Abstract 20536: ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR): the One Year Phase I Results

Abstract

Introduction: In CADUCEUS, autologous cardiosphere-derived cells decreased infarct size and increased viable tissue in post-myocardial infarction (MI) subject s. Hypothesis: The first-in-human Phase I ALLSTAR trial was designed to test the safety and feasibility of intracoronary infusion of allogeneic cardiosphere-derived cells (CAP-1002) in patients with an anterior MI, within the prior 12 months with a scar size >15% by Magnetic Resonance Imaging (MRI). Methods: A total of 14 adult subjects (mean age = 55.6 yr; range 40-66 years) with a recent (28 - 90 days; n=9) or chronic (91-365 days; n=5) anterior MI (mean infarct size 25.4%; range 15.3% - 32.7%) and LV dysfunction (mean LVEF 42%; range 26.7% - 55.1%) were prospectively enrolled and infused with CAP-1002 (n=4 at 12.5M dose; n=10 at 25M dose) via stop-flow intracoronary infusion. Primary safety endpoints were: MACE events (recurrent MI, hospitalization or ER treatment for heart failure, Left Ventricular Assist Device placement or heart transplantation), acute myocarditis, death due to arrhythmias or unwitnessed death. Humoral and cellular immunologic responses were assessed via single antigen bead and ELISpot assays. Results: No pre-specified safety endpoint occurred. Only two adverse events were treatment-related, both transient hypotension related to nitroglycerin. There were no clinically significant rises in peri-procedural cardiac enzymes. Donor specific antibodies (DSAs) were present in four subjects prior to infusion; one resolved and three presistent at 6 months of follow up. De novo DSA’s developed in four subjects, three resolved during follow up and one persisted at 6 months of follow up. All DSA levels were low (MFI<5000). ELISpot revealed no de novo cellular immune responses. One year follow-up safety data as well as full 6 month and available 12 month MRI results on scar size and LVEF will be presented. Conclusions: Intracoronary infusion of allogeneic cardiosphere-derived cells (CAP-1002) appears to be safe and feasible. On the basis of the Phase 1 findings, the ALLSTAR trial has proceeded to a Phase II randomized, double-blind trial, powered to assess reduction of scar size by MRI.