E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Crohn s Disease |
Enfermedad de Crohn |
|
E.1.1.1 | Medical condition in easily understood language |
Crohn's Disease |
Enfermedad de Crohn |
|
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 | 19.0 |
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 |
|
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 Crohn's disease 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 de la semana 52 en sujetos con EC activa de moderada a grave
que hayan alcanzado una respuesta clínica en la semana 6 tras la administración
de vedolizumab IV en las semanas 0 y 2. |
|
E.2.2 | Secondary objectives of the trial |
To determine the effect of vedolizumab SC maintenance treatment on enhanced 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 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. |
Evaluar el efecto del tratamiento de mantenimiento con vedolizumab SC en
respuestas clínicas aumentadas en la semana 52 en sujetos que hayan alcanzado
una respuesta clínica en la semana 6 tras la administración de vedolizumab IV en
las semanas 0 y 2. ? Evaluar el efecto del tratamiento de mantenimiento con
vedolizumab SC en la remisión sin corticoesteroides en la semana 52 en sujetos
que hayan alcanzado una respuesta clínica en la semana 6 tras la administración
de vedolizumab IV en las semanas 0 y 2. |
|
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 |
Ileonoscopy Sub-study (Version and Date per Main Study)
Related objective: To determine the effect of vedolizumab SC maintenance treatment on clinical remission at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2, using an alternate definition of clinical remission based on endoscopy (using simple endoscopic score for Crohn?s Disease [SES-CD]), abdominal pain (using the CDAI component) and loose/watery stool frequency (using the CDAI component).
Ileocolonoscopy assessments will be performed at sites with appropriate capabilities, in subjects who volunteer at screening. The purpose of this assessment is to explore an alternate definition of clinical remission at Week 52 based on endoscopy (using SES-CD), abdominal pain (using the CDAI component) and loose/watery stool frequency (using the CDAI
component). Ileocolonoscopy assessments (including terminal ileum plus ascending, traverse, decending and sigmoid colon and rectum) will be performed prior to Week 0 dosing and at Week 52 by a local endoscopist. |
Subestudio Ileonoscopia. (Version y Dia por Estudio principal). Determinar el
efecto del tratamiento de mantenimiento con vedolizumab SC en la remisión clínica en la semana 52 en sujetos que hayan alcanzado una respuesta clínica en la
semana 6 tras la administración de vedolizumab IV en las semanas 0 y 2, utilizando
una definición alternativa de remisión clínica basada en la endoscopia (mediante
SES-CD), el dolor abdominal (con el componente CDAI) y la frecuencia de
deposiciones sueltas/acuosas (con el componente CDAI). |
|
E.3 | Principal inclusion criteria |
1. The subject has a diagnosis of Crohn's disease (CD) established at least 3 months prior to screening, by clinical and endoscopic evidence
and corroborated by a histopathology report.
2. The subject has moderately to severely active CD.
3. The subject has CD involvement of the ileum and/or colon, at a minimum.
4. The subject has extensive colitis or pancolitis of >8 years duration or limited colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit.
5. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factors must be up-to-date on colorectal cancer surveillance at screening.
6. 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 antagonists. |
El sujeto se ha sometido a una resección colónica extensa o a colectomía subtotal
o total. El sujeto presenta antecedentes de >3 resecciones del intestino delgado o
síndrome del intestino corto diagnosticado. El sujeto presenta cualquier indicio de
infección activa durante la selección. El sujeto presenta una lista de verificación
subjetiva de la leucoencefalopatía multifocal progresiva (LMP) positiva antes de la
administración del fármaco del estudio. El sujeto ha recibido cualquier agente
biológico o biosimilar en investigación o aprobado en los 60 días o 5 semividas
previos a la selección, lo que sea más largo. El sujeto ha estado expuesto
previamente a vedolizumab. El sujeto ha estado expuesto previamente a
natalizumab, efalizumab o rituximab. |
|
E.4 | Principal exclusion criteria |
1. The subject has evidence of abdominal abscess at the initial Screening Visit.
2. The subject has had extensive colonic resection, subtotal or total colectomy.
3. The subject has a history of >3 small bowel resections or diagnosis of short bowel syndrome.
4. The subject has received tube feeding, defined formula diets, or parenteral alimentation within 21 days prior to the administration of the first dose of study drug.
5. The subject has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
6. 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 (which ever is longer).
7. 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).
8. The subject has used topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug.
9. The subject requires currently or is anticipated to require surgical intervention for CD during the study.
10. The subject has a history or evidence of adenomatous colonic polyps that have not been removed.
11. The subject has a history or evidence of colonic mucosal dysplasia.
12. The subject has a suspected or confirmed diagnosis of ulcerative colitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
13. The subject has evidence of an active infection during the Screening Period.
14. 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.
15. The subject has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
16. The subject has active or latent TB, regardless of treatment history, as evidenced by any of the following:
17. The subject has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
18. The subject has received any live vaccinations within 30 days prior to screening.
19. The subject has clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days prior to screening, or ongoing chronic infection. |
1. El sujeto presenta indicios clínicos de absceso abdominal en la visita
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36 de selección. 2. El sujeto se ha sometido a una resección colónica extensa o a
colectomía subtotal o total. 3. El sujeto presenta antecedentes de >3 resecciones
del intestino delgado o síndrome del intestino corto diagnosticado. 4. El sujeto ha
recibido alimentación por sonda, dietas con fórmulas definidas o alimentación
parenteral en los 21 días previos a la administración de la primera dosis del
fármaco del estudio. 5. El sujeto se ha sometido a ileostomía, colostomía o ha
tenido estenosis sintomática fija del intestino conocida. 6. El sujeto ha recibido
cualquiera de los tratamientos no biológicos aprobados o en investigación (p. ej.,
ciclosporina, tacrolimús, talidomida, metotrexato o tofacitinib, excepto los
específicamente enumerados en la sección 7.3.1 del protocolo, Medicamentos
permitidos para el tratamiento de la EC) para el tratamiento de la enfermedad
subyacente en los 30 días o 5 semividas antes de la selección (lo que sea más
largo). 7. El sujeto ha recibido cualquier agente biológico o biosimilar en
investigación o aprobado en los 60 días o 5 semividas previos a la selección (lo que
sea más largo). 8. El sujeto ha utilizado un tratamiento tópico (rectal) con
enemas/supositorios de 5-ASA o corticoesteroides en las 2 semanas previas a la
administración de la primera dosis del fármaco del estudio. 9. El sujeto requiere actualmente o se ha previsto que requiera una intervención quirúrgica para la EC
durante el estudio. 10. El sujeto presenta antecedentes o indicios de pólipos
colónicos adenomatosos sin extirpar. 11. El sujeto presenta antecedentes o indicios
de displasia de la mucosa del colon. 12. El sujeto tiene un diagnóstico presunto o
confirmado de colitis ulcerosa, colitis indeterminada, colitis isquémica, colitis por
radiación, enfermedad diverticular asociada a colitis o colitis microscópica. 13. El
sujeto presenta indicios de una infección activa durante el periodo de selección. 14.
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 de fármaco del
estudio. 15. El sujeto presenta infección crónica por el virus de la hepatitis B (VHB)
o por el virus de la hepatitis C (VHC). 16. El sujeto presenta TB activa o latente,
independientemente de los tratamientos previos, evidenciada por cualquier de los
siguientes aspectos: 17. El sujeto presenta cualquier inmunodeficiencia congénita o
adquirida identificada (p. ej., inmunodeficiencia común variable, infección por el
virus de la inmunodeficiencia humana [VIH], trasplante de órganos). 18. El sujeto ha
recibido cualquier vacuna atenuada en los 30 días previos a la selección. 19. El
sujeto presenta una infección clínicamente significativa (p. ej., neumonía,
pielonefritis) en los 30 días previos a la selección o infección crónica en curso. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with clinical remission, defined as Crohn s Disease Activity Index (CDAI) score ?150, at Week 52. |
la proporción de sujetos con remisión clínica, definida como la puntuación del índice
de actividad de la enfermedad de Crohn (CDAI) ?150, en la semana 52 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Proportion of subjects with enhanced clinical response, defined as a 100 point decrease in CDAI score from Baseline (Week 0), at Week 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 respuesta clínica aumentada, definida como la
disminución en 100 puntos de la puntuación CDAI con respecto al valor inicial (semana 0) en la semana 52. ? Proporción de sujetos con remisión sin
corticoesteroides, definidos como sujetos con corticoesteroides orales al inicio
(semana 0) que han dejado de tomarlos por vía oral y se encuentran en remisión
clínica en la semana 52. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | 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 | 7 |
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 |
|
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
|
End of trial will be the date of the last visit of the last subject at the Week 68 Follow-up visit |
Fin de ensayo será la fecha de la última visita del último sujeto en la visita de seguimiento de la semana 68 |
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |