E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Crohn’s disease (an Inflammatory Bowel Disease) |
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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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021315 |
E.1.2 | Term | Ileitis terminal |
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 |
To evaluate the efficacy of GED-0301 compared with placebo on clinical activity, as measured by the Crohn’s Disease Activity Index (CDAI) in subjects with active Crohn’s disease (CD). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of GED-0301 compared with placebo on endoscopic outcomes, as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD) 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 long-term efficacy of GED-0301 compared with placebo on clinical activity and endoscopic outcomes in subjects with active CD;
To evaluate the safety and tolerability of GED-0301 in subjects with active CD. |
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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 |
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 |
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E.3 | Principal inclusion criteria |
Diagnosis of CD with a duration of at least 3 months prior to the Screening Visit
Diagnosis of ileitis, ileocolitis or colitis, as determined by endoscopic, radiographic or any other imaging modality (eg, magnetic resonance imaging [MRI], computed tomography [CT] scan)
Active disease, defined as a CDAI score ≥ 220 and ≤ 450 at screening
Subject must have a 7-day average stool frequency ≥ 3.5 or abdominal pain ≥ 1.5 at screening
Subject 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: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (ie, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]); or biologics for the treatment of CD |
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E.4 | Principal exclusion criteria |
Diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis
Subject has local manifestations of CD such as strictures, abscesses, short bowel syndrome; or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy
Subject had any intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit
Subject had 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 treatment such as 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks prior to the Screening Visit
Use of cholestyramine within 3 weeks prior to the Screening Visit
Prior treatment with more than 3 biologics for the treatment of CD
Treatment with a biologic within 8 weeks prior to the Screening Visit
Prior treatment with natalizumab |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy as clinical remision: the proportion of subjects achieving clinical remission defined as a Crohn’s Disease Activity Index (CDAI) score < 150 at Week 4 |
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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 proportion of subjects with mucosal healing defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) ≤ 2 at Week 12, Week 52
The proportion of subjects with a reduction of at least 50% from baseline in SES-CD at Week 12, Week 52
The proportion of subjects achieving clinical remission defined as a CDAI score < 150 at Week 12, Week 52
The proportion of subjects who achieve corticosteroid-free clinical remission at Week 52 among subjects receiving oral corticosteroids at baseline
The proportion of subjects with an average daily liquid or soft stool frequency ≤ 3 and abdominal pain score ≤ 1 at Week 4, Week 12, Week 52
The proportion of subjects with an average daily liquid or soft stool frequency ≤ 1.5 and abdominal pain score ≤ 1 at Week 4, Week 12, Week 52
Type, frequency, severity, seriousness, and relationship of AEs to IP (Investigational Product) through Week 52
Number of subjects who discontinue IP due to any AE (Adverse Event) through Week 52
Clinically significant changes in vital signs and/or laboratory findings through Week 52 |
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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 | 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 | 11 |
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 |
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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 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. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
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 |