Abstract 16845: Non-Viral Gene Therapy Encoding Stromal Cell-Derived Factor-1 Improves Clinical Parameters Through 12 Months 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 human SDF-1 that expresses SDF-1 for ∼20 days. We have completed 12 month follow-up of a Phase 1 open-label dose-escalation multi-center study in patients with ischemic heart failure (HF) demonstrating safety and efficacy of JVS-100 delivered via endomyocardial injection.
Methods and Results: 17 patients with chronic NYHA class III HF symptoms and ejection fraction ≤ 40% received JVS-100: 5 mg (n=4), 15 mg (n=6) and 30 mg (n=7) delivered via 15 endomyocardial injections with the BioCardia Helical Infusion Catheter and were followed at 1, 4, and 12 months. Regarding safety, 26 serious adverse events were reported, none clearly attributable to JVS-100. Efficacy assessments using quality of life scores (QOL), 6-minute walk distances (6MWd), NYHA class, and echocardiographic parameters were prospectively designed based on preclinical studies to combine 15 and 30 mg dose groups. At 12 months: Structural Changes: echocardiography revealed stabilization of cardiac size, as change in end systolic volume from baseline in the combined group (7 ± 8 ml) was less than in the 5 mg group (19 ± 35 ml) (mean ± SEM). Clinical Changes: the combined group experienced improved QOL (-24 points [-56 to 7], p<0.01) and 6MWd (17 m [-96 to 112], p = n.s.) over baseline levels, with lesser changes seen in the 5 mg group (6MWd: -3 m [-75 to 90], QOL: -5 points [-25 to 18]), (median [range]).
Conclusions: These Phase 1 data suggest that re-establishing stem cell recruitment by SDF-1 expression in patients with severe chronic heart failure is safe and provides clinically significant improvements in 6MWd and QOL through 12 months. On the basis of these data, a 90 patient randomized, placebo-controlled Phase II trial will begin in summer 2012.
- © 2012 by American Heart Association, Inc.