Abstract 19216: Dose-Dependent Reversal of Adverse Remodeling in High-Risk Ischemic Cardiomyopathy Patients Receiving Stromal Cell-derived Factor 1 Plasmid DNA in a Randomized Blinded Phase II Trial (STOP-HF)
Background: STOP-HF is a Phase II, double-blind, randomized placebo controlled trial to evaluate safety and efficacy of a single treatment of DNA plasmid encoding Stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection (EMI) to patients with symptomatic ischemic heart failure (IHF). SDF-1 promotes tissue repair through activation of endogenous stem cell recruitment, cell survival, and vasculogenesis. We hypothesized that higher-risk patients in STOP-HF would demonstrate a more pronounced benefit.
Methods: Ninety-three IHF subjects on stable medical therapy with low ejection fraction (EF), poor quality of life and limited 6 minute walk distance were randomized to receive either 15 injections of 0, 1 or 2 mg/ml (placebo, 15 mg or 30 mg groups, respectively) of pSDF-1 via EMI with the BioCardia Helical Infusion Catheter. We assessed safety and efficacy at 4 months (changes in cardiac volume and function via echocardiography, cardiac biomarkers, NYHA class, 6MWd, MLWHFQ score, and exercise capacity). The high-risk IHF subpopulation was defined as patients with baseline left ventricular (LV) end systolic volume (ESV) greater than the median (151 ml).
Results: As previously reported, in the overall study, changes in LVESV were 2 ± 23 ml vs. -11 ± 42 ml (placebo vs. 30mg dose, p=0.44) and for LVEDV -1 ± 29 ml vs. -13 ± 45 ml (placebo vs. 30mg dose, p=0.44) at 4 months. In the high risk population, changes from placebo at 4 months (at 15 mg and 30 mg, respectively) for LVESV were -16 ml (p=0.24) and -31 ml (p < 0.05), and for LV end diastolic volume (LVEDV) were -1 ml (p=0.7) and -24 ml (p=0.11). Similarly, changes in NTproBNP were -394 pg/ml (p=0.47) and -742 pg/ml (p=0.12) and LVEF improved by 5.9% (p=0.09) and 5.3% (p=0.23) vs. placebo in 15 mg and 30 mg patients, respectively, showing concordant improvement of pSDF-1 treated patients in these objective clinical parameters.
Conclusions: Our data demonstrates, in high-risk IHF patients, pSDF-1 elicits reversal of LV remodeling leading to clinically meaningful reductions in volumes and NTproBNP relative to placebo. These concordant, dose-dependent improvements in objective clinical parameters following pSDF-1 delivery via EMI support further clinical development of pSDF-1 treatment of heart failure
Author Disclosures: L. Miller: None. W. Sherman: None. A. Patel: None. R. Anderson: None. F. Mendelsohn: Consultant/Advisory Board; Modest; Juventas Therapeutics. S. Fisher: Employment; Significant; Juventas Therapeutics. J. Pastore: Employment; Significant; Juventas Therapeutics. R. Aras: Employment; Significant; Juventas Therapeutics. E. Chung: Research Grant; Modest; Otsuka. Consultant/Advisory Board; Modest; Medtronic, Boston Scientific, Gambro, CardioMems. M.S. Penn: Consultant/Advisory Board; Significant; Juventas Therapeutics, SironRx Therapeutics, Athersys.
- © 2014 by American Heart Association, Inc.