Moderate to severe angina pectoris due to advanced coronary artery disease (CAD).
Conditions
Interventions
Product Name: BIOBYPASS
Pharmaceutical Form: Solution for injection
Other descriptive name: AdGVVEGF121.10NH
Concentration type: equal
Concentration number: 1.67e10 pu/mL-
Pharmaceutical form of the p
Sponsors
GenVec, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: · Age greater than or equal to 18 years and less than or equal to 80 years; · Written informed consent obtained prior to any study dictated procedure; · Moderate to severe angina (CCS Angina Class II-IV) despite optimal medical therapy; · Treated with optimal unchanged antianginal medical therapy for at least 2 months prior to the first baseline ETT. Optimal medical therapy must include the following medications (unless hemodynamic parameters or intolerance contraindicate their use): - Nitroglycerine; - Antianginal medications: Long-acting nitrates, calcium-channel blockers, potassium channel opener and beta-blockers (Note: All participants are required to be on at least 2 of the 4 antianginal medications listed above); and - Platelet aggregation inhibitor (e.g., aspirin, ticlopidine, or clopidogrel). · The participant must have, within 3 months prior to randomization, documented coronary angiographic evidence of significant 2- or 3- vessel disease, or equivalent disease in one dominant artery, and at least one remaining larger coronary vessel from which new collaterals/vessels could be supplied. · Any participant who has undergone CABG or PCI within 6 months of entry must have angiography performed within 1 month prior to entry, and at least 4 months after the previous intervention to rule out early restenosis. · Candidates must not be eligible for any other re-vascularization procedures. The participant and his coronary film must have been discussed with an independent cardiac surgeon and must have been denied for CABG or PTCA. Participants who are marginal or poor candidates for conventional revascularization will be considered eligible if the risks of performing a CABG or PTCA procedure outweigh the potential benefit and/or such a procedure is unlikely to offer a worthwhile clinical benefit. The criteria defining such cases may include, but may not be limited to, the following examples: - Diffuse or distal vessel disease - Chronic occlusions - Unprotected left main stenosis - Tortuous or severely angulated vessels - Severely calcified vessels - Small vessels ( 10 % of left ventricle. · Ventricular wall thickness of the treatment zone > 8mm as per baseline echocardiogram. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: · Pregnant or lactating women. It is required that both men and women use condoms or another barrier method of birth control for at least 8 weeks following administration of BIOBYPASSÒ and some form of birth control for at least one year; · Clinically significant anemia (e.g. hematocrit 12,000), or thrombocytopenia (platelet count 1.6 mg/dL); · Hepatic dysfunction (AST/ALT must be within normal limits); · Hematuria, unless of known, non-malignant etiology · Uncontrolled hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg) or significant hypotension (systolic blood pressure <90 mmHg); · Conditions other than angina that will limit exercise test (e.g. severe peripheral vascular disease, COPD); · Ophthalmologic conditions pertinent to proliferative retinopathy Conditions that preclude standard ophthalmologic examination. - Cataract surgery within 6 months of trial; - Vascular lesions of the anterior segment of the eye (infection or ulceration of the cornea, rubeotic glaucoma, etc); - Vascular lesions of the posterior segment of the eye or proliferative retinopathy in diabetics, macular edema, s/p photocoagulation for macular edema or proliferative retinopathy; nondiabetics with central or branch retinal vascular occlusions, sickle cell retinopathy, ischemic retinopathy due to retinal venous stasis or carotid artery disease); - Choroidal new vessels associated with age-related macular degeneration, myopic degeneration, presumed ocular histoplasmosis syndrome, angioid streaks, pseudoxanthoma elasticum, or without ocular disease; and - Large elevated choroidal nevi, choroidal vascular tumors (choroidal hemangioma), or melanomas. · Any acute illness within one week of the start of the study or any other illness considered by the Investigator to significantly interfere with study outcome; · Clinical evidence of active infection of any type, including adenovirus; (Paul – did you want ad-neutralizing antibody titer included?) · Immunocompromised status (in the investigator’s opinion) or currently receiving immunosuppressive therapy; · Left ventricular ejection fraction < 25% as measured by LV angiography. · Congestive heart failure NYHA class III-IV; · Valvular heart disease requiring surgical intervention or hemodynamically significant aortic valve disease; · Recent (less than 6 weeks prior to screening) Acute Coronary Syndrome with increase in CK-MB or Troponins/PCI/CABG/Stroke or TIA; · History of malignancy (except cured non-melanoma skin cancer) or suspicion of current malignancy; · Known allergy to the diluent used to suspend the virus; · Other experimental medications within the last four weeks prior to the second baseline ETT; · Revascularization procedure (percutaneous coronary intervention or coronary artery bypass) within 4 months of Day 1. · Participants who have previously received VEGF or any other angiogenic agent or gene therapy in the past, or who have participated in other investigational studies within the last year if the endpoints are overlapping.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of intramyocardial delivery of BIOBYPASS® (4xe10 pu) on exercise tolerance in participants with advanced CAD and angina pectoris at 26 weeks post-dosing, as determined by change from baseline in total exercise duration on exercise tolerance testing, compared to placebo.;Secondary Objective: To further assess the activity of BIOBYPASS® compared to placebo as estimated by exercise tolerance at 12 and 52 weeks, time to onset of 1mm additional ST-segment depression at 12, 26, and 52 weeks, and SPECT perfusion studies (using pharmacological stress) at 26 weeks post-dosing. To assess the safety and tolerability of intramyocardial administration of BIOBYPASS® in participants with advanced CAD and moderate to severe angina pectoris. Various additional functional and objective parameters (time to level 2 angina, peak rate-pressure product, and maximum workload on ETT, QOL, angina class, angina attacks and nitroglycerine consumption) will also be evaluated at 12, 26 and 52 weeks post-dosing. ;Primary end point(s): Change from baseline at week 26 in total exercise duration on exercise tolerance test (bicycle ergometry protocol). | — |
Countries
Denmark, Germany, United Kingdom
Outcome results
None listed