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
  Purpose

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.


Condition Intervention Phase
Angina Pectoris
Myocardial Infarction
Biological: VEGF-D gene transfer
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Kuopio University Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 30
Study Start Date: October 2009
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01002430

Contacts
Contact: Juha Hartikainen juha.hartikainen@kuh.fi

Locations
Finland
Kuopio University Hospital Recruiting
Kuopio, Finland
Contact: Juha Hartikainen       juha.hartikainen@kuh.fi   
Sponsors and Collaborators
Kuopio University Hospital
University of Eastern Finland
Investigators
Principal Investigator: Juha Hartikainen Kuopio University Hospital
  More Information

No publications provided

Responsible Party: Juha Hartikainen, Professor, Director, Heart Center, Kuopio University Hospital
ClinicalTrials.gov Identifier: NCT01002430     History of Changes
Other Study ID Numbers: KUH5101035
Study First Received: October 23, 2009
Last Updated: March 31, 2014
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Kuopio University Hospital:
Myocardial ischemia
Refractory angina pectoris
Vascular endothelial growth factor
Gene therapy
Perfusion

Additional relevant MeSH terms:
Angina Pectoris
Coronary Artery Disease
Coronary Disease
Heart Diseases
Infarction
Myocardial Infarction
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Chest Pain
Ischemia
Necrosis
Pain
Pathologic Processes
Signs and Symptoms
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014