E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Perianal fistulising Crohn´s disease |
Fístulas perianales en la enfermedad de Crohn |
|
E.1.1.1 | Medical condition in easily understood language |
Treatment for perianal fistulising Crohn´s disease |
Tratamiento para fístulas perianales en la 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002156 |
E.1.2 | Term | Anal fistula |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety of a single dose of darvadstrocel in subjects with CD and complex perianal fistula by evaluation of AEs, serious adverse events (SAEs), and adverse events of special interest (AESIs). |
Evaluar la seguridad a largo plazo de una dosis única de darvadstrocel en pacientes con EC y fístulas perianales complejas mediante la evaluación de los AA, los AAG y los AAEI. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy of a single dose of darvadstrocel for the treatment of complex perianal fistula(s) in subjects with CD. |
Evaluar la eficacia a largo plazo de una dosis única de darvadstrocel para el tratamiento de las fístulas perianales complejas en pacientes con EC. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria before entry into the study:
1. In the opinion of the investigator, the subject is capable of understanding and complying withprotocol requirements. 2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written ICF and any required privacy authorization before the initiation of any study procedures. 3. The subject has participated in and completed the ADMIRE-CD II study (ie, did not discontinue). |
La elegibilidad de los pacientes se determina antes de la incorporación al estudio de acuerdo con los siguientes criterios:
1. En opinión del investigador, el paciente es capaz de entender y cumplir los requisitos del protocolo. 2. El paciente o, cuando proceda, su representante legal firma y fecha un FCI impreso y todas las autorizaciones necesarias relativas a la privacidad antes del inicio de cualquier procedimiento del estudio. 3. El paciente ha participado en el estudio ADMIRE-CD II y lo ha finalizado (es decir, no se retiró). |
|
E.4 | Principal exclusion criteria |
Subjects will not be eligible for inclusion in the study if:
1. It has been more than 3 months since the subject completed the ADMIRE-CD II study. 2. Subjects are currently receiving, have received any investigational drug in the last 3 months before the inclusion in the study, or are planning to receive any investigational drug during the duration of this LTE study, except for prior participation in the ADMIRE-CD II study. |
Los pacientes no serán aptos para su inclusión en el estudio si:
1. Han transcurrido más de 3 meses desde que el paciente finalizó el estudio ADMIRE-CD II. 2. Están recibiendo, han recibido en los últimos 3 meses antes de la inclusión en el estudio, o tienen previsto recibir durante este estudio de ELP algún fármaco en investigación, excepto antes de la participación en el estudio ADMIRE-CD II. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- AEs. - SAEs. - Specific AESIs: – Immunogenicity/alloimmune reactions. – Tumorgenicity. – Ectopic tissue formation. |
-AA. -AAG. -AAEI específicos: – Inmunogenicidad/reacciones aloinmunes. – Carcinogénesis. – Formación de tejido ectópico. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Examinations/assessments at week 0, 52, 104. Telephone calls every 3 months. |
Examinación/evaluación a la semana 0,52,104 Llamadas telefónocas cada 3 meses |
|
E.5.2 | Secondary end point(s) |
Proportion of subjects who achieve clinical remission at Week 104 and Week 156 after IMP administration. – Clinical remission is defined as closure of all treated external fistula openings that were draining at baseline despite gentle finger compression. - Proportion of subjects who achieve clinical response at Week 104 and Week 156 after IMP administration. – Clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline despite gentle finger compression. Proportion of subjects with a relapse where a relapse is defined as: – Reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed in subjects who were in clinical remission at Week 52, or – The development of a perianal fluid collection >2 cm of the treated perianal fistulas confirmed by centrally read magnetic resonance imaging (MRI) assessment. - Proportion of subjects who achieve combined remission at Week 156 after IMP administration. –- Combined remission of complex perianal fistula(s), defined as the clinical assessment of closure of all treated external openings that were draining at baseline (ie, screening visit), despite gentle finger compression, and –- Absence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by centrally read blinded MRI assessment. - Proportion of subjects with new anal abscess in treated fistula. - Change from baseline to Week 104 and Week 156 after IMP administration in in scores of discharge and pain items of Perianal Disease Activity Index (PDAI) score. |
Proporción de pacientes que logran la remisión clínica en la semana 104 y en la semana 156 tras la administración del MI. – La remisión clínica se define como el cierre de todos los orificios externos de las fístulas tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera. -Proporción de pacientes que logran una respuesta clínica en la semana 104 y en la semana 156 tras la administración del MI. – La respuesta clínica se define como el cierre de, como mínimo, el 50 % de los orificios externos de las fístulas tratados que habían sido supurantes en el momento basal, a pesar de su compresión digital ligera. -Proporción de pacientes con una recidiva, que se define de la siguiente manera: – Reapertura de cualquier orificio externo de las fístulas tratadas con supuración activa, de acuerdo con la evaluación clínica, en pacientes que presentaban remisión clínica en la semana 52, o – Desarrollo de una acumulación de líquidos perianal >2 cm en las fístulas perianales tratadas, confirmada mediante RM de evaluación central. - Proporción de pacientes que logran la remisión combinada en la semana 156 tras la administración del MI. – La remisión combinada de las fístulas perianales complejas se define como el cierre de todos los orificios externos tratados que habían sido supurantes en el momento basal (es decir, en la visita de selección), a pesar de su compresión digital ligera, de acuerdo con la evaluación clínica – Ausencia de acumulaciones >2 cm (en como mínimo 2 dimensiones) en las fístulas perianales tratadas, confirmada mediante RM de evaluación central con enmascaramiento. -Proporción de pacientes con nuevos abscesos anales en las fístulas tratadas. -Cambio desde el valor basal hasta la semana 104 y la semana 156 tras la administración del MI en las puntuaciones de los ítems de supuración y dolor del Índice de Actividad de la Enfermedad Perianal (Perianal Disease Activity Index, PDAI). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Examinations/assessments at week 0, 52, 104. Telephone calls every 3 months. |
Examinación/evaluación a la semana 0,52,104 Llamadas telefónocas cada 3 meses |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 2 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Poland |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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 |
Último paciente última visita |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |