| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Small Bowel Crohn’s Disease |
|
| 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 | PT |
| E.1.2 | Classification code | 10011401 |
| E.1.2 | Term | Crohn's disease |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| 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, when compared to placebo, in establishing clinical remission at Week 24 |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
-To evaluate the impact of filgotinib, when compared to placebo, on change in segmental MaRIA score for all assessed small bowel segments at Week24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment level MaRIA remission at Week24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment level MaRIA response at Week24
-To evaluate the efficacy of filgotinib, when compared to placebo, in establishing subject level small bowel MaRIA remission at Week24
- To evaluate the efficacy of filgotinib, when compared to placebo, in
establishing subject level small bowel MaRIA response at Week24
-To evaluate the efficacy of filgotinib, when compared to placebo, in
establishing clinical remission, defined as CDAI<150, at Week10
-To evaluate the impact of filgotinib, when compared to placebo, on
change in CDAI scores
-To evaluate the safety and tolerability of filgotinib |
|
| 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. |
|
| 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) Moderately or severely active CD as defined by screening CDAI 200 to 450 (inclusive).
6) Minimum duration of CD of at least 6 months
7) Presence of diseased SB segments on MRE with segmental MaRIA score of ≥ 7 in at least 1 of the following segments: terminal ileum, distal ileum, or jejunum.
8) Patients with additional colonic involvement of CD are permitted in study as long as SBCD is present.
9) Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least 1 of the following agents (depending on current country treatment recommendations/guidelines):
a) Corticosteroids
b) Immunomodulators
c) TNFα Antagonists
d) Vedolizumab
e) Ustekinumab
10) Meet one of the following tuberculosis (TB) screening criteria:
a) No evidence of active or latent TB
b) Previously treated for TB
c) Newly identified latent TB during screening
11) Laboratory parameters within specified intervals
12) May be receiving the following drugs (subjects on these therapies must be willing to
remain on stable doses for the noted times):
a) Oral 5-aminosalicylate (5-ASA) compounds
b) Oral corticosteroid therapy
c) Azathioprine or 6-MP or methotrexate
d) Antibiotics for the treatment of CD
13) Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose of study drug.
14) Willing and able to undergo MRE per protocol requirements
15) Must be up to date on colorectal cancer screening and surveillance as standard of care according to local guidelines. |
|
| 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) Presence of symptomatic or clinically significant (eg, obstructive or symptomatic) strictures
or stenosis.
7) Presence of fistulae.
8) Evidence of short bowel syndrome.
9) Any other complication of CD that could preclude the use of CDAI to assess response to
therapy or would confound the evaluation of benefit from treatment with filgotinib.
10) Claustrophobia to a degree that prevents tolerance of MRE scanning procedure (sedation is permitted at discretion of investigator).
11) Metallic implant of any sort that prevents MRE 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 MRE examination.
12) Known hypersensitivity to gadolinium
13) Isolated colonic CD, or isolated CD that does not involve some segment of the small bowel.
14) Evidence of any other CD manifestation that might require imminent surgery or would
possibly confound the evaluation of benefit from treatment with filgotinib.
15) 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.
16) History of major surgery or trauma within 30 days prior to screening.
17) Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon.
18) Dependence on parenteral nutrition.
19) History of total colectomy, subtotal colectomy, presence of ileostomy or colostomy, or likely requirement for surgery during the study.
20) History or evidence of incompletely resected colonic mucosal dysplasia.
21) Stool sample positive for Clostridium difficile (C. diff) toxin, pathogenic Escherichia coli (E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp.
22) Stool sample positive for ova or parasites test (O&P) unless approved by the Medical Monitor
23) Has 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.
24) Use of any prohibited concomitant medication
25) History of leukocytapharesis ≤ 6 months prior to screening.
26) 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).
27) Co-Infection with human immunodeficiency virus (HIV), HBV, or HCV.
28) Presence of Child-Pugh Class C hepatic impairment
29) 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 study protocol.
30) 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.
31) History of opportunistic infection or immunodeficiency syndrome.
32) Active TB or history of latent TB that has not been treated (see Inclusion Criterion 10 for more details).
33) History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma.
34) History of treatment with lymphocyte depleting therapies, including but not limited to alemtuzumab, cyclophosphamide, total lymphoid irradiation, and rituximab.
35) Administration of live or attenuated vaccine within 30 days of randomization.
36) Currently on any chronic systemic (oral or intravenous) anti-infective therapy for chronic infection (such as pneumocystis, CMV, herpes zoster, atypical mycobacteria).
37) History of disseminated Staphylococcus aureus.
38) History of symptomatic herpes zoster or herpes simplex |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the proportion of subjects achieving clinical remission by CDAI < 150 at Week 24. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
- Change from baseline in terminal ileum segmental MaRIA score at
Week 24
- Change from baseline in distal ileum segmental MaRIA score at Week
24
- Change from baseline in jejunum segmental MaRIA score at Week 24
- Proportion of subjects achieving MaRIA remission in terminal ileum
segment at Week 24
- Proportion of subjects achieving MaRIA remission in distal ileum
segment at Week 24
- Proportion of subjects achieving MaRIA remission in jejunum segment
at Week 24
- Proportion of subjects achieving MaRIA response in terminal ileum
segment at Week 24
- Proportion of subjects achieving MaRIA response in distal ileum
segment at Week 24
- Proportion of subjects achieving MaRIA response in jejunum segment
at Week 24
- Proportion of subjects achieving subject level small bowel MaRIA
remission at Week 24
- Proportion of subjects achieving subject level small bowel MaRIA
response at Week 24
- Proportion of subjects achieving early clinical remission by CDAI at
Week 10
- Change from baseline in CDAI scores at Week 10
- Change from baseline in CDAI scores at Week 24 |
|
| 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 | 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| 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 |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Israel |
| Italy |
| Poland |
| Spain |
| 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 30 days after the last dose administered to
the last subject. |
|
| 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 | 20 |
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