| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderately to Severely Active Crohn’s Disease (CD) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10013099 |
| E.1.2 | Term | Disease Crohns |
| E.1.2 | System Organ Class | 100000004856 |
|
| 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 EU-specific 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 EU-specific 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 EU-specific 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 |
|
| E.2.2 | Secondary objectives of the trial |
EU-specific key secondary objectives of both Cohort A Induction Study & Cohort B Induction Study:
• To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by Crohn’s Disease Activity Index (CDAI) at Wk 10
• To evaluate the efficacy of filgotinib as compared to placebo in establishing both clinical remission by PRO2 score & endoscopic response at Wk 10
EU-specific 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 Wk 58
• To evaluate the efficacy of filgotinib as compared to placebo in establishing sustained clinical remission by PRO2 at Wks 10 & 58
• To evaluate the efficacy of filgotinib as compared to placebo in establishing both clinical remission by PRO2 & endoscopic response at Wk 58
• To evaluate the efficacy of filgotinib as compared to placebo in establishing 6-month corticosteroid-free remission by PRO2 at Wk 58
|
|
| 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 informed consent. In the PK substudy, the daily dose of study drug should be administered under supervision in the clinic (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 substudy 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. |
|
| 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 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 serum pregnancy test at screening and a negative urine pregnancy test at 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 3 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
•Must be up to date on colorectal cancer screening and surveillance as standard of care according to local guidelines
Biologic-Naïve 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
Biologic-Experienced subjects must meet all of the additional inclusion criteria to be eligible for Cohort A.
• 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) or discontinuation of use of at least one of the following agents for reasons other than inadequate clinical response, loss of response, or intolerance:
- TNFα Antagonists
- Vedolizumab
- Ustekinumab
• Must not have used any TNFα 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
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 (depending on current country treatment recommendations/guidelines):
- TNFα Antagonists
- Vedolizumab
- Ustekinumab
• Must not have used any TNFα 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
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 |
|
| 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
•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 its metabolites, or formulation excipients
•Currently have complications of CD
•Have any current or prior abscesses
•History of major surgery or trauma within 30 days prior to screening
•Presence of UC, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon
•History of total colectomy, subtotal-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 C. diff toxin, pathogenic E. coli, Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp
•Stool sample positive for 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, HBV or HCV
•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 cytapheresis ≤ 2 months prior to screening
•Use of any prohibited concomitant medications
•Any chronic medical condition 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
•Administration of a live or attenuated vaccine within 30 days of randomization
•History of opportunistic infection or immunodeficiency syndrome
•Currently on any chronic systemic anti-infective therapy for chronic infection
•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
Biologic-Naïve subjects who meet any of the following exclusion criteria are not eligible for Cohort A
•Prior or current use of TNFα antagonist, including (but not limited to) infliximab, adalimumab, golimumab, certolizumab or biosimilar agent
•Prior or current use of vedolizumab
•Prior or current use of ustekinumab
Biologic-Experienced subjects who meet the following exclusion criterion are not eligible for Cohort A
•Have used any TNFα 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. Subjects who have an undetectable serum level of a biologic agent since its last dose using a commercially available assay can undergo study screening without the above-mentioned waiting period.
Subjects who meet the following exclusion criterion are not to be enrolled in Cohort B induction study
•Have used any TNFα 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. Subjects who have an undetectable serum level of a biologic agent since its last dose using a commercially available assay can undergo study screening without the above-mentioned waiting period. 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 &/or plan to undergo egg donation or egg harvesting
•Male subjects unwilling to refrain from sperm donation during the study & for at least 90 days after the last dose of study drug
•Use of any prohibited concomitant medications |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The EU-specific primary endpoints for the Cohort A Induction Study are:
• The proportion of subjects achieving clinical remission by PRO2 at Week 10
• The proportion of subjects achieving endoscopic response at Week 10
The EU-specific primary endpoints for the Cohort B Induction Study are:
• The proportion of subjects achieving clinical remission by PRO2 at Week 10
• The proportion of subjects achieving endoscopic response at Week 10
The EU-specific primary endpoints for the Maintenance Study are:
• The proportion of subjects achieving clinical remission by PRO2 at Week 58
• The proportion of subjects achieving endoscopic response at Week 58 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The EU-specific key secondary endpoints for the Cohort A Induction Study are:
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
The EU-specific key secondary endpoints for Cohort B Induction Study are:
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
The EU-specific key secondary endpoints for Maintenance Study are:
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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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) | No |
| 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 |
|
| 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 |
| Belgium |
| Bulgaria |
| Canada |
| Croatia |
| Czechia |
| 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 |
|
| 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
|
| End of Study is defined as when the last subject has completed 58 weeks of treatment plus 30 days follow-up. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 30 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| 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 | 30 |
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