E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Perianal fistulising Crohn´s disease
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E.1.1.1 | Medical condition in easily understood language |
Treatment for perianal fistulising Crohn´s disease
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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 |
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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).
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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.
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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).
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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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- AEs. - SAEs. - Specific AESIs: – Immunogenicity/alloimmune reactions. – Tumorgenicity. – Ectopic tissue formation.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Examinations/assessments at week 0, 52, 104. Telephone calls every 3 months. |
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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 of ADMIRE -CD II 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 of ADMIRE-CD IIdespite gentle finger compression • Proportion of subjects with a relapse where a relapse is defined as patients who were in combined remission at Week 52 of ADMIRE-CD II, and who have either: – Reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed, 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 of ADMIRE-CD II, 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 at Week156. • Change from baseline of ADMIRE-CD II to Week 104 and Week 156 in scores of discharge and pain items of Perianal Disease Activity Index (PDAI) score. |
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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. |
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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) | 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 | 3 |
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 |
Canada |
Israel |
United States |
France |
Poland |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Hungary |
United Kingdom |
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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
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The end of the study is defined as the last scheduled procedure for the last participant in the study. |
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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 | 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 |