Angina PectorisPhase 1KAT301NCT01002430
EndocardialVascularEndothelialGrowth Factor D(VEGF-D)Gene Therapy for the Treatment of Severe Coronary Heart Disease
A Phase 1 study testing VEGF-D gene transfer in people with Angina Pectoris and Myocardial Infarction, run by Kuopio University Hospital at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Angina Pectoris, Myocardial Infarction
- What is being tested?
- VEGF-D gene transfer
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFinland
- Study dates
- 10 Jan 2010to 15 Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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).
Who cannot join
- 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),
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- VEGF-D gene transfer
- Keywords
- Myocardial ischemia, Refractory angina pectoris, Vascular endothelial growth factor, Gene therapy, Perfusion
- Medical subject headings
- Angina Pectoris, Myocardial Infarction, Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VEGF-D gene transferBiological
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).
| Study group | Role | What they receive |
|---|---|---|
| Gene therapy | Experimental | Not described Receives: Biological: VEGF-D gene transfer |
| Control | No intervention | Control patients will have electroanatomic mapping procedure but no gene injections. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (3)
Efficacy of GT to increase myocardial perfusion in MRI and PET.
Measured: 1 year
Functional capacity in exercise test, LV-function in echocardiography, arrhythmias in 24-hours Holter-recording will be analyzed.
Measured: 1 year
Improvement in symptoms, QOL and medication.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2009 (estimated)
- Study start10 Jan 2010
- Primary completion15 Jun 2015
- Study completion15 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Angina PectorisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kuopio University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Eastern Finland
- Responsible party
- Principal investigator, Juha Hartikainen, Kuopio University Hospital
- Investigators
- Juha Hartikainen, Principal investigator, Kuopio University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01002430
- Sponsor's protocol ID
- KUH5101035
- Acronym
- KAT301
- Status last verified
- Mar 2018
- First submitted
- 23 Oct 2009
- Last updated
- 8 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Leikas AJ, Hassinen I, Kivela A, Hedman A, Mussalo H, Yla-Herttuala S, Hartikainen JEK. Intramyocardial adenoviral vascular endothelial growth factor-D∆N∆C gene therapy does not induce ventricular arrhythmias. J Gene Med. 2022 Aug;24(8):e3437. doi: 10.1002/jgm.3437. Epub 2022 Jul 6.
PubMed 35750637
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01002430
- Acronym / sponsor ID
- KAT301 / KUH5101035
- Conditions
- Angina Pectoris, Myocardial Infarction
- Keywords
- Myocardial ischemia, Refractory angina pectoris, Vascular endothelial growth factor, Gene therapy, Perfusion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Kuopio University HospitalUniversity, hospital or other
- Collaborators
- University of Eastern Finland
- Study start
- 10 Jan 2010 (actual)
- Primary completion
- 15 Jun 2015 (actual)
- Study completion
- 15 Jun 2015 (actual)
- First posted
- 27 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gene therapy | Experimental | Biological: VEGF-D gene transfer |
| Control | No intervention | –Control patients will have electroanatomic mapping procedure but no gene injections. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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,
Key exclusion criteria (18 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VEGF-D gene transferGene 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). | Biological | Gene therapy |
Primary outcome
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
3 secondary outcomes
Efficacy of GT to increase myocardial perfusion in MRI and PET.
Time frame: 1 year
Functional capacity in exercise test, LV-function in echocardiography, arrhythmias in 24-hours Holter-recording will be analyzed.
Time frame: 1 year
Improvement in symptoms, QOL and medication.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2018.
- Derived from this study: PubMed 35750637Leikas AJ, Hassinen I, Kivela A, Hedman A, Mussalo H, Yla-Herttuala S, Hartikainen JEK. Intramyocardial adenoviral vascular endothelial growth factor-D∆N∆C gene therapy does not induce ventricular arrhythmias. J Gene Med. 2022 Aug;24(8):e3437. doi: 10.1002/jgm.3437. Epub 2022 Jul 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juha Hartikainen principal investigator
Kuopio University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VEGF-D gene transfer in people with Angina Pectoris and Myocardial Infarction, run by Kuopio University Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01002430, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2018.