E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Ulcerative Colitis (UC) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic (PK) Substudy
An optional PK substudy will be performed in a subset of subjects (approximately 30 subjects each in Cohort A and Cohort B) who provide a separate consent. In the PK substudy, the daily dose of study drug should be administered under supervision in the clinic (at one visit between Week 2 and Week 10, inclusive), and additional PK samples should be collected predose and at 0.5, 1, 2, 3, 4, and 6 hours post dose.
If a sub-study PK sample is scheduled to be collected at the same time as a sparse PK sample, only one sample should be collected.
Genomic Substudy
An optional genomic substudy will be performed in all subjects who agree to participate and provide their additional specific consent. The genomic sample should be collected at the Day 1 visit, but may be collected at any time during the study. |
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E.3 | Principal 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 the protocol 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 (TNFα) Antagonists
- Vedolizumab
• Must not have used any TNFα 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 |
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E.4 | Principal 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, subtotalcolectomy, 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 simplex, disseminated herpes zoster, ophthalmic zoster, or central nervous system zoster
Subjects who meet any of the following exclusion criteria are not to be enrolled in Cohort A Induction Study.
• Prior use of any TNFα antagonist including (but not limited to) infliximab, adalimumab, golimumab, certolizumab, or biosimilar agents at any time
• Prior or current use of vedolizumab at any time
Subjects who meet the following exclusion criterion are not eligible to be enrolled in Cohort B Induction Study:
• Have used any TNFα antagonist or vedolizumab within ≤ 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 who meet any of the following exclusion criteria are not to be enrolled in the
Maintenance Study:
• 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 during the study and for at least 90 days after last dose of the study drug
• Use of prohibited concomitant medications as described in the protocol |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Combined induction and maintenance phase study design |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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 |
Sri Lanka |
Sweden |
Switzerland |
Taiwan |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of Study is defined as when the last subject has completed 58 weeks of treatment plus 30 days follow-up. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 26 |