E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Perianal fistulising Crohn´s disease |
Fistole perianali nella malattia di Crohn |
|
E.1.1.1 | Medical condition in easily understood language |
Treatment for perianal fistulising Crohn´s disease |
Trattamento delle fistole perianali nella malattia di Crohn |
|
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). |
Valutare la sicurezza a lungo termine di una dose singola di darvadstrocel in soggetti con MC e fistola perianale complessa mediante valutazione degli EA, SAE e AESI. |
|
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. |
Valutare l’efficacia a lungo termine di una dose singola di darvadstrocel per il trattamento di fistole perianali complesse in soggetti con MC. |
|
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). |
L’idoneità del soggetto è determinata in base ai seguenti criteri prima dell’ingresso nello studio: 1. In base all’opinione dello sperimentatore, il soggetto è in grado di comprendere e attenersi ai requisiti del protocollo. 2. Il soggetto o, se del caso, il rappresentante legale autorizzato del soggetto firmerà e daterà un ICF scritto, e un’eventuale autorizzazione alla privacy richiesta, prima dell’inizio di qualsiasi procedura dello studio. 3. Il soggetto ha partecipato a, e completato, lo studio ADMIRE-CD II (ovvero, non si è/è stato ritirato). |
|
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. |
I soggetti non risulteranno idonei per essere inclusi nello studio se: 1. Sono passati più di 3 mesi da quando il soggetto ha completato lo studio ADMIRE-CD II. 2. I soggetti sono attualmente in trattamento o sono stati in trattamento con un qualsiasi farmaco sperimentale negli ultimi 3 mesi prima dell’inclusione nello studio, o prevedono di essere trattati con un qualsiasi farmaco sperimentale durante il periodo di questo studio LTE, fatta eccezione per la precedente partecipazione allo studio 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. |
• EA. • SAE. • AESI specifici: - Immunogenicità/reazioni alloimmuni. - Tumorigenicità. - Formazione di tessuto ectopico. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Examinations/assessments at week 0, 52, 104. Telephone calls every 3 months. |
Esaminazioni/valutazioni alla settimana 0, 52, 104. Contatti telefonici ogni 3 mesi. |
|
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. |
Percentuale di soggetti che raggiungono la remissione clinica alla Settimana 104 e alla Settimana 156 dopo la somministrazione dell’IMP. – La remissione clinica è definita come la chiusura di tutte le aperture esterne trattate della fistola che erano drenanti al basale nonostante una lieve pressione del dito. - Percentuale di soggetti che raggiungono la risposta clinica alla Settimana 104 e alla Settimana 156 dopo la somministrazione dell’IMP. – La risposta clinica è definita come la chiusura di almeno il 50% di tutte le aperture esterne trattate della fistola che erano drenanti al basale nonostante una lieve pressione del dito. Percentuale di soggetti con una recidiva, ove per recidiva si intende: – Riapertura delle aperture esterne della/e fistola/e trattata/e con drenaggio attivo, secondo la valutazione clinica in soggetti in remissione clinica alla Settimana 52, o – Sviluppo di una raccolta di ascesso perianale > 2 cm delle fistole perianali trattate, confermato da valutazione RM letta a livello centrale. - Percentuale di soggetti che raggiungono la remissione combinata alla Settimana 156 dopo la somministrazione dell’IMP. – Remissione combinata di fistola/e perianale/i complessa/e, definita come la valutazione clinica della chiusura di tutte le aperture esterne trattate che erano drenanti al basale (ovvero, alla visita di screening), nonostante una lieve pressione del dito, e – Assenza di raccolta/e > 2 cm (in almeno 2 dimensioni) della/e fistola/e perianale/i trattata/e, confermata da valutazione RM in cieco letta a livello centrale. - Percentuale di soggetti con nuovo ascesso anale nella fistola trattata. - Variazione dal basale alla Settimana 104 e alla Settimana 156, dopo la somministrazione dell’IMP, dei punteggi delle voci “ascesso” e “dolore” sull’Indice di attività della malattia perianale (PDAI). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Examinations/assessments at week 0, 52, 104. Telephone calls every 3 months. |
Esaminazioni/valutazioni alla settimana 0, 52, 104. Contatti telefonici ogni 3 mesi. |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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 |
Canada |
Israel |
United States |
Belgium |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
Czechia |
|
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
|
|
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 |