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 | 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 | 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 |
Evaluate efficacy of GED-0301 at Week 12, administered as either a single 160 mg tablet or as four 40 mg tablets, compared with placebo on clinical activity in subjects with active CD |
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E.2.2 | Secondary objectives of the trial |
• evaluate efficacy of GED-0301 compared with placebo on endoscopic outcomes
• evaluate efficacy of GED-0301 at Week 4 and Week 12 compared with placebo on clinical activity
• evaluate efficacy of GED-0301 compared with placebo on clinical activity in adolescent subjects (aged 12 to 17 years, inclusive)
• evaluate systemic exposure of GED-0301 using PK sampling
• evaluate safety and tolerability of GED-0301
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E.2.3 | Trial contains a sub-study | No |
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 daily liquid or soft 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, AZA, 6-MP, or MTX); or biologics for the treatment of CD (ie, infliximab, adalimumab, certolizumab, or vedolizumab)
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E.4 | Principal exclusion criteria |
1. diagnosis of UC, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis, diverticular disease-associated colitis, or colitis due to immunodeficiency.
2. local manifestations of CD such as abscesses, short bowel syndrome, or other disease complications for which surgery might be indicated or which could confound the evaluation of efficacy.
3. strictures with prestenotic dilatation, requiring procedural intervention, or with obstructive symptoms. In addition, subjects with colonic strictures that are not passable with an age-appropriate colonoscope, or strictures in the ileum or ileocecal valve that are fibrotic in nature, will be excluded.
4. intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit.
5. ileostomy or a colostomy.
6. prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®) within 8 weeks prior to the Screening Visit.
7. intravenous (IV) corticosteroids within 2 weeks prior to the Screening Visit.
8. changed or discontinued the dose of oral aminosalicylates within 2 weeks prior to the Screening Visit.
9. changed or discontinued the dose of oral corticosteroids (prednisone ≤ 20 mg/day or equivalent, budesonide ≤ 9 mg/day) within 3 weeks prior to the Screening Visit.
10. Adolescents with delayed growth or pubertal development who are on corticosteroids at baseline and who should not continue treatment with the same dose of corticosteroids until Week 12 visit.
11. immunosuppressants (eg, AZA, 6-MP, or MTX) within 12 weeks prior to the Screening Visit and has changed or discontinued the dose of immunosuppressants within 8 weeks prior to the Screening Visit.
12. topical GI treatments, such as, 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks prior to the Screening Visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects achieving clinical remission, defined as a CDAI score < 150 |
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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) |
Proportion of subjects who have a clinical response, defined as a decrease from baseline in CDAI score ≥ 100 points, at Week 12
Proportion of subjects with endoscopic response-25 (ER-25), defined as a reduction of at least 25% from baseline in SES-CD, at Week 12
Proportion of subjects who have a clinical response, 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
Proportion of subjects with endoscopic response–50 (ER-50), defined as a reduction of at least 50% in SESCD
compared with baseline, at Week 12
Proportion of subjects achieving clinical remission, defined as a PCDAI score ≤ 10 at Week 12 (adolescent subjects only)
plasma concentration of GED-0301 at Week 4 and Week 8
Type, frequency, severity, seriousness, and relationship of AEs to IP
Number of subjects who discontinue IP due to any AE through Week 12
Clinically significant changes in vital signs, ECG, and/or laboratory findings through Week 12 and 4-week Follow-up
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 192 |
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 |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
Colombia |
Croatia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Korea, Republic of |
Latvia |
Malaysia |
Mexico |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
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 | 2 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |