E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to severely active Crohn's disease |
Enfermendad de Crohn de actividad moderada a severa |
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E.1.1.1 | Medical condition in easily understood language |
Crohn's disease |
Enfermedad de Crohn |
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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 | 14.0 |
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 |
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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 objectives are: - To evaluate clinical remission for the 2 SC maintenance regimens of ustekinumab in subjects with moderately to severely active Crohn?s disease induced into clinical response with ustekinumab in the induction studies, CNTO1275CRD3001 and CNTO1275CRD3002. - To evaluate the safety of 2 SC maintenance regimens of ustekinumab in subjects with moderately to severely active Crohn?s disease. |
Los objetivos principales son: ? Evaluar la remisión clínica de las dos pautas SC de mantenimiento de ustekinumab en sujetos con enfermedad de Crohn de actividad moderada a severa que presentan respuesta clínica inducida con ustekinumab en los estudios de inducción, CNTO1275CRD3001 y CNTO1275CRD3002. ? Evaluar la seguridad de dos pautas SC de mantenimiento de ustekinumab en sujetos con enfermedad de Crohn de actividad moderada a severa. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To evaluate the efficacy of ustekinumab in maintaining clinical response in subjects induced into clinical response. - To evaluate the efficacy of ustekinumab in maintaining clinical remission in subjects induced into clinical remission. - To evaluate the efficacy of ustekinumab in achieving corticosteroid free remission. - To evaluate the pharmacokinetics, immunogenicity, and pharmacodynamics of Ustekinumab therapy, including changes in C-reactive protein (CRP), fecal calprotectin, fecal lactoferrin, and other pharmacodynamic biomarkers. - To evaluate the effect of ustekinumab on health related quality of life. |
Los objetivos secundarios son: ? Evaluar la eficacia de ustekinumab para mantener la respuesta clínica en sujetos a los que se les ha inducido dicha respuesta clínica. ? Evaluar la eficacia de ustekinumab para mantener la remisión clínica en sujetos a los que se les ha inducido dicha remisión clínica. ? Evaluar la eficacia de ustekinumab para alcanzar la remisión sin que el sujeto precise corticosteroides. ? Evaluar la farmacocinética, la inmunogenia y la farmacodinamia del tratamiento con ustekinumab, como las variaciones de la proteína C reactiva (CRP), la calprotectina fecal, la lactoferrina fecal y otros biomarcadores farmacodinámicos. ? Evaluar el efecto de ustekinumab en la calidad de vida relacionada con la salud. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have received study agent at Week 0 in study CNTO1275CRD3001 or CNTO1275CRD3002 and completed the Week 8 CDAI score evaluation.
2. Be able to complete the Week 0 visit in study CNTO1275CRD3003 within 4 days of the Week 8 visit in study CNTO1275CRD3001 or CNTO1275CRD3002. At the discretion of the investigator, the window may be extended to 8 days to allow appropriate treatment and/or recovery of nonserious infections (eg, acute upper respiratory tract infection, simple urinary tract infection).
3. Be able and willing to adhere to the study visit schedule and comply with other protocol requirements
4. Be capable of providing informed consent, which must be obtained prior to any study-related procedures |
1. Haber recibido el fármaco del estudio en la semana 0 de los estudios CNTO1275CRD3001 o CNTO1275CRD3002 y haber completado la evaluación del CDAI en la semana 8. 2. Ser capaz de completar la visita de la semana 0 del estudio CNTO1275CRD3003 en un plazo de 4 días desde la visita 8 de los estudios CNTO1275CRD3001 o CNTO1275CRD3002. A criterio del investigador, el margen se podrá ampliar hasta los 8 días para posibilitar el tratamiento adecuado y/o la resolución de infecciones no graves (por ejemplo, infección respiratoria superior aguda, infección urinaria simple). 3. Ser capaz y estar dispuesto a cumplir el calendario de visitas del estudio y satisfacer otros requisitos del protocolo. 4. Ser capaz de otorgar su consentimiento informado, que debe obtenerse antes de todo procedimiento relacionado con el estudio. |
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E.4 | Principal exclusion criteria |
1. Had any of the following changes to their concomitant medications due to Crohn?s disease (ie, lack of efficacy) since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002 a. Increase in physician-prescribed daily dose of oral corticosteroids of more than 5 mg or more of prednisone (or equivalent increase in prednisone-equivalent dose of other corticosteroids), b. Initiation of oral budesonide or increase in daily dose c. Initiation of parenteral, and oral corticosteroids for Crohn?s disease, except for dose equivalent substitutions among oral corticosteroids d. Initiation or increased physician-prescribed daily dose of methotrexate (MTX), 6-MP, or azathioprine (AZA), except for dose equivalent substitutions
2. Initiated a protocol prohibited medication since Week 0 of studies CNTO1275CRD3001 and CNTO1275CRD3002: a. Immunomodulatory agents other than 6-MP/AZA or MTX (including but not limited to 6-TG, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil) b. Immunomodulatory biologic agents (including but not limited to TNF-antagonists, natalizumab, abatacept, commercial ustekinumab) c. Experimental Crohn?s disease medications (including but not limited to thalidomide, briakinumab, vedolizumab, traficet, AMG-827)
3. Underwent a Crohn?s disease related surgery since Week 0 of induction study CNTO1275CRD3001 or CNTO1275CRD3002. Seton placement and recent cutaneous and perianal abscesses which have been drained and adequately treated at least 3 weeks prior to receiving baseline study agent are not exclusionary provided that there is no anticipated need for any further surgery
4. Subjects from countries with high multidrug-resistant TB burden (eg, South Africa, Bulgaria, and the Russian Federation) diagnosed with latent TB during induction study CNTO1275CRD3001 or CNTO1275CRD3002, or any subject who has discontinued or is noncompliant with appropriate therapy for the treatment of latent TB.
5. Are diagnosed with any medical condition (or signs or symptoms thereof) which would have precluded enrollment in induction studies CNTO1275CRD3001 and CNTO1275CRD3002. This includes any lymphoproliferative disorder or malignancy (other than basal cell carcinoma of the skin), opportunistic or other significant infection, or other severe, progressive, or uncontrolled medical (eg renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, or autoimmune) or psychiatric disease, including recent significant instability in a previous condition.
6. Have signs and symptoms of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis.
7. Is a woman who is pregnant, or breast-feeding, or planning to become pregnant or is a man who plans to father a child while enrolled in this study or within 20 weeks after the last dose of study agent. |
1. Ha efectuado alguno de los siguientes cambios en sus medicamentos concomitantes debido a la enfermedad de Crohn (es decir, por falta de eficacia) desde la semana 0 de los estudios CNTO1275CRD3001 o CNTO1275CRD3002: a. Aumento de la dosis diaria de corticosteroides orales, prescrita por un médico, de más de 5 mg de prednisona (o aumento equivalente de la dosis de otros corticosteroides) b. Inicio de budesónida oral o aumento de su dosis diaria c. Inicio de corticosteroides parenterales y orales para la enfermedad de Crohn, excepto las sustituciones entre corticosteroides orales en dosis equivalentes d. Inicio o aumento de la dosis diaria de metotrexato (MTX), 6-MP o azatioprina (AZA), prescrita por un médico, excepto las sustituciones en dosis equivalentes 2. Ha iniciado un medicamento prohibido por el protocolo desde la semana 0 de los estudios CNTO1275CRD3001 o CNTO1275CRD3002: a. Inmunomoduladores distintos de 6-MP/AZA o MTX (como, entre otros, 6-TG, ciclosporina, tacrolimus, sirolimus, micofenolato de mofetilo) b. Productos biológicos inmunomoduladores (como, entre otros, antagonistas del TNF, natalizumab, abatacept, ustekinumab comercial) c. Medicamentos experimentales para la enfermedad de Crohn (como, entre otros, talidomida, briakinumab, vedolizumab, traficet, AMG-827) 3. Ha sido sometido a una intervención quirúrgica relacionada con la enfermedad de Crohn desde la semana 0 de los estudios de inducción CNTO1275CRD3001 o CNTO1275CRD3002. La colocación de un setón y el drenaje de abscesos cutáneos y perianales recientes, tratados adecuadamente, por lo menos 3 semanas antes de la administración basal del fármaco del estudio no son motivo de exclusión, siempre que no esté previsto que se vayan a necesitar intervenciones quirúrgicas ulteriores. 4. Es de un país en el que sea frecuente la TB resistente a múltiples fármacos (p. ej., Sudáfrica, Bulgaria y la Federación de Rusia) y ha sido diagnosticado de TB latente durante los estudios de inducción CNTO1275CRD3001 o CNTO1275CRD3002, o ha suspendido o incumple el tratamiento adecuado de la TB latente. 5. Se le ha diagnosticado cualquier proceso médico (o presenta signos o síntomas de padecerlo) que habría impedido su reclutamiento en los estudios de inducción CNTO1275CRD3001 y CNTO1275CRD3002. Se incluyen los trastornos linfoproliferativos, neoplasias malignas (distintas del carcinoma cutáneo basocelular), infecciones oportunistas o de otro tipo importantes, u otra enfermedad médica (por ejemplo, renal, hepática, hematológica, endocrina, pulmonar, cardíaca, neurológica o autoinmunitaria) o psiquiátrica que sea grave, progresiva o mal controlada, lo que incluye la inestabilidad reciente importante de un proceso previo. 6. Presenta signos y síntomas de infección granulomatosa latente o activa, como TB, histoplasmosis o coccidioidomicosis. 7. Es una mujer embarazada o en período de lactancia o que tiene previsto quedarse embarazada, o es un varón que pretende engendrar un hijo durante su participación en este estudio o hasta 20 semanas después de la última dosis del fármaco del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint analysis and the major secondary endpoint analyses will include only subjects in clinical response to ustekinumab at Week 8 from 1 of the induction studies (CNTO1275CRD3001 or CNTO1275CRD3002) who were randomized at Week 0 of this study into 1 of the maintenance regimens.
The primary endpoint is clinical remission at Week 44, where clinical remission is defined as a CDAI score of < 150 points. |
En el análisis del criterio de valoración principal y en los análisis de los criterios de valoración secundarios mayores solamente se incluirá a sujetos que hayan presentado respuesta clínica austekinumab en la semana 8 de uno de los estudios de inducción, CNTO1275CRD3001 o CNTO1275CRD3002, y que hayan sido aleatorizados en la semana 0 a una de las pautas de mantenimiento. El criterio de valoración principal es la remisión clínica en la semana 44, definida como un CDAI de < 150 puntos. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At week 44 |
En la semana 44 |
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E.5.2 | Secondary end point(s) |
The major secondary endpoints in order of importance are: 1. Clinical response at Week 44. 2. Clinical remission at Week 44 among subjects in clinical remission to ustekinumab at Week 0. 3. Corticosteroid-free remission at Week 44. 4. Clinical remission at Week 44 in the subset of subjects who were refractory or intolerant to TNF-antagonist therapy (ie, subjects from induction study CNTO1275CRD3001). |
Los criterios de valoración secundarios mayores, por orden de importancia, son: 1. Respuesta clínica en la semana 44. 2. Remisión clínica en la semana 44 en los sujetos en remisión clínica tras ustekinumab en la semana 0. 3. Remisión sin que el sujeto precise corticosteroides en la semana 44. 4. Remisión clínica en la semana 44 en la subpoblación de sujetos con resistencia o intolerancia al tratamiento con un antagonista del TNF (es decir, sujetos del estudio de inducción CNTO1275CRD3001). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At week 44 |
En la 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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 113 |
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 |
European Union |
Australia |
Brazil |
Canada |
Croatia |
Iceland |
Israel |
Japan |
Korea, Republic of |
New Zealand |
Russian Federation |
Serbia |
South Africa |
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
|
The end of the study is defined as the completion of the final safety follow-up visit for the last subject after his or her last SC administration of study agent in the study extension phase of the study. |
El final del estudio corresponde a la finalización de la última visita de seguimiento de la seguridad del último sujeto después de que reciba la última administración SC del fármaco del estudio en la fase de extensión del estudio. |
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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 | 7 |
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 | 7 |
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 |