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 |
Substudy 1 (randomized, double-blind, placebo-controlled maintenance): To evaluate the efficacy and safety of two doses of upadacitinib versus placebo as maintenance therapy in subjects with moderately to severely active Crohn's disease (CD) who responded to upadacitinib induction treatment in Studies M14-431 or M14-433. Substudy 2 (long-term extension [LTE]): To evaluate safety and efficacy of long-term administration of upadacitinib in subjects with moderately to severely active CD who participated in the Phase 3 upadacitinib induction and maintenance studies. |
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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 | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Substudy 1 - 52-Week, Randomized, Double-Blind, Maintenance Substudy 2 - 240-Week Long-Term-Extension |
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E.3 | Principal inclusion criteria |
For Substudy 1: - Subject who receive double-blind treatment in Study M14- 431 or Study M14-433 and achieve clinical response. - Subject completes Week 12 or Week 24 study procedures in study M14-431 or study M14-433. The final endoscopy for studies M14-431 or M14-433 may be missing, if the endoscopy cannot be performed during the coronavirus SARS-CoV-2 pandemic. For Substudy 2: - Subject completes Substudy 1 of Study M14-430. The week 52 endoscopy may be missing, if the endoscopy cannot be performed during the coronavirus SARS-CoV-2 pandemic. - Subject achieved clinical response at Week 24 and completed Week 24 visit and procedures in Part 3/Cohort 3 of Study M14-431. |
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E.4 | Principal exclusion criteria |
For Sub-studies 1 and 2: - Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study. - Subject who has a known hypersensitivity to upadacitinib or its excipients, or had an adverse event during Study M14-431, M14-433,or Substudy 1 of Study M14-430 that in the investigator's judgment makes the subject unsuitable for this study. - Subject with any active or chronic recurring infections based on the investigator's assessment that makes the subject an unsuitable candidate for the study. Subjects with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed and the infection is resolved, based on the investigator's assessment. - Subject with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Study M14-431, M14-433,or Substudy 1 of Study M14-430 (Week 52). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Substudy 1, Cohort 1 (Upadacitinib vs Placebo) Co-Primary Endpoints: Proportion of subjects with clinical remission per PROs at Week 52, AND Proportion of subjects with endoscopic response at Week 52
Substudy 2 Primary Endpoint: Incidence of AEs over time
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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) |
Substudy 1 1. Proportion of subjects with clinical remission per CDAI at Week 52 2. Proportion of subjects with endoscopic remission at Week 52 3. Change from Baseline in IBDQ at Week 52 4. Proportion of subjects achieving CR-100 at Week 52 5. Proportion of subjects without corticosteroid use for CD at least 90 days prior to Week 52 and achieved clinical remission per PROs at Week 52 (among all subjects) 6. Proportion of subjects who discontinued corticosteroid use for CD at least 90 days prior to Week 52 and achieved clinical remission per PROs at Week 52 in subjects taking corticosteroids for CD at Baseline of induction 7. Proportion of subjects with clinical remission per PROs at Week 0 and Week 52 8. Change from Baseline in FACIT-F at Week 52 9. Proportion of subjects with clinical remission per PROs and endoscopic remission at Week 52 10. Proportion of subjects with CD-related hospitalizations during the 52 Week double-blind maintenance period. 11. Proportion of subjects with resolution of EIMs at Week 52, in subjects with EIMs at Baseline
Substudy 2 Proportion of subjects with clinical remission over time with enhanced clinical response over time with clinical response over time with CR-100 over time with endoscopic remission at Week 0, and every 48 weeks thereafter with endoscopic response at Week 0, and every 48 weeks thereafter without corticosteroid use for CD and achieve clinical remission over time
Time loss of enhanced clinical response clinical remission
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Substudy 1 1. week 52 2. week 52 3. week 52 4. week 52 5. week 52 6. week 52 7. week 52 8. week 52 9. week 52 10. week 52 11. week 52
Substudy 2 Over study duration |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Substudy 1 Randomized, double-blind. Substudy 2 Both open-label and double-blind |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 146 |
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 |
Brazil |
Canada |
Chile |
China |
Colombia |
Egypt |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Puerto Rico |
Singapore |
South Africa |
Taiwan |
United States |
Switzerland |
Bosnia and Herzegovina |
Russian Federation |
Turkey |
Ukraine |
Serbia |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 14 |