E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis (UC) |
Colitis Ulcerosa (CU) |
|
E.1.1.1 | Medical condition in easily understood language |
UC is a chronic, inflammatory bowel disease that results in bloody diarrhea |
CU es una enfermedad crónica e inflamatoria del intestino que resulta en diarreas sangrantes |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033007 |
E.1.2 | Term | Other ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
|
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 | 10045366 |
E.1.2 | Term | Ulcerative colitis, unspecified |
E.1.2 | System Organ Class | 100000004856 |
|
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 | 10066678 |
E.1.2 | Term | Acute ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075635 |
E.1.2 | Term | Acute hemorrhagic ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
|
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 evaluate the efficacy of UTTR1147A compared with placebo and compared with vedolizumab based on clinical remission |
•Evaluar la eficacia de UTTR1147A en comparación con placebo y en comparación con vedolizumab basado en remisión clinica |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of UTTR1147A compared with placebo and compared with vedolizumab based on sustained remission, clinical response, endoscopic healing, endoscopic remission, UC bowel movement/abdominal signs and symptoms, and patient-reported health-related quality of life (QOL) • To evaluate the safety of UTTR1147A compared with placebo and compared with vedolizumab • To characterize the pharmacokinetics of UTTR1147A in patients with UC • To evaluate the immune response to UTTR1147A |
• Evaluar la eficacia de UTTR1147A en comparación con placebo y en comparación con vedolizumab basado en Remisión mantenida, Respuesta clínica, Curación endoscópica, Remisión endoscópica, Cambio en los signos y síntomas defecatorios /abdominales de la CU y Cambios en la CdV relacionada con la salud comunicada por el paciente • Evaluar la seguridad de UTTR1147A en comparación con placebo y en comparación con vedolizumab. • Caracterizar la farmacocinética de UTTR1147A en los pacientes con CU. • Evaluar la respuesta inmunitaria a UTTR1147A. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 18-80 years - Diagnosis of UC - Moderate to severely active UC, defined by the Mayo Clinic Score - Inadequate response, loss of response, or intolerance to prior immunosuppressant treatment and and/or corticosteroid treatment - Use of highly effective contraception as defined by the protocol |
-Edad de 18 a 80 años -Diagnóstico de CU -Confirmación de CU de moderada a grave, definida por la Clinica Mayo -Respuesta inadecuada, desaparición de la respuesta o intolerancia al tratamiento inmunosupresor previo y/o al tratamiento con corticoesteroides. -Uso de métodos anticonceptivos altamente eficaces definidos por el protocolo |
|
E.4 | Principal exclusion criteria |
- History of psoriasis or psoriatic arthritis; any other inflammatory skin disorders requiring oral corticosteroids, immunosuppressants, or biological therapy within the previous year and primary sclerosing cholangitis - History of cancer as defined by the protocol - Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or GI disorders (excluding UC) - Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC - Diagnosis of indeterminate colitis or granulomatous (Crohn's) colitis and toxic megacolon within 12 months prior to screening - Suspicion of ischemic colitis, radiation colitis, or microscopic colitis - Current fistula or history of fistula, current pericolonic abscess and Stricture (stenosis) of the colon - History or current evidence of unresectable colonic mucosal dysplasia and high-grade colonic mucosal dysplasia - Prior treatment with vedolizumab, etrolizumab, natalizumab, efalizumab, or any other anti-integrin agents and rituximab - Use of prohibited therapies as defined by the protocol prior to randomization - Evidence or treatment of infections or history of infections as defined by the protocol |
-Antecedentes de psoriasis o de artritis psoriásica; cualquier otro trastorno inflamatorio de la piel que haya requerido corticoesteroides orales, inmunosupresores o un tratamiento biológico en el año anterior y colangitis esclerosante primaria -Antecedentes de cáncer tal y como están definidos en el protocolo. -Enfermedad concomitante no controlada e importante, como trastornos cardíacos, pulmonares, renales, hepáticos, endocrinos o GI (salvo la CU). -Antecedentes de resección colónica extensa, de colectomía subtotal o total, o de proctocolectomía, o intervención quirúrgica programada para la CU. -Diagnóstico de colitis indeterminada o de colitis granulomatosa (Crohn) o megacolon tóxico en los 12 meses previos a la selección. -Sospecha de colitis isquémica, colitis por radiación o colitis microscópica. -Antecedentes o presencia de fístulas, absceso pericolónico en curso y estenosis del colon. -Antecedentes o signos de displasia de la mucosa colónica no resecable y de displasia de la mucosa colónica de alto grado. -Tratamiento previo con vedolizumab, etrolizumab, natalizumab, efalizumab o cualquier otro inhibidor de integrinas y rituximab -Uso de terapias prohibidas tal y como están definidas en el protocolo antes de la randomización -Evidencia o tratamiento de infección o antecedentes de infecciones tal y como está definido en el protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Clinical remission |
1. Remision clinica |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At Week 10 |
1. En la semana 10 |
|
E.5.2 | Secondary end point(s) |
1. Sustained remission 2. Clinical response 3. Endoscopic healing 4. Endoscopic remission 5. Change from baseline in ulcerative colitis bowel movement signs and symptoms, as assessed by Ulcerative Colitis-Patient-Reported Outcome Signs and Symptoms score (UC PRO/SS) 6. Change from baseline in UC abdominal signs and symptoms, as assessed by UC PRO/SS score 7. Change from baseline in patient-reported health related QOL, as assessed by Inflammatory Bowel Disease Questionnaire score 8. Occurrence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events scale 9. Change in targeted vital signs, physical findings, and clinical laboratory test results during and following study drug administration 10. Serum concentration of UTTR1147A at specified time points 11. Presence of anti-drug antibody (ADA) during the study relative to the presence of ADAs at baseline |
1. Remisión mantenida 2. Respuesta clínica 3. Curación endoscópica 4. Remisión endoscópica 5. Cambio en los signos y síntomas defecatorios desde el momento basal de la CU evaluado mediante la puntuación de Ulcerative Colitis-Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS). 6. Cambio en los signos y síntomas abdominales de la CU desde el momento basal evaluado mediante la puntuación de Ulcerative Colitis-Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) 7. Cambio en la CdV relacionada con la salud comunicada por el paciente desde el momento basal evaluado mediante la puntuación en el cuestionario IBDQ. 8. Incidencia e intensidad de los acontecimientos adversos, con la intensidad determinada según los CTCAE del NCI 9. Variación de las constantes vitales, los datos de la exploración física y los resultados analíticos durante la administración del fármaco del estudio y después 10. Concentración sérica de UTTR1147A en puntos temporales especificados. 11. Presencia de ACF durante el estudio en comparación con su presencia en el momento basal. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4: At Weeks 10 and 30 5-7: Baseline to Weeks 10 and 30 8-9: Up to 45 months 10: At Weeks 0, 1, 2, 4, 6, 8, 10, 14, 30 and at safety follow-up visit (4 weeks after the last dose of study drug) and at unscheduled visit or disease evaluation or early termination 11: At Weeks 0, 6, 10, 22, 30 and at safety follow-up visit (8 weeks after the last dose of study drug) and at unscheduled visit or disease evaluation or early termination |
1-4. En las semanas 10 y 30 5-7. Desde Basal a las semanas 10 y 30 8-9. Hasta un maximo de 45 meses 10. En las semanas 0, 1, 2, 4, 6, 8, 10, 14, 30 y en la visita de seguimiento de seguridad (4 semanas después de la ultima dosis del fármaco del estudio) y en visitas no programadas o de evaluación de la enfermedad o terminación temprana. 11. En las semanas 0, 6, 10, 22, 30 y en la visita de seguimiento de seguridad (8 semanas después de la ultima dosis del fármaco del estudio) y en visitas no programadas o de evaluación de la enfermedad o 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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity; predictive, prognostic, safety, pharmacodynamic biomarkers |
Inmunogenicidad, predictiva, prognosis, seguridad, y biomarcadores farmacodinamicos. |
|
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 | 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 | 10 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Bulgaria |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Netherlands |
Poland |
Russian Federation |
Serbia |
Spain |
Ukraine |
United Kingdom |
United States |
|
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 this study is defined as the date when the last patient completes his or her final study visit. |
El final de este estudio se define como la fecha en que el último paciente completa la última visita de seguimiento de seguridad. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |