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 |
Colitis Ulcerosa |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009900 |
E.1.2 | Term | Colitis ulcerative |
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 |
Evaluate the efficacy and safety of ABT-494 in induction and maintenance of remission in subjects with moderately to severely active ulcerative colitis |
Evaluar la eficacia y seguridad de ABT-494 para la inducción y el mantenimiento de la remisión en pacientes con colitis ulcerosa moderada/ severa. |
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E.2.2 | Secondary objectives of the trial |
Evaluate the pharmacokinetics of ABT-494 in subjects with moderately to severely active ulcerative colitis; Characterize the dose-response, efficacy and safety of ABT-494 compared to placebo in inducing clinical remission in subjects with moderately to severely active ulcerative colitis; Evaluate the efficacy and safety of ABT-494 compared to placebo in achieving clinical remission in subjects with moderately to severely active ulcerative colitis who had a response following induction with ABT-494. |
Evaluar la farmacocinética de ABT-494 en pacientes con colitis ulcerosa activa severa /moderada; determinar la dosis-respuesta, eficacia y seguridad de ABT-494 comparada con placebo en inducir la remisión clínica en pacientes con colitis ulcerosa activa severa/moderada; evaluar la eficacia de ABT-494 comparado con placebo en conseguir una remisión clínica en pacientes con colitis ulcerosa moderada /severa que han tenido respuesta tras la inducción de ABT-494. |
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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 |
This is a Phase IIb/III, multicenter, randomized, double-blind, placebo-controlled study consisting of the following Substudies: Substudy 1 is a Phase IIb dose-ranging study designed to evaluate the efficacy, safety, and pharmacokinetics of oral administration of multiple different doses of ABT-494 compared to placebo as induction therapy for 8 weeks in subjects with moderately to severely active ulcerative colitis (UC). Substudy 2 is a Phase III dose-confirming study designed to evaluate the efficacy and safety of oral administration of one dose of ABT-494, based on the dose identified from Substudy 1, compared to placebo as induction therapy for 8 weeks in subjects with moderately to severely active UC. Substudy 3 is a Phase III study designed to evaluate the efficacy and safety of oral administration of two doses of ABT-494 compared to placebo as maintenance therapy for 44 weeks in subjects with moderately to severely active ulcerative colitis who achieved response following induction with ABT-494 in Substudy 1 or 2. |
Este es un estudio de fase IIb / III, multicéntrico, aleatorizado, doble ciego, estudio controlado con placebo que consta de los siguientes Subestudios: Subestudio 1 es un estudio de búsqueda de dosis de Fase IIb diseñado para evaluar la eficacia, seguridad y farmacocinética de la administración oral de dosis múltiples diferentes de ABT-494 en comparación con placebo como tratamiento de inducción durante 8 semanas en pacientes con colitis ulcerosa activa moderada a grave (CU). Subestudio 2 es un estudio de confirmación de dosis de Fase III diseñado para evaluar la eficacia y seguridad de la administración oral de una dosis de ABT-494, basado en la dosis identificada a partir de Subestudio 1, en comparación con placebo como terapia de inducción durante 8 semanas en sujetos con CU activa moderada a grave. Subestudio 3 es un estudio de Fase III diseñado para evaluar la eficacia y seguridad de la administración oral de dos dosis de ABT-494 en comparación con placebo como tratamiento de mantenimiento durante 44 semanas en pacientes con colitis ulcerosa activa moderada a grave que alcanzó respuesta después de la inducción con ABT-494 en Subestudio 1 o 2. |
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E.3 | Principal inclusion criteria |
1. Male or female between 18 and 75 years of age at Baseline. 2. Diagnosis of ulcerative colitis for 90 days or greater prior to Baseline, confirmed by colonoscopy 3. Moderately to severely active ulcerative colitis 4. Demonstrated an inadequate response to, loss of response to, or intolerance to immunosuppressants, corticosteroids or biologic therapies 5. Negative pregnancy test for female subjects of childbearing potential |
1. Hombre o mujer entre 18 y 75 años en el momento basal 2. Diagnosticados con colitis ulcerosa desde hace 90 días o antes del momento basal, confirmado con colonoscopia. 3. Colitis ulcerosa activa severa/ moderada 4. Respuesta inadecuada demostrada, pérdida de respuesta, o intolerancia a los inmunodepresivos, corticosteroides o terapias biológicas. 5. Resultado negativo en test de embarazo para mujeres potencialmente fértiles. |
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E.4 | Principal exclusion criteria |
1. Subject with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC). 2. Current diagnosis of fulminant colitis and/or toxic megacolon. 3. Subject with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy. 4. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. 5. Subject with previous exposure to JAK inhibitor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Substudy 1 and 2: The proportion of subjects who achieve clinical remission per Adapted Mayo score at Week 8. Substudy 3: The proportion of subjects who achieve clinical remission per Adapted Mayo score at Week 44. |
Subestudio 1 y 2: la proporción de pacientes que han conseguido remisión clínica en la semana 8 según el índice adaptado de Mayo. Subestudio 3: la proporción de pacientes que han conseguido remisión clínica en la semana 44 según el índice adaptado de Mayo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Substudy 1 and 2: Week 8. Substudy 3: Week 44. |
Subestudio 1 y 2: semana 8 Subestudio 3: semana 44 |
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E.5.2 | Secondary end point(s) |
Substudy 1 and 2: 1. Proportion of subjects with endoscopic subscore ≤ 1 at Week 8 2. Proportion of subjects achieving clinical remission per Full Mayo score at Week 8 3. Proportion of subjects achieving clinical response per Adapted Mayo score at Week 8
Substudy 3: 1. Proportion of subjects with endoscopic subscore ≤1 at Week 44 2. Proportion of subjects achieving clinical remission per Full Mayo score at Week 44 3. Proportion of subjects who discontinued corticosteroid use for at least 90 days and achieved clinical remission per Adapted Mayo score at Week 44 |
Subestudio 1 y 2 1.Proporción de sujetos con una sub-puntuación ≤ 1 en la semana 8 2.Proporción de sujetos que consiguieron una remisión clínica por el índice de Mayo completo en la semana 8 3.Proporción de sujetos que consiguieron una respuesta clínica por el índice de Mayo adaptado en la semana 8
Subestudio 3 1. Proporción de sujetos con una sub-puntuación endoscópica ≤ 1 en la semana 44 2. Proporción de sujetos que han conseguido una remisión Clinica por el índice de Mayo completo en la semana 44 3. Proporción de pacientes que discontinuaron el uso de corticosteroides en almenos 90 días y consiguieron una remisión clínica por el índice de Mayo adaptado en la semana 44. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Substudy 1 and 2: Week 8. Substudy 3: Week 44. |
Subestudio 1 y 2: semana 8 Subestudio 3: semana 44 |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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 | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
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 |
Belarus |
Bosnia and Herzegovina |
Brazil |
Canada |
Chile |
China |
Colombia |
Egypt |
European Union |
Israel |
Japan |
Kazakhstan |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Norway |
Puerto Rico |
Russian Federation |
Saudi Arabia |
Serbia |
Singapore |
South Africa |
Switzerland |
Taiwan |
Ukraine |
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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 5 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 5 |