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 is a type of inflammatory bowel disease that causes the lining of the large intestine (colon) to become inflamed (irritated and swollen) which may cause ulcers and bleeding. |
La Colitis Ulcerosa es un tipo de trastorno inflamatorio del intestino que causa inflamación (irritación e hinchazón) del revestimiento del intestino grueso (colon) que puede causar úlceras y sangrado |
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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 | 20.1 |
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 compare the efficacy of brazikumab with that of placebo to achieve clinical remission |
- Comparar la eficacia de brazikumab con la del placebo para conseguir remisión clínica |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of brazikumab with that of placebo to achieve sustained clinical remission - To compare the efficacy of brazikumab with that of placebo to achieve corticosteroid-free (CS-free) clinical remission - To evaluate the pharmacokinetics (PK) and immunogenicity of brazikumab in participants with UC - To characterize the exposure-response relationships of brazikumab |
- Comparar la eficacia de brazikumab con la del placebo para conseguir remisión clínica prolongada - Comparar la eficacia de brazikumab con la del placebo para conseguir remisión clínica sin corticosteroides (sin CS) - Evaluar la farmacocinética (FC) y la inmunogenicidad de brazikumab en participantes con CU - Describir las relaciones exposición-respuesta de brazikumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to provide written informed consent prior to any study procedures and willing and able to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study period. 2. Aged 18 to 80 years of age, inclusive, at screening. 3. Diagnosis of UC with an onset of symptoms for a minimum of 3 months prior to screening as determined by the investigator based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings. 4. Evidence of UC extending proximal to the rectum (≥ 15 cm of involved colon). 5. Moderately to severely active UC as defined by Stool Frequency and Rectal Bleeding subscores and Modified Mayo endoscopic subscore. 6. Participant had an inadequate, failed response, or intolerance to intervention with oral corticosteroids, azathioprine, methotrexate, or 6-mercaptopurine, or demonstrated corticosteroid dependence for the treatment of ulcerative colitis. 7. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 acceptable methods of contraception. |
1. Capacidad para dar su consentimiento informado por escrito antes de cualquier procedimiento del estudio y estar dispuesto y ser capaz de asistir a todas las visitas del estudio, cumplir con los procedimientos del estudio, leer y escribir para completar cuestionarios y ser capaz de completar el período del estudio. 2. Tener entre 18 y 80 años de edad, inclusive, en el momento de la selección. 3. Diagnóstico de CU con inicio de los síntomas un mínimo de 3 meses antes de la selección, según lo determine el investigador principal sobre la base de la historia clínica, exclusión de causas infecciosas y resultados endoscópicos e histológicos característicos. 4. Pruebas de que la CU se esté extendiendo de manera proximal al recto (≥ 15 cm de colon afectado). 5. CU activa de moderada a intensa definida según la Subpuntuación de frecuencia de las deposiciones y de hemorragia rectal y la Subpuntuación endoscópica modificada Mayo. 6. El participante tuvo una respuesta inadecuada, fallida o intolerancia a la intervención con aminosalicilatos orales, corticosteroides orales, azatioprina, metotrexato o 6-mercaptopurina, o mostró dependencia de los corticosteroides para el tratamiento de la colitis ulcerosa. 7. Las mujeres en edad fértil que son sexualmente activas y que tienen una pareja masculina no esterilizada deben usar 2 métodos anticonceptivos aceptables. |
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E.4 | Principal exclusion criteria |
1. Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge) 2. History of fulminant colitis, a diagnosis of Crohn’s disease or indeterminate colitis, presence or history of a fistula consistent with Crohn’s disease, primary sclerosing cholangitis, celiac disease, or bile acid malabsorption. Participants with a history of toxic megacolon within 12 months of screening. 3. History of subtotal colectomy with ileorectostomy or colectomy with ileonal pouch, Koch pouch, ileostomy, or other prior colonic resection, or need for surgical intervention for control of UC anticipated within 6 months. 4. Participant has received the following treatment: - Infliximab: within 8 weeks prior to Baseline (Visit 2) - Adalimumab, certolizumab pegol, or golimumab: within 10 weeks prior to Baseline (Visit 2) - Vedolizumab within 18 weeks prior to Baseline (Visit 2) - Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to Baseline (Visit 2) 5. Participant has previously received vedolizumab, and was intolerant to intervention or had met the criteria for primary or secondary non-response to intervention.
6. Participant is pregnant, breastfeeding, or plans to become pregnant during the study. |
1. El participante tiene CU limitada al recto (es decir, no más allá de 15 cm del borde anal) 2. Antecedentes de colitis fulminante, diagnóstico de enfermedad de Crohn o colitis no determinada, presencia o antecedentes de una fístula compatible con enfermedad de Crohn, colangitis esclerosante primaria, enfermedad celíaca o mala absorción del ácido biliar. Quedan excluidos los participantes con antecedentes de megacolon tóxico en los 12 meses anteriores. 3. Antecedentes de colectomía subtotal con ileorrectostomía o colectomía con reservorio ileoanal, reservorio de Koch, ileostomía u otras resecciones de colon previas, o necesidad de intervención quirúrgica para el control de la CU prevista para los próximos 6 meses. 4. El participante ha recibido el siguiente tratamiento: - Infliximab: en las 8 semanas previas al inicio (visita 2) - Adalimumab, certolizumab pegol, o golimumab: en las 10 semanas previas al inicio (visita 2) - Vedolizumab: en las 18 semanas previas al inicio (visita 2) - Otros medicamentos prohibidos, tratamientos biológicos o tratamiento con pequeñas moléculas en 5 semividas previas al inicio (visita 2) 5. El participante ha recibido vedolizumab previamente y presentó intolerancia a la intervención o había cumplido con los criterios de falta de respuesta primaria o secundaria a la intervención. 6. La participante está embarazada, en período de lactancia o planea quedarse embarazada durante el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical remission: - modified Mayo Score (mMS) at Week 10: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 |
Remisión clínica: - Índice de Mayo modificado (IMm) en la semana 10: Subíndice endoscópico = 0 o 1; Subíndice de sangrado rectal = 0 Y Subíndice de frecuencia de deposición = 0. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Mayo score items: Stool frequency - Visit 1 through Follow-up 2 (e-diary) Rectal bleeding - Visit 1 through Follow-up 2 (e-diary) Findings of endoscopy - Visits 1, 6, 17 Physician’s global assessment - Visits 1, 6, 17 Each individual item assessed on 0-3 ordinal scale described in Mayo Scoring System for Assessment of Ulcerative Colitis Activity. |
Elementos Indice Mayo: Frecuencia de Deposición - Visita 1 hasta Seguimiento 2 (diario electrónico) Sangrado rectal Visita 1 hasta Seguimiento 2 (diario electrónico) Resultados de endoscopia . Visitas 1, 6, 17 Evaluación global del medico - Visitas 1, 6, 17 Cada elemento individual evaluado de 0-3 en la escala ordinal descrita en el Sistema de Puntuación Mayo para la evaluación de la actividad de la Colitis Ulcerosa. |
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E.5.2 | Secondary end point(s) |
1. Sustained clinical remission: - mMS at both Week 10 and Week 54: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 2. CS-free clinical remission: - mMS at Week 54 for participants who are CS-free for at least the last 12 weeks before the assessment at Week 54: Endoscopy subscore = 0 or 1, AND Rectal bleeding subscore = 0, AND Stool frequency subscore = 0 3. Population PK model of serum concentrations of brazikumab and analysis for serum anti-brazikumab antibodies 4. Exposure-response model linking primary endpoints to metrics of model-predicted individual brazikumab exposures |
1. Remisión clínica prolongada: - IMm en la semana 10 y en la semana 54: Subíndice endoscópico = 0 o 1; Subíndice de sangrado rectal = 0 Y Subíndice de frecuencia de deposición = 0. 2. Remisión clínica sin CS: - IMm en 54 participantes sin CS durante al menos las últimas 12 semanas antes de la evaluación de la semana 54: Subíndice endoscópico = 0 o 1; Subíndice de sangrado rectal = 0 Y Subíndice de frecuencia de deposición = 0. 3. Modelo FC poblacional de concentraciones séricas de brazikumab y análisis de anticuerpos séricos anti-brazikumab 4. Modelo de exposición-respuesta al relacionar los criterios de valoración principales con los parámetros de exposiciones individuales a brazikumab pronosticados por el modelo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
as listed above |
Como se lista arriba |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Blood and stool samples will be collected and analyzed to evaluate protein, nucleic acid, and cellular biomarkers, optional blood sample for genetic research |
Las muestras de sangre y heces se recogerán y analizarán para evaluar proteina, ácido nucleico y marcadores celulares, muestra de sangre opcional para investigación genética |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 5 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
China |
Colombia |
Czech Republic |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Poland |
Romania |
Russian Federation |
Singapore |
South Africa |
Spain |
Switzerland |
Taiwan |
Turkey |
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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LVLS |
Última Visita del último sujeto |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 15 |