EndocardialVascularEndothelialGrowth Factor D(VEGF-D)Gene Therapy for the Treatment of Severe Coronary Heart Disease
Condition: Angina Pectoris; Myocardial Infarction
MeSH terms: Heart Diseases; Myocardial Infarction; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Angina Pectoris; Infarction
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to evaluate the safety and efficacy of catheter mediated
      endocardial adenovirus VEGF-D gene therapy in patients with severe coronary heart disease.
    

Detailed description: 
      Study objective(s):

      The purpose of the study is to evaluate the safety and efficacy of catheter mediated
      endocardial adenovirus VEGF-D gene transfer in patients with severe coronary heart disease to
      whom revascularisation cannot be performed ("no option -patients"). The primary objective is
      safety of the gene therapy and the secondary objective is the efficacy of gene therapy to
      improve myocardial perfusion as measured by MRI, PET and left ventricular function as
      measured by echocardiography as well as to improve functional status as measured by bicycle
      ergometer test. Quality of life will be monitored with a personal interview and the
      consumption of nitrate medication.

      Study design:

      This is a randomised, single-blinded, placebo controlled single centre Phase I study for
      patients with coronary heart disease to whom no other treatment than standard medication is
      available. Patients will be randomized 4:1 to the treatment group and control group. Control
      patients will not be treated with gene injections but only with cardiac electroanatomical
      mapping.

      Study population:

      Up to thirty patients will be recruited from the area of Kuopio University Hospital in the
      study. The patients will be selected for the trial on the basis of coronary angiogram
      imaging. Only those patients who are not eligible for the coronary angioplasty or bypass
      operation ("no option -patients") due to diffuse coronary stenosis, small coronary vessels,
      repeated revascularisation or too high risk for operation, will be included.

      Assessments:

      Assessments for safety are recording of adverse events (Appendix 4), laboratory assessments
      and transthoracic echocardiography. Assessments for efficacy are clinical symptoms and need
      for nitrate medication, cardiac MRI, PET and bicycle ergometer test. Other assessments are
      24-hour Holter recording, transthoracal echocardiography, quality of life and PCR reactions
      for the detection of gene and virus vector.

      Investigational drug product:

      First generation replication-deficient AdVEGF-D produced in 293 cells (refer to product
      master file (PMF-VD-08-001)) will be injected into ten sites in the endocardium. In the
      beginning, an escalating dose of 1x109, 1x1010 and 1x1011 vpu of virus in a total volume of 2
      ml (10 times 0.2 ml) will be used. On the basis of fifteen patients an interim analysis will
      be performed to evaluate the most suitable dose of virus which will be used for the rest of
      the study patients. Control patients will not be treated with drug product, only
      electroanatomical mapping will be performed.
    

Intervention name(s): VEGF-D gene transfer
Intervention type(s): Biological
Intervention description(s): Gene transfer will be performed by using endocardial injection system (NOGATM) and an escalating dose of 1x109, 1x1010 and 1x1011 vpu of AdVEGF-D will be injected into 10 sites of the myocardium (0.2 ml per site).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Myocardial ischemia; Refractory angina pectoris; Vascular endothelial growth factor; Gene therapy; Perfusion