E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ischemic heart disease and heart failure |
Ishemična bolezen srca in srčno popuščanje |
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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 |
Bolniki s srčnim popuščanjem, ki imajo oslabljeno delovanje srca in zmanjšano telesno zmogljivost kljub zdravljenju z zdravili s konadidati za zdravljenje z matičnimi celicemi |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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. |
Preučiti vpliv zdravljenja s produktom CSCC_ASC pri bolnikih s srčnim popuščanjem |
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E.2.2 | Secondary objectives of the trial |
Improvement in cardiac function and clinical symptoms |
Izboljšanje delovanja srca in telesne zmogljivosti |
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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 |
Starost 30-80 let Podpisana privolitev Kronična stabilna ishemična bolezen srca Srčno popuščanje NYHA 2-3 LVEF<45% Plazemski NT.proBNP > 300 pg/ml pri bolnikih v sinusnem ritmu Ni možnosti revaskularizacije |
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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 |
Srčno popuščanje NYHA 1 ali 4 Akutni koronarni sindrom Revaskularizacijski poseg znotraj 4 mesecev pred vključitivijo Aortan stenoza (AVA<1.3 cm2) KOPB s FEV<1 L/min Anemija, levkopenija ali trombocitopenija
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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 and placebo patients |
Sprememba ESV po 6 mesecih po aplikaciji CSCC_ASC in placeba |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after treatment |
6 mesecev po zdravljenju |
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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. |
Sprememba LVEF, LVEDD, LVEDV in mase miokarda |
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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 mesec, 6 mesecev; 1, 2,3 leta po zdravljenju |
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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 | 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
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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 |
Bolnike bomo pregledalii 4x v prvem letu po zdravljenju, nato ponovno 2 leti in 3 leta po zdravljenju |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |