E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ischemic heart disease and heart failure |
Ischaemisch hart ziekte en hartfalen |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with heart failure have reduced cardiac pump function, physical
functional capacity and quality of life in spite of maximal tolerated
therapy and are candidates for stem cell therapy |
Patienten met hartfalen met verminderde pompfunctie, verminderde inspanningscapaciteit en kwaliteit van leven die maximale medicale therapie gebruiken en zijn kandidaten vor stamcel therapie. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To perform at clinical double-blind placebo-controlled CSCC_ASC
multicentre study in heart failure patients to investigate the
regenerative capacity of the CSCC_ASC treatment. |
Uitvoeren van een klinische dubbel geblindeerde placebo gecontroleerde CSCC_ASC multicenter studie in patienten met hartfalen. Doel is om de regeneratieve eigenschappen van CSCC_ASC therapie te onderzoeken. |
|
E.2.2 | Secondary objectives of the trial |
Improvement in cardiac function and clinical symptoms |
Verbetering in cardiale functie en klinische synptomen |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria:
1. 30 to 80 years of age
2. Signed informed consent
3. Chronic stable ischemic heart disease
4. Heart failure (NYHA II-III)
5. LVEF ≤45%
6. Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L) in sinus rhythm
7. Maximal tolerable heart failure medication
8. Medication unchanged two months prior to inclusion
9. No option for percutaneous coronary intervention (PCI) or coronary
artery bypass graft (CABG)
10. Patients who have had PCI or CABG within six months of inclusion
must have a new angiography less than one month before inclusion or at
least four months after the intervention to rule out early restenosis
11. Patients cannot be included until three months after implantation of
a cardiac resynchronisation therapy device |
1. Leeftijd tussen de 30 en 80 jaar
2. Getekende informed consent
3. Chronische stabiele ischaemisch hartlijden
4. Symptomatisch hartfalen (NYHA II-III)
5. LVEF ≤ 45% echocardiografisch vastgesteld
6. Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L)
7. Maximaal getolereerde hartfalen medicatie
8. Medicatie ongewijzigd 2 maanden voor inclusie
9. Geen optie voor percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)
10. Patienten die PCI danwel CABG binnen 6 maanden van inclusie hebben ondergaan moeten een nieuwe angiografisch onderzoek ondergaan; tijdsframe: minder dan 1 maand voor inclusie of tenminste 4 maanden na interventie om restenose uit te sluiten
11. patienten kunnen niet worden geincludeerd tot 3 maanden na implantatie van een cardiac resynchronisation therapy device (CRTD) en tot 1 maand na een ICD unit. |
|
E.4 | Principal exclusion criteria |
Exclusion criteria
1. Heart Failure (NYHA I or IV)
2. Acute coronary syndrome with elevation of CKMB or troponins,
stroke or transitory cerebral ischemia within six weeks of inclusion
3. Other revascularisation treatment within four months of treatment
4. If clinically indicated the patient should have a coronary angiography
before inclusion
5. Moderate to severe aortic stenosis (valve area < 1.3 cm2) or
valvular disease with option for surgery.
6. Diminished functional capacity for other reasons such as: obstructive
pulmonary disease (COPD) with forced expiratory volume (FEV) <1
L/min, moderate to severe claudication or morbid obesity
7. Clinical significant anaemia (haemoglobin < 6 mmol/L), leukopenia
(leucocytes < 2 109/L), leucocytosis (leucocytes >14 109/L) or
thrombocytopenia (thrombocytes < 50 109/L)
8. Anticoagulation treatment that cannot be paused during cell
injections
9. Patients with reduced immune response
10. History with malignant disease within five years of inclusion or
suspected malignity – except treated skin cancer other than melanoma
11. Pregnant women
12. Other experimental treatment within four weeks of baseline tests
13. Participation in another intervention trial |
Exclusie criteria:
1. Hartfalen (NYHA I of IV)
2. Acuut coronair syndroom met acute reservibele elevatie van CKMB of troponine, beroerte of transient cerebrale inschaemie binnen 6 weken van inclusie.
3. Andere revascularisatie therapie binnen 4 maanden van onderzoek
4. Als er klinische noodzaak is behoort patient coronairangiografie voor inclusie te krijgen
5. Matig tot ernstige artaklepstenose (klepoppervlak < 1.3 cm2) of kleplijden met optie tot operatie.
6. Verminderde inspanningscapaciteit tgv andere redenen zoals: obstruciteve pulmonaire ziekte (COPD) met een geforceerde expiratoire volume (FEV) <1 L/min, matige tot ernstige claudicatie of morbide obesitas
7. Klinisch significante anemie (hemoglobine < 6 mmol/L), leukopenie (leucocyten < 2 109/L), leucocytose (leucocyten > 14 109/L) or thrombocytopenie (thrombocyten < 50 109/L)
8. Behandeling met anticoagulantie dat niet (tijdelijk) gestaakt kan worden gedurende stamcel injecties. Patienten mogen bloedplaatjesremmers continueren.
9. patienten met verminderde immuunrespons
10. Voorgeschiedenis met maligniteiten binnen vijf jaar van inclusie of vermoeden tot maligniteit - uitzondering is behandelde huidkanker anders dan melanomen
11. Zwangere vrouwen
12. andere experimentele behandeling binnen vier maanden van de baseline onderzoeken
13. Participatie in andere interventie trials. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is change in left ventricle end-systolic volume
(LVESV) at 6 months follow-up between CSCC_ASC treatment and placebo patients |
Primaire eindpunt is verandering in linker ventrikel eind systolische volume 9LSESV) na 6 maanden follow-up tussen CSCC_ASC behandeling en placebo |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after treatment |
6 maanden na behandeling |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are safety evaluated by development of
allogeneic antibodies and laboratory safety measurements 1 and 6
months after treatment and changes in left ventricular ejection fraction
(LVEF), end-diastolic volume and myocardial mass at 6 months followup.
The changes in left ventricle function will be measured by echocardiography
(ECHO) or computed tomography (CT). Other secondary endpoints are changes in NYHA, CCS,
Kansas City Cardiomyopathy Questionnaire (KCCQ), 6 min walking test and NT-pro-
BNP. In addition, safety of allogeneic CSCC_ASCs with respect to
incidence and severity of serious adverse events and suspected
unrelated serious adverse events will be evaluated at 12 months followup.
A combined endpoint of
1. death, hospitalization for worsening heart failure including inserting
of a bi-ventricular pacemaker, hospitalization because of ventricular
tachycardia or fibrillation and increased heart failure medical treatment
1, 2 and 3 years after treatment
2. death, hospitalization for any cardiovascular reason, hospitalization
for worsening heart failure including inserting of a bi-ventricular
pacemaker, hospitalization because of ventricular tachycardia or
fibrillation and increased heart failure medical treatment 1, 2 and 3
years after treatment. |
Secundaire eindpunten:
-veiligheid geëvalueerd door de meting van de vorming van allogene antilichamen en bloedafnames 1, 3 en 6 maanden na de behandeling
-veranderingen in de linker ventrikel ejectiefractie (LVEF), eind-diastolische volume en myocardiale massa bij 6 maanden follow-up. De veranderingen in linker ventrikel functie wordt gemeten met echocardiografie (ECHO), computertomografie (CT) en/of MRI. LVESV is een veel gebruikte maat voor de functionele status van het linker ventrikel en is superieur aan LVEF voor de voorspelling van overleving bij patiënten met LVEF dan 50%
-veranderingen in NYHA, CCS
-Kansas City Cardiomyopathie Vragenlijst, Seattle Angina Questionnaire
-6 min looptest
-aanvullende echocardiografische parameters (Global strain%, linker atrium volume, e ', s')
-NT-pro-BNP
-Daarnaast zal de veiligheid van allogene CSCC_ASCs met betrekking tot de incidentie en ernst van ernstige ongewenste voorvallen (SAR) en vermoedelijke ongerelateerde ernstige bijwerkingen (SUSAR) worden geëvalueerd na 12 maanden follow-up. Een gecombineerde eindpunt van
1. overlijden, hospitalisatie voor verergering van hartfalen inclusief inbrengen van een bi-ventriculaire pacemaker, ziekenhuisopname als gevolg van ventriculaire tachycardie of fibrillatie 1, 2 en 3 jaar na de behandeling
2. overlijden, ziekenhuisopname tgv cardiovasculaire redenen, hospitalisatie voor verergering van hartfalen inclusief inbrengen van een bi-ventriculaire pacemaker, ziekenhuisopname als gevolg van ventriculaire tachycardie of fibrillatie 1, 2 en 3 jaar na de behandeling |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 and 6 months after treatment and 1, 2 and 3 years |
1 en 6 maanden na therapie en 1, 2, 3 jaar |
|
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
| 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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
|
The patients will have four follow-up visits the first year after treatment, then the
safety of the study will be follow year 2 and 3 after the therapy in hospital registries |
Patietnen zullen na 1 jaar therapie follo-up ondergaan en daarna na jaar 2 en 3. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |