Refractory Angina PectorisPhase 2ReGenHeartNCT03039751
Adenovirus Vascular Endothelial Growth Factor D (AdvVEGF-D) Therapy for Treatment of Refractory Angina Pectoris
A Phase 2 study testing AdvVEGF-D in people with Refractory Angina Pectoris and Gene Transfer, run by Kuopio University Hospital at 2 sites in 2 countries.
Trial summary
The purpose of the study is to evaluate the safety and efficacy of catheter mediated endocardial adenovirus-mediated vascular endothelial growth factor-D (AdVEGF-D) regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed. Read more about this study
- Who is it for?
- Ages 30 to 85 years
- Conditions the study is for
- Refractory Angina Pectoris, Gene Transfer, Coronary Artery Disease
- What is being tested?
- AdvVEGF-D
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 19 Oct 2019to 31 Dec 2023
- Phase
- Phase 2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- informed consent signed
- age > 30 but < 85 years
- significant angina pectoris (CCS 2-3) despite of optimal medication
- significant stenosis (> 60%) in coronary angiography (< 6 months)
- contraindication to CABG or PCI due to diffuse or distal stenosis, chronic total occlusion, vessels with difficult anatomy, stenosis with severe calcifications and stenosis in small vessels (<2.5 mm))
- angina pectoris or equivalent symptoms in the 6-minute walking exercise test
- left ventricle wall > 8 mm detected by transthoracic echocardiography or magnetic resonance imaging (treatment area)
Who cannot join
- women in fertile age
- diabetes mellitus with severe complications such as diabetic retinopathy or nephropathy
- 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 (P-creatinine > 160 mg/l)
- liver insufficiency (P-alanine aminotransferase or P-alkaline phosphatase over 2 x normal)
- haematuria of unknown origin
Show all 15Show fewer
- severe hypertension (systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg) or significant hypotension (systolic blood pressure < 90 mmHg)
- significant obesity (Body Mass Index > 35)
- acute infection
- immunosuppressive medication
- significant impairment of left ventricular function (ejection fraction < 25% in echocardiography)
- symptomatic congestive heart failure (New York Heart Association class 3-4)
- haemodynamically significant (grade 3-4/4) aortic or mitral regurgitation or other heart disease needing surgery
- recent (< 6 weeks) acute coronary syndrome or myocardial infarction, PCI or CABG, stroke or transient ischemic attack (TIA)
- current or suspected malignancy
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Clinical Development and Proof of Principle Testing of New Regenerative Adenovirus Vascular Endothelial Growth Factor (VEGF-D) Therapy for Cost-effective Treatment of Refractory Angina. A Phase II Randomized, Double-blinded, Placebo-controlled Study (ReGenHeart)
The purpose of the study is to evaluate the safety and efficacy of catheter mediated endocardial adenovirus-mediated vascular endothelial growth factor-D (AdVEGF-D) regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.
Read the detailed description
Study overview:
The purpose of the study is to evaluate the safety and efficacy of catheter mediated AdVEGF-D regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.
Primary objectives:
To test the efficacy of the therapy to improve functional capacity using 6 minute walking test after 6 months follow-up and improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class.
Secondary objectives:
Efficacy of the gene transfer to increase to improve functional capacity using 6 minute walking test and improvement of symptoms assessed by CCS class after 12 months as well as increase in myocardial perfusion assessed 6 months after the gene transfer. In addition, at 6 and 12 months timepoints, the improvement quality of life (QoL), the use of angina pectoris medication, major adverse cardiac events related to coronary artery disease (cardiovascular death, myocardial infarction, stroke, revascularization and hospital admission due to coronary artery disease) or a combined endpoint of the above (Major Adverse Cardiac Events, MACE) will be evaluated.
Study design:
ReGenHeart is a randomized, double-blinded, placebo-controlled multicentre phase II study which will be conducted at 6 centers. The study will evaluate the efficacy and safety of catheter mediated endocardial AdVEGF-D regenerative gene transfer in 180 patients with angina pectoris or equivalent symptom despite optimal medical therapy and who are not suitable candidates for coronary revascularization with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (refractory angina patients).
Study population:
180 patients will be recruited from the six centers in 2 years. The patients will be selected for the trial on the basis of medical history, general status, laboratory analyses, coronary angiogram and 6-minute walking test. Patients with CCS 2-3 angina pectoris despite optimal medical therapy and who are not eligible for coronary angioplasty or bypass operation due to diffuse coronary stenosis, small coronary vessels, repeated revascularization or too high risk for operation, will be included.
The number of subjects to be recruited and randomized to the trial will be 180 (2:1 ratio to the treatment and control groups).
Investigational drug product:
First generation replication-deficient AdVEGF-D produced in 293 cells will be injected into ten sites in the endocardium. The dose of 1x1011 vp in a total volume of 2 ml (10 times 0.2 ml) will be used. Control patients will be treated and operated exactly in the same way except that placebo (buffer solution without gene) injection into the myocardium is used.
- Being tested
- AdvVEGF-D, Control Rx
- Medical subject headings
- Angina Pectoris, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdvVEGF-DDrug
AdvVEGF-D will be injected into 10 sites of the myocardium
Control RxDrug
Placebo (buffer solution without gene) will be injected into 10 sites of the myocardium
| Study group | Role | What they receive |
|---|---|---|
| AdvVEGF-D | Experimental | Intramyocardial AdVEGF-D Receives: Drug: AdvVEGF-D |
| Control | Placebo comparator | Intramyocardial placebo (buffer solution without gene) Receives: Drug: Control Rx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional capacity at 6 months
Improvement of exercise capacity 6 months after the treatment as measured by 6 minute walking test (walking distance in meters)
Measured: 6 months after gene transfer
Severity of angina pectoris symptoms at 6 months
Relieve of angina symptoms 6 months after the treatment (CCS class)
Measured: 6 months after gene transfer
Secondary outcomes (8)
Functional capacity at 12 months
Improvement of exercise capacity 12 months after the treatment as measured by a 6 minute walking test (walking distance in meters)
Measured: 12 months after gene transfer
Severity of angina pectoris symptoms at 12 months
Relieve of angina symptoms 12 months after the treatment (CCS class)
Measured: Time Frame: 12 months after gene transfer
Myocardial perfusion at 6 months
Improvement of myocardial perfusion (myocardial perfusion reserve, MPR) at 6 months assessed with positron emission tomography (PET) or single-photon emission computed tomography (SPECT)
Measured: 6 months after gene transfer
Quality of Life (EQ-5) at 6 and 12 months
Improvement of QoL assessed with EQ-5 score with three levels of severity and visual analogue scale (VAS) at 6 and 12 months
Measured: 6 and 12 months after gene transfer
Quality of Life (Short-Form Health Survey) at 6 and 12 months
Improvement of QoL assessed with Short-Form Health Survey (SF-36) score at 6 and 12 months
Measured: 6 and 12 months after gene transfer
Quality of Life (Seattle Angina Questionnaire ) at 6 and 12 months
Improvement of QoL assessed with Seattle Angina Questionnaire score at 6 and 12 months
Measured: 6 and 12 months after gene transfer
Angina pectoris medication at 6 and 12 months
Use of short-acting nitrates to relieve symptoms of angina pectoris at 6 and 12 months (number of oral/sublingual nitrate tablets or nitrate spray inhalations during the preceding 4 weeks).
Measured: 6 and 12 months after gene transfer
Adverse cardiac events at 6 and 12 months
Incidence of cardiovascular death, myocardial infarction, stroke, revascularization or hospital admission due to coronary artery disease and a combined endpoint of Major Adverse Cardiac Events MACE (combined endpoint of cardiovascular death, myocardial infarction, stroke, revascularization or hospital admission due to coronary artery disease) at 6 and 12 months.
Measured: 6 and 12 months after gene transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2017 (estimated)
- Study start19 Oct 2019
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kuopio University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Queen Mary University of London, University College, London, Medical University of Vienna, Servicio Madrileño de Salud, Madrid, Spain, FinVector Vision Therapies Oy, Śląski Uniwersytet Medyczny w Katowicach, Copenhagen University Hospital, Rigshospitalet, Euram Limited
- Responsible party
- Sponsor
- Investigators
- Seppo Ylä-Herttuala, Study director, Kuopio University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03039751
- Sponsor's protocol ID
- KUH5101111
- Acronym
- ReGenHeart
- Status last verified
- Jan 2025
- First submitted
- 3 Jan 2017
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data wil be shared to Partners of ReGenHeart Consortium
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Development and Proof of Principle Testing of New Regenerative Adenovirus Vascular Endothelial Growth Factor (VEGF-D) Therapy for Cost-effective Treatment of Refractory Angina. A Phase II Randomized, Double-blinded, Placebo-controlled Study (ReGenHeart)
- ClinicalTrials.gov ID
- NCT03039751
- Acronym / sponsor ID
- ReGenHeart / KUH5101111
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Kuopio University HospitalUniversity, hospital or other
- Collaborators
- Queen Mary University of London, University College, London, Medical University of Vienna, Servicio Madrileño de Salud, Madrid, Spain, FinVector Vision Therapies Oy, Śląski Uniwersytet Medyczny w Katowicach, Copenhagen University Hospital, Rigshospitalet, Euram Limited
- Study start
- 19 Oct 2019 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 1 Feb 2017 (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-mediated vascular endothelial growth factor-D (AdVEGF-D) regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.
Detailed description
Study overview:
The purpose of the study is to evaluate the safety and efficacy of catheter mediated AdVEGF-D regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.
Primary objectives:
To test the efficacy of the therapy to improve functional capacity using 6 minute walking test after 6 months follow-up and improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class.
Secondary objectives:
Efficacy of the gene transfer to increase to improve functional capacity using 6 minute walking test and improvement of symptoms assessed by CCS class after 12 months as well as increase in myocardial perfusion assessed 6 months after the gene transfer. In addition, at 6 and 12 months timepoints, the improvement quality of life (QoL), the use of angina pectoris medication, major adverse cardiac events related to coronary artery disease (cardiovascular death, myocardial infarction, stroke, revascularization and hospital admission due to coronary artery disease) or a combined endpoint of the above (Major Adverse Cardiac Events, MACE) will be evaluated.
Study design:
ReGenHeart is a randomized, double-blinded, placebo-controlled multicentre phase II study which will be conducted at 6 centers. The study will evaluate the efficacy and safety of catheter mediated endocardial AdVEGF-D regenerative gene transfer in 180 patients with angina pectoris or equivalent symptom despite optimal medical therapy and who are not suitable candidates for coronary revascularization with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (refractory angina patients).
Study population:
180 patients will be recruited from the six centers in 2 years. The patients will be selected for the trial on the basis of medical history, general status, laboratory analyses, coronary angiogram and 6-minute walking test. Patients with CCS 2-3 angina pectoris despite optimal medical therapy and who are not eligible for coronary angioplasty or bypass operation due to diffuse coronary stenosis, small coronary vessels, repeated revascularization or too high risk for operation, will be included.
The number of subjects to be recruited and randomized to the trial will be 180 (2:1 ratio to the treatment and control groups).
Investigational drug product:
First generation replication-deficient AdVEGF-D produced in 293 cells will be injected into ten sites in the endocardium. The dose of 1x1011 vp in a total volume of 2 ml (10 times 0.2 ml) will be used. Control patients will be treated and operated exactly in the same way except that placebo (buffer solution without gene) injection into the myocardium is used.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AdvVEGF-D | Experimental | Drug: AdvVEGF-DIntramyocardial AdVEGF-D |
| Control | Placebo comparator | Drug: Control RxIntramyocardial placebo (buffer solution without gene) |
Who may qualify
- Ages
- 30 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- informed consent signed
- age > 30 but < 85 years
- significant angina pectoris (CCS 2-3) despite of optimal medication
- significant stenosis (> 60%) in coronary angiography (< 6 months)
- contraindication to CABG or PCI due to diffuse or distal stenosis, chronic total occlusion, vessels with difficult anatomy, stenosis with severe calcifications and stenosis in small vessels (<2.5 mm))
Key exclusion criteria (15 listed)
- women in fertile age
- diabetes mellitus with severe complications such as diabetic retinopathy or nephropathy
- 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 (P-creatinine > 160 mg/l)
- liver insufficiency (P-alanine aminotransferase or P-alkaline phosphatase over 2 x normal)
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 |
|---|---|---|
| AdvVEGF-DAdvVEGF-D will be injected into 10 sites of the myocardium | Drug | AdvVEGF-D |
| Control RxPlacebo (buffer solution without gene) will be injected into 10 sites of the myocardium | Drug | Control |
Primary outcome
Functional capacity at 6 months
Time frame: 6 months after gene transfer
Improvement of exercise capacity 6 months after the treatment as measured by 6 minute walking test (walking distance in meters)
Severity of angina pectoris symptoms at 6 months
Time frame: 6 months after gene transfer
Relieve of angina symptoms 6 months after the treatment (CCS class)
8 secondary outcomes
Functional capacity at 12 months
Time frame: 12 months after gene transfer
Severity of angina pectoris symptoms at 12 months
Time frame: Time Frame: 12 months after gene transfer
Myocardial perfusion at 6 months
Time frame: 6 months after gene transfer
Quality of Life (EQ-5) at 6 and 12 months
Time frame: 6 and 12 months after gene transfer
Quality of Life (Short-Form Health Survey) at 6 and 12 months
Time frame: 6 and 12 months after gene transfer
Quality of Life (Seattle Angina Questionnaire ) at 6 and 12 months
Time frame: 6 and 12 months after gene transfer
Angina pectoris medication at 6 and 12 months
Time frame: 6 and 12 months after gene transfer
Adverse cardiac events at 6 and 12 months
Time frame: 6 and 12 months after gene transfer
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 13 Jan 2025.
- Individual participant dataSharing planned: No. Data wil be shared to Partners of ReGenHeart Consortium
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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.
Seppo Ylä-Herttuala study director
Kuopio University Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AdvVEGF-D in people with Refractory Angina Pectoris and Gene Transfer, run by Kuopio University Hospital at 2 sites in 2 countries.
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 7 inclusion and 15 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 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark, 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Functional capacity at 6 months (time frame: 6 months after gene transfer). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2025.