E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Crohn's Disease |
Enfermedad de Crohn de moderada a intensamente activa |
|
E.1.1.1 | Medical condition in easily understood language |
Inflammatory bowel disease (IBD) |
Enfermedad inflamatoria intestinal (EII) |
|
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 | 20.0 |
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 |
|
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 |
Phase 2 and Phase 3 Studies: - To evaluate the clinical efficacy of guselkumab in participants with Crohn’s disease - To evaluate the safety of guselkumab |
Estudios Fase 2 y Fase 3: -Evaluar la eficacia clínica de guselkumab en participantes con enfermedad de Crohn -Evaluar la seguridad de guselkumab |
|
E.2.2 | Secondary objectives of the trial |
Phase 2: - To evaluate the dose-response of guselkumab to inform dose selection for the Phase 3 portion of this protocol - To evaluate the efficacy of guselkumab on endoscopic improvement - To evaluate the pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of guselkumab therapy
Phase 3: - To evaluate the efficacy of guselkumab on endoscopic improvement - To evaluate the impact of guselkumab on HRQOL - To evaluate the PK, immunogenicity, and PD of guselkumab therapy |
Fase 2: -Evaluar la dosis-respuesta de guselkumab con el fin de sentar las bases de la selección de la dosis para la parte en fase III de este protocol -Evaluar la eficacia de guselkumab sobre la mejoría endoscópica -Evaluar la farmacocinética (FC), la inmunogenicidad y la farmacodinámica (FD) del tratamiento con guselkumab.
Fase 3: -Evaluar la eficacia de guselkumab sobre la mejoría endoscópica -Evaluar el impacto de guselkumab sobre la CVRS -Evaluar la FC, la inmunogenicidad y la FD del tratamiento con guselkumab. |
|
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 |
Phase 2 and Phase 3 study: - Optional Week 4 ileocolonoscopy sub-study: Exploratory analyses of intestinal mucosal tissue obtained by biopsy at Week 4 will be performed to delineate the mechanisms of action of guselkumab and ustekinumab.
- Optional pharmacogenomic sub-study: Collect DNA to allow for the identification of genetic factors that may influence the PK, PD, efficacy, safety, or tolerability of guselkumab and to identify genetic factors associated with Crohn’s disease or the response to guselkumab or ustekinumab treatment. |
Estudio de Fase 2 y Fase 3: -Subestudio opcional de ileocolonoscopia en la semana 4: análisis exploratorios del tejido de la mucosa intestinal obtenido mediante biopsia en la semana 4 para perfilar los mecanismos de acción de guselkumab y de ustekinumab
-Subestudio opcional de farmacogenómica: recoger ADN para permitir la identificación de los factores genéticos que pueden influir en la FC, la FD, la eficacia, la seguridad o la tolerabilidad de guselkumab, así como para conocer los factores genéticos asociados a la enfermedad de Crohn o a la respuesta al tratamiento con guselkumab o ustekinumab |
|
E.3 | Principal inclusion criteria |
- Have Crohn’s disease (CD) or fistulizing Crohn’s disease of at least 3 months duration (defined as a minimum of 12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy - Have moderate to severe CD as assessed by CDAI, stool frequency (SF), and abdominal pain (AP) scores, and Simple Endoscopic Score for Crohn's Disease (SES-CD) - Have screening laboratory test results within the protocol specified parameters - A female participant of childbearing potential must have a negative urine pregnancy test result at screening and baseline - Demonstrated intolerance or inadequate response to conventional or to biologic therapy for CD |
-Tener enfermedad de Crohn o enfermedad de Crohn fistulizante de al menos 3 meses de duración (definida como un mínimo de 12 semanas), con colitis, ileítis o ileocolitis, confirmada en cualquier momento del pasado mediante radiografía, histología o endoscopia. -Tener enfermedad de Crohn de moderada a intensamente activa evaluada mediante puntuación CDAI, Frecuencia de deposiciones (Fd) y dolor abdominal (DA) y SES-CD - Tener resultados en las pruebas analíticas de la selección dentro de los parámetros especificados en el protocolo - Las mujeres participantes con capacidad de concebir deben dar un resultado negativo en la prueba de embarazo en orina de la selección y el inicio. -Intolerancia demostrada o respuesta inadecuada al tratamiendo convencional o biológico de la enfermedad de Crohn |
|
E.4 | Principal exclusion criteria |
- Current diagnosis of ulcerative colitis or indeterminate colitis - Has complications of Crohn’s disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation - Unstable doses of concomitant Crohn's disease therapy - Receipt of Crohn’s disease approved biologic agents, investigational agents, or procedures outside of permitted timeframe as specified in the protocol - Prior exposure to p40 inhibitors or p19 inhibitors - Any medical contraindications preventing study participation |
-Diagnostico actual de colitis ulcerosa o colitis indeterminada - Tener complicaciones de la enfermedad de Crohn, como estrechamientos o estenosis sintomáticos, síndrome del intestino corto o cualquier otra manifestación -Dosis inestables de medicación concomitante para la enfermedad de Crohn - Recibo de agentes biológicos aprobados para la enfermedad de Crohn, fármaco experimental o procedimientos fuera del período de tiempo permitido según lo especificado en el protocolo - Exposición previa a inhibidores p40 e inhibidores p19 - Cualquier contraindicación médica que impida la participación en el estudio |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase 2: Change from Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12 Phase 3: Clinical remission at week 12 (defined as CDAI score <150) |
Fase 2: Cambio desde el inicio en la puntuación del CDAI en la semana 12 Fase 3: Remisión clínica en la semana 12 (definida como una puntuación CDAI <150) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Phase 2: - Clinical remission at Week 12 (defined as CDAI score <150) - Clinical response at Week 12 (defined as ≥100-point reduction from baseline in CDAI score or CDAI score <150) - PRO-2 remission at Week 12 (defined based on average daily stool frequency (SF) and average daily abdominal pain (AP) score) - Clinical-biomarker response at Week 12 (clinical response based on CDAI score and reduction from baseline in CRP or fecal calprotectin) - Endoscopic response at Week 12 (measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD is based on the evaluation of 4 endoscopic components across 5 ileocolonic segments, with a total score ranging from 0 to 56.)
Phase 3: - Clinical remission at Week 48 (defined as CDAI < 150) - Durable clinical remission at Week 48 (defined as CDAI<150 for the majority of visits between Week 12 and Week 48.) - Corticosteroid-free clinical remission at Week 48 (defined as CDAI score <150 at Week 48 and not receiving corticosteroids at Week 48) - PRO-2 remission at Week 12 and 48 (based on average daily stool frequency (SF) and average daily abdominal pain (AP) score) - Endoscopic response at Week 12 and 48 (measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD)) • Fatigue response at Week 12 (based on the PROMIS Fatigue Short Form 7a) |
Fase 2: -Remisión clínica en la semana 12 (definida como una puntuación CDAI <150). -Respuesta clínica en la semana 12 (definida como una reducción ≥100 puntos con respecto al inicio en la puntuación CDAI o puntuación CDAI <150). - Remisión en RNP-2 en la semana 12 (definida como una puntuación diaria media de la frecuencia de deposiciones (Fd) y una puntuación diaria media en dolor abdonimal (DA) - Respuesta según los biomarcadores clínicos en la semana 12 (respuesta clínica basada en la puntuación del CDAI y reducción con respecto al inicio en la PCR o en la calprotectina fecal). - Respuesta endoscópica en la semana 12 (medida segun Puntuación endoscópica simple para la enfermedad de Crohn (SES-CD.) La SES-CD esta basada en la evaluación de 4 componentes endoscópicos a lo largo de 5 segmentos ileocolónicos, con una puntuación total q oscila entre 0 y 56) Fase 3: - Remisión clínica en la semana 48 (definida como CDAI <150) - Remisión clínica duradera en la semana 48 (definida como CDAI <150 en la mayoría de las visitas entre la semana 12 y la semana 48) -Remisión clínica sin corticoesteroides en la semana 48 (definida como puntuación CDAI <150 en la semana 48 y no recibir corticoesteroides en la semana 48) -Remisión en RNP-2 en la semana 12 y 48 (basada en puntuación diaria media en Fd y una puntuación diaria media en DA) -Respuesta endoscópica en la semana 12 y 48 (medida según la puntuación SES-CD) -Respuesta de la fatiga en la semana 12 (según el formulario breve de fatiga PROMIS 7a) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 12 or 48 as listed above |
Semana 12 o 48 como se indica arriba |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | 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 | 9 |
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 | 121 |
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 |
Austria |
Belarus |
Belgium |
Bosnia and Herzegovina |
Brazil |
Canada |
China |
Colombia |
Croatia |
Czech Republic |
France |
Georgia |
Germany |
Greece |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lebanon |
Lithuania |
Macedonia, the former Yugoslav Republic of |
Netherlands |
New Zealand |
Poland |
Portugal |
Russian Federation |
Saudi Arabia |
Serbia |
Slovakia |
South Africa |
Spain |
Taiwan |
Tunisia |
Turkey |
Ukraine |
United Kingdom |
United States |
Jordan |
|
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
|
LVLS |
Última visita ultimo paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 |