CARE-MI completes recruitment for Phase I/IIa clinical trial for acute myocardial infarct treatment with allogeneic cardiac stem cells


Researchers from the CARE-MI consortium, which includes iBET, have announced completion of recruitment for the randomized double blind and placebo-controlled phase of the CAREMI study. This study will evaluate the efficacy and safety of a new product based on cardiac stem cells (CSC) from unrelated donors for the treatment of acute myocardial infarction. The phase I/IIa clinical trial involves 55 patients, who will be followed for one year to evaluate safety and efficacy endpoints. Final results of the study are expected in the first trimester of 2017.

Acute myocardial infarction is one of the major challenges facing health care systems in developed countries. Although prompt angioplasty to re-establish myocardial perfusion has reduced mortality considerably, infarction is responsible for a large proportion of cases of chronic heart failure and it remains a serious health problem that requires new, innovative solutions.

The CAREMI trial has been supported by the European Union's Seventh Framework Programme for Research (FP7) and was carried out through the collaborative efforts of the members of the CARE-MI consortium. The central objective of the CARE-MI consortium is to advance the therapeutic potential of cardiac stem cells (CSC) in myocardial disease.

Over the last five years, the CARE-MI consortium has worked on developing a cell product for treatment of the damage caused by infarction, based on activation of the heart’s natural repair mechanisms. AlloCSC-01, the cell product candidate developed by Coretherapix (part of the TiGenix group since July 2015) and tested in the CAREMI study, is made of allogeneic cardiac stem cells that are supplied frozen and ready to use at clinical centres. Preclinical results indicate that its administration during the first week post-infarction limits cardiac remodeling and promotes cardiac regeneration.
Nine clinical centres are participating in the trial, under the leadership of Prof. Francisco Fernández-Avilés of the Hospital Gregorio Marañón in Madrid and Prof. Stefan Janssens of UZ Leuven, Belgium. The remaining centres involved in the study are the Hospital de Navarra, Hospital Clínico Universitario de Valladolid, Hospital Universitario de Donostia, Hospital Universitario de Salamanca, Hospital Clínico Universitario de Valencia, Hospital Vall d´Hebron in Barcelona and Hospital Virgen de la Victoria de Málaga, all based in Spain.

About the CAREMI consortium

The CAREMI consortium, funded with an €11.3 million grant from the European Union's Seventh Framework Programme for Research, brought together specialists in basic and applied research, pharmaceutical development and clinical centers, under the coordination of the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid to advance understanding and development of cardiac regeneration therapies.

The technological development core of the project, led by Coretherapix, was the advancement of a novel cardiac stem cell therapy (AlloCSC-01) through the preclinical validation stage, industrial manufacturing, regulatory approval and finally, the first-in-human clinical trial currently under way. In this collaborative effort, the project has benefited from the complementary contributions of all partners. The Centro de Cirugía de Mínima Invasión Jesús Usón (Cáceres, Spain) and KU Leuven (Belgium) developed the key large animal models necessary for preclinical validation. Two Spanish contract research organizations (CRO), Vivotecnia (Madrid) and Farma-Cros (Albacete), generated the biosafety and biodistribution data during the early phases of preclinical development. With the co-sponsorship of Coretherapix, the contract manufacturing organization (CMO) 3P Biopharmaceuticals (Pamplona, Spain) was subcontracted to manufacture the AlloCSC-01 product under cGMP conditions. The KU Leuven and Hospital General Universitario Gregorio Marañón in Madrid led the clinical trial. Finally, the HLA-Med group of the Hôpital St. Louis in Paris also had a key role in characterizing the immune interaction of the allogeneic cell product during the preclinical phase, which it will continue during the clinical trial. In parallel to the product development effort, the CNIC, the Centro Nacional de Biotecnología (CNB-CSIC) and the Instituto de Biología Experimental e Tecnológica (IBET, Lisbon, Portugal) carried out exhaustive molecular and cellular characterization of the cell product, studied its response to various stimuli and experimented with new technologies for future large scale manufacturing. Philips (in Madrid and Amsterdam) also contributed new approaches to monitoring cardiac function with magnetic resonance imaging. Research questions surrounding the field of myocardial regeneration were explored at the Liverpool John Moores University, King’s College London (UK), CNB/CNIC, the University of Goettingen (Germany), University of Ljubliana (Slovenia) and Hospital Vall d’Hebrón (Spain). In a separate development stream of the project, the use of advanced growth factor formulations to provide non-cellular alternatives for cardioprotection following acute myocardial infarction have also been developed by the Dutch companies Innocore and Nanomi (recently acquired by the multinational Lupin).