NCT01002430

EndocardialVascularEndothelialGrowth Factor D(VEGF-D)Gene Therapy for the Treatment of Severe Coronary Heart Disease

Endocardial VEGF-D Gene Therapy for the Treatment of Severe Coronary Heart Disease - A Phase 1 Single-blinded Placebo-controlled Phase 1 Clinical Trial

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Kuopio University Hospital · Academic / Other
• Sex: All
• Age: 30 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Angina Pectoris
• Myocardial Infarction

Interventions

Type	Name	Description
BIOLOGICAL	VEGF-D gene transfer	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).

Timeline

• Start date: 2010-01-10
• Primary completion: 2015-06-15
• Completion: 2015-06-15
• First posted: 2009-10-27
• Last updated: 2018-03-08

Locations

1 site across 1 country: Finland