<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03039751</url>
  </required_header>
  <id_info>
    <org_study_id>KUH5101111</org_study_id>
    <nct_id>NCT03039751</nct_id>
  </id_info>
  <brief_title>Adenovirus Vascular Endothelial Growth Factor D (AdvVEGF-D) Therapy for Treatment of Refractory Angina Pectoris</brief_title>
  <acronym>ReGenHeart</acronym>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kuopio University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Queen Mary University of London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Servicio Madrileño de Salud, Madrid, Spain</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>FinVector Vision Therapies Oy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Śląski Uniwersytet Medyczny w Katowicach</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Euram Limited</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Kuopio University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the safety and efficacy of catheter mediated&#xD;
      endocardial adenovirus-mediated vascular endothelial growth factor-D (AdVEGF-D) regenerative&#xD;
      gene transfer in patients with refractory angina to whom revascularisation cannot be&#xD;
      performed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study overview:&#xD;
&#xD;
      The purpose of the study is to evaluate the safety and efficacy of catheter mediated AdVEGF-D&#xD;
      regenerative gene transfer in patients with refractory angina to whom revascularisation&#xD;
      cannot be performed.&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
      To test the efficacy of the therapy to improve functional capacity using 6 minute walking&#xD;
      test after 6 months follow-up and improvement of symptoms assessed by Canadian Cardiovascular&#xD;
      Society (CCS) class.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      Efficacy of the gene transfer to increase to improve functional capacity using 6 minute&#xD;
      walking test and improvement of symptoms assessed by CCS class after 12 months as well as&#xD;
      increase in myocardial perfusion assessed 6 months after the gene transfer. In addition, at 6&#xD;
      and 12 months timepoints, the improvement quality of life (QoL), the use of angina pectoris&#xD;
      medication, major adverse cardiac events related to coronary artery disease (cardiovascular&#xD;
      death, myocardial infarction, stroke, revascularization and hospital admission due to&#xD;
      coronary artery disease) or a combined endpoint of the above (Major Adverse Cardiac Events,&#xD;
      MACE) will be evaluated.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      ReGenHeart is a randomized, double-blinded, placebo-controlled multicentre phase II study&#xD;
      which will be conducted at 6 centers. The study will evaluate the efficacy and safety of&#xD;
      catheter mediated endocardial AdVEGF-D regenerative gene transfer in 180 patients with angina&#xD;
      pectoris or equivalent symptom despite optimal medical therapy and who are not suitable&#xD;
      candidates for coronary revascularization with coronary artery bypass grafting (CABG) or&#xD;
      percutaneous coronary intervention (PCI) (refractory angina patients).&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      180 patients will be recruited from the six centers in 2 years. The patients will be selected&#xD;
      for the trial on the basis of medical history, general status, laboratory analyses, coronary&#xD;
      angiogram and 6-minute walking test. Patients with CCS 2-3 angina pectoris despite optimal&#xD;
      medical therapy and who are not eligible for coronary angioplasty or bypass operation due to&#xD;
      diffuse coronary stenosis, small coronary vessels, repeated revascularization or too high&#xD;
      risk for operation, will be included.&#xD;
&#xD;
      The number of subjects to be recruited and randomized to the trial will be 180 (2:1 ratio to&#xD;
      the treatment and control groups).&#xD;
&#xD;
      Investigational drug product:&#xD;
&#xD;
      First generation replication-deficient AdVEGF-D produced in 293 cells will be injected into&#xD;
      ten sites in the endocardium. The dose of 1x1011 vp in a total volume of 2 ml (10 times 0.2&#xD;
      ml) will be used. Control patients will be treated and operated exactly in the same way&#xD;
      except that placebo (buffer solution without gene) injection into the myocardium is used.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 19, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Functional capacity at 6 months</measure>
    <time_frame>6 months after gene transfer</time_frame>
    <description>Improvement of exercise capacity 6 months after the treatment as measured by 6 minute walking test (walking distance in meters)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of angina pectoris symptoms at 6 months</measure>
    <time_frame>6 months after gene transfer</time_frame>
    <description>Relieve of angina symptoms 6 months after the treatment (CCS class)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Functional capacity at 12 months</measure>
    <time_frame>12 months after gene transfer</time_frame>
    <description>Improvement of exercise capacity 12 months after the treatment as measured by a 6 minute walking test (walking distance in meters)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of angina pectoris symptoms at 12 months</measure>
    <time_frame>Time Frame: 12 months after gene transfer</time_frame>
    <description>Relieve of angina symptoms 12 months after the treatment (CCS class)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial perfusion at 6 months</measure>
    <time_frame>6 months after gene transfer</time_frame>
    <description>Improvement of myocardial perfusion (myocardial perfusion reserve, MPR) at 6 months assessed with positron emission tomography (PET) or single-photon emission computed tomography (SPECT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (EQ-5) at 6 and 12 months</measure>
    <time_frame>6 and 12 months after gene transfer</time_frame>
    <description>Improvement of QoL assessed with EQ-5 score with three levels of severity and visual analogue scale (VAS) at 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (Short-Form Health Survey) at 6 and 12 months</measure>
    <time_frame>6 and 12 months after gene transfer</time_frame>
    <description>Improvement of QoL assessed with Short-Form Health Survey (SF-36) score at 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (Seattle Angina Questionnaire ) at 6 and 12 months</measure>
    <time_frame>6 and 12 months after gene transfer</time_frame>
    <description>Improvement of QoL assessed with Seattle Angina Questionnaire score at 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Angina pectoris medication at 6 and 12 months</measure>
    <time_frame>6 and 12 months after gene transfer</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse cardiac events at 6 and 12 months</measure>
    <time_frame>6 and 12 months after gene transfer</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Refractory Angina Pectoris</condition>
  <condition>Gene Transfer</condition>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>AdvVEGF-D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intramyocardial AdVEGF-D</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intramyocardial placebo (buffer solution without gene)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AdvVEGF-D</intervention_name>
    <description>AdvVEGF-D will be injected into 10 sites of the myocardium</description>
    <arm_group_label>AdvVEGF-D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Control Rx</intervention_name>
    <description>Placebo (buffer solution without gene) will be injected into 10 sites of the myocardium</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  informed consent signed&#xD;
&#xD;
          -  age &gt; 30 but &lt; 85 years&#xD;
&#xD;
          -  significant angina pectoris (CCS 2-3) despite of optimal medication&#xD;
&#xD;
          -  significant stenosis (&gt; 60%) in coronary angiography (&lt; 6 months)&#xD;
&#xD;
          -  contraindication to CABG or PCI due to diffuse or distal stenosis, chronic total&#xD;
             occlusion, vessels with difficult anatomy, stenosis with severe calcifications and&#xD;
             stenosis in small vessels (&lt;2.5 mm))&#xD;
&#xD;
          -  angina pectoris or equivalent symptoms in the 6-minute walking exercise test&#xD;
&#xD;
          -  left ventricle wall &gt; 8 mm detected by transthoracic echocardiography or magnetic&#xD;
             resonance imaging (treatment area)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  women in fertile age&#xD;
&#xD;
          -  diabetes mellitus with severe complications such as diabetic retinopathy or&#xD;
             nephropathy&#xD;
&#xD;
          -  clinically significant anemia (hemoglobin count &lt; 120 mg/l in male, &lt; 110 mg/l in&#xD;
             female; hematocrit &lt; 0.36), leukopenia (b-leukocyte count &lt; 3.0x109/l), leukocytosis&#xD;
             (b-leukocyte count &gt; 12.0x109/l) or thrombocytopenia (b-thrombocyte count &lt; 100x109/l)&#xD;
&#xD;
          -  renal insufficiency (P-creatinine &gt; 160 mg/l)&#xD;
&#xD;
          -  liver insufficiency (P-alanine aminotransferase or P-alkaline phosphatase over 2 x&#xD;
             normal)&#xD;
&#xD;
          -  haematuria of unknown origin&#xD;
&#xD;
          -  severe hypertension (systolic blood pressure &gt; 200 mmHg or diastolic blood pressure &gt;&#xD;
             110 mmHg) or significant hypotension (systolic blood pressure &lt; 90 mmHg)&#xD;
&#xD;
          -  significant obesity (Body Mass Index &gt; 35)&#xD;
&#xD;
          -  acute infection&#xD;
&#xD;
          -  immunosuppressive medication&#xD;
&#xD;
          -  significant impairment of left ventricular function (ejection fraction &lt; 25% in&#xD;
             echocardiography)&#xD;
&#xD;
          -  symptomatic congestive heart failure (New York Heart Association class 3-4)&#xD;
&#xD;
          -  haemodynamically significant (grade 3-4/4) aortic or mitral regurgitation or other&#xD;
             heart disease needing surgery&#xD;
&#xD;
          -  recent (&lt; 6 weeks) acute coronary syndrome or myocardial infarction, PCI or CABG,&#xD;
             stroke or transient ischemic attack (TIA)&#xD;
&#xD;
          -  current or suspected malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Seppo Ylä-Herttuala</last_name>
    <role>Study Director</role>
    <affiliation>Kuopio University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Juha EK Hartikainen, professor</last_name>
    <phone>+358447113945</phone>
    <email>juha.hartikainen@kuh.fi</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Seppo Ylä-Herttuala, professor</last_name>
    <phone>+358505924067</phone>
    <email>seppo.ylaherttuala@uef.fi</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jens Kastrup, professor</last_name>
      <email>jens.kastrup@regionh.dk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kuopio University Hospital</name>
      <address>
        <city>Kuopio</city>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juha Hartikainen, professor</last_name>
      <email>juha.hartikainen@kuh.fi</email>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>October 19, 2022</last_update_submitted>
  <last_update_submitted_qc>October 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Angina Pectoris</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data wil be shared to Partners of ReGenHeart Consortium</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03039751
org study id: KUH5101111
nct id: NCT03039751
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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:

      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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Functional capacity at 6 months
time frame: 6 months after gene transfer
description: Improvement of exercise capacity 6 months after the treatment as measured by 6 minute walking test (walking distance in meters)
measure: Severity of angina pectoris symptoms at 6 months
time frame: 6 months after gene transfer
description: Relieve of angina symptoms 6 months after the treatment (CCS class)
measure: Functional capacity at 12 months
time frame: 12 months after gene transfer
description: Improvement of exercise capacity 12 months after the treatment as measured by a 6 minute walking test (walking distance in meters)
measure: Severity of angina pectoris symptoms at 12 months
time frame: Time Frame: 12 months after gene transfer
description: Relieve of angina symptoms 12 months after the treatment (CCS class)
measure: Myocardial perfusion at 6 months
time frame: 6 months after gene transfer
description: Improvement of myocardial perfusion (myocardial perfusion reserve, MPR) at 6 months assessed with positron emission tomography (PET) or single-photon emission computed tomography (SPECT)
measure: Quality of Life (EQ-5) at 6 and 12 months
time frame: 6 and 12 months after gene transfer
description: Improvement of QoL assessed with EQ-5 score with three levels of severity and visual analogue scale (VAS) at 6 and 12 months
measure: Quality of Life (Short-Form Health Survey) at 6 and 12 months
time frame: 6 and 12 months after gene transfer
description: Improvement of QoL assessed with Short-Form Health Survey (SF-36) score at 6 and 12 months
measure: Quality of Life (Seattle Angina Questionnaire ) at 6 and 12 months
time frame: 6 and 12 months after gene transfer
description: Improvement of QoL assessed with Seattle Angina Questionnaire score at 6 and 12 months
measure: Angina pectoris medication at 6 and 12 months
time frame: 6 and 12 months after gene transfer
description: 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).
measure: Adverse cardiac events at 6 and 12 months
time frame: 6 and 12 months after gene transfer
description: 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.
arm group label: AdvVEGF-D
arm group type: Experimental
description: Intramyocardial AdVEGF-D
arm group label: Control
arm group type: Placebo Comparator
description: Intramyocardial placebo (buffer solution without gene)
intervention type: Drug
intervention name: AdvVEGF-D
description: AdvVEGF-D will be injected into 10 sites of the myocardium
arm group label: AdvVEGF-D
intervention type: Drug
intervention name: Control Rx
description: Placebo (buffer solution without gene) will be injected into 10 sites of the myocardium
arm group label: Control
criteria: 
gender: All
minimum age: 30 Years
maximum age: 85 Years
healthy volunteers: No
last name: Seppo Ylä-Herttuala
role: Study Director
affiliation: Kuopio University Hospital
last name: Juha EK Hartikainen, professor
phone: +358447113945
email: juha.hartikainen@kuh.fi
last name: Seppo Ylä-Herttuala, professor
phone: +358505924067
email: seppo.ylaherttuala@uef.fi
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Denmark
country: Finland
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Angina Pectoris
sharing ipd: No
ipd description: Data wil be shared to Partners of ReGenHeart Consortium