This trial will test the drug filgotinib for the treatment of small bowel Crohn’s disease.

• Register: EUCTR
• Last refreshed on: 7 June 2021
• Main ID: EUCTR2016-003179-23-DE
• Date of registration: 14/02/2017
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: This trial will test the drug filgotinib for the treatment of small bowel Crohn’s disease.
• Scientific title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of Filgotinib in the Treatment of Small Bowel Crohn’s Disease (SBCD)
• Date of first enrolment: 19/12/2017
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003179-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Poland, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
For a complete list of study inclusion criteria, please refer to study protocol (sections 4.2):
1) Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
2) Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of screening visit
3) Females of childbearing potential must have a negative pregnancy test at screening and baseline
4) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
5) Moderately or severely active CD as defined by screening CDAI 200 to 450 (inclusive).
6) Minimum duration of CD of at least 6 months
7) Presence of diseased SB segments on MRE with segmental MaRIA score of = 7 in at least 1 of the following segments: terminal ileum, distal ileum, or jejunum.
8) Patients with additional colonic involvement of CD are permitted in study as long as SBCD is present.
9) 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):
a) Corticosteroids
b) Immunomodulators
c) TNFa Antagonists
d) Vedolizumab
e) Ustekinumab
10) Meet one of the following tuberculosis (TB) screening criteria:
a) No evidence of active or latent TB
b) Previously treated for TB
c) Newly identified latent TB during screening
11) Laboratory parameters within specified intervals
12) May be receiving the following drugs (subjects on these therapies must be willing to
remain on stable doses for the noted times):
a) Oral 5-aminosalicylate (5-ASA) compounds
b) Oral corticosteroid therapy
c) Azathioprine or 6-MP or methotrexate
d) Antibiotics for the treatment of CD
13) Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose of study drug.
14) Willing and able to undergo MRE per protocol requirements
15) Must be up to date on colorectal cancer screening and surveillance as standard of care according to local guidelines.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 92
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion criteria:
For a complete list of study exclusion criteria, please refer to study protocol (Sections 4.3):
1) Pregnant or lactating females.
2) Males and females of reproductive potential who are unwilling to adhere to contraceptive guidance
3) Females who may wish to become pregnant and/or plan to undergo egg donation or egg harvesting for the purpose of current or future fertilization during the course of the study and up to 35 days after the last dose of the study drug.
4) Male subjects unwilling to refrain from sperm donation during the study and for at least 90 days after the last dose of study drug.
5) Known hypersensitivity to filgotinib, its metabolites, or formulation excipients
6) Presence of symptomatic or clinically significant (eg, obstructive or symptomatic) strictures
or stenosis.
7) Presence of fistulae.
8) Evidence of short bowel syndrome.
9) Any other complication of CD that could preclude the use of CDAI to assess response to
therapy or would confound the evaluation of benefit from treatment with filgotinib.
10) Claustrophobia to a degree that prevents tolerance of MRE scanning procedure (sedation is permitted at discretion of investigator).
11) Metallic implant of any sort that prevents MRE examination, not limited to but including aneurysm clips, metallic foreign body, vascular grafts or cardiac implants, neural stimulator, metallic contraceptive device, body piercing that cannot be removed, cochlear implant; or other contraindication to MRE examination.
12) Known hypersensitivity to gadolinium
13) Isolated colonic CD, or isolated CD that does not involve some segment of the small bowel.
14) Evidence of any other CD manifestation that might require imminent surgery or would
possibly confound the evaluation of benefit from treatment with filgotinib.
15) Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to Day 1 and are not anticipated to require surgery.
16) History of major surgery or trauma within 30 days prior to screening.
17) Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon.
18) Dependence on parenteral nutrition.
19) History of total colectomy, subtotal colectomy, presence of ileostomy or colostomy, or likely requirement for surgery during the study.
20) History or evidence of incompletely resected colonic mucosal dysplasia.
21) Stool sample positive for Clostridium difficile (C. diff) toxin, pathogenic Escherichia coli (E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp.
22) Stool sample positive for ova or parasites test (O&P) unless approved by the Medical Monitor
23) Have used any TNFa antagonist or vedolizumab = 8 weeks prior to screening ustekinumab IV or SC = 12 weeks prior to screening, or any other biologic agent = 8 weeks prior to screening or within 5 times the half-life of the biologic agent prior to screening, whichever is longer.
24) Use of any prohibited concomitant medication
25) History of leukocytapharesis = 6 months prior to screening.
26) Active clinically significant infection or any infection requiring hospitalization or treatment
with intravenous anti-infectives within 30 days of screening (or 8 weeks of Day 1); or any infection requiring oral anti-infective therapy within 2 weeks of screening (or 6 weeks of Day 1).
27) Co-Infection with human immunodeficiency virus (HIV), HBV, or HCV.
28) Presence of Child-Pugh Class C

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Small Bowel Crohn’s Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: Filgotinib
Product Code: GS-6034
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FILGOTINIB
Other descriptive name: FILGOTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Filgotinib
Product Code: GS-6034
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FILGOTINIB
Other descriptive name: FILGOTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical remission at Week 24

Secondary Objective: The secondary objectives of this study are:
-To evaluate the impact of filgotinib, when compared to placebo, on change in segmental MaRIA score for all assessed small bowel segments at Week 24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment level MaRIA remission at Week 24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment level MaRIA response at Week 24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing subject level small bowel MaRIA remission at Week 24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing subject level small bowel MaRIA response at Week 24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical remission, defined as CDAI<150, at Week 10
-To evaluate the impact of filgotinib, when compared to placebo, on change in CDAI scores
-To evaluate the safety and tolerability of filgotinib

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): The primary endpoint is the proportion of subjects achieving clinical remission by CDAI < 150 at Week 24.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints are:
- Change from baseline in terminal ileum segmental MaRIA score at Week 24
- Change from baseline in distal ileum segmental MaRIA score at Week 24
- Change from baseline in jejunum segmental MaRIA score at Week 24
- Proportion of subjects achieving MaRIA remission in terminal ileum segment at Week 24
- Proportion of subjects achieving MaRIA remission in distal ileum segment at Week 24
- Proportion of subjects achieving MaRIA remission in jejunum segment at Week 24
- Proportion of subjects achieving MaRIA response in terminal ileum segment at Week 24
- Proportion of subjects achieving MaRIA response in distal ileum segment at Week 24
- Proportion of subjects achieving MaRIA response in jejunum segment at Week 24
- Proportion of subjects achieving subject level small bowel MaRIA remission at Week 24
- Proportion of subjects achieving subject level small bowel MaRIA response at Week 24
- Proportion of subjects achieving early clinical remission by CDAI at Week 10
- Change from baseline in CDAI scores at Week 10
- Change from baseline in CDAI scores at Week 24

Timepoint(s) of evaluation of this end point: Week 24

Secondary ID(s)

2016-003179-23-GB

GS-US-419-4015

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date: 19/12/2017
Contact: