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 |
Inflammation of the ileal pouch - an artificial rectum surgically created out of ileal gut tissue in patients who have undergone a colectomy. |
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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 | 10036463 |
E.1.2 | Term | Pouchitis |
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 |
To compare the efficacy of vedolizumab IV and placebo in terms of the percentage of subjects with chronic or recurrent pouchitis achieving clinically relevant remission. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of vedolizumab IV by: -Percentage of subjects achieving mPDAI <5 and a reduction of overall score by ≥2 points from Baseline. -Percentage of subjects achieving PDAI <7 and a reduction of overall score by ≥3 points from Baseline. -Time to remission (defined as a PDAI score <7 and a decrease in PDAI score of ≥3 points from Baseline). -Percentage of subjects achieving a partial response (defined as reduction of mPDAI score by ≥2 points from Baseline). -Change in PDAI endoscopic subscore. -Change in PDAI histologic subscore. -Change in total PDAI. -Change in Inflammatory Bowel Disease Questionnaire (IBDQ), and Cleveland Global Quality of Life (CGQL, Fazio Score, 3 items). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male or female subjects aged 18 to 80 years, inclusive. -History of IPAA for UC completed at least 1 year prior to the Day 1 (Randomization) Visit. -Pouchitis that is chronic or recurrent, defined by an mPDAI score ≥5 assessed as the average from 3 days immediately prior to the Baseline endoscopy and a minimum endoscopic subscore of 2 (outside the staple or suture line) with either (a) ≥3 recurrent episodes within 1 year prior to the Screening Period treated with ≥2 weeks of antibiotic or other prescription therapy, or (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately prior to the Baseline Endoscopy Visit. |
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E.4 | Principal exclusion criteria |
-Crohn’s disease (CD), CD of the pouch, irritable pouch syndrome (IPS), isolated or predominant cuffitis, diverting stoma, or mechanical complications of the pouch. -Previous treatment with vedolizumab, natalizumab, efalizumab, rituximab, etrolizumab, or anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) therapy. -Any investigational or approved biologic or biosimilar agent within 60 days of randomization. -Nonbiologic investigational therapy within 30 days prior to randomization. -Active or latent tuberculosis. -Chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection or a known history of human immunodeficiency virus (HIV) infection (or is found to be seropositive at Screening) or subject is immunodeficient. -Active, severe infection. -Positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of subjects with chronic or recurrent pouchitis achieving clinically relevant remission after 14 weeks of treatment. Clinically relevant remission is defined as an mPDAI score <5 and a reduction of overall score by ≥2 points from Baseline. |
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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) |
-Percentage of subjects achieving an mPDAI score <5 and a reduction of overall score by ≥2 points from Baseline after 34 weeks of treatment (last dosing at Week 30). -Percentage of subjects achieving PDAI score <7 and a reduction of overall score by ≥3 points from Baseline PDAI score after 14 weeks of treatment and after 34 weeks of treatment (last dosing at Week 30). -Time to remission (defined as a PDAI score <7 and a decrease in PDAI score of ≥3 points from Baseline). -Percentage of subjects achieving a partial response (defined as reduction in mPDAI score by ≥2 points from Baseline) after 14 and after 34 weeks of treatment (last dosing at Week 30). -Change in PDAI endoscopic subscore at Weeks 14 and 34 compared to Baseline. -Change in PDAI histologic subscore at Weeks 14 and 34 compared to Baseline. -Change in total PDAI score at Weeks 14 and 34 compared to Baseline. -Change in Inflammatory Bowel Disease Questionnaire (IBDQ), and Cleveland Global Quality of Life (CGQL, Fazio Score, 3 items) at Weeks 14, 22, and 34 compared to Baseline. |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of trial will be the date of the last visit of the last subject at the Week 48 Follow-up Visit |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |