E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Crohn's disease |
Enfermedad de Crohn |
|
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] - Digestive System Diseases [C06] |
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 objective of this study is to monitor the safety and tolerability of PF 00547659 during long term treatment. |
El objetivo principal de este estudio consiste en vigilar la seguridad y la tolerabilidad de PF 00547659 durante el tratamiento a largo plazo. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess pharmacokinetics and immunogenicity of PF 00547659. |
El objetivo secundario es evaluar la farmacocinética y la inmunogenicidad de PF 00547659. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into this study: 1. Subjects previously enrolled in study A7281006 who have completed the blinded 84 day (12 week) induction period or in study A7281008 and have demonstrated a clinical response as defined by that protocol. 2. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 3. All women of childbearing potential (WOCBP) as determined during studies A7281006 and A7281008 (data must be available as source documents for this study) must have a negative urine pregnancy test result at the Baseline visit and throughout the duration of this study (defined as the time of the signing of the ICD through the end of this study). ? Women of non childbearing potential (WONCBP) as determined during the previous study do not require urine pregnancy tests in this study. 4. WOCBP who have sexual intercourse with a non surgically sterilized male partner must agree and commit to the use one of the following highly effective methods of contraception for the duration of the study (defined as the time of the signing of the ICD through the conclusion of subject participation or for approximately 6 months from the last dose of investigational product for any subject who discontinues early from the study). Contraceptive methods considered acceptable for use in this study include:Established use [?2 months prior to the screening visit] of oral, injected or implanted hormonal methods of contraception. Subjects who have used such methods for less than 2 months at the screening visit are required to use one of the methods decribed under b) or c) until the establishment of hormonal contraception methods. a. Double barrier contraception: use of occlusive diaphragm (cap or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. In countries that spermicidal condoms are not allowed ordinary condoms could be used in combination with spermicidal creams. Appropriate measures are to be determined by the investigator together with the subject, in accordance with the standard of care in the country where treatment is administered. A female condom and a male condom should not be used together as friction between the two can result in either, or both product(s) failing. Appropriate measures are to be determined by the investigator together with the subject, in accordance with the standard of care in the country where treatment is administered. b. An intrauterine device or system.
5. All men (unless surgically sterile, as defined below) who have sexual intercourse with a WOCBP must agree and commit to use a highly effective method of contraception as described under WOCBP for the duration of this study (defined as the time of the signing of the ICD through the conclusion of subject participation or for 6 months from the last dose of investigational product for any subject who terminates early from this study). Highly effective methods of contraception include properly used spermicidal condom. 6. To be considered surgically sterilized, a male partner must have had a vasectomy at least 24 weeks or bi lateral orchiectomy >30 days before the Baseline visit of this study. 7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
Los sujetos deberán cumplir todos los siguientes criterios de inclusión para poder participar en este estudio: 1. Sujetos incluidos previamente en el estudio A7281006 que hayan completado el período de inducción ciego de 84 días (12 semanas) o en el estudio A7281008 y que hayan mostrado una respuesta clínica según lo definido por el protocolo de dicho estudio. 2. Evidencia de un documento de consentimiento informado, firmado y fechado personalmente, que indique que se ha informado al sujeto (o a su representante legal) de todos los aspectos pertinentes del estudio. 3. Todas las mujeres potencialmente fértiles (MPF), según se haya determinado en los estudios A7281006 y A7281008 (los datos deberán estar disponibles como documentos originales para este estudio) deben tener una prueba de embarazo en orina negativa en la visita basal y durante este estudio (definido como el tiempo transcurrido desde la firma del DCI hasta el final del estudio). ? Las mujeres no potencialmente fértiles (MNPF), según se haya determinado durante el estudio previo, no precisan pruebas de embarazo en orina en este estudio. 4. Las MPF que mantengan relaciones sexuales con un hombre no esterilizado quirúrgicamente deberán acceder y comprometerse a utilizar uno de los siguientes métodos anticonceptivos altamente efectivos durante el estudio (definido como el tiempo desde la firma del DCI hasta el final de la participación del sujeto, o durante aproximadamente 6 meses después de la última dosis del producto en investigación en aquellos sujetos que abandonen el estudio de forma prematura). Los métodos anticonceptivos que se consideran aceptables para este estudio incluyen: Uso establecido [? 2 meses antes de la visita de selección] de métodos anticonceptivos hormonales orales, inyectables o implantables. Los sujetos que en la visita de selección lleven menos de 2 meses utilizando tales métodos deberán utilizar uno de los métodos descritos en b) o c) hasta el establecimiento del método anticonceptivo hormonal. a. Método de doble barrera: uso de diafragma oclusivo (capuchón cervical/vaginal) con espuma/gel/película/crema/supositorio espermicida. En aquellos países donde no se permita el uso de preservativos con espermicida incorporado se podrán utilizar preservativos normales en combinación con cremas espermicidas. El investigador determinará, junto con el sujeto, las medidas apropiadas de acuerdo con la norma asistencial en el país donde se administre el tratamiento. No podrán utilizarse a la vez un preservativo femenino y otro masculino porque la fricción entre ambos puede hacer que falle uno de ellos o los dos. El investigador determinará, junto con el sujeto, las medidas apropiadas de acuerdo con la norma asistencial en el país donde se administre el tratamiento. b. Dispositivo o sistema intrauterino. 5. Todos los varones (salvo que hayan sido esterilizados por métodos quirúrgicos, como se define más adelante) que mantengan relaciones sexuales con una MPF deberán acceder y comprometerse a utilizar un método anticonceptivo altamente efectivo, tal como se define en el apartado sobre MPF, durante el estudio (definido como el tiempo desde la firma del DCI hasta el final de la participación del sujeto, o durante 6 meses después de la última dosis del producto en investigación en aquellos sujetos que abandonen el estudio de forma prematura). Entre los métodos anticonceptivos de alta eficacia figura el preservativo con espermicida utilizado correctamente. 6. Para ser considerada esterilizada quirúrgicamente, su pareja masculina deberá haberse sometido a una vasectomía al menos 24 semanas antes, o a una orquiectomía bilateral más de 30 días antes, de la visita basal de este estudio. 7. Sujetos dispuestos a cumplir las visitas programadas, el plan de tratamiento, los análisis clínicos y otros procedimientos del estudio, y capaces de hacerlo. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in this study: 1. Subjects that have completed Day 84 (Week 12) of study A7281006 or completed study A7281008 but have experienced serious event(s) related to the investigational product, an unstable medical condition, or any other reason, in the opinion of the investigator, would preclude entry or participation in this study. 2. Subjects who are taking any dose of AZA, 6 MP or MTX. 3. Pregnant or breastfeeding women. 4. Entero-vesicular fistulae are prohibited. Other fistulae are allowed (eg enterocutaneous fistulae). Documentation of active and inactive fistulae are required. 5. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate entry into this study. 6. Received any prohibited treatment during studies A7281006 and A7281008 that, in the opinion of the investigator, compromised the safety or efficacy of this study. 7. Planned live (attenuated) vaccination during the course of this study. 8. Planned major elective medical or surgical procedure during the course of this study. 9. Participation in other interventional studies during participation in this study. 10. The inability to complete any of the five neurological assessments. |
No podrán participar en el estudio los sujetos que se encuentren en cualquiera de las circunstancias siguientes: 1. Sujetos que hayan completado el día 84 (semana 12) del estudio A7281006 o que hayan finalizado el estudio A7281008 pero que hayan experimentado acontecimientos graves relacionados con el producto en investigación, una enfermedad inestable o cualquier otro motivo que, en opinión del investigador, impediría la inclusión o la participación en el estudio. 2. Sujetos que estén tomando cualquier dosis de AZA, 6-MP o MTX. 3. Mujeres embarazadas o en período de lactancia. 4. Están prohibidas las fístulas enterovesiculares. Se permiten otras fístulas (p. ej., fístulas enterocutáneas). Es preciso aportar documentación de las fistulas activas e inactivas. 5. Otro trastorno médico o psiquiátrico grave, agudo o crónico, o anomalía analítica que pueda aumentar el riesgo asociado con la participación en el estudio o con la administración del producto en investigación o pueda interferir en la interpretación de los resultados del estudio y, en opinión del investigador, desaconsejase la entrada del sujeto en este estudio. 6. Sujetos que hayan recibido cualquier tratamiento prohibido en los estudios A7281006 y A7281008 que, en opinión del investigador, haya comprometido la seguridad o la eficacia de este estudio. 7. Vacunación prevista con microorganismos vivos (atenuados) durante este estudio. 8. Intervención quirúrgica o médica importante de elección programada durante este estudio. 9. Participación en otros estudios intervencionales durante la participación en este estudio. 10. Incapacidad para realizar alguna de las cinco evaluaciones neurológicas |
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E.5 End points |
E.5.1 | Primary end point(s) |
Frequency of on-treatment AEs, AEs leading to withdrawls, and SAEs. |
Frecuencia de AA durante el tratamiento, AA motivo de retirada y AAG. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
All visits |
Todas las visitas. |
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E.5.2 | Secondary end point(s) |
Immunogenicity ? Frequency of the development of anti-drug antibodies (ADAs). Pharmacokinetics ? Plasma trough concentrations of PF 00547659 will be analyzed using Population PK methodology. |
Inmunogenicidad ? Frecuencia de desarrollo de anticuerpos contra el fármaco (ACF). Farmacocinética ? Las concentraciones plasmáticas mínimas de PF 00547659 se analizarán utilizando la metodología de farmacocinética poblacional. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ADAS: VISITS: 1,2,5,8,11,14,17,20,21,22,23,24,25
PK - all visits |
ADAS: VISITAS: 1,2,5,8,11,14,17,20,21,22,23,24,25
PK - todas las visitas |
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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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Canada |
Croatia |
France |
Germany |
Netherlands |
Norway |
Portugal |
Serbia |
Slovakia |
South Africa |
Spain |
Sweden |
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 | 5 |
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 | 5 |
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 |