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 |
CD is an inflamatory bowel disease affects the lining of the digestive tract, often spreads into the layers of affected bowel tissue, can lead to abdominal pain, severe diarrhea, fatigue, weight loss. |
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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 | 10011401 |
E.1.2 | Term | Crohn's disease |
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 this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in participants with moderately and severely active Crohn's disease (CD). |
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E.2.2 | Secondary objectives of the trial |
To evaluate improvements in several efficacy parameters, including steroid discontinuation, laboratory parameters and quality of life questionnaires. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Confirmed diagnosis of CD for at least 3 months prior to Baseline. - Confirmed diagnosis of moderate to severe CD as assessed by stool frequency (SF), abdominal pain (AP) score. - Evidence of mucosal inflammation based on the Simplified Endoscopic Score for Crohn's disease (SES-CD) on an endoscopy confirmed by a central reader. - Demonstrated an inadequate response or intolerance to one or more conventional and/or biologic therapies, in the opinion of the investigator, as defined below: Oral locally acting steroids Intravenous or oral corticosteroids Immunosuppressants Biologic therapies for CD Note: Non-bio-IR subjects who have received prior biologic for up to 1 year but have not failed may be enrolled; however, participants must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease), - If female, subject must meet the contraception recommendations. |
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E.4 | Principal exclusion criteria |
- Subject with a current diagnosis of ulcerative colitis or indeterminate colitis. - Subject not on stable doses of CD related antibiotics, oral aminosalicylates, corticosteroids or methotrexate (MTX). - Subject with the following known complications of CD: abscess (abdominal or peri-anal), > 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum, symptomatic bowel strictures, fulminant colitis, toxic megacolon, or any other manifestation that might require surgery while enrolled in the study. - Subject with ostomy or ileoanal pouch - Subject diagnosed with short gut or short bowel syndrome - Screening laboratory and other analyses show abnormal results. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary Endpoints: 1. Proportion of subjects with clinical remission per PROs at Week 12, and 2. Proportion of subjects with endoscopic response at Week 12. |
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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) |
1. Proportion of subjects with clinical remission per CDAI (CDAI < 150) 2. Proportion of subjects with clinical remission at Week 4 3. Proportion of subjects with endoscopic remission at Week 12 4. Proportion of subjects who discontinue corticosteroid use for CD and achieve clinical remission at Week 12, in subjects taking corticosteroids for CD at Baseline 5. Change from Baseline in FACIT-F at Week 12 6. Change from Baseline in IBDQ at Week 12 7. Proportion of subjects achieving CR-100 at Week 2 8. Proportion of subjects achieving CR-100 at Week 12 9. Proportion of subjects with hospitalizations due to CD during the 12 week double-blind induction period 10. Proportion of subjects with resolution of extra-intestinal manifestation (EIM) at week 12, in subjects with EIM at Baseline
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. week 12 2. week 4 3. week 12 4. week 12 5. week 12 6. week 12 7. week 2 8. week 12 9. week 12 10. week 12 |
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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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 124 |
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 |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
China |
Colombia |
Egypt |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Puerto Rico |
Russian Federation |
Serbia |
Singapore |
South Africa |
Taiwan |
Turkey |
Ukraine |
United States |
Switzerland |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 14 |