E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe ulcerative colitis |
Colitis ulcerosa de moderada a severa |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative colitis in a moderate or severe form |
Colitis ulcerosa en forma moderada o severa. |
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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 |
The primary objective is to assess the efficacy of a top-down approach in achieving histological improvement at week 52, without colectomy and without UC-related hospitalization versus a standard step-up approach. |
El objetivo primario es evaluar la eficacia de la aproximación top-down en la consecución de la mejoría histológica a la semana 52, sin colectomía y sin hospitalización relacionada con la colitis ulcerosa versus la aproximación estándar step-up. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will be: - to compare the efficacy of the top-down approach to induce histological remission and histological healing in the short-term (week 16) vs. the standard step-up approach - to compare the efficacy of the top-down approach to induce clinical remission (combined clinical and endoscopic improvement=sub-score of 0 or 1) in the short- and long-term (week 16 and week 52) vs. the standard step-up approach - to compare the efficacy of the top-down approach to induce short- and long-term mucosal healing (endoscopic and histologic improvement) vs. the standard step-up approach - to compare the safety of the top-down approach through week 52 vs. the standard step-up approach - to compare the quality of life of patients treated with the top-down approach through week 52 vs. the standard step-up approach - To compare the need for colectomies and UC-related hospitalizations in patients treated with the top-down approach vs. the step-up approach. |
Objetivos secundarios -Comparar la eficacia de la aproximación top-down para inducir remisión y curación histológica en la aproximación a corto plazo (semana 16), vs aproximación step-up estándar. -Comparar la eficacia de la aproximación top-dowm para inducción de remisión clínica (mejoría clínica y endoscópica=sub puntuación 0 ó 1) en las aproximaciones a corto y a largo plazo (semanas 16 y 52) vs.aproximación estándar step-up. -Comparar la eficacia de la aproximación top-down para la inducción a corto y a largo plazo de la curación mucosa (mejoría endoscópica e histológica) vs. aproximación estándar step-up. -Comparar la seguridad de la aproximación top-down en semana 52 vs. aproximación step-up. -Comparar la calidad de vida de los pacientes tratados mediante aproximación top-down a semana 52 vs. la aproximación step-up. -Comparar la necesidad de colostomías y hospitalizaciones relacionadas con la colitis ulcerosa tratada con aproximación top-down vs. aproximación top-down. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients (age ≥ 18 years and < 75 years) - Established diagnosis of UC (confirmed clinically, endoscopically and histologically) since at least 3 months - Disease duration no longer than 24 months before the screening visit - Ongoing oral 5-ASA treatment ≥1.6g/day - Having objective signs of moderate-to-severe UC activity, defined by a total Mayo score of 6 to 12. - Proctitis, left-sided or extensive UC - Ability to perform study requirements - Ability to give informed consent according to ICH/ GCP, and national/local regulations. |
-Pacientes adultos (edad entre 18 y 75 años). -Diagnóstico confirmado de colitis ulcerosa (confirmado clínicamente, endoscópicamente e histológicamente) desde al menos 3 meses. -Duración de la enfermedad no superior a 24 meses anteriores a la visita de selección. -Tratamiento oral 5-ASA en curso superior o igual a 1.6g/día. -Presentar signos objetivos de actividad de colitis ulcerosa moderada a severa definida por una puntuación Mayo de entre 6 y 12. - Proctitis, de lado izquierdo o CU extensiva - Capacidad de seguir los requerimientos del estudio. - Capacidad de otorgar consentimiento informado de acuerdo con la ICH/ GCP, y la regulaciones nacionales |
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E.4 | Principal exclusion criteria |
- Have received any kind of treatment approved for UC (thiopurine, biologics, tofacitinib) apart from 5-ASA compounds, sulphasalazine or EcN during their UC history or currently receiving local or systemic steroids (past steroids treatments are accepted) - Have concomitant history of segmental colitis associated to diverticula - Have active infections during the screening phase (patients can be rescreened after the infection is resolved - Have a diagnosis of Crohn’s disease - Have any contra-indication to study drugs or procedures - Are pregnant or in active breastfeeding at the time of inclusion. - Have planned intestinal surgery at time of randomization - Any contra-indication to anti-TNF therapy |
-Haber recibido algún tipo de tratamiento approbado para la colitis ulcerosa( tiopurina, biológico, tofacitinib) aparte de componetes 5_ASA, sulfasalacina o EcN durante su historia de colitis ulcerosa o estar recibiendo actualmente esteriodes locales o sistémicos (los tratamientos con esteriodes anteriores están aceptados). -Presentar historia de colitis segmental asociada a los divertículos concomitantemente. -Presentar infeccioens activas durante la fase de selección (los pacientes pueden ser re-seleccionados posteriormente a la resolución de la infección). -Presentar un diagnóstico de enfermedad de Crohn. -Presentar alguna contraindicación al farmaco en estudio o a los procedimientos del estudio. -Embarazo o lactancia en el periodo de selección. -Encontrase en espera de cirugía intestinal en el momento de la randomización. -Alguna contra-indicación frente a la terapia anti TNF. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Histological improvement (defined as a Nancy index ≤ 1) at week 52, without colectomy and without UC-related hospitalization. |
Mejoría histológica (definida como un índice de Nancy menor o igual a 1) ala semana 52, sin colectomía y sin hospitalización relacionada con la colitis ulcerosa. |
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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) |
- Histological remission (Nancy Index =0) at week 16 - Histological remission (Nancy Index =0) at week 52 - Histological healing (defined as a Nancy score ≤ 1) at week 16 - Clinical remission (PRO2 remission + endoscopic remission) at week 52 - Clinical remission (PRO2+endoscopic remission) at week 16 - Symptomatic remission (PRO2 remission) at week 16 - Symptomatic remission (PRO2 remission) at week 52 - Endoscopic improvement at week 16 Endoscopic improvement at week 52 - Endoscopic remission at week 16 - Endoscopic remission at week 52 - Mucosal healing (endoscopic and histologic improvement) at week 16 - Mucosal healing (endoscopic and histologic improvement) at week 52 - Changes in fecal calprotectin levels from baseline - Need for corticosteroids at weeks 16 and 52 - To evaluate and compare the safety of the two strategies in terms of adverse events, serious adverse events, and adverse events leading to discontinuation - quality of life (measured by the S-IBDQ and SF-36) at weeks 16 and 52 - Rates of colectomies at weeks 16, 52, and 104 (or end of study) - UC-related hospitalizations at weeks 16, 52, and 104 (or end of study) |
-Remisión histológica (Índice de Nancy=0) a la semana 16. -Remisión histológica (Indice de Nancy=0) a la semana 52. -Remisión histológica (definida como puntuación de Nancy menor o igual a 1) a la semana 16 -Remisión clínica (remisión PRO2 +remisión endoscópica) a la semana 52. -Remisión clínica (remisión PRO2+remisión endoscópica) a la semana 16. -Remisión sintomática (remisión PRO2) a la semana 16. -Remisión sintomática (remisión PRO2) a la semana 52. - Mejoría endoscópica a la semana 16 - Mejoría endoscópica a la semana 52 -Remisión endoscópica ala semana 16 -Remisión endoscópica a la semana 52 -Curación mucosa (mejoría endoscópica e histológica) a la semana 16 -Curación mucosa (mejoría endoscópica e histológica) a la semana 52 -Cambios en los niveles de calprotectina fecal desde la visita basal -Necesidad de corticosteroides a las semanas 16 y 52. -Comparación y evaluación de la seguridad de las dos estrategias en términos de acontecimientos adversos, acontecimientos adversos graves, y acontecimientos adversos que conduzcan a la retirada del estudio. -Calidad de vida (medica con los cuestionarios S-IBDQ y SF-36) a las semanas 16 y 52. -Rangos de colostomías a las semanas 16, 52 y 104 (final del estudio). -Hospitalización relacionada con la colitis ulcerosa a las semanas 16, 52 y 104 (final dele estudio). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weekd 16 and/or week 52, depending on the endpoints |
Semanas 16 y /o semana 52 dependiendo de los hitos. |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Two different therapeutic approaches are compared: step-up and top-down |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 |
Austria |
Belgium |
France |
Germany |
Italy |
Portugal |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |