We have recently completed our Phase I/IIa randomised, controlled, single-blinded feasibility, safety, dose-finding and potential efficacy trial with intramyocardial AdVEGF-D. The trial showed that regenerative AdVEGF-D gene transfer is safe and increases myocardial perfusion in patients with refractory angina after 1 year follow-up.
Our phase I trial included a total of 30 patients who were randomized to intramyocardial AdVEGF-D gene transfer (VEGF-D group) or placebo (control group) with a 4:1 ratio. The VEGF-D group underwent electroanatomical mapping of the left ventricle with the NOGA catheter system, and assessment of myocardial perfusion at rest and perfusion reserve during adenosine stress with 15O radiowater PET. AdVEFG-D was injected intramyocardially to areas with impaired perfusion reserve or reduced contraction but viable myocardium. The control group underwent a similar catheterization procedure, PET perfusion imaging, left ventricle mapping and intracardiac saline infusion. Vital signs and laboratory assessments were measured at baseline and at 1, 2, 7, 14 days and 3 and 12 months after the gene therapy to evaluate the safety and feasibility of the treatment. Myocardial perfusion and blood flow reserve were assessed at baseline, and at 3 and 12 months after the procedure.
Mild transient elevation in body temperature and CRP (C-reactive protein - a blood test marker for inflammation in the body) and a moderate drop in blood pressure were detected in the VEGF-D group after the procedure. Troponine-T (a skeletal and smooth muscle protein released into the blood stream when damage to the heart muscle occurs) was elevated in both groups after the procedure but normalized within two days. No significant differences were found in adverse events. Perfusion reserve at twelve months in the myocardial segment with the lowest perfusion reserve at baseline increased significantly in the VEGF-D group but not in the controls. No antibody responses were found against the transgene in the VEGF-D group after the treatment.
We concluded that intramyocardial AdVEGF-D gene therapy is safe and well tolerated in refractory angina patients. Changes in PET analysis at 3 and 12 months indicated that gene therapy can increase myocardial perfusion reserve in segments with impaired perfusion reserve at baseline. Based on our results we concluded that a randomized, controlled, blinded phase II/III trial was justified.