at 27 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Fistulizing Crohn's Disease
- What is being tested?
- Filgotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 27 sitesin 9 countries
- Study dates
- 6 Apr 2017to 17 Feb 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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/Exclusion criteria may apply.
Trial locations and contacts
27 sites in 9 countries.
27 sites in 9 countries
United States13 sites
Texas Clinical Research Institute
Arlington, Texas, 76012
John Hopkins Gastroenterology and Hepatology Services at the Green Spring Station Clinic
Baltimore, Maryland, 21224
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Gastro Center of Maryland
Columbia, Maryland, 21045
DHAT Research Institute
Garland, Texas, 75044
Gastro One
Germantown, Tennessee, 38138
University of Louisville Clinical Trials Unit
Louisville, Kentucky, 40202
University of Miami Crohn's and Colitis Center
Miami, Florida, 33136
Vanderbilt University Medical Center - IBD Clinic
Nashville, Tennessee, 37212-2702
Center for Interventional Endoscopy - Florida Hospital
Orlando, Florida, 32804
McGuire DVAMC
Richmond, Virginia, 23249
Texas Digestive Disease Consultants
Southlake, Texas, 76092
University of South Florida South Tampa Campus
Tampa, Florida, 33606
France3 sites
CHU Grenoble Alpes - Hopital Michallon (main office)
La Tronche, 38700
CHU de Rennes - Hôpital Pontchaillou (main office)
Rennes, 85809
CHU Nancy - Hopital de Brabois
Vandœuvre-lès-Nancy, 54511
Austria2 sites
Klinikum Klagenfurt am Wörthersee
Klagenfurt, 9020
Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology
Vienna, 1090
Canada2 sites
Mount Sinai Hospital
Toronto, M5T 3L9
Toronto Digestive Disease Associates Inc.
Toronto, M9V 4B8
Germany2 sites
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 01307
Universitatsklinkum Jena
Jena, 07747
Hungary2 sites
Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórháza
Békéscsaba, Bekes County, 5600
Bugát Pál Kórház, Gasztroenterológiai osztály
Gyöngyös, Heves County, 3200
United Kingdom1 site
Royal Devon and Exeter Hospital, Department of Gastroenterology
Exeter, EX2 5DW
About this study
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease
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.
- Conditions
- Fistulizing Crohn's Disease
- Being tested
- Filgotinib, Placebo to match filgotinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FilgotinibDrug
Also called GS-6034, GLPG0634
Tablet(s) administered orally once daily
Placebo to match filgotinibDrug
Tablet(s) administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Filgotinib 200 mg | Experimental | Filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks Receives: Drug: Filgotinib; Drug: Placebo to match filgotinib |
| Filgotinib 100 mg | Experimental | Filgotinib 100 mg + placebo to match filgotinib 200 mg for 24 weeks Receives: Drug: Filgotinib; Drug: Placebo to match filgotinib |
| Placebo | Experimental | Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks Receives: Drug: Placebo to match filgotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 24
Secondary outcomes (4)
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.
Measured: Week 24
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.
Measured: 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 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.
Measured: 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
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.
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2017
- Study start6 Apr 2017
- Primary completion20 Jan 2021
- Study completion17 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fistulizing Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Lakefront Biotherapeutics NV
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03077412
- Sponsor's protocol ID
- GS-US-419-4016
- Other IDs
- 2016-003153-15, 2016
- Acronym
- Divergence2
- Status last verified
- Apr 2022
- First submitted
- 8 Mar 2017
- Last updated
- 8 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Reinisch W, Colombel JF, D'Haens GR, Rimola J, Masior T, McKevitt M, Ren X, Serone A, Schwartz DA, Gecse KB. Efficacy and Safety of Filgotinib for the Treatment of Perianal Fistulising Crohn's Disease [DIVERGENCE 2]: A Phase 2, Randomised, Placebo-controlled Trial. J Crohns Colitis. 2024 Jun 3;18(6):864-874. doi: 10.1093/ecco-jcc/jjae003.
PubMed 38366672
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease
- ClinicalTrials.gov ID
- NCT03077412
- Acronym / sponsor ID
- Divergence2 / GS-US-419-4016
- Conditions
- Fistulizing Crohn's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Collaborators
- Lakefront Biotherapeutics NV
- Study start
- 6 Apr 2017 (actual)
- Primary completion
- 20 Jan 2021 (actual)
- Study completion
- 17 Feb 2021 (actual)
- First posted
- 13 Mar 2017 (actual)
- Results
- Posted 8 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Filgotinib 200 mg | Experimental | Drug: Filgotinib, Drug: Placebo to match filgotinibFilgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks |
| Filgotinib 100 mg | Experimental | Drug: Filgotinib, Drug: Placebo to match filgotinibFilgotinib 100 mg + placebo to match filgotinib 200 mg for 24 weeks |
| Placebo | Experimental | Drug: Placebo to match filgotinibPlacebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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):
- Is willing and able to undergo MRI per protocol requirements
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FilgotinibAlso: GS-6034, GLPG0634Tablet(s) administered orally once daily | Drug | Filgotinib 100 mg, Filgotinib 200 mg |
| Placebo to match filgotinibTablet(s) administered orally once daily | Drug | Filgotinib 100 mg, Filgotinib 200 mg, Placebo |
Primary outcome
Percentage of Participants Who Achieved Combined Fistula Response at Week 24
Time frame: 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.
4 secondary outcomes
Percentage of Participants Who Achieved Combined Fistula Remission at Week 24
Time frame: Week 24
Time to Clinical Fistula Response up to Week 24
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
Time to Clinical Fistula Remission up to Week 24
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
Percentage of Participants Who Achieved Proctitis Remission at Week 24
Time frame: Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38366672Reinisch W, Colombel JF, D'Haens GR, Rimola J, Masior T, McKevitt M, Ren X, Serone A, Schwartz DA, Gecse KB. Efficacy and Safety of Filgotinib for the Treatment of Perianal Fistulising Crohn's Disease [DIVERGENCE 2]: A Phase 2, Randomised, Placebo-controlled Trial. J Crohns Colitis. 2024 Jun 3;18(6):864-874. doi: 10.1093/ecco-jcc/jjae003.
- Individual participant dataSharing planned: No
Related trials for Fistulizing Crohn's Disease
Active, not recruitingPhase 3
A Study of Guselkumab in Participants With Fistulizing, Perianal Crohn's Disease
Fistulizing Crohns Disease, Perianal Crohns Disease
RecruitingPhase 4
Risankizumab for Refractory Perianal Fistulizing Crohn's Disease
Crohn Disease, Perianal Fistula
Not yet recruitingPhase 1/2
Hyperbaric Oxygen Therapy for Perianal Fistulizing Crohn's Disease Not Responsive or Intolerant to Conventional Care: HYPNOTIC Pilot Study
Inflammatory Bowel Disease (IBD), Crohn Disease
Not yet recruitingPhase 4
MIRICURE: Mirikizumab With Curettage and Repair (Closure) for Perianal Fistulizing Crohn's Disease
Crohn's Disease, Perianal Fistula
Recruiting
Regenerative Endoscopy in Refractory Perianal Crohn's Disease
Crohn Disease (CD), Perianal Crohns Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
27 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Filgotinib in people with Fistulizing Crohn's Disease, run by Gilead Sciences at 27 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, France, Austria, Canada, Germany and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Achieved Combined Fistula Response at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03077412, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2022.