EndocardialVascularEndothelialGrowth Factor D(VEGF-D)Gene Therapy for the Treatment of Severe Coronary Heart Disease (KAT301)
Biological: VEGF-D gene transfer
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Endocardial VEGF-D Gene Therapy for the Treatment of Severe Coronary Heart Disease - A Phase 1 Single-blinded Placebo-controlled Phase 1 Clinical Trial|
- Assessments for safety and tolerability as measured as the acute and late adverse effects, laboratory parameters, biodistribution of the vector, anti-adenovirus antibodies and VEGF-levels before and in several time points after the gene transfer. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Efficacy of GT to increase myocardial perfusion in MRI and PET. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Functional capacity in exercise test, LV-function in echocardiography, arrhythmias in 24-hours Holter-recording will be analyzed. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Improvement in symptoms, QOL and medication. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
|Experimental: Gene therapy||
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).
No Intervention: Control
Control patients will have electroanatomic mapping procedure but no gene injections.
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.
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.
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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01002430
|Kuopio University Hospital|
|Principal Investigator:||Juha Hartikainen||Kuopio University Hospital|