E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis |
Colitis Ulcerosa |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis |
Colitis Ulcerosa |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 assess the effect of vedolizumab SC maintenance treatment on clinical remission at Week 52 in subjects with moderately to severely active UC who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2. |
Evaluar el efecto del tratamiento de mantenimiento con vedolizumab SC en la remisión clínica en la semana 52 en sujetos con CU de moderada a gravemente activa que han mostrado una respuesta clínica en la semana 6 después de la administración de vedolizumab IV en las semanas 0 y 2. |
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E.2.2 | Secondary objectives of the trial |
? To determine the effect of vedolizumab SC maintenance treatment on mucosal healing at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2. ? To determine the effect of vedolizumab SC maintenance treatment on durable clinical response at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2. ? To determine the effect of vedolizumab SC maintenance treatment on durable clinical remission at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2. ? To determine the effect of vedolizumab SC maintenance treatment on corticosteroid free remission at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2. |
? Determinar el efecto: del tratamiento de mantenimiento con vedolizumab SC en la cicatrización de la mucosa en la semana 52 en sujetos que han mostrado una respuesta clínica en la semana 6 después la administración de vedolizumab IV en las semanas 0 y 2 del tratamiento de mantenimiento con vedolizumab SC en la respuesta clínica perdurable de la semana 52 en sujetos que han mostrado una respuesta clínica en la semana 6 después la administración de vedolizumab IV en las semanas 0 y 2. del tratamiento de mantenimiento con vedolizumab SC en la remisión clínica perdurable de la semana 52 en sujetos que han mostrado una respuesta clínica en la semana 6 después la administración de vedolizumab IV en las semanas 0 y 2. del tratamiento de mantenimiento con vedolizumab SC en la remisión sin corticosteroides en la semana 52 en pacientes que han mostrado una respuesta clínica en la semana 6 después la administración de vedolizumab IV en las semanas 0 y 2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject has a diagnosis of UC established at least 6 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report. 2. The subject has moderately to severely active UC as determined by a complete Mayo score of 6-12 with an endoscopic subscore ?2 within 10 days prior to the first dose of study drug. 3. The subject has evidence of UC extending proximal to the rectum (?15 cm of involved colon). 4. The subject has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents: immunomodulators, corticosteroids, or TNF-alpha. |
El sujeto presenta un diagnóstico de CU establecido al menos 6 meses antes de la selección por medio de evidencia clínica y endoscópica y corroborado por un informe histopatológico. El sujeto presenta CU de moderada a gravemente activa según se determina mediante una puntuación Mayo completa de 6 a 12 con una subpuntuación endoscópica ? 2 en los 10 días previos a la primera dosis del fármaco del estudio. El sujeto presenta indicios de CU que se extiende en sentido proximal al recto (? 15 cm de colon afectados). El sujeto ha presentado una respuesta inadecuada, una pérdida de respuesta o intolerancia al menos a 1 de los siguientes fármacos: inmunomoduladores, corticosteroides o TNF-?. |
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E.4 | Principal exclusion criteria |
1. The subject has clinical evidence of abdominal abscess or toxic megacolon at the initial Screening Visit. 2. The subject has had extensive colonic resection, subtotal or total colectomy. 3. The subject has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine. 4. The subject has received any of the investigational or approved non-biologic therapies (eg, cyclosporine, tacrolimus, thalidomide, methotrexate or tofacitinib, except for those specifically listed in the protocol) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer). 5. The subject has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (which ever is longer). 6. The subject currently requires or is anticipated to require surgical intervention for UC during the study. 7. The subject has a history or evidence of adenomatous colonic polyps that have not been removed, or has a history or evidence of colonic mucosal dysplasia. 8. The subject has a suspected or confirmed diagnosis of Crohn?s entercolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis. 9. The subject has evidence of an active infection during the Screening Period. 10. The subject has evidence of, or treatment for, C. difficile infection or other intestinal pathogen with 28 days prior to first dose of study drug. 11. The subject has chronic HBV or HCV infection. 12. The subject has active or latent TB, regardless of treatment history. 13. The subject has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation). 14. The subject has received any live vaccinations within 30 days prior to screening. 15. The subject had a clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days prior to screening, or ongoing chronic infection. 16. The subject has used a topical (rectal) treatment with 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug. |
1. El sujeto presenta indicios clínicos de absceso abdominal o megacolon tóxico en la visita de selección inicial. 2. El sujeto se ha sometido a una resección colónica extensa o a colectomía subtotal o total. 3. El sujeto se ha sometido a ileostomía, colostomía o ha tenido estenosis sintomática fija del intestino conocida. 4. El sujeto ha recibido alguno de los tratamientos no biológicos aprobados o en investigación (por ejemplo, ciclosporina, tacrolimús, talidomida, metotrexato o tofacitinib excepto los específicamente listados en la sección del protocolo ?7.3.1 Medicamentos permitidos para el tratamiento de la CU) para el tratamiento de la enfermedad subyacente en los 30 días o 5 semividas tras la selección (lo que sea más largo). 5. El sujeto ha recibido algún fármaco biológico o biosimilar en investigación o aprobado en los 60 días o 5 semividas tras la selección (lo que sea más largo). 6. El sujeto requiere actualmente o se ha previsto que requiera una intervención quirúrgica para la CU durante el estudio. 7. El sujeto presenta antecedentes o indicios de pólipos colónicos adenomatosos sin extirpar o antecedentes o indicios de displasia mucosa colónica. 8. El sujeto tiene un presunto diagnóstico o un diagnóstico confirmado de enterocolitis de Crohn, colitis indeterminada, colitis isquémica, colitis por radiación, enfermedad diverticular asociada a colitis o colitis microscópica. 9. El sujeto presenta indicios de una infección activa durante el periodo de selección. 10. El sujeto presenta indicios, o está en tratamiento de infección por C. difficile u otro patógeno intestinal durante los 28 días previos a la primera dosis del fármaco del estudio. 11. El sujeto presenta infección crónica por el virus de la hepatitis B (VHB) o por el virus de la hepatitis C (VHC). 12. El sujeto presenta TB activa o latente, independientemente de los tratamientos previos. 13. El sujeto presenta alguna inmunodeficiencia congénita o adquirida identificada (p. ej., inmunodeficiencia común variable, infección por el virus de la inmunodeficiencia humana [VIH], trasplante de órganos). 14. El sujeto ha recibido todas las vacunas atenuadas en los 30 días previos a la selección. 15. El sujeto ha presentado una infección clínicamente significativa (p. ej., neumonía, pielonefritis) en los 30 días previos a la selección o infección crónica en curso. 16. El sujeto ha utilizado un tratamiento tópico (rectal) con ácido 5 aminosalicílico (5-ASA) o enemas/supositorios de corticosteroides en las 2 semanas tras la administración de la primera dosis del fármaco del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
? Proportion of subjects with clinical remission, defined as a complete Mayo score of ?2 points and no individual subscore >1 point, at Week 52. |
El criterio de valoración principal de este estudio es la proporción de sujetos con remisión clínica, definida como una puntuación Mayo completa ? 2 puntos y sin subpuntuaciones individuales > 1 punto, en la semana 52. |
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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) |
? Proportion of subjects with mucosal healing, defined as Mayo endoscopic subscore of ?1 point, at Week 52. ? Proportion of subjects with durable clinical response, defined as clinical response at Weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of ?3 points and ?30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ?1 point or absolute rectal bleeding subscore of ?1 point. ? Proportion of subjects with durable clinical remission, defined as clinical remission at Weeks 6 and 52. ? Proportion of subjects with corticosteroid-free remission, defined as subjects using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. |
? Proporción de sujetos con cicatrización de la mucosa (definida con una subpuntuación endoscópica Mayo ? 1 punto) en la semana 52. ? Proporción de sujetos con respuesta clínica perdurable (definida como respuesta clínica en las semanas 6 y 52, donde la respuesta clínica se define como una reducción en la puntuación Mayo completa ? 3 puntos y ? 30 % desde el inicio [semana 0] con un descenso concomitante de la subpuntuación del sangrado rectal ? 1 punto o de la subpuntuación absoluta del sangrado rectal ? 1 punto). ? Proporción de sujetos con remisión clínica perdurable (definida como remisión clínica en las semanas 6 y 52). ? Proporción de sujetos con remisión sin corticosteroides (definida como sujetos que toman corticosteroides por vía oral al inicio [semana 0] que han dejado de tomarlos y se encuentran en remisión clínica en la semana 52). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 52: Mucosal healing and corticosteroid-free remission. Week 6 and Week 52: Durable clinical response and durable clinical remission. |
Semana 52: curación de la mucosa y remisión libre de corticosteroides. Semana 6 Semana 52: respuesta clínica duradero y remisión clínica duradera. |
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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 | No |
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 | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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) | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
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 |
Australia |
Belgium |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Canada |
Chile |
Croatia |
Czech Republic |
Denmark |
Estonia |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Lithuania |
Mexico |
Netherlands |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Turkey |
Ukraine |
United Kingdom |
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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End of trial will be the date of the last visit of the last subject at the Week 68 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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |