Results of the Phase I/IIb EXCELLENT trial evaluating the safety and efficacy of transendocardial injection of expanded autologous CD34+ cells in patients with recent myocardial infarction

Abstract

Background & Aim

Acute myocardial infarction is followed by irreversible cardiomyocyte necrosis that leads to left ventricular (LV) disfunction and detrimental clinical outcomes. CD34+ cell-based therapy has emerged as an option to repair the myocardium and improve outcomes. After AMI, CD34+ cells are mobilized from the bone marrow to the peripheral blood and the extent of this mobilization is significantly correlated with heart regeneration and functional improvement. In a pilot study, we showed that intramyocardial administration of autologous CD34+ cells leads to long term improvement with average survival of 17 years, compared to the 5-year survival generally observed in 50% of AMI patients. CD34+ cells promote revascularization and cardiomyocyte regeneration through the secretion of paracrine factors. Here, we describe the results of the EXCELLENT study, an international multicenter randomized open label Phase 1/2b clinical trial to evaluate the safety and efficacy of transendocardial injections of autologous expanded CD34+ cells in post-AMI patients (NCT02669810).

Methodology

Thirty-three participants with a large AMI and LV ejection fraction <50% were randomized to the treatment plus standard of care arm and 16 participants to the standard of care arm. Participants randomized to intervention were treated with lenograstim for 5 days before blood cell harvest from which autologous CD34+ cells were purified and expanded using an automated GMP compliant platform. The primary endpoint was the incidence of major adverse cardiac events over 6 months. The main secondary endpoints included the improvement of LV end systolic volume index and the viability of the infarcted segments over 6 months.

Results

There were no significant differences in baseline values between the patients in the two treatment arms and more than 90% of patients presented with microvascular obstructions. The transendocardial injection procedure was considered feasible and safe and there were no serious adverse events related to the product. There were favorable changes in blinded central reading secondary endpoints. Autologous expanded CD34+ cells improved remodeling as suggested by congruent favorable changes in viability (infarcted zone), left ventricular dimensions, NT-proBNP, and quality of life.

Conclusion

The long-term effects on these patients are being evaluated in a 10-year follow-up study. As observed in the pilot study, we believe that this therapy has the potential to improve the long-term clinical outcome of these patients.