A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in @entity1 With XXXX .

@entity1 @entity712 @entity63 @entity299 @entity583 @entity204
RATIONALE: Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of @entity63 and non- @entity63 @entity712 ( @entity712 ). OBJECTIVE: To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million [M] cells) of immunoselected allogeneic MPCs in chronic @entity712 @entity1 in a phase 2 trial. METHODS AND RESULTS: We sequentially allocated 60 @entity1 to a dosing cohort (20 per dose-group) and randomized them to transendocardial MPC injections (n=15) or mock procedures (n=5). The primary objective was safety, including antibody testing. Secondary efficacy endpoints included major adverse @entity299 (MACE; @entity204 , @entity583 , or revascularization), left ventricular imaging, and other clinical-event surrogates. Safety and MACE were evaluated for up to 3 years. MPC injections were feasible and safe. Adverse events were similar across groups. No clinically symptomatic immune responses were noted. MACE was seen in 15 @entity1 : 10/45 (22%) MPC-treated and 5/15 (33%) control @entity1 . We found no differences between MPC-treated and control @entity1 in survival probability, MACE-free probability, and all-cause mortality. We conducted a post-hoc analysis of @entity712 -related MACE ( @entity712 hospitalization, successfully resuscitated @entity204 , or @entity204 ); events were significantly reduced in the 150M group (0/15) versus control (5/15;33%), 25M (3/15;20%), and 75M (6/15;40%); the 150M group differed significantly from all groups according to Kaplan-Meyer statistics over 3 years (P=0.025 for 150M vs control). CONCLUSIONS: Transendocardial injections of allogeneic MPCs were feasible and safe in chronic @entity712 @entity1 . High-dose allogeneic MPCs may provide benefits in this population.
