E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Chest pain due to coronary artery disease occurring in spite of optimal medication and which cannot be treated with balloon angioplasty or bypass surgery. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064262 |
E.1.2 | Term | Refractory angina pectoris |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
The study also investigates the effect of VEGF-D-therapy on myocardial perfusion, patients' symptoms, quality of life and safety of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent signed 2. Age > 30 but ≤ 85 years 3. Significant angina pectoris (CCS 2-3) despite of optimal medication 4. Significant stenosis (≥ 60%) in coronary angiography (≤ 12 months) 5. 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) 7. Angina pectoris or equivalent symptoms in the 6-minute walking exercise test 8. left ventricle wall ≥ 8 mm detected by transthoracic echocardiography (treatment area) |
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E.4 | Principal exclusion criteria |
1. Women of childbearing potential 2. Diabetes mellitus with severe complications such as proliferative diabetic retinopathy or nephropathy with renal insufficiency (see below) 3. Clinically significant anemia (hemoglobin count < 120 mg/l in male, < 110 mg/l in female; hematocrit < 0.36) 4. Leukopenia (b-leukocyte count < 3.0x109/l), leukocytosis (b-leukocyte count > 12.0x109/l) or thrombocytopenia (b-thrombocyte count < 100x109/l) 5. Renal insufficiency (P-creatinine > 160 mg/l) 6. Liver insufficiency (P-alanine aminotransferase or P-alkaline phosphatase over 2 x normal) 7. Hematuria of unknown origin 8. Severe hypertension (systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg) or significant hypotension (systolic blood pressure < 90 mmHg) 9. Significant obesity (BMI > 35) 10. Acute infection 11. Immunosuppressive medication 12. Significant impairment of left ventricular function (EF < 25%) 13. Symptomatic congestive heart failure (NYHA 3-4) 14. Hemodynamically significant (grade 3-4/4) aortic or mitral regurgitation or other heart disease needing surgery 15. Recent (< 3 months) acute coronary syndrome or myocardial infarction (elevated CK-MB or cardiac troponin), PCI, CABG or TIA/stroke 16. Current or suspected malignancy |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Improvement of functional capacity using 6-minute walking test 2. Improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. After 6 months follow-up 2. After 6 months follow-up |
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E.5.2 | Secondary end point(s) |
1. Improvement of functional capacity using 6-minute walking test 2. Improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class 3. Increase in myocardial perfusion |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 12 months follow-up 2. After 12 months follow-up 3. After 6 months follow-up |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject in 12-months control. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |