A study to assess a new treatment in patients with moderately to Severely active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 4 May 2020
• Main ID: EUCTR2016-001392-78-AT
• Date of registration: 13/12/2016
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A study to assess a new treatment in patients with moderately to Severely active Ulcerative Colitis
• Scientific title: Combined Phase 2b/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 Ulcerative Colitis
• Date of first enrolment: 31/01/2017
• Target sample size: 1300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001392-78
• 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): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, 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 informed consent form, 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 UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge.
• A surveillance colonoscopy is required prior to screening in subjects with a history of UC for 8 or more years, if one was not performed in the prior 24 months
• Moderately to severely active UC
• Meet one of the protocol specified tuberculosis (TB) screening criteria
• Laboratory parameters (subjects who fail to meet specified reference laboratory tests may be re tested once at discretion of investigator prior to being considered a screen failure)
• May be receiving the following drugs (subjects on these therapies should be willing to remain on stable doses for the times specified in the protocol):
- Oral 5-aminosalicylate (5-ASA) compounds
- Azathioprine, 6-mercaptopurine (6-MP) or methotrexate (MTX)
- Oral corticosteroid therapy
• 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 following inclusion criteria to be eligible for participation in Cohort A Induction Study:
• 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):
- Corticosteroids
- Immunomodulators

Subjects must meet all the additional following inclusion criteria to be eligible for participation in Cohort B Induction Study:
• Previously demonstrated an inadequate clinical response, loss of response to, or intolerance of at least one of the following agents (depending on current country treatment recommendations/guidelines):
- Tumor necrosis factor-alpha (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 MCS response or EBS remission based on Week 10 assessments
• 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 1196
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 104

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 last dose of the study drug
• Male subjects unwilling to refrain from sperm donation for at least 90 days after last dose of the study drug
• Known hypersensitivity to filgotinib, its metabolites, or formulation excipients
• Exhibit acute severe UC as defined in the protocol
• Use of rectal formulations of 5-aminosalicylate (5-ASA) compounds or rectal corticosteroids 2 weeks prior to screening
• History of major surgery or trauma within 30 days prior to screening
• Presence of Crohn’s diease (CD), indeterminate colitis, ischemic colitis, fulminant colitis, ulcerative proctitis, or toxic mega-colon
• Prior surgical intervention for UC (eg, total colectomy, subtotal colectomy,partial or hemicolectomy, 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, pathogenic 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 in the last 5 years except for subjects who have been successfully treated 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 alemtuzab, cyclophosphamide, total lymphoid radiation, and rituximab
• History of cytapherisis = 2 months prior to screening
• Use of prohibited concomitant medications as described in the protocol
• Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease, or substance abuse) or psychiatric problem that, in the opinion of the Investigator or Sponsor, would make the subject unsuitable for the study or would prevent compliance with the study protocol procedures
• 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

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

Health Condition(s) or Problem(s) studied

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

Moderately to Severely Active Ulcerative Colitis (UC)
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

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)

Main Objective: The primary objective of Cohort A Induction Study is:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing endoscopy/bleeding/stool (EBS) remission at Week 10

The primary objective of Cohort B Induction Study is:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing EBS remission at Week 10

The primary objective of the Maintenance Study is:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing EBS remission at Week 58

Primary end point(s): Cohort A Induction Study
• The proportion of subjects achieving EBS remission at Week 10

Cohort B Induction Study
• The proportion of subjects achieving EBS remission at Week 10

Maintenance Study
• The proportion of subjects achieving EBS remission at Week 58

Secondary Objective: The key secondary objectives of both Cohort A and Cohort B Induction Study are to evaluate the efficacy of filgotinib as compared to placebo in establishing:
• Mayo Clinic Score (MCS) remission at Week 10
• An endoscopic subscore of 0 at Week 10
• Geboes histologic remission at Week 10
• MCS remission (alternative definition) at Week 10

The key secondary objectives of the Maintenance Study are to evaluate the efficacy of filgotinib as compared to placebo in establishing:
• MCS remission at Week 58
• Sustained EBS remission at Week 58, defined as EBS remission at both Weeks 10 and 58
• 6-month corticosteroid-free EBS remission at Week 58
• An endoscopic subscore of 0 at Week 58
• Geboes histologic remission at Week 58
• MCS remission (alternative definition) at Week 58

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

Secondary Outcome(s)

Secondary end point(s): Cohort A Induction Study
• The proportion of subjects achieving MCS remission at Week 10
• The proportion of subjects achieving endoscopic subscore of 0 at Week 10
• The proportion of subjects achieving Geboes histologic remission at Week 10
• The proportion of subjects achieving MCS remission (alternative definition) at Week 10

Cohort B Induction Study
• The proportion of subjects achieving MCS remission at Week 10
• The proportion of subjects achieving endoscopic subscore of 0 at Week 10
• The proportion of subjects achieving Geboes histologic remission at Week 10
• The proportion of subjects achieving MCS remission (alternative definition) at Week 10

Maintenance Study
• The proportion of subjects achieving MCS remission at Week 58
• The proportion of subjects achieving sustained EBS remission, defined as establishing EBS remission at both Weeks 10 and 58
• The proportion of subjects achieving 6-month corticosteroid-free EBS remission at Week 58
• The proportion of subjects achieving endoscopic subscore of 0 at Week 58
• The proportion of subjects achieving Geboes histologic remission at Week 58
• The proportion of subjects achieving MCS remission (alternative definition) at Week 58

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

Secondary ID(s)

GS-US-418-3898

2016-001392-78-HU

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date: 31/01/2017
Contact: