A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Non-Ischemic Heart Failure
Rationale: Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of ischemic and non-ischemic heart failure (HF).
Objective: To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million [M] cells) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial.
Methods and Results: We sequentially allocated 60 patients 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 cardiac events (MACE; cardiac death, myocardial infarction, 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 patients: 10/45 (22%) MPC-treated and 5/15 (33%) control patients. We found no differences between MPC-treated and control patients in survival probability, MACE-free probability, and all-cause mortality. We conducted a post-hoc analysis of HF-related MACE (HF hospitalization, successfully resuscitated cardiac death, or cardiac death); 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 HF patients. High-dose allogeneic MPCs may provide benefits in this population.
- Received February 24, 2015.
- Revision received June 19, 2015.
- Accepted July 6, 2015.