E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Crohn’s disease (an Inflammatory Bowel Disease) |
|
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 | 10021315 |
E.1.2 | Term | Ileitis terminal |
E.1.2 | System Organ Class | 100000016693 |
|
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 |
To evaluate the efficacy of GED-0301 compared with placebo on clinical activity at Week 12 in subjects with active Crohn’s disease (CD). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of GED-0301 compared with placebo on endoscopic outcomes in subjects with active CD
To evaluate the long-term efficacy of GED-0301 compared with placebo on clinical activity in subjects with active CD
To evaluate the efficacy of GED-0301 compared with placebo on corticosteroid-free clinical remission in subjects with active CD
To evaluate the safety and tolerability of GED-0301 in subjects with active CD. |
|
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 |
A PK substudy (sparse PK study) was incorporated into the study at selected study sites to monitor for
systemic exposure of GED-0301 in subjects with active CD. Intensive collection of PK samples will be performed in a subset of subjects that have a CDAI score of ≥ 300 and ≤ 450, with a minimum of 16 participants. An intensive PK sub-study is not taking place in the Member State concerned by this application. |
|
E.3 | Principal inclusion criteria |
Diagnosis of CD with a duration of at least 3 months prior to the Screening Visit
Presence of ileitis, ileocolitis or colitis, as determined by ileocolonoscopy at screening.
Active disease, defined as a CDAI score ≥ 220 and ≤ 450 at screening
Must have a 7-day average stool frequency ≥ 3.5 or abdominal pain ≥ 1.5 at screening.
Must have a total SES-CD ≥ 6 at screening, or the ileum segmental SES-CD ≥ 4 at screening
Must have failed or experienced intolerance to at least one of the following: budesonide; systemic corticosteroids; immunosuppressants (ie, azathioprine [AZA], 6-mercaptopurine
[6-MP], or methotrexate [MTX]); or biologics for the treatment of CD (ie, infliximab, adalimumab, certolizumab or vedolizumab) |
|
E.4 | Principal exclusion criteria |
Diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis
Local manifestations of CD such as abscesses, short bowel syndrome; or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy
Strictures with prestenotic dilatation, requiring procedural intervention, or with obstructive symptoms. In addition, colonic strictures that are not passable with an adult colonoscope, or strictures in the ileum or ileocecal valve that are fibrotic in nature, will be excluded.
Any intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit
Prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®) within 8 weeks prior to the Screening Visit
Use of intravenous (IV) corticosteroids within 2 weeks prior to the Screening Visit
Use of topical GI treatments such as 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks prior to the Screening Visit
Use of bile acid sequestrants, (eg, cholestyramine) within 3 weeks prior to the Screening Visit
Prior treatment with biologics for the treatment of CD (approved or investigational), other than infliximab, adalimumab, certolizumab or vedolizumab
Prior treatment with more than 3 biologics for the treatment of CD (ie, infliximab, adalimumab, certolizumab or vedolizumab). Treatment with a biologic within 8 weeks prior to the Screening Visit, or 5 elimination half lives, whichever is longer. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects achieving clinical remission defined as a CDAI score < 150, at Week 12. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Proportion of subjects achieving:
- clinical remission, defined as a CDAI score < 150, at Week 52.
- endoscopic response-50 (ER-50), defined as a reduction of at least 50% in SES-CD compared with baseline, at Week 52.
Proportion of subjects with clinical response:
- defined as a decrease from baseline in CDAI ≥ 100 points, at Week 12.
- defined as a decrease from baseline in CDAI ≥ 100 points, at Week 4.
Proportion of subjects:
- achieving clinical remission, defined as a CDAI score < 150, at Week 4.
- who achieve corticosteroid-free clinical remission (CDAI <150) at Week 52 among subjects receiving oral corticosteroids for CD at baseline.
- achieving sustained clinical remission, defined as a CDAI score < 150, at both Week 12 and Week 52.
- with endoscopic response-25 (ER-25), defined as a reduction of at least 25% in the SES-CD compared with baseline, at Week 12.
- endoscopic remission, defined as SES-CD ≤ 2, at Week 52.
Type, frequency, severity, seriousness, and relationship of AEs to IP.
Number of subjects who discontinue investigational product (IP) due to any AE.
Clinically significant changes in vital signs, ECG and/or laboratory findings. |
|
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 | No |
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 | No |
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 | 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 | 4 |
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 | 311 |
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 |
Australia |
Austria |
Belgium |
Bulgaria |
Canada |
Croatia |
Czech Republic |
Denmark |
Estonia |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Korea, Republic of |
Latvia |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Turkey |
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 either the date of the LVLS to complete the post-treatment follow-up, or the date of receipt of the last data point from the LS that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |