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 |
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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 | PT |
E.1.2 | Classification code | 10009900 |
E.1.2 | Term | Colitis ulcerative |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 objective of Study M14-675 (Phase 3 induction) is to evaluate the efficacy and safety of upadacitinib 45 mg once daily (QD) compared to placebo in inducing clinical remission (per Adapted Mayo score) in subjects with moderately to severely active ulcerative colitis. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate the efficacy of upadacitinib 45 mg QD comparing with placebo in ranked secondary endpoints of achieving endoscopic improvement, endoscopic remission, clinical response per Adapted Mayo Score, clinical response per Partial Adapted Mayo score, histologic-endoscopic mucosal improvement, no bowel urgency, no abdominal pain, histologic mprovement, mucosal healing, and change in IBDQ total core and FACIT-F score. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female between 16 and 75 years of age at Baseline. - Adolescent subjects at the age of 16 and 17 years old will be enrolled if approved by the country or regulatory/health authority. If these approvals have not been granted, only subjects = 18 years old will be enrolled. - Adolescent subjects at the age of 16 and 17 years old must weigh = 40 kg and meet the definition of Tanner Stage 5 refer to Appendix J) at the screening Visit. 2. Diagnosis of ulcerative colitis for 90 days or greater prior to Baseline, confirmed by colonoscopy 3. Moderately to severely active ulcerative colitis 4. Demonstrated an inadequate response to, loss of response to, or intolerance to immunosuppressants, corticosteroids or biologic therapies 5. Negative pregnancy test for female subjects of childbearing potential |
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E.4 | Principal exclusion criteria |
1. Subject with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC). 2. Current diagnosis of fulminant colitis and/or toxic megacolon. 3. Subject with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy. 4. Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline. 5. Subject who received azathioprine or 6-mercaptopurine within 10 days of Baseline. 6. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. 7. Subject with previous exposure to JAK inhibitor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for Study M14-675 is the proportion of subjects who achieve clinical remission per Adapted Mayo score (defined as SFS ≤ 1 and not greater than baseline, RBS of 0, and endoscopic sub score ≤ 1) at Week 8. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1: Week 8 and Part 2: Week 16 (Extended Treatment Period; as applicable) |
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E.5.2 | Secondary end point(s) |
1. Proportion of subjects with endoscopic improvement at Week 8 2. Proportion of subjects with endoscopic remission at Week 8 3. Proportion of subjects achieving clinical response per Adapted Mayo Score at Week 8 4. Proportion of subjects achieving clinical response per Partial Adapted Mayo score (defined as decrease from Baseline = 1 points and = 30% from Baseline, PLUS a decrease in RBS = 1 or an absolute RBS = 1 ) at Week 2 5. Proportion of subjects achieving histologic-endoscopic muscosal improvement at Week 8 6. Proportion of subjects who reported no bowel urgency at Week 8 7. Proportion of subjects who reported no abdominal pain at Week 8 8. Proportion of subjects who achieved histologic improvement at Week 8 9. Change from Baseline in IBDQ total score at Week 8 10. Proportion of subjects with mucosal healing at Week 8 11. Change from Baseline in FACIT-F score at Week 8 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For points 1,2,3,5,6,7,8,9,10,11 - week 8 For point 4 - Week 2 |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 175 |
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 |
Belarus |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
China |
Colombia |
Croatia |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Norway |
Puerto Rico |
Russian Federation |
Serbia |
Singapore |
South Africa |
Switzerland |
Taiwan |
Turkey |
Ukraine |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 23 |
E.8.9.2 | In all countries concerned by the trial days | 0 |