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

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ClinicalTrials.gov Identifier: NCT02928094
Recruitment Status : Not yet recruiting
First Posted : October 10, 2016
Last Update Posted : April 27, 2021
Sponsor:
Collaborator:
Huapont Life Sciences
Information provided by (Responsible Party):
Angionetics Inc.

Tracking Information
First Submitted Date  ICMJE October 6, 2016
First Posted Date  ICMJE October 10, 2016
Last Update Posted Date April 27, 2021
Estimated Study Start Date  ICMJE January 1, 2022
Estimated Primary Completion Date March 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2020)
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2016)
Change in ETT duration limited by angina grade 3 [ Time Frame: Baseline and 6 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2020)
  • Change in patient functional status (CCS class) [ Time Frame: Baseline and Month 6 ]
    Canadian Cardiovascular Society (CCS) angina classification
  • Change in weekly angina frequency [ Time Frame: Baseline and Month 6 ]
    Average weekly angina episodes
  • Change in weekly nitroglycerin usage [ Time Frame: Baseline and Month 6 ]
    Average weekly nitroglycerin usage
  • Change in quality of life [ Time Frame: Baseline and Month 6 ]
    Seattle Angina Questionnaire
  • Safety of Ad5FGF-4 [ Time Frame: Through Month 6 ]
    Adverse events and clinical laboratory testing
  • Long-term safety of Ad5FGF-4 [ Time Frame: Through Month 60 ]
    Occurrence of clinically significant events
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2016)
  • Change in patient functional status using Canadian Cardiovascular Society (CCS) angina classification [ Time Frame: Baseline and Months 3, 6, and 12 ]
  • Change in weekly angina frequency [ Time Frame: Baseline and Months 3 and 6 ]
  • Change in weekly nitroglycerin usage [ Time Frame: Baseline and Months 3 and 6 ]
  • Change in quality of life using the Seattle Angina Questionnaire [ Time Frame: Baseline and Months 3, 6, and 12 ]
  • Safety of Ad5FGF-4 as assessed by adverse events and clinical laboratory testing [ Time Frame: Through Month 6 ]
  • Long-term safety of Ad5FGF-4 as assessed by the occurrence of clinically significant events [ Time Frame: Through Month 60 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ad5FGF-4 In Patients With Refractory Angina Due to Myocardial Ischemia
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Angina, Stable
Intervention  ICMJE
  • Biological: Ad5FGF-4
    Ad5FGF-4 administered via intracoronary infusion using standard balloon catheter, and under conditions of transient ischemia.
    Other Names:
    • Generx
    • alferminogene tadenovec
  • Biological: Placebo
    Placebo buffer administered via intracoronary infusion using standard balloon catheter, without transient ischemia.
Study Arms  ICMJE
  • Experimental: A: Ad5FGF-4
    Ad5FGF-4, administered one time at 6x10e9 viral particles in buffer, and maximally-tolerated medical therapy for angina.
    Intervention: Biological: Ad5FGF-4
  • Placebo Comparator: B: Placebo
    Placebo buffer, administered one time, and maximally-tolerated medical therapy for angina.
    Intervention: Biological: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 24, 2020)
160
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2016)
320
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date March 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients 55-75 years of age inclusive
  2. Refractory angina CCS Class III or IV
  3. At least 3 angina episodes per week
  4. 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)
  5. 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.
  6. 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)].
  7. 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
  8. Left ventricular ejection fraction (LVEF) of ≥ 30%
  9. 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
  10. 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
  11. Willing and able to comply with all study requirements, including adherence to the assigned strategy, medical therapy, and follow-up
  12. Provided written informed consent

Exclusion Criteria

  1. 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.
  2. Patients with unstable angina for whom an immediate revascularization procedure (PCI or CABG) is indicated
  3. Patients for whom a cardiac revascularization procedure (PCI or CABG) is planned in the next 3 months
  4. Myocardial infarction within the past 3 months prior to the Screening visit
  5. Congestive heart failure New York Heart Association (NYHA) Class IV
  6. Myocarditis or restrictive pericarditis
  7. 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)
  8. 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)
  9. 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.
  10. Clinically significant aortic or mitral valvular heart disease
  11. 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
  12. Coronary artery to venous communications, which bypass the coronary capillary bed
  13. Untreated life-threatening ventricular arrhythmias
  14. Uncontrolled arterial hypertension with systolic blood pressure >140 mm Hg and/or diastolic pressure >100 mm Hg
  15. CABG surgery within the past 6 months, unless those grafts are now occluded
  16. Percutaneous coronary intervention (PCI) within the past 3 months, unless the stented/dilated vessel(s) are now occluded
  17. Enhanced external counterpulsation (EECP) within 3 months prior to the start of screening evaluations
  18. Prior treatment with spinal cord stimulation
  19. Prior treatment with coronary sinus reducer
  20. Transmyocardial or percutaneous myocardial laser revascularization within the past 12 months
  21. Prior treatment with any cardiovascular gene or cell therapy within the past 12 months
  22. Active SARS-CoV-2 infection (COVID-19)
  23. Any major organ disease or any medical disease or condition that substantially impairs life expectancy
  24. 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
  25. Moderate to severe non-proliferative or proliferative retinopathy from any cause, clinically significant macular edema, or previous pan-retinal photocoagulation therapy
  26. Heparin induced thrombocytopenia or history of idiopathic thrombocytopenic purpura or other medical condition causing thrombocytopenia
  27. Serum glutamic pyruvic transaminase (SGPT) level greater than 2.0 times the upper limit of the laboratory normal range.
  28. Bilirubin level ≥ 2.0 mg/dL
  29. Serum creatinine ≥ 2.5 mg/dL
  30. Platelet count < 100,000/μL
  31. White blood cell count < 3,000/μL
  32. HbA1c > 9% in patients with diabetes
  33. Positive test for hepatitis B or C
  34. Positive test for human immunodeficiency virus (HIV)
  35. Prior anaphylaxis reaction to iodinated contrast agents
  36. Patients who are known to be immunosuppressed or are receiving chronic treatment with immunosuppressive drugs
  37. Received an investigational drug or biologic within 30 days of screening or are currently participating in an investigational drug, biologic or device trial
  38. History of alcohol or drug abuse
  39. History of non-compliance with medical therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lois A Chandler, PhD 858-386-8416 lchandler@angionetics.com
Contact: Christopher Reinhard 858-414-1477 creinhard@angionetics.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02928094
Other Study ID Numbers  ICMJE CT-3-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Angionetics Inc.
Study Sponsor  ICMJE Angionetics Inc.
Collaborators  ICMJE Huapont Life Sciences
Investigators  ICMJE Not Provided
PRS Account Angionetics Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP