A Study to Treat Patients Whose Chronic Angina Symptoms Are Not Relieved by Medication and Have an Area of the Heart That Cannot be Treated by Standard Therapies

NCT00215696 | Completed Phase 2

• 1 other identifier: GV-002.001
• Study Type: interventional
• Target: 129
• Locations: 2 countries
• Sites: 3

Brief Summary

The primary purpose of this study is to determine whether treatment with an experimental gene therapy (BIOBYPASS®) will reduce angina in study participants by stimulating the growth of new blood vessels. This will be measured by testing whether participants are able to exercise longer without experiencing angina after treatment, as compared to before treatment. Additionally, this study will collect information about any side effects that might be related to the treatment with the experimental therapy.

Conditions

Moderate to Severe Angina Pectoris

Outcome Measures

Primary Outcomes (1)

• Change from baseline in total exercise duration on exercise tolerance test (ETT, using the bicycle ergometry test protocol) at week 26.

Secondary Outcomes (8)

• Change of reversible perfusion defect size in SPECT perfusion study at week 26

• Total exercise duration at weeks 12 and 52

• Time-to-onset of 1mm ST depression on ETT at weeks 12, 26, 52

• Peak rate-pressure product and maximal workload (in METS) during ETT at weeks 12, 26, 52

• CCS class at weeks 12, 26, 52

Interventions

BioBypass® GENETIC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• Platelet aggregation inhibitor (e.g., aspirin, ticlopidine, or clopidogrel)
• ACE inhibitor
• Statin (HMG-CoA Reductase Inhibitor)
• 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

You may not qualify if:

• 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 BIOBYPASS® and some form of birth control for at least one year;
• Clinically significant anemia (e.g. hematocrit \< 36% or hemoglobin \< 12 g/dL for men and \< 11 g/dL for women), leukopenia (WBC\<3,000/µL), leukocytosis (WBC \> 12,000), or thrombocytopenia (platelet count \< 100,000 billion/l);
• Abnormal prothrombin or partial thromboplastin time or anticoagulant therapy that cannot be withheld for treatment;
• Significant renal dysfunction (serum creatinine \> 1.6 mg/dL);
• Hepatic dysfunction (AST/ALT must be within normal limits);
• Hematuria, unless of known, non-malignant etiology (any unexplained hematuria would require the candidate to be excluded);
• 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 or 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;

Sponsors & Collaborators

• GenVec: lead

Study Sites (3)

Skejby Sygehus, Caridology Laboratory

Århus N, DK-8200, Denmark

Location

Cardiovascular Laboratory 2014, The Heart Center, University hospital Rigshospitalet

Copenhagen, 2100, Denmark

Location

Cardiac Catheterization Laboratories, Cardiology Department, Rabin Medical Center

Petah, Tikva, 49100, Israel

Location

Study Officials

• Dr. Jens Kastrup

  The Heart Center, University hospital Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 22, 2005
• Study Start: April 1, 2005
• Last Updated: May 13, 2011

Record last verified: 2011-05

Locations

DK (2); IL (1)