Safety and Efficacy Evaluation of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With AMI (CAREMI)
Development of myocardial reparative therapy for the treatment of acute ischemic cardiac disease, based on the intracoronary administration of allogeneic Cardiac Stem Cells (CSCs) to ameliorate myocardial cell death and promote cardio-regeneration.
The study comprises two phases:
- 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.
- Randomized double-blind placebo-controlled safety and efficacy phase in which the TD will be injected if the dose-escalation phase is completed successfully.
|Acute Myocardial Infarction||Other: Allogeneic human cardiac stem cells (CSCs) Other: Human Serum Albumin-HSA 5%||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||First-in-human, Double Blind, Randomized With Placebo, Open for the 6 First Patients (Dose Ranging) to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human CSCs in Patients With AMI and Left Ventricular Dysfunction|
- Safety measured as the number of deaths and number of Major Adverse Cardiac Events (MACE) [ Time Frame: 12 months ]The primary objective is to demonstrate the safety of the intra-coronary infusion of allogeneic cardiac stem cells in patients with a 7 days evolution first myocardial infarction and left ventricle dysfunction. Safety will be assessed a) evaluating the number of deaths from any cause within 30 days after cell medicine administration; b) evaluating the number of Major Adverse Cardiac Events (MACE) during the first 30 days (composite endpoint), defined as death from any cause, new Acute Myocardial Infarction (AMI), hospitalization due to Heart Failure (HF), sustained Ventricular Tachycardia (VT), Ventricular Fibrillation (VF), and stroke within 12 months after cell medicine administration.
- Efficacy measured by MRI as the infarct size change [ Time Frame: 6 and 12 months ]Change of the Infarct Size as percentage (%) of LV mass analysed by MRI at 6 and 12 months after treatment administration versus screening MRI and 1 month MRI.
- Efficacy measured by MRI as the evolution of biomechanical parameters [ Time Frame: 6 and 12 months ]Percentage of change of the End Systolic Volume (ESV) and End Diastolic Volume (EDV), of the Wall Motion score as segmental contraction score, of the Sphericity Index, of the Systolic thickening by segment and of the Absolute change of Ejection Fraction (EF) analysed by MRI at 6 and 12 months after treatment administration versus screening MRI and 1 month MRI.
- Efficacy measured by MRI as the evolution of edema [ Time Frame: 1 month ]Percentage of change in the edema volume analysed by MRI at 1 month after treatment administration versus screening MRI.
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||December 2016|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: 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.
Other: 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.
Other Name: AlloCSC-01
Placebo Comparator: 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%).
Other: 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.
This is a "First in Patient" Clinical Trial to obtain safety and efficacy results about the intracoronary administration of a suspension of allogeneic cardiac stem cells (CSCs) for the treatment of ST elevation Myocardial Infarction (STEMI). This clinical trial will have a first dose-escalation phase in which the safety of 10, 20 and 35 million CSCs administration will be evaluated in 6 patients. A second double-blind randomized and placebo controlled phase will be initiated, if no major safety effects are observed during the first week after cell administration. The 35 million cells dose is the one expected to be used during the randomized phase.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02439398
|Coretherapix (Tigenix Group)|
|Tres Cantos, Madrid, Spain, 28760|
|Study Director:||Marie Paule Richard, MD||Coretherapix (Tigenix Group)|