E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe acute myocardial Infarction. Indication : Injection of in vitro expanded peripheral blood CD34+ stem cells output by the StempXpand Automated Process, in patients with an acute myocardial infarction and a LVEF remaining below 50%. |
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E.1.1.1 | Medical condition in easily understood language |
Stem cells injection in acute myocardial infarction patients. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
The primary objective is to compare the incidence of adjudicated MACE between both treatment arms |
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E.2.2 | Secondary objectives of the trial |
The main secondary objective is to establish the efficacy profile of the interventional procedure from the randomization to 6 months after the autologous expanded CD34+ stem cells injection in AMI patients with a LVEF < 50% versus Standard of Care.
The other secondary objective is to determine the benefit/risks profile of the interventional procedure from the randomization to 6 months after the autologous expanded CD34+ stem cells injection in AMI patients with a LVEF < 50% versus Standard of Care. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. LV main AMI with or without ST segment elevation and with a detection of rise of troponin with at least one value 70 times above the upper reference limit. 2. Index MI within 1 week after first symptoms. (D0 = day of last stent implantation or; D0 = day of hospital presentation when no stent implanted.) 3. Combination of LVEF < 50% and LV akinetic or dyskinetic segment(s) - by post-MI echography as per local practice 4. Age must be ≥ 18 and ≤ 85 years 5. Men and Non-pregnant non-lactating women who take efficacious contraceptive measures such as oral contraceptive medications or efficacious and permanent intra-uterine device (drug eluted or not) (IUD) or subcutaneous permanent contraceptive implants or menopaused women (at least 2 years confirmed menopause) or surgically sterilized women. 6. Having previously signed a written informed consent prior to any study-specific procedure 7. LVEF remaining < 50% assessed by cMRI at D8 (± 3) 8. Identification of LV segment(s) both non-viable (transmural scar extend >50%) and akinetic (no cardiac wall thickening during systole) or dyskinetic (cardiac wall thickening in the wrong orientation during systole) by cMRI at D8 (± 3)
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E.4 | Principal exclusion criteria |
1. History of CABG surgery 2. History of former significant mitral valve replacement surgery or heart transplantation. 3. History of severe valve disease: mitral, aortic stenosis / insufficiency. 4. History of non-ischemic dilated cardiomyopathy due to valvular dysfunction, mitral regurgitation, tachycardia, or myocarditis 5. Aortic stenosis as determined as valve area less than 1 cm2 that prohibits catheter access to LV 6. Presence of a prosthetic / mechanical aortic or mitral valve or heart constrictive device. 7. Sepsis 8. Endocarditis 9. Infectious pericarditis 10. Pericardial tamponade 11. Cardiac thrombus detected at echo or MRI 12. Severe peripheral vascular disease precluding femoral artery access as determined at the time of original catheterization. 13. Any condition leading to unexploitable cMRI. 14. History of metallic foreign body in their eye 15. Former or current aortic dissection 16. Previous G-CSF or other hematopoietic growth factor administration. 17. Hepatic failure, history of liver cirrhosis or hepatic severe impairment. 18. Constitutional or acquired coagulopathy 19. Treated chronic renal failure, haemodialysis or renal severe impairment (creatinine clearance < 30 ml/min). 20. Prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer or previous cancer in complete response without any treatment in the last 5 years. 21. History of prior mediastinal radiation exposure 22. Serious underlying medical condition at the investigator’s discretion, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, active autoimmune disease, Amyotrophic Lateral Sclerosis, Systemic Lupus, Multiple Sclerosis). 23. Chronic immunomodulatory or cytotoxic drug treatment intake. 24. Active bleeding or major surgery within 1 month. 25. History or current Human immunodeficiency HIV1-2, HTLV1, HTLV2 (according to 2006/17/EC) 26. Current Active Hepatitis B (according to 2006/17/EC) 27. History or current Hepatitis C (according to 2006/17/EC) 28. Syphilis (according to 2006/17/EC) 29. Active participation in any other clinical trials 30. Current or recent treatment (within two months) with another investigational drug or procedure. 31. Any other co-existing conditions that will preclude participation in the study or compromise ability to give informed consent. 32. Impairment of cognitive function. If patient is 75-85 years old (included), score < 24 at Mini Mental State Examination (MMSE) 33. History of Splenomegaly 34. History of Phenylketonuria 35. History of iron-Dextran allergy 36. History of murine protein allergy 37. Diagnosis of Takotsubo
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of Major Adverse Cardiac Events (MACE) which have been adjudicated and confirmed to be MACE by an independent and blinded Clinical Events Committee (CEC) from randomization up to 6 months in both treatment arms. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This endpoint will be evaluated from randomisation up to 6 months. |
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E.5.2 | Secondary end point(s) |
The improvement of the Left Ventricle End Systolic Volume index (LVESVi) Viability improvement of the infarcted segment(s) Adverse event profile Cardiac event free Survival Median time before cardiac relapse Quality of life assessment (SF36) Healthcare consumption and cost-effectiveness.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The improvement of LVESVi will be assessed by cMRI and will be performed at baseline, at 3 months and at 6 months. The viability assessment of infarcted segment(s) will be performed cMRI at baseline, at 3 months and at 6 months and by SPECT (optional) at baseline and at 6 months. SF36 scale will be carried out at baseline, M1, M3 and M6 |
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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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Corelab assessment in a blinded manner for MRI |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
France |
Slovenia |
United Kingdom |
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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 end of trial is the last assessment of the last patient (Last Visit of the Last Patient) at 6 months of follow-up, after the last patient treatment. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 100 |
E.8.9.2 | In all countries concerned by the trial days | 0 |