Overview
Sponsor-declared trial summary
Clinical development and proof of principle testing of new regenerative VEGF-D therapy for cost- effective treatment of refractory angina. A phase II randomized, double-blinded, placebo-controlled study.
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 revascularization cannot be performed.
Key facts
- Sponsor
- Pohjois-Savon hyvinvointialue
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- completed 31 May 2024
- Decision date (initial)
- 2024-05-31
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- The study is funded by EU Horizon 2020 program (ReGenHeart; grant no 731532)
External identifiers
- EU CT number
- 2024-512255-20-00
- EudraCT number
- 2017-000789-31
- ClinicalTrials.gov
- NCT03039751
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
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 revascularization cannot be performed.
Secondary objectives 1
- The study also investigates the effect of VEGF-D-therapy on myocardial perfusion, patients' symptoms, quality of life and safety of treatment.
Conditions and MedDRA coding
Clinical development and proof of principle testing of new regenerative VEGF-D therapy for cost- effective treatment of refractory angina. A phase II randomized, double-blinded, placebo-controlled study.
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Informed consent signed
- Age > 30 but ≤ 85 years
- Significant angina pectoris (CCS 2-3) despite of optimal medication
- Significant stenosis (≥ 60%) in coronary angiography (≤ 12 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 (treatment area)
Exclusion criteria 16
- Women of childbearing potential
- Diabetes mellitus with severe complications such as proliferative diabetic retinopathy or nephropathy with renal insufficiency (see below)
- 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), leukocytosie 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)
- Hematuria 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 (BMI > 35)
- Acute infection
- Immunosuppressive medication
- Significant impairment of left ventricular function (EF < 25%)
- Symptomatic congestive heart failure (NYHA 3-4)
- Hemodynamically significant (grade 3-4/4) aortic or mitral regurgitation or other heart disease needing surgery
- Recent (< 3 months) acute coronary syndrome or myocardial infarction (elevated CK-MB or cardiac troponin), PCI, CABG or TIA/stroke
- Current or suspected malignancy
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Improvement of functional capacity using 6-minute walking test
- Improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class
Secondary endpoints 3
- Improvement of functional capacity using 6-minute walking test
- Improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class
- Increase in myocardial perfusion
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD11250995 · Product
- Active substance
- Adenovirus Vector Serotype 5 Containing the Vascular Endothelial Growth Factor D Isoform (Preprocessed Short Form)
- Substance synonyms
- Ad.VEGF-D Delta N Delta C
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRACARDIAC USE
- Max daily dose
- 2 Other
- Max total dose
- 2 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- POHJOIS-SAVON HYVINVOINTIALUE
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
Placebo to AdsVEGF-D Delta N Delta C test product
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Pohjois-Savon hyvinvointialue
- Sponsor organisation
- Pohjois-Savon hyvinvointialue
- Address
- Puijonlaaksontie 2, P. O. Box 1711 P. O. Box 1711
- City
- Kuopio
- Postcode
- 70211
- Country
- Finland
Scientific contact point
- Organisation
- Pohjois-Savon hyvinvointialue
- Contact name
- Aleksi Leikas
Public contact point
- Organisation
- Pohjois-Savon hyvinvointialue
- Contact name
- Aleksi Leikas
Locations
2 EU/EEA countries · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ended | 17 | 1 |
| Finland | Ended | 22 | 1 |
| Rest of world
United Kingdom
|
— | 6 | — |
Investigational sites
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-22 | Finland | Acceptable 2024-05-29
|
2024-05-29 |