AFFIRM: Ad5FGF-4 In Patients With Refractory Angina Due to Myocardial Ischemia

Sponsor

Angionetics Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT02928094

Collaborator

Huapont Life Sciences (Other)

160

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether a single intracoronary infusion of an adenovirus serotype 5 virus expressing the gene for human fibroblast growth factor-4 (Ad5FGF-4) is effective in improving angina-limited exercise duration, angina functional class, frequency of angina attacks, frequency of nitroglycerin usage, and quality of life. Half of the study participants will receive Ad5FGF-4, and half will receive placebo. The primary endpoint is the change from baseline to Month 6 in Exercise Tolerance Test (ETT) duration. Long-term safety of Ad5FGF-4 will also be assessed.

Condition or Disease	Intervention/Treatment	Phase
Angina, Stable	Biological: Ad5FGF-4 Biological: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter, Phase 3 Study to Evaluate the Safety and Efficacy of Ad5FGF-4 in Patients With Refractory Angina Due to Myocardial Ischemia

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: Ad5FGF-4 Ad5FGF-4, administered one time at 6x10e9 viral particles in buffer, and maximally-tolerated medical therapy for angina.	Biological: Ad5FGF-4 Ad5FGF-4 administered via intracoronary infusion using standard balloon catheter, and under conditions of transient ischemia. Other Names: Generx alferminogene tadenovec
Placebo Comparator: B: Placebo Placebo buffer, administered one time, and maximally-tolerated medical therapy for angina.	Biological: Placebo Placebo buffer administered via intracoronary infusion using standard balloon catheter, without transient ischemia.

Arm

Intervention/Treatment

Experimental: A: Ad5FGF-4

Ad5FGF-4, administered one time at 6x10e9 viral particles in buffer, and maximally-tolerated medical therapy for angina.

Biological: Ad5FGF-4

Ad5FGF-4 administered via intracoronary infusion using standard balloon catheter, and under conditions of transient ischemia.

Other Names:

Generx

alferminogene tadenovec

Placebo Comparator: B: Placebo

Placebo buffer, administered one time, and maximally-tolerated medical therapy for angina.

Biological: Placebo

Placebo buffer administered via intracoronary infusion using standard balloon catheter, without transient ischemia.

Outcome Measures

Primary Outcome Measures

Change in Exercise Tolerance Test (ETT) duration [Baseline and Month 6]
Modified Bruce Protocol with exercise duration limited by angina or angina equivalent

Secondary Outcome Measures

Change in patient functional status (CCS class) [Baseline and Month 6]
Canadian Cardiovascular Society (CCS) angina classification
Change in weekly angina frequency [Baseline and Month 6]
Average weekly angina episodes
Change in weekly nitroglycerin usage [Baseline and Month 6]
Average weekly nitroglycerin usage
Change in quality of life [Baseline and Month 6]
Seattle Angina Questionnaire
Safety of Ad5FGF-4 [Through Month 6]
Adverse events and clinical laboratory testing
Long-term safety of Ad5FGF-4 [Through Month 60]
Occurrence of clinically significant events

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients 55-75 years of age inclusive
Refractory angina CCS Class III or IV
At least 3 angina episodes per week
Diagnostic coronary angiogram in the past 12 months confirming the presence of coronary artery disease in patients who are not candidates for standard interventions (PCI or CABG)
Patients without significant and adequate reduction or relief of angina in spite of treatment with at least two functional classes of chronic anti-angina medication at the maximally tolerated dose. Functional classes of anti-angina medications include β-blockers, calcium channel blockers, nitrates, and metabolic modulators (i.e. ranolazine). Participants must have been on a stable anti-angina medication regimen for at least 4 weeks before signing the informed consent form.
Documented clinical evidence of inducible ischemia on stress testing within the past 6 months [e.g. nuclear perfusion imaging (stress SPECT or PET), stress ECHO, stress MRI, stress ETT (≥1 mm ST Segment depression)].
Maximal exercise duration of 3-8 minutes on ETT (Modified Bruce Protocol), with patient physically unable to continue due to angina or angina equivalent (e.g. exhaustion/dyspnea), or when ETT is stopped by person administering the ETT. Patient develops ≥1mm ST segment depression on each of the qualifying baseline ETT
Left ventricular ejection fraction (LVEF) of ≥ 30%
Postmenopausal female patients, women of childbearing potential and men willing to use an effective contraception method while in the study and/or who agree not to become pregnant or make their partner pregnant throughout the study and during one year after administration of the study drug
Female subjects of childbearing potential who have a negative urine pregnancy test and are willing to use an acceptable form of birth control during the study. For the purpose of this study, a female of childbearing potential is a female who is not postmenopausal for greater than 2 years, has not had a tubal ligation, and has not had a hysterectomy. For the purpose of this study, the following are considered acceptable methods of birth control:

Oral contraceptives, contraceptive patches/implants
Intrauterine device (IUD) together with condom or spermicide for at least three months
Condom and spermicide
Abstinence with a documented second acceptable method of birth control should the subject become sexually active

Willing and able to comply with all study requirements, including adherence to the assigned strategy, medical therapy, and follow-up
Provided written informed consent

Exclusion Criteria

Female patients who are pregnant, lactating (breast milk feeding), or planning a pregnancy during the course of the study and one year after administration of the study drug. Women of childbearing potential who are not using an acceptable method of birth control (i.e., IUD, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive or condom in combination with contraceptive cream, jelly or foam). Women of childbearing potential with a positive urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) before randomization.
Patients with unstable angina for whom an immediate revascularization procedure (PCI or CABG) is indicated
Patients for whom a cardiac revascularization procedure (PCI or CABG) is planned in the next 3 months
Myocardial infarction within the past 3 months prior to the Screening visit
Congestive heart failure New York Heart Association (NYHA) Class IV
Myocarditis or restrictive pericarditis
Diagnostic coronary angiogram finding of 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)
A single patent coronary conduit (for example, totally occluded RCA and LCx with no bypass grafts. Patient will not tolerate balloon occlusion of the LAD for infusion)
Patients whose angiogram shows a good anatomy for angioplasty and who are candidates for that procedure. Patients without a prior angiogram or angiogram report are excluded.
Clinically significant aortic or mitral valvular heart disease
Life-threatening coronary ostial stenosis that precludes adequate catheter engagement in any target vessel, unless the vessel can be accessed via a patent bypass graft
Coronary artery to venous communications, which bypass the coronary capillary bed
Untreated life-threatening ventricular arrhythmias
Uncontrolled arterial hypertension with systolic blood pressure >140 mm Hg and/or diastolic pressure >100 mm Hg
CABG surgery within the past 6 months, unless those grafts are now occluded
Percutaneous coronary intervention (PCI) within the past 3 months, unless the stented/dilated vessel(s) are now occluded
Enhanced external counterpulsation (EECP) within 3 months prior to the start of screening evaluations
Prior treatment with spinal cord stimulation
Prior treatment with coronary sinus reducer
Transmyocardial or percutaneous myocardial laser revascularization within the past 12 months
Prior treatment with any cardiovascular gene or cell therapy within the past 12 months
Active SARS-CoV-2 infection (COVID-19)
Any major organ disease or any medical disease or condition that substantially impairs life expectancy
History of cancer within the past 5 years, other than basal cell carcinoma, or patients with any laboratory or physical exam or diagnostic procedure finding suggestive of current malignancy
Moderate to severe non-proliferative or proliferative retinopathy from any cause, clinically significant macular edema, or previous pan-retinal photocoagulation therapy
Heparin induced thrombocytopenia or history of idiopathic thrombocytopenic purpura or other medical condition causing thrombocytopenia
Serum glutamic pyruvic transaminase (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
HbA1c > 9% in patients with diabetes
Positive test for hepatitis B or C
Positive test for human immunodeficiency virus (HIV)
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
History of alcohol or drug abuse
History of non-compliance with medical therapy