E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis
Crohn?s Disease |
Colitis Ulcerosa
Enfermedad de Crohn |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis
Crohn?s Disease |
Colitis Ulcerosa
Enfermedad de Crohn |
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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 | 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.1.2 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 | 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 obtain data on long term safety and tolerability of vedolizumab SC in Ulcerative Colitis (UC) and Crohn?s Disease (CD) subjects. |
Obtener datos a largo plazo de la seguridad y tolerabilidad de vedolizumab SC en sujetos con Colitis Ulcerosa y Enfermedad e Crohn |
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E.2.2 | Secondary objectives of the trial |
? To obtain data on adverse events of special interest (AESIs; serious infections including opportunistic infection such as PML, liver injury, malignancies, injection site reactions or systemic reactions and hypersensitivity) in UC and CD subjects receiving long-term vedolizumab SC treatment.
? To obtain data on maintaining clinical response and clinical remission in UC and CD subjects receiving long-term vedolizumab SC treatment.
? To obtain data on patient reported outcomes (PRO) in UC and CD subjects receiving long-term vedolizumab SC treatment.
? To obtain data on work productivity and activity impairment (WPAI-UC; WPAI-CD) in UC and CD subjects receiving long-term vedolizumab SC treatment.
? To obtain data on time to major UC and CD-related events (hospitalizations, bowel surgeries,
and procedures) in UC and CD subjects receiving long-term vedolizumab SC treatment. |
Obtener datos:
-Acontecimientos adversos de especial interés (AAEI; infecciones graves incluidas infecciones oportunistas como LMP, lesión hepática, neoplasias malignas, reacciones en el lugar de la inyección o reacciones sistémicas y de hipersensibilidad) en sujetos con CU y EC que reciban tratamiento a largo plazo con vedolizumab SC.
-Mantenimiento de la respuesta clínica y la remisión clínica en sujetos con CU y EC que reciban tratamiento con vedolizumab SC a largo plazo
-Resultados comunicados por los pacientes (RCP) en sujetos con CU y EC que reciban tratamiento con vedolizumab SC a largo plazo
-Productividad laboral y el deterioro de la actividad (WPAI-CU; WPAI-EC) en sujetos con CU y EC que reciban tratamiento a largo plazo con vedolizumab SC
-Tiempo hasta la aparición de acontecimientos importantes relacionados con la CU y EC (hospitalizaciones, cirugías intestinales y procedimientos) en sujetos con CU y EC que reciban tratamiento a largo plazo con vedolizumab SC
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject has previously participated in Study MLN0002SC-3027 or MLN0002SC-3031, and, in the opinion of the investigator, tolerated the study drug well. Subjects who withdraw early from Study MLN0002SC-3027 or MLN0002SC-3031 must have withdrawn due to treatment failure (ie, as determined by disease worsening or need for rescue medications from Week 14) during the Maintenance Period.
2. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance.
3. Subjects with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial Screening Visit of MLN0002SC-3027 or MLN0002SC-3031.
4. May be receiving a therapeutic dose of the following drugs provided that the dose has been stable throughout the qualifying double-blind study:
? Oral 5-ASA compounds.
? Oral corticosteroid therapy (prednisone or equivalent steroid at a dose ?30 mg/day, budesonide at a dose ?9 mg/day).
? Topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories.
? Probiotics (eg, Culturelle, Saccharomyces boulardii).
? Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
? Antibiotics used for treatment of IBD (ie, ciprofloxacin, metronidazole).
? Azathioprine or 6-mercaptopurine, provided the patient was receiving this medication during prior participation in Study MLN002SC-3027.
? Methotrexate, provided the patient was receiving this medication during prior participation
in Study MLN002SC-3031. |
-El sujeto ha participado previamente en el estudio MLN0002SC-3027 o MLN0002SC-3031 y, en la opinión del investigador, toleró bien el fármaco del estudio. Durante el periodo de mantenimiento, los sujetos que se retiraron de forma temprana del estudio MLN0002SC-3027 o MLN0002SC-3031 deben de haberlo hecho debido a un fracaso en el tratamiento (es decir, determinado por el empeoramiento de la enfermedad o la necesidad de medicamentos de rescate desde la semana 14 del estudio en cuestión).
-Los sujetos con antecedentes familiares de cáncer colorrectal, antecedentes personales de aumento del riesgo de cáncer colorrectal, mayores de 50 años o con otros factores de riesgo conocidos deben llevar una vigilancia actualizada de estos factores de riesgo de cáncer colorrectal.
-El sujeto con colitis extensa o pancolitis > 8 años de duración o colitis del lado izquierdo > 12 años de duración deberá tener indicios documentados de que se ha realizado una colonoscopia de vigilancia durante los 12 meses previos a la visita de selección inicial de MLN0002SC-3027 o MLN0002SC-3031.
-9. Puede estar recibiendo una dosis terapéutica de los siguientes fármacos siempre que la dosis se haya mantenido estable a lo largo del estudio apto de doble ciego:
• Compuestos de 5-ASA oral.
• Tratamiento oral con corticosteroides (prednisona o esteroide equivalente a dosis de ≤ 30 mg/día, budesonida a dosis de ≤ 9 mg/día).
• Tratamiento tópico (rectal) con 5-ASA o supositorios/enemas de corticosteroides.
• Probióticos (p. ej., Culturelle, Saccharomyces boulardii).
• Antidiarreicos (p. ej., loperamida, difenoxilato con atropina) para el control de la diarrea crónica.
• Antibióticos usados para el tratamiento de la EII (es decir, ciprofloxacina, metronidazola).
• Azatioprina o 6-mercaptopurina, siempre que el paciente estuviera recibiendo esta medicación antes de la participación en el estudio MLN002SC-3027.
• Metotrexato, siempre que el paciente estuviera recibiendo esta medicación antes de la participación en el estudio MLN002SC-3031.
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E.4 | Principal exclusion criteria |
1. The subject required surgical intervention for IBD during or after participation in Study MLN0002SC-3027 or MLN0002SC-3031, currently requires surgical intervention for IBD, or is anticipated to require surgical intervention for IBD during this study.
2. The subject has had previous exposure to approved or investigational anti-intergins (eg, natalizumab, efalizumab, etrolizumab, AMG 181) or anti-MAdCAM1 antibodies or rituximab.
3. The subject has had hypersensitivity to any of the vedolizumab excipients.
4. Any live vaccinations within 30 days prior to vedolizumab SC administration.
5. The subject has developed a chronic or severe infection, or, any new, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, oncologic, or other medical disorder during or after participation in a prior vedolizumab study that, in the opinion of the investigator, would confound the study results or compromise subject safety.
6. The subject has withdrawn from Study MLN0002SC-3027 or MLN0002SC-3031due to a study-drug related AE.
7. The subject is unwilling or unable to self inject, or does not have a caregiver (defined as a legal adult) to inject the study medication.
8. The subject has any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to enrollment; and (c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to enrollment. Subjects with remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to enrollment.
9. The subject has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or demylinating neurodegenerative disease.
10. The subject has a positive PML subjective symptom checklist prior to the administration of study drug. |
1. El sujeto ha necesitado intervención quirúrgica para EII durante o tras la participación en el estudio MLN0002SC-3027 o MLN0002SC-3031, actualmente necesita intervención quirúrgica para EII, o se prevé que necesitará intervención quirúrgica para EII durante este estudio.
2. El sujeto había estado expuesto anteriormente a antiintegrinas aprobadas o en investigación (p. ej., natalizumab, efalizumab, etrolizumab, AMG 181) o anticuerpos anti-MAdCAM1 o rituximab.
3. El sujeto había tenido hipersensibilidad a cualquier excipiente de vedolizumab.
5. El sujeto ha desarrollado una infección crónica o grave, o cualquier trastorno nuevo inestable o incontrolado de tipo cardiovascular, pulmonar, hepático, renal, GI, genitourinario, hematológico, de coagulación, inmunológico, endocrino/metabólico, neurológico, oncológico u otro tipo de trastorno médico durante o después de la participación en un estudio previo con vedolizumab que, en opinión del investigador, podría confundir los resultados del estudio y comprometer la seguridad del sujeto.
6. El sujeto se ha retirado del estudio MLN0002SC-3027 o MLN0002SC-3031 debido a un AA relacionado con el fármaco de estudio.
7. El sujeto no quiere o no puede autoinyectarse, o no tiene un cuidador (definido como un adulto legal) que le inyecte el fármaco del estudio.
8. El sujeto tiene antecedentes de neoplasia maligna, excepto los siguientes casos: (a) cáncer de piel basocelular no metastásico adecuadamente tratado, (b) cáncer de piel de células escamosas adecuadamente tratado y que no ha presentado recurrencia durante al menos un año antes de la selección; y (c) antecedentes de carcinoma de cuello uterino in situ adecuadamente tratado y que no ha presentado recurrencia durante al menos los 3 años previos a la selección. Se considerará a los sujetos con antecedentes remotos de neoplasia maligna (p. ej., > 10 años desde la finalización del tratamiento curativo sin recurrencia) en función de la naturaleza de la neoplasia maligna y del tratamiento recibido y deberá discutirse con el promotor caso por caso antes de la inscripción.
9. El sujeto presenta antecedentes de cualquier trastorno neurológico importante, como accidente cerebrovascular, esclerosis múltiple, tumor cerebral, enfermedad desmielinizante neurodegenerativa.
10. El sujeto presenta una lista de verificación de síntomas subjetivos de la LMP positiva previa a la administración del fármaco del estudio.
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E.5 End points |
E.5.1 | Primary end point(s) |
? Subject year adjusted treatment emergent-related AEs and SAEs during long-term vedolizumab SC treatment. |
• AA y AAG relacionados con la emergencia del tratamiento ajustado por año-sujeto durante el tratamiento con vedolizumab SC a largo plazo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Collection of AEs will commence from the time that the subject is first administered study medication (Week 0). Routine collection of AEs will continue until 18 weeks post last dose of medication.
AE/SAE assessments:
QW: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Q2W: Weeks 0, 2, 4, 6, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit. |
Colección de AA que se iniciará desde el momento en que el sujeto se le administra la primera medicación del estudio (semana 0). Recolección rutinaria de AA que continuará hasta las 18 semanas después de la última dosis del medicamento.
Evaluaciones AA/ AAG:
QW: semanas 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 y luego cada 8 semanas, más visitas no programadas y de seguridad/terminación temprana.
Q2W: las semanas 0, 2, 4, 6, 8, 16 y luego cada 8 semanas, más visitas no programadas y de seguridad/terminación temprana.
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E.5.2 | Secondary end point(s) |
? Subject year adjusted AESIs during long-term vedolizumab SC treatment.
? Proportion of subjects with clinical response during long-term vedolizumab SC treatment using partial Mayo scores in UC subjects and Harvey-Bradshaw Index (HBI) scores in CD subjects.
? Proportion of subjects with clinical remission during long-term vedolizumab SC treatment using partial Mayo scores in UC subjects and Harvey-Bradshaw Index (HBI) scores in CD subjects. |
• AAEI ajustados por año-sujeto durante el tratamiento con vedolizumab SC a largo plazo.
• Proporción de sujetos con respuesta clínica durante el tratamiento a largo plazo con vedolizumab SC usando las puntuaciones parciales de Mayo en sujetos con CU y las puntuaciones del índice de Harvey-Bradshaw (IHB) en sujetos con EC.
• Proporción de sujetos con remisión clínica durante el tratamiento con vedolizumab SC usando las puntuaciones parciales de Mayo en sujetos con CU y las puntuaciones del índice de Harvey-Bradshaw (IHB) en sujetos con EC.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Collection of AEs will commence from the time that the subject is first administered study medication (Week 0). Routine collection of AEs will continue until 18 weeks post last dose of medication.
AE/SAE assessments:
QW: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Q2W: Weeks 0, 2, 4, 6, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit.
Disease activity (Mayo/HBI):
QW and Q2W: Weeks 0, 4, 8, 16 then every 8 weeks, plus unscheduled and final safety/early termination visit. |
Colección de AA que se iniciará desde el momento en que el sujeto se le administra la primera medicación del estudio (semana 0). Recolección rutinaria de AA que continuará hasta las 18 semanas después de la última dosis del medicamento.
Evaluaciones AA/ AAG:
QW: semanas 0, 1, 2, 3, 4, 5, 6, 7, 8, 16 y luego cada 8 semanas, más visitas no programadas y de seguridad/terminación temprana.
Q2W: las semanas 0, 2, 4, 6, 8, 16 y luego cada 8 semanas, más visitas no programadas y de seguridad/terminación temprana.
Actividad de la enfermedad (Mayo/HBI):
QW and Q2W: Semanas 0, 4, 8, 16 y luego cada 8 semanas, más visitas no programadas y de seguridad/terminación temprana.
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 112 |
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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Subjects enrolled onto the study will be eligible to continue receiving vedolizumab SC until the vedolizumab SC formulation becomes commercially available in their country of residence, the subject withdraws from the study, or the sponsor decides to close the study. |
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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |