E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Perianal Fistulizing Crohn’s Disease |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075465 |
E.1.2 | Term | Fistulizing Crohn's disease |
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 this study is to evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula response at Week 24 |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: - To evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula remission at Week 24 - To assess the time to clinical fistula response - To assess the time to clinical fistula remission -To evaluate the efficacy of filgotinib as compared to placebo in establishing proctitis remission at Week 24, in subjects that had moderately to severely active proctitis at baseline - To evaluate the safety and tolerability of filgotinib |
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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 |
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 |
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) Documented diagnosis of Crohn’s disease with a minimum disease duration of 3 months documented by the following as described in the protocol (section 4.2) 6) At screening, has a minimum of 1 (maximum of 3) draining perianal fistulae external openings of ≥ 4 weeks’ duration as a complication of CD, confirmed by MRI. At least 1 (maximum of 3) of the draining perianal fistulae external openings present at screening must still be draining at the time of randomization. 7) May have concurrent noncutting perianal seton(s) at screening, which should be removed by the time of randomization 8) 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) as described in the protocol (section 4.2) 9) Is willing and able to undergo MRI per protocol requirements 10) Is willing and able to undergo flexible sigmoidoscopy per protocol requirements 11) Meet one of the following tuberculosis (TB) screening criteria as described in the protocol (section 4.2) 12) Laboratory parameters (subjects who fail to meet the parameters of any of the below reference laboratory tests may be retested once at discretion of investigator prior to being considered a screen failure) as described in the protocol (section 4.2) 13) May be receiving the following drugs (subjects on these therapies should be willing to remain on stable doses for the noted times) as described in the protocol (section 4.2) 14) Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose of study drug 15) Must be up to date on colorectal cancer screening and surveillance as standard of care according to the local guidelines |
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E.4 | Principal 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) Claustrophobia to a degree that prevents tolerance of MRI scanning procedure (sedation is permitted at discretion of investigator). 7) Metallic implant of any sort that prevents MRI 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 MRI examination. 8) Known hypersensitivity to gadolinium 9) Currently have complications of CD as any of the following as described in protocol section 4.3. 10) Presence of current rectovaginal, anovaginal or enterovesicular fistulae 11) Has an abscess > 2 cm or an abscess that the Investigator feels requires drainage based oneither clinical assessment or MRI, unless drained and treated at least 4 weeks prior to Day 1, and are not anticipated to require surgery during the study 12) Has a CDAI score > 400 13) History of major surgery or trauma within 30 days prior to screening 14) Presence of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon 15) History of total colectomy, hemi-colectomy, presence of ileostomy or colostomy, or likely requirement for surgery during the study 16) Dependence on parenteral nutrition 17) History or evidence of incompletely resected colonic mucosal dysplasia 18) Infection with human immunodeficiency virus (HIV), HBV or HCV 19) Presence of Child-Pugh Class C hepatic impairment 20) Stool samples positive for pathogenic Clostridium difficile (C. difficile) toxin, pathogenic Escherichia coli (E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp. 21) Stool sample positive for ova and parasites test (O&P) unless approved by the medical monitor 22) Use of any prohibited concomitant medications as described in Section 5.4.2 23) Has used any TNFα antagonist ≤ 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. 24) 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 other than related to the fistula(s) requiring oral anti-infective therapy within 2 weeks of screening (or 6 weeks of Day 1) 25) Active TB or history of latent TB that has not been treated (see inclusion criterion 11 for further information) 26) History of opportunistic infection or immunodeficiency syndrome 27) History of disseminated Staphylococcus aureus 28) 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 29) Administration of live or attenuated vaccine within 30 days of randomization 30) 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 31) 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 32) History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma 33) History of treatment with lymphocyte-depleting therapies, including but not limited to alemtuzumab, cyclophosphamide, total lymphoid irradiation, and rituximab 34) History of leukocytapheresis ≤ 6 months prior to Screening 35) Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, and upadacitinib) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of subjects establishing combined fistula response at Week 24 |
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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) |
The secondary efficacy endpoints are: - Proportion of subjects establishing combined fistula remission at Week 24 - Time to clinical fistula response - Time to clinical fistula remission - Proportion of subjects achieving proctitis remission at Week 24, in subjects that had moderately to severely active proctitis at baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 24 for the proportion of subjects establishing combined fistula remission |
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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 | No |
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 | No |
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) | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Austria |
Belgium |
Canada |
Czechia |
France |
Germany |
Hungary |
Israel |
Italy |
Poland |
Spain |
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 24 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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 19 |