E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
systemic sclerosis |
systemische sclerose |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042953 |
E.1.2 | Term | Systemic sclerosis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue 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 |
Determining the safety and efficacy of intramuscularly administered mesenchymal stem cells for the treatment of digital ucers in systemic sclerosis. |
Het vaststellen van de veiligheid en werkzaamheid van intramusculaire toediening van mesenchymale stamcellen ter behandeling van digitale ulcera bij systemische sclerose. |
|
E.2.2 | Secondary objectives of the trial |
To assess the accuracy of various parameters related to inflammation, endothelial activation and angiogenesis to predict therapeutic efficacy and/or serve as biomarkers |
Beoordelen of diverse parameters gerelateerd aan inflammatie, endotheelactivatie en angiogenese verband houden met het therapeutische effect en mogelijk als biomarkers kunnen dienen. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >18 years
- Established diagnosis of SSc according to criteria of the American College of Rheumatology (2013)
- At least one active digital ulcer (painful area, >2 mm in diameter with visible depth and loss of dermis) refractory to intravenous prostacyclins
------------‘Refractory to prostacyclins’ is defined as
-Worsening of ulcer(s) at 1 month after prostacyclins iv
-No improvement of ulcer(s) at 2 months after prostacyclins iv, as judged by the referring physician
-Recurrence of exactly the same ulcer(s) (same location) at 3 months after prostacyclins iv
- Written informed consent |
- ouder dan 18 jaar
- diagnose systemische sclerose in overeenstemming met de criteria van de American College of Rheumatology (2013)
minimaal 1 actief digitaal ulcus (pijnlijk, groter dan 2mm, met zichtbare diepte en verlies van dermis) en niet reageert intraveneuze prostacyclines
------------------ 'niet reageren' wordt gedefiniëerd als
- Verslechtering van het ulcus 1 mnd na toediening prostacyclines
- Geen verbetering van het ulcus 2 mnd na toediening prostacyclines, beoordeeld door de verwijzend specialist
- Terugkeren van hetzelfde ulcus (zelfde locatie) 3 mnd na toediening
- Informed consent |
|
E.4 | Principal exclusion criteria |
- Ulcer with underlying calcinosis (ruled out by X-ray prior to referral)
-History of neoplasm or malignancy in the past 10 years
- Pregnancy or unwillingness to use adequate contraception during study
- Serious known concomitant disease with life expectancy <1 year
- Uncontrolled hypertension
- Uncontrolled acute or chronic infection
- Follow-up impossible.
|
Ulcus ten gevolge van onderliggende calcinose (uitgesloten door röntgenfoto vóór verwijzing)
Maligniteit in de voorgeschiedenis
Zwangerschap of niet bereid anticonceptie te gebruiken gedurende de studie
Ernstige comorbiditeit met een levensverwachting <1 jaar
Ongereguleerde hypertensie
Ongereguleerde acute of chronische infectie
Follow-up niet mogelijk |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of serious adverse events |
Aantal ernstige ongewenste voorvallen/bijwerkingen |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Safety:
- treatment related toxicity as assessed with the WHO parameters
Efficacy:
-ulcer count, ulcer area
-ulcer VAS
-quality of life as determined with the S-HAQ, SF-36, EQ5D, CHFS
-capillaroscopy semi-quantitative score
- change in biomarkers
|
Veiligheid:
- Toxiciteit tgv de behandeling (WHO parameters)
Effectiviteit:
- aantal en oppervlakte van de wondjes
- VAS mbt de wondjes
- kwaliteit van leven zoals blijkt uit de S-HAQ, SF-36 en EQ5D, CHFS
- capillaroscopie semi-quantitative score
- verandering in biomarkers |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
Treatment-related mortality within 7 days after administration |
Behandelingsgerelateerde mortaliteit binnen 7 dagen na toediening |
|
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 | |
E.8.9.1 | In the Member State concerned days | |