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EndocardialVascularEndothelialGrowth Factor D(VEGF-D)Gene Therapy for the Treatment of Severe Coronary Heart Disease (KAT301)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Kuopio University Hospital
Sponsor:
Collaborator:
University of Eastern Finland
Information provided by (Responsible Party):
Juha Hartikainen, Kuopio University Hospital
ClinicalTrials.gov Identifier:
NCT01002430
First received: October 23, 2009
Last updated: March 31, 2014
Last verified: March 2014

October 23, 2009
March 31, 2014
October 2009
December 2016   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01002430 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
  • Angina Pectoris
  • Myocardial Infarction
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).
  • Experimental: Gene therapy
    Intervention: Biological: VEGF-D gene transfer
  • No Intervention: Control
    Control patients will have electroanatomic mapping procedure but no gene injections.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
December 2016
December 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • informed consent signed,
  • age between 30 and 80 years,
  • significant angina pectoris (CCS II-III) despite of maximal medication,
  • significant stenosis in coronary angiography (stenosis > 60 %),
  • contraindication to coronary angioplasty or by pass operation (diffuse or distal stenosis,
  • chronic total occlusion,
  • vessels with difficult anatomy,
  • stenosis with severe calcifications,
  • stenosis in small vessels (< 2.5 mm)),
  • reversible myocardial perfusion defects detected by pharmacological adenosine or dobutamine assisted perfusion MRI,
  • angina pectoris or ischemic ST-depression (> 1 mm) in the exercise test,
  • left ventricle wall > 8 mm detected by transthoracal echocardiography (treatment area).

Exclusion Criteria:

  • women in fertile age,
  • patients with type 1 diabetes mellitus or severe end-stage type 2 diabetes mellitus,
  • diabetic retinopathy,
  • atrial fibrillation,
  • clinically significant anemia (hemoglobin count < 120 mg/l in male, < 110 mg/l in female; hematocrit < 0.36), leukopenia (b-leukocyte count < 3.0x109/l), leukocytosis (b-leukocyte count > 12.0x109/l) or thrombocytopenia (b-thrombocyte count < 100x109/l), renal insufficiency (s-creatinine > 160mg/l),
  • liver insufficiency (s-alanine amino transferase and s-alcaline phosphatase over 2 x normal),
  • haematuria of unknown origin,
  • severe hypertension (systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg) or significant hypotension (systolic blood pressure < 90mmHg),
  • significant obesity (BMI > 35),
  • cardiac pacemaker,
  • acute infection,
  • immunosuppressive medication,
  • significant impairment of the left ventricular function (EF < 25% in TTE or CO < 2 l in MRI),
  • congestive heart failure,
  • haemodynamically significant (gradus 3-4/4) aortic regurgitation or other heart disease needing surgery,
  • recent ( < 6 weeks) acute coronary syndrome or myocardial infarction (elevated CK-MB or cardiac troponin),
  • PCI or CABG or TIA/stroke,
  • previous or current malignancy.
Both
30 Years to 80 Years
No
Contact: Juha Hartikainen juha.hartikainen@kuh.fi
Finland
 
NCT01002430
KUH5101035
No
Juha Hartikainen, Kuopio University Hospital
Kuopio University Hospital
University of Eastern Finland
Principal Investigator: Juha Hartikainen Kuopio University Hospital
Kuopio University Hospital
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP