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

NCT02928094 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: CT-3-003
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Angina, Stable

Keywords

refractory angina; myocardial ischemia; angiogenesis

Outcome Measures

Primary Outcomes (1)

• Change in Exercise Tolerance Test (ETT) duration

  Modified Bruce Protocol with exercise duration limited by angina or angina equivalent

  Baseline and Month 6

Secondary Outcomes (6)

• Change in patient functional status (CCS class)

  Baseline and Month 6

• Change in weekly angina frequency

  Baseline and Month 6

• Change in weekly nitroglycerin usage

  Baseline and Month 6

• Change in quality of life

  Baseline and Month 6

• Safety of Ad5FGF-4

  Through Month 6

Study Arms (2)

A: Ad5FGF-4

EXPERIMENTAL

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

Biological: Ad5FGF-4

B: Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

Ad5FGF-4 BIOLOGICAL

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

Also known as: Generx, alferminogene tadenovec

A: Ad5FGF-4

Placebo BIOLOGICAL

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

B: Placebo

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Angionetics Inc.: lead
• Huapont Life Sciences: collaborator

Related Publications (3)

• Henry TD, Grines CL, Watkins MW, Dib N, Barbeau G, Moreadith R, Andrasfay T, Engler RL. Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials. J Am Coll Cardiol. 2007 Sep 11;50(11):1038-46. doi: 10.1016/j.jacc.2007.06.010. Epub 2007 Aug 24.

  PMID: 17825712 BACKGROUND

• Grines CL, Watkins MW, Mahmarian JJ, Iskandrian AE, Rade JJ, Marrott P, Pratt C, Kleiman N; Angiogene GENe Therapy (AGENT-2) Study Group. A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J Am Coll Cardiol. 2003 Oct 15;42(8):1339-47. doi: 10.1016/s0735-1097(03)00988-4.

  PMID: 14563572 BACKGROUND

• Rubanyi GM. Angiogenic gene therapy for refractory angina. Expert Opin Biol Ther. 2016;16(3):303-15. doi: 10.1517/14712598.2016.1122753. Epub 2015 Dec 14.

  PMID: 26581236 BACKGROUND

MeSH Terms

Conditions

Angina, Stable; Angina Pectoris; Myocardial Ischemia

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Christopher Reinhard

CONTACT

858-414-1477; creinhard@angionetics.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 10, 2016
• Study Start: January 1, 2023
• Primary Completion: March 1, 2024
• Study Completion: December 31, 2024
• Last Updated: July 19, 2022

Record last verified: 2022-07