An Open Label Dose Escalation Study to Evaluate the Safety of Administration of Non-Viral SDF-1 Plasmid to Treat Symptomatic Ischemic Heart Failure
Rationale: Preclinical studies indicate adult stem cells induce tissue repair by activating endogenous stem cells through the SDF-1:CXCR4 axis. JVS-100 is a DNA plasmid encoding human SDF-1.
Objective: Test in a Phase I open-label dose-escalation study with 12 months follow-up in subjects with ischemic cardiomyopathy (IsCM) to see if JVS-100 improves clinical parameters.
Methods and Results: Seventeen subjects with IsCM, NYHA Class III heart failure, with an ejection fraction ≤ 40% on stable medical therapy were enrolled to receive 5, 15 or 30 mg of JVS-100 via endomyocardial injection. The primary endpoints for safety and efficacy were at 1 and 4 months, respectively. The primary safety endpoint was major adverse cardiac events. Efficacy endpoints were change in quality of life (QOL), NYHA Class, 6 minute walk distance (6MWd), SPECT, NT-proBNP and echocardiography at 4 and 12 months. The primary safety endpoint was met. At 4 months, all cohorts demonstrated improvements in 6MWd, QOL and NYHA class. Subjects in the 15 mg and 30 mg dose groups exhibited improvements in 6MWd (15 mg: Median [Range]: 41 [3 to 61] m, 30 mg: 31 [22 to 74] m) and QOL (15 mg: -16 [+1 to -32] points; 30 mg: -24 [+17 to -38] points) over baseline. At 12 months improvements in symptoms were maintained.
Conclusions: These data highlight the importance of defining the molecular mechanisms of stem cell based tissue repair and suggest that over-expression of SDF-1 via gene therapy is a strategy for improving heart failure symptoms in patients with IsCM.
- Received October 31, 2012.
- Revision received January 20, 2013.
- Accepted January 23, 2013.
- Copyright © 2013 American Heart Association