• Cardiology Clinical Trials
• Heart Failure

• Cardiology Clinical Trials
• Cardiology & Cardiovascular Medicine
• Heart Failure

Patients with heart failure (HF) and previous myocardial infarctions (MIs) demonstrated favorable outcomes after treatment with JVS-100, a plasmid that encodes for stromal cell–derived factor-1. Marc S. Penn, MD, PhD, Summa Cardiovascular Research, Akron, Ohio, USA, presented data from the Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure trial [STOP-HF; NCT01643590].

Although ischemic tissue could potentially be repaired by stem cells, it may be inefficient because key molecular signals are either dysfunctional or expressed short term. Early studies suggest that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell–derived factor-1/chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell–derived factor-1; therefore, it has been hypothesized that administration in patients with HF could improve outcomes through improved stem cell homing. This was previously investigated in a Phase 1 open-label trial demonstrating that JVS-100 was safe, with initial signs of potential efficacy [Penn MS et al. Circ Res 2013]. The purpose of the current trial was to further evaluate the efficacy and safety of JVS-100 in patients with HF.

In the multicenter, Phase 2 STOP-HF trial, 93 patients with HF and prior MIs were randomly assigned to receive placebo (cohort 1), 15 mg of JVS-100 (cohort 2), or 30 mg of JVS-100 (cohort 3) by endomyocardial injection. Patients qualified if they had 6-minute walk distances ≤400 m, left ventricular ejection fractions (LVEF) ≤40%, and Minnesota Living With Heart Failure Questionnaire scores ≥20. Baseline characteristics included a mean age of 65 years, history of MI 11 years previously with a mean LV end-systolic volume (LVESV) of 168 mL and a mean LVEF of 28.5%.

The primary end points for this analysis were (1) the impact of the JVS-100 injection on 6-minute walk distance compared with placebo at 4-month follow-up and (2) the impact of the injection on the quality of life. Safety assessments included the numbers of major adverse cardiac events, serious adverse events, and adverse events up to 12 months.

At 4 months, there were no significant differences in clinical or structural parameters of efficacy with JVS-100. There were, however, trends that favored 30 mg of JVS-100 compared with placebo. Treatment with either dose of JVS-100 resulted in a decrease in LVESV from baseline compared with placebo. There was a promising trend toward a greater negative change from baseline in left ventricular end-diastolic volume (LVEDV) with 30 mg of JVS-100 compared with placebo and 15 mg of JVS-100 (p=0.11). In addition, patients who received 15 or 30 mg of JVS-100 experienced a trend toward a greater positive change from baseline in ejection fraction compared with patients who received placebo, who experienced a negative change from baseline. Similarly, there was a dose-dependent decrease in N-terminal prohormone of brain natriuretic peptide. Although there were no significant differences with therapy, the observed trends were seen primarily in patients with LVESVs above the median at baseline, whereas patients with LVESVs below the median did not demonstrate the same beneficial trends in change from baseline in LVESV, LVEDV, or LVEF. Although there was no significant difference in terms of efficacy with this early phase trial, JVS-100 appeared to be well tolerated with no serious adverse events reported.

Dr. Penn concluded that the data from the STOP-HF study suggest that JVS-100 may provide benefits in patients with HF and previous MIs. Although there was no significant benefit in this early-phase trial of treatment with JVS-100, it appeared safe and showed promising trends for efficacy.

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