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

NCT03039751 | Completed Phase 2 DMC

• 1 other identifier: KUH5101111
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Refractory Angina Pectoris; Gene Transfer; Coronary Artery Disease

Outcome Measures

Primary Outcomes (2)

• 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)

  6 months after gene transfer

• Severity of angina pectoris symptoms at 6 months

  Relieve of angina symptoms 6 months after the treatment (CCS class)

  6 months after gene transfer

Secondary Outcomes (8)

• Functional capacity at 12 months

  12 months after gene transfer

• Severity of angina pectoris symptoms at 12 months

  Time Frame: 12 months after gene transfer

• Myocardial perfusion at 6 months

  6 months after gene transfer

• Quality of Life (EQ-5) at 6 and 12 months

  6 and 12 months after gene transfer

• Quality of Life (Short-Form Health Survey) at 6 and 12 months

  6 and 12 months after gene transfer

Study Arms (2)

AdvVEGF-D

EXPERIMENTAL

Intramyocardial AdVEGF-D

Drug: AdvVEGF-D

Control

PLACEBO COMPARATOR

Intramyocardial placebo (buffer solution without gene)

Drug: Control Rx

Interventions

AdvVEGF-D DRUG

AdvVEGF-D will be injected into 10 sites of the myocardium

AdvVEGF-D

Control Rx DRUG

Placebo (buffer solution without gene) will be injected into 10 sites of the myocardium

Control

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kuopio University Hospital: lead
• Queen Mary University of London: collaborator
• University College, London: collaborator
• Medical University of Vienna: collaborator
• Servicio Madrileño de Salud, Madrid, Spain: collaborator
• FinVector Vision Therapies Oy: collaborator
• Śląski Uniwersytet Medyczny w Katowicach: collaborator
• Rigshospitalet, Denmark: collaborator
• Euram Limited: collaborator

Study Sites (2)

Rigshospitalet

Copenhagen, Denmark

Location

Kuopio University Hospital

Kuopio, Finland

Location

MeSH Terms

Conditions

Angina Pectoris; Coronary Artery Disease

Interventions

Tin Fluorides

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Fluorides; Hydrofluoric Acid; Fluorine Compounds; Inorganic Chemicals; Tin Compounds; Cariostatic Agents; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Seppo Ylä-Herttuala

  Kuopio University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: February 1, 2017
• Study Start: October 19, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); FI (1)