Safety and Efficacy Evaluation of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With AMI
NCT ID: NCT02439398
Last Updated: 2017-11-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1/PHASE2
55 participants
INTERVENTIONAL
2014-06-30
2016-11-14
Brief Summary
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The study comprises two phases:
1. Initial dose-escalation open-label safety phase comprising 6 patients. Escalation will start with the Maximum Recommended Safe Dose (MRSD) calculated from Non-Observed Adverse Events Level (NOAEL) and it is expected to finish with the target dose (TD). There will be no placebo group for this initial phase.
2. Randomized double-blind placebo-controlled safety and efficacy phase in which the TD will be injected if the dose-escalation phase is completed successfully.
Detailed Description
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Patients with EF\<45% and with infarct sizes \> 25% will be selected by magnetic resonance image (MRI). 49 patients will be included in the randomized phase with the aim of having 38 patients for efficacy analysis at the end of the follow up period (12 months). In this phase, patients will be randomly allocated for receiving CSCs or placebo in a 2:1 scheme. Three bioequivalent cellular batches obtained from different donors will be indistinctly used during the assay.
CSCs or placebo treatment will be infused into the coronary artery responsible for the ischemic event. Placebo will be a commercial preparation of human serum albumin 5% in saline solution that will also be used for cell product reconstitution.
After treatment, patients will be monitored overnight in a coronary care unit for any toxicity and discharged from hospital 24h after treatment if no adverse events are observed.
Subsequent safety follow-up will be done first at day 7 after treatment and then monthly or quarterly thereafter for 12 months. In addition, efficacy evaluations will be performed by MRI and clinical parameters at 1, 6 and 12 months after treatment.
Finally, cellular and humoral immunological response (screening for anti-HLA (Human Leukocyte Antigen) class I and class II antibodies, HLA typing, cross-matching between cells and treated patient and cytokine profiling in blood samples) will be analysed during the clinical trial.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Allogeneic human cardiac stem cells
After randomization, subjects will received a suspension of allogeneic human cardiac stem cells (35 millions of CSCs - cell medicine) infused into the coronary artery responsible for the ischemic event.
Allogeneic human cardiac stem cells (CSCs)
Allogeneic human CSCs is a new cell medicine based on cells isolated from human heart biological samples (right atrium appendage of donors) and expanded in vitro.
Placebo: Human Serum Albumin-HSA 5%
After randomization, subjects will received placebo (which is also the cell medicine diluent). The placebo consists of a final administered volume of human serum albumin 5% in saline solution equivalent to the reconstituted cell medicine (18 mL). The placebo to be used is a marketed product (HSA 5%).
Human Serum Albumin-HSA 5%
Human Serum Albumin (HSA) is a well-known physiologic protein widely used in clinical practice and without known toxicity after parenteral administration.
Interventions
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Allogeneic human cardiac stem cells (CSCs)
Allogeneic human CSCs is a new cell medicine based on cells isolated from human heart biological samples (right atrium appendage of donors) and expanded in vitro.
Human Serum Albumin-HSA 5%
Human Serum Albumin (HSA) is a well-known physiologic protein widely used in clinical practice and without known toxicity after parenteral administration.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients presenting a ST-segment-elevation myocardial infarction (STEMI) according to the universally accepted definition found in the STEMI management guide of the European Society of Cardiology
* Killip ≤ 2 on admission
* Successful primary coronary revascularization by Percutaneous Coronary Intervention- PCI - (Thrombolysis In Myocardial Infarction \[TIMI\] = 3) within 12h after the onset of infarct symptoms
* Bare-metal or drug-eluting stents (DES) of second generation (including new second generation stents, e.g. biolimus, novolimus and bioreabsorbable stents) at coronary revascularization by PCI
* Ejection Fraction (EF) ≤45% by magnetic resonance imaging (MRI). This MRI will be done between day 3 and day 5 after infarction and will be used as inclusion MRI
* Infarct size in left ventricle (LV) tested in the screening MRI ≥25% The presence of microvascular obstruction at inclusion MRI is permitted
* The affected coronary artery is adequate for cells infusion at the administration time. The administration procedure is technically feasible on day 4-7 after coronary revascularization by PCI
* The patient is stable and in adequate clinical condition to undergo the procedure.
Exclusion Criteria
* Previous allogeneic transplant (blood transfusions are allowed) or treated with cell or gene therapy
* Previous Q-wave infarction
* Significant valve disease, relapsing pericarditis, history of cardiac tamponade, cardiomyopathies
* Severe stenotic lesions (\>90%) in a coronary vessel with size \>2.75 mm not treated by PCI at least 24 hours before the baseline MRI study
* Previous EF≤45%, NYHA \> 2 (New York Heart Association Functional Classification) or hospital admission for heart failure before STEMI
* Sustained VT that does not revert with treatment or requires \>6 hours to be controlled in the 48 hours prior to the product administration procedure
* Complete atrioventricular blockade, or acute left bundle branch block in the 48 hours prior to the product administration procedure
* History of cardioembolic disease
* Platelets \<100,000 and/or Hb\<8.5g/dL
* Acute or chronic renal failure with creatinine ≥2.5 mg/dl or creatinine clearance ≤30 mL/min
* Infection with systemic involvement
* Cancer disease, except that eradicated at least 5 years before inclusion, and without receiving radiotherapy on chest. It is permitted coetaneous non-melanoma neoplasms completely eliminated (at any time) and that do not require subsequent chemotherapy or radiotherapy on chest.
* Child-Pugh's C stage chronic liver disease
* Baseline respiratory failure requiring oxygen at home
* Uncontrolled hypertension at screening despite treatment (systolic blood pressure \[BP\] ≥180 and/or diastolic BP ≥110)
* Very poorly controlled diabetes (Hb1Ac ≥8.5 g/dL) or with serious target organ lesion (peripheral vascular disease requiring revascularization or non revascularize)
* History of autoimmune disease
* Primary or acquired immune deficiency or immunosuppressant treatment (including treatments with immunosuppressants in the previous three months, or foreseeable need for those treatments during the course of the study).
* Women who are pregnant or breastfeeding or women of childbearing potential who do not agree to use contraceptives during the study period
* Life expectancy of less than 2 years for any reason.
* Allergy to aminoglycoside antibiotics or HSA hypersensitivity
* Contraindications preventing the use of Magnetic Resonance Imaging: Pacemaker, Implantable cardioverter-defibrillator (ICD), known reaction to gadolinium, claustrophobia, cochlear implants
18 Years
80 Years
ALL
No
Sponsors
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European Commission
OTHER
Universitaire Ziekenhuizen KU Leuven
OTHER
Saint-Louis Hospital, Paris, France
OTHER
Hospital General Universitario Gregorio Marañon
OTHER
Complejo Hospitalario de Navarra
OTHER
Hospital Clínico Universitario de Valladolid
OTHER
Hospital Donostia
OTHER
Hospital Clínico Universitario de Valencia
OTHER
University of Salamanca
OTHER
Hospital Universitario Virgen de la Victoria
OTHER
Coretherapix
INDUSTRY
Responsible Party
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Principal Investigators
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Marie Paule Richard, MD
Role: STUDY_DIRECTOR
Coretherapix (Tigenix Group)
Locations
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Coretherapix (Tigenix Group)
Tres Cantos, Madrid, Spain
Countries
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References
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Boukouaci W, Lauden L, Siewiera J, Dam N, Hocine HR, Khaznadar Z, Tamouza R, Borlado LR, Charron D, Jabrane-Ferrat N, Al-Daccak R. Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence. Cardiovasc Res. 2014 Nov 1;104(2):290-302. doi: 10.1093/cvr/cvu208. Epub 2014 Sep 11.
Lauden L, Boukouaci W, Borlado LR, Lopez IP, Sepulveda P, Tamouza R, Charron D, Al-Daccak R. Allogenicity of human cardiac stem/progenitor cells orchestrated by programmed death ligand 1. Circ Res. 2013 Feb 1;112(3):451-64. doi: 10.1161/CIRCRESAHA.112.276501. Epub 2012 Dec 12.
Crisostomo V, Baez C, Abad JL, Sanchez B, Alvarez V, Rosado R, Gomez-Mauricio G, Gheysens O, Blanco-Blazquez V, Blazquez R, Toran JL, Casado JG, Aguilar S, Janssens S, Sanchez-Margallo FM, Rodriguez-Borlado L, Bernad A, Palacios I. Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heart-derived cells. Stem Cell Res Ther. 2019 May 31;10(1):152. doi: 10.1186/s13287-019-1237-6.
Fernandez-Aviles F, Sanz-Ruiz R, Bogaert J, Casado Plasencia A, Gilaberte I, Belmans A, Fernandez-Santos ME, Charron D, Mulet M, Yotti R, Palacios I, Luque M, Sadaba R, San Roman JA, Larman M, Sanchez PL, Sanchis J, Jimenez MF, Claus P, Al-Daccak R, Lombardo E, Abad JL, DelaRosa O, Corcostegui L, Bermejo J, Janssens S. Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With ST-Segment Elevation Myocardial Infarction and Left Ventricular Dysfunction. Circ Res. 2018 Aug 17;123(5):579-589. doi: 10.1161/CIRCRESAHA.118.312823.
Sanz-Ruiz R, Casado Plasencia A, Borlado LR, Fernandez-Santos ME, Al-Daccak R, Claus P, Palacios I, Sadaba R, Charron D, Bogaert J, Mulet M, Yotti R, Gilaberte I, Bernad A, Bermejo J, Janssens S, Fernandez-Aviles F. Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction). Circ Res. 2017 Jun 23;121(1):71-80. doi: 10.1161/CIRCRESAHA.117.310651. Epub 2017 May 22.
Related Links
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Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence.
Allogenicity of human cardiac stem/progenitor cells orchestrated by programmed death ligand
Sponsor web page
European Clinical Trial Data Base
Other Identifiers
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CTPX01
Identifier Type: -
Identifier Source: org_study_id