Adenovirus Vascular Endothelial Growth Factor D (AdvVEGF-D) Therapy for Treatment of Refractory Angina Pectoris (ReGenHeart)

January 9, 2025 updated by: Kuopio University Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
63

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
      • Copenhagen, Denmark
        • Rigshospitalet
  • Finland
      • Kuopio, Finland
        • Kuopio University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AdvVEGF-D
Intramyocardial AdVEGF-D
Drug: AdvVEGF-D
AdvVEGF-D will be injected into 10 sites of the myocardium
Placebo Comparator: Control
Intramyocardial placebo (buffer solution without gene)
Drug: Control Rx
Placebo (buffer solution without gene) will be injected into 10 sites of the myocardium

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
6 months after gene transfer
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)
6 months after gene transfer

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Functional capacity at 12 months
Time Frame: 12 months after gene transfer
Improvement of exercise capacity 12 months after the treatment as measured by a 6 minute walking test (walking distance in meters)
12 months after gene transfer
Severity of angina pectoris symptoms at 12 months
Time Frame: Time Frame: 12 months after gene transfer
Relieve of angina symptoms 12 months after the treatment (CCS class)
Time Frame: 12 months after gene transfer
Myocardial perfusion at 6 months
Time Frame: 6 months after gene transfer
Improvement of myocardial perfusion (myocardial perfusion reserve, MPR) at 6 months assessed with positron emission tomography (PET) or single-photon emission computed tomography (SPECT)
6 months after gene transfer
Quality of Life (EQ-5) at 6 and 12 months
Time Frame: 6 and 12 months after gene transfer
Improvement of QoL assessed with EQ-5 score with three levels of severity and visual analogue scale (VAS) at 6 and 12 months
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
Improvement of QoL assessed with Short-Form Health Survey (SF-36) score at 6 and 12 months
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
Improvement of QoL assessed with Seattle Angina Questionnaire score at 6 and 12 months
6 and 12 months after gene transfer
Angina pectoris medication at 6 and 12 months
Time Frame: 6 and 12 months after gene transfer
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).
6 and 12 months after gene transfer
Adverse cardiac events at 6 and 12 months
Time Frame: 6 and 12 months after gene transfer
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.
6 and 12 months after gene transfer

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kuopio University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical University of Vienna
Rigshospitalet, Denmark
University College, London
Queen Mary University of London
Servicio Madrileño de Salud, Madrid, Spain
FinVector Vision Therapies Oy
Śląski Uniwersytet Medyczny w Katowicach
Euram Limited

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Seppo Ylä-Herttuala, Kuopio University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 19, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 3, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 30, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 1, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KUH5101111

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data wil be shared to Partners of ReGenHeart Consortium

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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