Angina, StablePhase 3AFFIRMNCT02928094
Ad5FGF-4 In Patients With Refractory Angina Due to Myocardial Ischemia
A Phase 3 study testing Ad5FGF-4 in people with Angina, Stable, run by Angionetics Inc..
Trial 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… Read more about this study
- Who is it for?
- Ages 55 to 75 years
- Conditions the study is for
- Angina, Stable
- What is being tested?
- Ad5FGF-4
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2023to 31 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)].
Show all 16Show fewer
- 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
Who cannot join
- 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
Show all 39Show fewer
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
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
- Being tested
- Ad5FGF-4, Placebo
- Keywords
- refractory angina, myocardial ischemia, angiogenesis
- Medical subject headings
- Angina, Stable, Angina Pectoris, Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad5FGF-4Biological
Also called Generx, alferminogene tadenovec
Ad5FGF-4 administered via intracoronary infusion using standard balloon catheter, and under conditions of transient ischemia.
PlaceboBiological
Placebo buffer administered via intracoronary infusion using standard balloon catheter, without transient ischemia.
| Study group | Role | What they receive |
|---|---|---|
| A: Ad5FGF-4 | Experimental | Ad5FGF-4, administered one time at 6x10e9 viral particles in buffer, and maximally-tolerated medical therapy for angina. Receives: Biological: Ad5FGF-4 |
| B: Placebo | Placebo comparator | Placebo buffer, administered one time, and maximally-tolerated medical therapy for angina. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Exercise Tolerance Test (ETT) duration
Modified Bruce Protocol with exercise duration limited by angina or angina equivalent
Measured: Baseline and Month 6
Secondary outcomes (6)
Change in patient functional status (CCS class)
Canadian Cardiovascular Society (CCS) angina classification
Measured: Baseline and Month 6
Change in weekly angina frequency
Average weekly angina episodes
Measured: Baseline and Month 6
Change in weekly nitroglycerin usage
Average weekly nitroglycerin usage
Measured: Baseline and Month 6
Change in quality of life
Seattle Angina Questionnaire
Measured: Baseline and Month 6
Safety of Ad5FGF-4
Adverse events and clinical laboratory testing
Measured: Through Month 6
Long-term safety of Ad5FGF-4
Occurrence of clinically significant events
Measured: Through Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2016 (estimated)
- Study start1 Jan 2023 (estimated)
- Primary completion1 Mar 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Angina, StableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Angionetics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Huapont Life Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02928094
- Sponsor's protocol ID
- CT-3-003
- Acronym
- AFFIRM
- Status last verified
- Jul 2022
- First submitted
- 6 Oct 2016
- Last updated
- 19 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 17825712Grines 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.
PubMed 14563572Rubanyi 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.
PubMed 26581236
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02928094
- Acronym / sponsor ID
- AFFIRM / CT-3-003
- Conditions
- Angina, Stable
- Keywords
- refractory angina, myocardial ischemia, angiogenesis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Angionetics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Huapont Life Sciences
- Study start
- 1 Jan 2023 (estimated)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 10 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Ad5FGF-4 | Experimental | Biological: Ad5FGF-4Ad5FGF-4, administered one time at 6x10e9 viral particles in buffer, and maximally-tolerated medical therapy for angina. |
| B: Placebo | Placebo comparator | Biological: PlaceboPlacebo buffer, administered one time, and maximally-tolerated medical therapy for angina. |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (39 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ad5FGF-4Also: Generx, alferminogene tadenovecAd5FGF-4 administered via intracoronary infusion using standard balloon catheter, and under conditions of transient ischemia. | Biological | A: Ad5FGF-4 |
| PlaceboPlacebo buffer administered via intracoronary infusion using standard balloon catheter, without transient ischemia. | Biological | B: Placebo |
Primary outcome
Change in Exercise Tolerance Test (ETT) duration
Time frame: Baseline and Month 6
Modified Bruce Protocol with exercise duration limited by angina or angina equivalent
6 secondary outcomes
Change in patient functional status (CCS class)
Time frame: Baseline and Month 6
Change in weekly angina frequency
Time frame: Baseline and Month 6
Change in weekly nitroglycerin usage
Time frame: Baseline and Month 6
Change in quality of life
Time frame: Baseline and Month 6
Safety of Ad5FGF-4
Time frame: Through Month 6
Long-term safety of Ad5FGF-4
Time frame: Through Month 60
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2022.
- Background: PubMed 17825712Henry 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.
- Background: PubMed 14563572Grines 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.
- Background: PubMed 26581236Rubanyi 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.
- Individual participant dataSharing planned: Undecided
Related trials for Angina, Stable
Recruiting
Intracoronary Cryotherapy Effect on Stabilization of Vulnerable Plaque in Patients With Stable Angina or ACS - A Traditional Feasibility Study
Coronary Arterial Disease (CAD), Plaque
Recruiting
Multivessel Balloon Occlusion to Investigate Obstructive Coronary Artery Disease and aNgina
Stable Angina, Multivessel Coronary Artery Disease
Recruiting
Study of Lesion-Specific Invasive Haemodynamic Angina Thresholds
Angina (Stable), Coronary Artery Disease(CAD)
Active, not recruitingObservational study
REDUCER-I: An Observational Study of the Neovasc Reducer™ System
Angina Pectoris, Angina Pectoris, Stable
RecruitingObservational study
Identification of Lesion Characteristics in Coronary Plaques Using Multimodality Intravascular Imaging and Novel Photon-counting CT in Stable Angina
Coronary Artery Disease (CAD), Stable Angina Pectoris
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ad5FGF-4 in people with Angina, Stable, run by Angionetics Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Christopher Reinhard (858-414-1477, creinhard@angionetics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Exercise Tolerance Test (ETT) duration (time frame: Baseline and Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02928094, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2022.