E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Pouchitis |
Pouchitis Crónica |
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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. |
Inflamación del reservorio ileal, es decir del recto artificial creado quirúrjicamente a partir del íleon en pacientes que se han sometido a colectomía. |
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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 | 19.0 |
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 |
The primary objective is to assess the efficacy of vedolizumab IV in terms of the percentage of subjects achieving remission (defined as a Pouchitis Disease Activity Index [PDAI] score <7 and a decrease in PDAI score of ≥3 points from baseline) in subjects with chronic or recurrent pouchitis, after 14 weeks of treatment, compared to placebo. |
Comparar la eficacia de vedolizumab i.v. con el placebo en términos de porcentaje de sujetos que alcanzan la remisión (definida como una puntuación del índice de actividad de la enfermedad pouchitis (Pouchitis Disease Activity Index [PDAI]) < 7 y una disminución de dicha puntuación PDAI de ≥ 3 puntos con respecto al valor inicial) en los sujetos con pouchitis crónica o recurrente, después de 14 semanas de tratamiento. |
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E.2.2 | Secondary objectives of the trial |
- Evaluating time to symptomatic remission (defined as a PDAI score <7 and a decrease in PDAI score of ≥3 points from Baseline). - Evaluating change in PDAI endoscopic subscore at Weeks 14 and 34 compared to Screening. - Evaluating change in PDAI histologic subscore at Weeks 14 and 34 compared to Screening. - Evaluating change in total PDAI at Weeks 14 and 34 compared to Screening. - Evaluating change in Inflammatory Bowel Disease Questionnaire (IBDQ), and Cleveland Global Quality of Life (CGQL, the Fazio Score, 3 items) at Weeks 14, 22, and 34 compared to Day 1. |
1. El tiempo hasta la remisión sintomática (definida como una puntuación PDAI < 7 y una disminución de dicha puntuación PDAI de ≥ 3 puntos con respecto al valor inicial). 2. Cambio en la subpuntuación endoscópica PDAI en las semanas 14 y 34 en comparación con la selección. 3. Cambio en la subpuntuación histológica PDAI en las semanas 14 y 34 en comparación con la selección. 4. Cambio en la puntuación PDAI total en las semanas 14 y 34 en comparación con la selección. 5. Cambio en el cuestionario de la enfermedad inflamatoria intestinal (Inflammatory Bowel Disease Questionnaire [IBDQ]) y en la puntuación de calidad de vida global de Cleveland (Cleveland Global Quality of Life [CGQL], puntuación Fazio de 3 ítems) en las semanas 14, 22 y 34 en comparación con el día 1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects 18 to 80 years of age. 2. History of IPAA for UC that was created at least 1 year before Screening. 3. Diagnosis of pouchitis that is recurrent, defined by an mPDAI ≥5 and >2 episodes within 1 year of Screening or requiring long-term continuous low-dose antibiotic therapy (taken daily on an ongoing basis) or frequent pulse antibiotic therapy. |
• Sujetos de ambos sexos de 18 a 80 años de edad. • Antecedentes de AIAR para la CU realizada al menos 1 año antes de la selección. • Diagnóstico de pouchitis que es recurrente, definida por una mPDAI ≥ 5 y > 2 episodios durante el año anterior a la visita de selección o necesidad de tratamiento continuo prolongado con antibióticos a baja dosis (toma diaria de antibióticos de forma continuada) o tratamiento con pulsos de antibióticos frecuentes. |
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E.4 | Principal exclusion criteria |
1. The subject has Crohn’s disease (CD), CD of the pouch, irritable pouch syndrome (IPS), cuffitis, or mechanical complications of the pouch. 2. The subject has received previous treatment with vedolizumab, natalizumab, efalizumab, rituximab, etrolizumab, or anti-mucosal addressin cell adhesion molecule-1(MAdCAM-1) therapy. 3. The subject has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of randomization (whichever is longer). 4. The subject has received nonbiologic investigational therapy within 30 days prior to randomization. 5. The subject has active or latent tuberculosis. 6. The subject has a known history of hepatitis B virus (HBV), hepatitis C virus (HCV), acquired human immunodeficiency virus (HIV), or is found to be seropositive at Screening. 7. The subject has an active, severe infection. 8. The subject has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of study drug. |
• El sujeto padece enfermedad de Crohn (EC), EC del reservorio, síndrome de reservorio irritable (SRI), cuffitis o complicaciones mecánicas del reservorio. Quedarán excluidos aquellos sujetos en los que el investigador sospeche que existe un cuadro de inflamación, atendiendo al resultado de la endoscopia, que pueda deberse a la EC. • El sujeto ha recibido tratamiento previo con vedolizumab, natalizumab, efalizumab, rituximab, etrolizumab o terapia frente a la molécula de adhesión celular adresina de la mucosa 1 (Mucosal Vascular Addressin Cell Adhesion Molecule 1 [MAdCAM-1]). • El sujeto ha recibido cualquier agente biológico o biosimilar en investigación o aprobado en los 60 días o 5 semividas previos a la aleatorización (lo que sea más largo). • El sujeto ha recibido terapia no biológica en investigación en los 30 días previos a la aleatorización. • El sujeto presenta tuberculosis activa o latente. • El sujeto tiene antecedentes conocidos de infección por el virus de la hepatitis B (VHB), virus de la hepatitis C (VHC), virus de la inmunodeficiencia humana adquirida (VIH) o se encuentra que es seropositivo en la selección. • El sujeto presenta una infección activa severa. • El sujeto tiene una lista de verificación de síntomas subjetivos de la leucoencefalopatía multifocal progresiva (LMP) positiva antes de la administración del fármaco del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of subjects who achieve remission at Week 14. Remission will be defined as a PDAI score <7 and a decrease in PDAI score of ≥3 points from Baseline. |
La variable principal es el porcentaje de sujetos que alcanzan remisión en la semana 14. La remisión se definirá como una puntuación PDAI < 7 y una disminución de dicha puntuación PDAI de ≥ 3 puntos con respecto al valor inicial. |
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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. Time to the occurrence of symptomatic remission (defined as a PDAI score <7 and a decrease in PDAI score of ≥3 points from Baseline). 2. Change in PDAI endoscopic score from Screening to Weeks 14 and 34. 3. Change in PDAI histologic findings from Screening to Weeks 14 and 34. 4. Change in PDAI score from Screening to Weeks 14 and 34. 5. Change in IBDQ total and subscale scores from Day 1 to Weeks 14, 22, and 34. 6. Change in 3-item CGQL (Fazio Score) from Day 1 to Weeks 14, 22, and 34. |
(1) El tiempo hasta la aparición de remisión (definida como una puntuación PDAI < 7 y una disminución de dicha puntuación PDAI de ≥ 3 puntos con respecto al valor inicial). (2) Cambio en la subpuntuación endoscópica PDAI desde la selección a las semanas 14 y 34. (3) Cambio en la subpuntuación histológica PDAI desde la selección a las semanas 14 y 34. (4) Cambio en la puntuación total PDAI desde la selección a las semanas 14 y 34. (5) Cambio en las puntuaciones IBDQ, tanto total como de subescalas, desde el día 1 hasta las semanas 14, 22 y 34. (6) Cambio en el CGQL de 3 ítems (puntuación Fazio) desde el día 1 a las semanas 14, 22 y 34. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 14, 22 and 34 |
Semanas 14, 22 y 34 |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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
|
The end of trial will be the date of the last visit of the last subject at the Week 48 Follow-up Visit |
La finalización del ensayo será la fecha de la última visita del último sujeto en la visita de seguimiento de la semana 48 |
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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 |