E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis |
Colitis Ulcerosa |
|
E.1.1.1 | Medical condition in easily understood language |
Moderate to severe active Ulcerative colitis |
Colitis ulcerosa activa de moderada a severa |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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 |
To demonstrate the efficacy of CP-690,550 as maintenance therapy in subjects with
UC. |
Demostrar la eficacia de CP-690.550 como tratamiento de mantenimiento en pacientes con CU. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of CP-690,550 as maintenance therapy in
subjects with UC.
- To evaluate the efficacy of CP-690,550 maintenance therapy in achieving mucosal
healing in subjects with UC.
- To evaluate the CP-690,550 pharmacokinetic exposure during maintenance therapy in subjects with UC.
- To evaluate the effect of CP-690,550 as maintenance therapy on quality-of-life in
subjects with UC. |
Evaluar la seguridad y la tolerabilidad de CP-690.550 como tratamiento de mantenimiento en pacientes con CU.
Evaluar la eficacia del tratamiento de mantenimiento con CP-690.550 en lo que se refiere a lograr la cicatrización de la mucosa en pacientes con CU.
Evaluar la exposición farmacocinética a CP-690.550 durante el tratamiento de mantenimiento en pacientes con CU.
Evaluar el efecto de CP-690.550 como tratamiento de mantenimiento sobre la calidad de vida en pacientes con CU. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who met study entry criteria and completed 8-week induction treatment from Study A3921094 or A3921095.
2. Subjects who achieved clinical response in Study A3921094 or A3921095.
- Clinical response is defined by a decrease from the induction study baseline (A3921094 or A3921095) Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. For eligibility assessment, clinical response will be determined based on the central-read endoscopy performed at Week 8 of Study A3921094 or A3921095 and the central-read endoscopy performed at Week 0 of Study A3921094 or A3921095.
3. Women of childbearing potential must test negative for pregnancy prior to study enrollment.
- Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 4 weeks after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active.
4. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
5. Evidence of a personally signed and dated informed consent document(s) indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. |
1.Pacientes que cumplan los criterios de participación en el estudio y que hayan finalizado un tratamiento de inducción de 8 semanas en el estudio A3921094 o A3921095.
2. Pacientes que hayan logrado una respuesta clínica en el estudio A3921094 o A3921095.
La respuesta clínica se define como una disminución de la puntuación de Mayo con respecto al período basal del estudio de inducción (A3921094 o A3921095) en al menos 3 puntos y al menos un 30%, acompañada de una disminución de la subpuntuación de rectorragia en al menos 1 punto o una subpuntuación de rectorragia absoluta de 0 o 1. A efectos de evaluación de la elegibilidad, la respuesta clínica se determinará a partir de la endoscopia interpretada de forma centralizada realizada en la semana 8 del estudio A3921094 o A3921095 y la endoscopia interpretada de forma centralizada realizada en la semana 0 del estudio A3921094 o A3921095.
3. Las mujeres en edad fértil han de tener una prueba de embarazo negativa antes de su inclusión en el estudio.
Las mujeres en edad fértil tendrán que comprometerse a utilizar un método anticonceptivo muy eficaz durante todo el estudio y durante al menos 4 semanas después de la última dosis del tratamiento asignado. Una paciente se encuentra en edad fértil si, en opinión del investigador, es biológicamente capaz de tener hijos y es sexualmente activa.
4. Pacientes que se muestran dispuestos a cumplir las visitas programadas, el plan de tratamiento, las pruebas analíticas y otros procedimientos del estudio y son capaces de hacerlo.
5. Prueba de un documento de consentimiento informado, firmado y fechado personalmente, en el que se indique que el paciente (o su representante legal) ha sido informado de todos los aspectos pertinentes del estudio. |
|
E.4 | Principal exclusion criteria |
1. Subjects who had major protocol violation (as determined by the Sponsor) in Study A3921094 or A3921095.
2. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn?s disease.
3. Subjects who have had surgery for UC or in the opinion of the investigator, are likely to require surgery for UC during the study period.
4. Subjects who are expected to receive any of prohibited concomitant medications, including medications that are either moderate to potent CYP3A inducers or inhibitors, during the study period as specified in Appendix 2 of the protocol.
5. Subjects who are expected to receive live or attenuated virus vaccination during study period and for 6 weeks after last dose of study drug.
6. Women who are pregnant or lactating, or planning to become pregnant during the study period.
7. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results (ie, baseline QTcF >450 ms, complete LBBB, acute or indeterminate age myocardial infarction, 2nd-3rd degree AV block, or serious bradyarrhythmias or tachyarrhythmias; see Appendix 4 of the protocol.
8. Subjects who, in the opinion of the investigator or Pfizer, will be uncooperative or unable to comply with study procedures.
9. Subjects who are investigational site staff members of relatives of those site staff member or subject who are Pfizer employees directly involved in the conduct of the trial.
10. Any 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 for entry into this study.
11. Subjects who are participating in or interested in participating in other investigational studies during study A3921096. |
Pacientes que hayan cometido una infracción importante del protocolo (según lo determinado por el promotor) en el estudio A3921094 o A3921095.
2. Presencia de colitis indeterminada, colitis microscópica, colitis isquémica, colitis infecciosa o datos clínicos indicativos de enfermedad de Crohn.
Pacientes que se han sometido a cirugía para la CU o que, en opinión del investigador, es probable que la precisen durante el período del estudio.
4. Pacientes que tienen previsto recibir alguno de los medicamentos concomitantes prohibidos, como medicamentos que son inductores o inhibidores moderados o potentes de la enzima CYP3A, durante el período del estudio tal como se especifica en el protocolo (véase el Apéndice 2).
5. Pacientes que tienen previsto recibir una vacuna de virus vivos o atenuados durante el período del estudio y durante 6 semanas después de la última dosis de medicamento del estudio.
6. Mujeres embarazadas o lactantes o que tienen previsto quedarse embarazadas durante el período del estudio.
7. ECG de 12 derivaciones basal que ponga de manifiesto anomalías clínicamente importantes que puedan afectar a la seguridad del paciente o la interpretación de los resultados del estudio (es decir, QTcF basal > 450 ms, bloqueo de rama izquierda completo, infarto de miocardio agudo o de antigüedad indeterminada, bloqueo auriculoventricular de 2º-3er grado o bradiarritmias o taquiarritmias graves; véase el Apéndice 4).
8. Pacientes que, en opinión del investigador o de Pfizer, no vayan a cooperar o no puedan cumplir los procedimientos del estudio.
9. Pacientes que son miembros del personal del centro de investigación o familiares de miembros del personal del centro o pacientes que son empleados de Pfizer directamente implicados en la realización del ensayo.
10. Cualquier otro trastorno médico o psiquiátrico grave, agudo o crónico, o cualquier alteración analítica que pueda aumentar el riesgo asociado a la participación en el estudio o a la administración del producto en investigación o interferir en la interpretación de los resultados del estudio y que, en opinión del investigador, impida al paciente participar en este estudio.
11. Pacientes que están participando o que se muestran interesados en participar en otros estudios de investigación durante el estudio A3921096. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects in remission at Week 52. Remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. |
Proporción de pacientes en remisión en la semana 52. La remisión se define como una puntuación de Mayo total de 2 puntos o menos, sin subpuntuaciones individuales que superen 1 punto y con una subpuntuación de rectorragia de 0. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint is the proportion of subjects in remission at Week 52. |
Proporción de pacientes en remisión en la semana 52. |
|
E.5.2 | Secondary end point(s) |
Key Secondary Endpoint:
- The proportion of subjects with mucosal healing at Week 52. Mucosal healing is defined by a Mayo endoscopic subscore of 0 or 1.
- The proportion of subjects in sustained steroid-free remission among subjects in remission at baseline of Study A3921096. Sustained steroid-free remission is defined by being in remission and steroid-free at both Week 24 and Week 52. Steroid-free
remission is defined by being in remission (a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0) in addition to not requiring any treatment with corticosteroid for at least 4 weeks prior to the visit. Other secondary, exploratory, pharmacokinetic, biomarker, Health Outcome and safety endpoints are described within the protocol. |
Proporción de pacientes con cicatrización de la mucosa en la semana 52. La cicatrización de la mucosa se define como una subpuntuación endoscópica de Mayo de 0 o 1.
Proporción de pacientes en remisión sin esteroides mantenida entre los pacientes que se encuentren en remisión en el período basal del estudio A3921096. La remisión sin esteroides mantenida se define como el hecho de encontrarse en remisión y sin utilizar esteroides en las semanas 24 y 52. La remisión sin esteroides se define como el hecho de encontrarse en remisión (puntuación de Mayo total de 2 puntos o menos, sin subpuntuaciones individuales que superen 1 punto y una subpuntuación de rectorragia de 0), además de no necesitar ningún tratamiento con corticoides durante al menos 4 semanas antes de la visita. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints are measured at Weeks 24 and 52. |
Se valorarán en las semanas 24 y 52 |
|
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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life |
calidad de vida |
|
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
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 |
Belgium |
Brazil |
Canada |
Colombia |
Croatia |
Czech Republic |
Denmark |
Estonia |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Netherlands |
New Zealand |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
|
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
|
Last visit last subject |
Ultima visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |