Abstract 10186: Re-establishment of SDF-1 Expression Through Non-viral Gene Therapy (JVS-100) Significantly Improves Clinical Parameters In Patients with Ischemic Class III Heart Failure
Background: Stromal cell-derived factor-1 (SDF-1) has been shown to promote tissue repair following injury in multiple organ systems by promoting stem cell recruitment and vasculogenesis. JVS-100 is a non-viral DNA plasmid encoding hSDF-1. We have completed a Phase 1 open-label dose-escalation study demonstrating the safety and efficacy of JVS-100 delivered via the BioCardia Helical Infusion Catheter (HIC) in patients (pts) with ischemic cardiomyopathy and NYHA class III heart failure (HF).
Methods and Results: 17 pts with chronic NYHA class III ischemic HF and ejection fraction ≤ 40% were enrolled to receive JVS-100: 5 mg (n=4), 15 mg (n=6) and 30 mg (n=7) delivered to the peri-MI region via 15 endomyocardial injections with the HIC. Pts are being followed at 1, 4, and 12 months after injection. The primary safety endpoint, the number of major adverse cardiac events (MACE) at 1 month, was met. Efficacy assessment included changes from baseline in: echocardiographic parameters, NYHA class, 6 minute walk distance (6MWd) and quality of life score (QOL). At 4 months pts in the mid (15 mg) and high (30 mg) dose groups had greater improvements than the low dose group, as they demonstrated clinically relevant improvements from baseline in 6MWd (15 mg: Median [Range]: 41 [3 to 61] m, 30 mg: Median [Range]: 31 [22 to 74] m) and QOL (15 mg: Median [Range]: -16 [+1 to -32] points; 30 mg: Median [Range]: -24 [+17 to -38] points). The prespecified analysis of combined data from Cohorts 2 and 3 showed a statistically significant increase in 6MWd and QOL (p<0.03 for both), and 45% of patients improved at least one NYHA class (mean change -0.6, p<0.03). Importantly, we observed a dose dependent increase in troponin release in our porcine study and this phase I clinical trial at 6 hours after JVS-100 injection. Moreover, efficacy weakly correlated with troponin elevation. These data suggest that troponin release following gene transfer could be a marker of transfection.
Conclusions: These data suggest that re-establishing SDF-1 expression through the delivery of JVS-100 to patients with severe chronic heart failure is safe. Combined mid and high dose group data shows clinically-relevant, statistically significant improvements in 6MWd, QOL and NYHA class at 4 months.
- © 2011 by American Heart Association, Inc.