Angiogenesis in Women With Angina Pectoris Who Are Not Candidates for Revascularization (AWARE)

Cardium Therapeutics

Status and phase

Unknown

Phase 3

Conditions

Angina Pectoris

Treatments

Genetic: Placebo

Genetic: Ad5FGF-4

Study type

Interventional

Funder types

Industry

Identifiers

NCT00438867

CT-3-001

Details and patient eligibility

About

The purpose of this study is to determine whether a one-time intracoronary infusion of Ad5FGF-4 is effective in reducing the time to onset myocardial ischemia as measured by exercise treadmill testing and improving myocardial blood flow as measured by SPECT imaging. Exercise capacity, angina functional class, patient symptoms and quality of life will also be evaluated to characterize the efficacy of Ad5FGF-4. Short-term and long-term safety of Ad5FGF-4 will also be evaluated.

Enrollment

300 estimated patients

Sex

Female

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Female patients 18-75 years of age inclusive
Stable angina classified as CCS III or IV
Receiving treatment with at least two classes of chronic anti-anginal medication, of which two are at the maximally tolerated dose
Left ventricular ejection fraction (LVEF) of ≥30%
Not a candidate for, or unlikely to benefit from standard revascularization procedures as verified by an independent cardiologist or cardiothoracic surgeon (not a study investigator) at each center
Can undergo ETT using the modified Bruce protocol and;
1. ECG changes diagnostic of myocardial ischemia occur during the first 10 minutes of exercise
2. Variability of the time to onset of ECG changes diagnostic of myocardial ischemia is ≤25% or within 60 seconds if the time to onset of myocardial ischemia occurs within the first 4 minutes of exercise as determined by two consecutive screening treadmill tests
Evidence of stress induced myocardial ischemia by adenosine SPECT, defined as a reversible perfusion defect size of ≥9%
Willing and able to comply with the study requirements including long-term follow-up
Provided written informed consent

Exclusion criteria

Patients of childbearing potential (must be surgically sterile or post-menopausal)
Patients for whom an immediate revascularization procedure is indicated (CABG surgery or PCI)
Myocardial infarction within the past 3 months
Unstable angina or hospitalization requiring intravenous anti-anginal therapy within the 14 days prior to the start of screening evaluations
Congestive heart failure NYHA Class IV
Electrocardiogram that precludes accurate assessment of exercise induced myocardial ischemia (e.g., left bundle branch block, Wolf-Parkinson-White syndrome, atrial fibrillation)
Myocarditis or restrictive pericarditis
Left main coronary stenosis ≥70% (unless the patient has a patent graft or collateral vessels supplying the left coronary circulation) or proximal stenoses ≥70% in all major coronary conduit vessels (coronary arteries and bypass grafts)
Clinically significant aortic or mitral valvular heart disease
Coronary ostial stenosis that precludes adequate catheter engagement in any target vessel
Coronary artery to venous communications, which bypass the coronary capillary bed
Untreated life-threatening ventricular arrhythmias
CABG surgery within the past 6 months, unless those grafts are now occluded.
Percutaneous transluminal angioplasty (PTCA) within the past 3 months, unless the dilated vessel(s) are now occluded
Enhanced external counterpulsation (EECP) within 3 months prior to the start of screening evaluations
Transmyocardial or percutaneous myocardial laser revascularization within the previous year
Prior treatment with any cardiovascular gene or stem cell therapy.
Any intercurrent illness that may interfere with their ability to perform a maximal ETT
Any major organ disease that substantially impairs life expectancy.
History of cancer, other than basal cell carcinoma, or patients with any laboratory or physical exam or diagnostic procedure finding suggestive of current malignancy
Moderate to severe nonproliferative or proliferative retinopathy from any cause (ETDRS score >35), clinically significant macular edema, or previous panretinal photocoagulation therapy
Heparin induced thrombocytopenia or history of idiopathic thrombocytopenic purpura or other medical condition causing thrombocytopenia
SGPT level greater than 2.0 times the upper limit of the laboratory normal range
Bilirubin level ≥2.0 mg/dL
Serum creatinine ≥2.5 mg/dL
Platelet count <100,000/μL
White blood cell count <3,000/μL
Positive test for hepatitis B or C
Positive test for HIV
History of colon cancer in a first degree relative (i.e., parent, sibling or offspring) unless the patient has undergone a colonoscopy in the past 36 months with negative findings
History of breast cancer in a first degree relative
Patient in a family with any documented hereditary cancer syndrome
Prior anaphylaxis reaction to iodinated contrast agents
Patients who are known to be immunosuppressed or are receiving chronic treatment with immunosuppressive drugs
Received an investigational drug or biologic within 30 days of screening or are currently participating in an investigational drug, biologic or device trial