A Study to Assess a New Treatment in Patients with Moderately to Severely Active Crohn’s Disease

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2016-001367-36-IS
• Date of registration: 27/12/2016
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A Study to Assess a New Treatment in Patients with Moderately to Severely Active Crohn’s Disease
• Scientific title: Combined Phase 3, Double-blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Crohn’s Disease
• Date of first enrolment: 09/05/2017
• Target sample size: 1320
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001367-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Combined induction and maintenance phase study design 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): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Croatia, Czech Republic, France, Georgia, Germany, Greece, Hong Kong, Hungary, Iceland, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, 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:
Subjects must meet all of the following inclusion criteria to be eligible for participation in either the Cohort A or B Induction Study.
• Must have the ability to understand and sign a written ICF, which must be obtained prior to initiation of study procedures
• Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit
• Females of childbearing potential must have a negative pregnancy test at screening and baseline
• Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Documented diagnosis of CD with a minimum disease duration of 6 months with involvement of the ileum and/or colon at a minimum
• Moderately or severely active CD
• Meet one of the protocol specified tuberculosis (TB) screening criteria
• May be receiving the following drugs (subjects on these therapies must be willing to remain on stable doses for the times noted in the protocol)
- Oral 5-aminosalicylate (5-ASA) compounds
- Azathioprine or 6-mercaptopurine (6-MP) or methotrexate (MTX)
- Oral corticosteroid therapy
- Antibiotics for the treatment of CD
• Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose

Subjects must meet all of the additional inclusion criteria to be eligible for participation in Cohort A Induction Study.
• Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least one of the following agents (depending on current country treatment recommendations/guidelines):
- Corticosteroids
- Immunomodulators

Subjects must meet all of the additional inclusion criteria to be eligible for participation in Cohort B induction study.
• Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least one of the following agents:
- TNFa Antagonists
- Vedolizumab
• Must not have used any TNFa antagonist or vedolizumab = 8 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

Subjects must meet all of the following inclusion criteria to be eligible for participation in the Maintenance Study.
• Completion of Cohort A or B induction study with either clinical remission by PRO2 or endoscopic response at Week 10
• Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose
• May be on oral corticosteroid therapy (prednisone prescribed at a stable dose = 30 mg/day or budesonide at a dose of = 9 mg/day); dose must remain stable to Week 14
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 1214
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 106

Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in either the Cohort A or B induction study
• Pregnant or lactating females
• Males and females of reproductive potential who are unwilling to abide by protocol-specified contraceptive methods
• 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
• Male subjects unwilling to refrain from sperm donation during the study and for at least 90 days after the last dose of study drug
• Known hypersensitivity to filgotinib
• Currently have complications of CD
• 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
• History of major surgery or trauma within 30 days prior to screening
• Presence of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon
• History of total colectomy, hemi-colectomy, presence of ileostomy or colostomy, or likely requirement for surgery during the study
• Dependence on parenteral nutrition
• History or evidence of incompletely resected colonic mucosal dysplasia
• Stool sample positive for Clostridium difficile (C. diff) toxin, Escherichia coli (E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp
• Stool sample positive for ova and parasites test (O&P) unless approved by the medical monitor
• 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)
• Infection with HIV, hepatitis B, or hepatitis C
• Presence of Child-Pugh Class C hepatic impairment
• Active TB or history of latent TB that has not been treated
• History of malignancy within the last 5 years except for subjects who have been treated or resected for non-melanoma skin cancer or cervical carcinoma in situ
• History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma
• History of treatment with lymphocyte-depleting therapies, including but not limited to alemtuzumab, cyclophosphamide, total lymphoid radiation, and rituximab
• History of leukocytapheresis = 6 months prior to screening
• Use of any prohibited concomitant medications as described in the protocol
• Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) or psychiatric problem (including, but not limited to alcohol or drug abuse) that, in the opinion of the Investigator, would make the subject unsuitable for the study or would prevent compliance with the study protocol
• Administration of a live or attenuated vaccine within 30 days of randomization
• History of opportunistic infection or immunodeficiency syndrome
• Currently on any chronic systemic (oral or intravenous) anti-infective therapy for chronic infection (such as pneumocystis (PCP), cytomegalovirus (CMV), herpes zoster, atypical mycobacteria)
• History of disseminated Staphylococcus aureus
• History of symptomatic herpes zoster or herpes simplex within 12 weeks of screening, or any history of disseminated herpes simplex, herpes zoster, ophthalmic zoster, or cen

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

Health Condition(s) or Problem(s) studied

Moderately to Severely Active Crohn’s Disease (CD)
MedDRA version: 19.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856

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

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: 100-
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: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Cohort A Induction Study
• The proportion of subjects achieving clinical remission by PRO2 at Week 10
• The proportion of subjects achieving endoscopic response at Week 10

Cohort B Induction Study
• The proportion of subjects achieving clinical remission by PRO2 at Week 10
• The proportion of subjects achieving endoscopic response at Week 10

Maintenance Study
• The proportion of subjects achieving clinical remission by PRO2 at Week 58
• The proportion of subjects achieving endoscopic response at Week 58

Main Objective: The primary objectives of Cohort A Induction Study are:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by Patient Reported Outcomes (PRO2) at Week 10
• To evaluate the efficacy of filgotinib as compared to placebo in establishing endoscopic response at Week 10

The primary objectives of Cohort B Induction Study are:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by PRO2 at Week 10
• To evaluate the efficacy of filgotinib as compared to placebo in establishing endoscopic response at Week 10

The primary objectives of the Maintenance Study are:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by PRO2 at Week 58
• To evaluate the efficacy of filgotinib as compared to placebo in establishing endoscopic response at Week 58

Timepoint(s) of evaluation of this end point: Week 10 and Week 58

Secondary Objective: Key secondary objectives of both Cohort A Induction Study & Cohort B Induction Study are:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by Crohn’s Disease Activity Index (CDAI) at Week 10
• To evaluate the efficacy of filgotinib as compared to placebo in establishing both clinical remission by PRO2 score & endoscopic response at Week 10

Key secondary objectives of the Maintenance Study are:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by CDAI at Week 58
• To evaluate the efficacy of filgotinib as compared to placebo in establishing sustained clinical remission by PRO2 at Weeks 10 & 58
• To evaluate the efficacy of filgotinib as compared to placebo in establishing both clinical remission by PRO2 & endoscopic response at Week 58
• To evaluate the efficacy of filgotinib as compared to placebo in establishing 6-month corticosteroid-free remission by PRO2 at Week 58

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 10 and Week 58

Secondary end point(s): Cohort A Induction Study
The key secondary endpoints are:
• The proportion of subjects achieving clinical remission by CDAI at Week 10
• The proportion of subjects achieving both clinical remission by PRO2 and endoscopic response (combined into a single endpoint on a patient level) at Week 10

Cohort B Induction Study
The key secondary endpoints are:
• The proportion of subjects achieving clinical remission by CDAI at Week 10
• The proportion of subjects achieving both clinical remission by PRO2 and endoscopic response (combined into a single endpoint on a patient level) at Week 10

Maintenance Study
The key secondary endpoints are:
• The proportion of subjects achieving clinical remission by CDAI at Week 58
• The proportion of subjects achieving sustained clinical remission by PRO2 at Weeks 10 and 58
• The proportion of subjects achieving both clinical remission by PRO2 and endoscopic response (combined into a single endpoint on a patient level) at Week 58
• The proportion of subjects achieving 6 month corticosteroid-free remission by PRO2 at Week 58

Secondary ID(s)

2016-001367-36-HU

GS-US-419-3895

Source(s) of Monetary Support

Gilead Sciences, Inc.