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 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.
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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 | 4 |
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 |
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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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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 |