Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina
Condition: Chronic Myocardial Ischemia; Refractory Angina Pectoris; Advanced Coronary Heart Disease
MeSH terms: Heart Diseases; Angina Pectoris; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Ischemia
Intervention: Auto-CD34+ cells; Placebo: Diluent used to suspend Auto-CD34+ cells; Standard of care
Intervention description: 10 intramyocardial injections of 0.2 mL per injection site of Auto-CD34+ cells; 10 intramyocardial injections of 0.2 mL per injection site of placebo; Standard of care for refractory angina
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 291.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to assess the safety and efficacy of targeted intramyocardial
      delivery of Auto-CD34+ cells for increasing exercise time and amelioration of anginal
      symptoms in subjects with refractory angina and chronic myocardial ischemia.
    

Eligibility criteria:

        Main Inclusion Criteria:

          -  Male or female participants who are 21 to 80 years of age at the time of signing the
             informed consent.

          -  Participants with Canadian Cardiovascular Society (CCS) class III or IV chronic
             refractory angina.

          -  Participants without control of their angina symptoms in spite of maximal tolerated
             doses of anti-angina drugs. Participants must be on optimal therapy for their angina
             and must have been on a stable anti-anginal medication regimen for at least 4 weeks
             before signing the informed consent form.

          -  Participants with obstructive coronary disease unsuitable for conventional
             revascularization due to unsuitable anatomy or comorbidity as determined at the site
             and confirmed by an independent adjudication committee.

          -  Participants must have evidence of inducible myocardial ischemia.

          -  Participants must experience angina episodes.

          -  Participants must be able to complete 2 exercise tolerance tests on the treadmill
             within 3 weeks of randomization.

          -  If female of childbearing potential, subject must not be pregnant and agree to employ
             adequate birth control measures for the duration of the study.

        Main Exclusion Criteria:

          -  Cardiovascular hospitalization within 60 days prior to potential study enrollment.
             Participant has had a successful or partially successful coronary artery bypass graft
             (CABG) within 6 months or PCTA within 60 days of potential study enrollment.

          -  Participant has had a placement of a bi-ventricular pacemaker for cardiac
             resynchronization therapy (CRT) for heart failure within 180 days of potential study
             enrollment.

          -  Participant has documented stroke or transient ischemic attacks (TIAs) within 60 days
             of potential study enrollment.

          -  Participant has a history of moderate to severe aortic stenosis; or severe aortic
             insufficiency; or severe mitral stenosis; or severe mitral insufficiency.

          -  Participant has a prosthetic aortic valve or a mechanical mitral valve replacement.

          -  Participant has severe co-morbidity associated with a reduction in life expectancy to
             less than 3 years as a result of chronic medical illnesses.

          -  Participants with cancer are excluded with the following exceptions:

               -  Subjects with in-situ non-melanoma skin cancer or in-situ cervical cancer are not
                  excluded.

               -  Participants that have been cancer free for >= 5 years as determined by their
                  oncologist are not excluded. Subjects with a prior history of stem cell
                  transplant for cancer are excluded no matter how long they have been cancer-free.

          -  Participants with a history of leukemia or other bone marrow disease.

          -  Participant has sickle cell disease or sickle cell trait.

          -  Participants with proliferative retinopathy.

          -  Participants with Hb A1c > 9%.

          -  Participant has platelet counts >10% above the upper limit of normal (ULN) or platelet
             counts < 70,000.

          -  Participant has a hematocrit < 30% prior to potential study enrollment.

          -  Participant has a serum creatinine > 2.5 mg/dL prior to potential study enrollment.

          -  Participant tests positive for HIV, hepatitis B, or hepatitis C, or is on chronic
             immunosuppressive medications, or has had a previous stem cell transplant.

          -  Participant has a known contraindication to Neupogen (filgrastim) or G-CSF.

          -  Participant was previously enrolled in an active treatment group of cell therapy
             trials for cardiovascular disease including any phase of CD34+ stem cell trials.

          -  Left ventricular (LV) thickness of < 7 mm in the target areas of injection as measured
             by during a 2-D echocardiogram (ECHO).

          -  Atrial fibrillation, atrial flutter, or other uncontrolled arrhythmias that would
             prohibit accurate electromechanical mapping and NOGA-guided intramyocardial injection.

          -  Bleeding diathesis with an INR > 1.8 when not receiving anti-thrombotic therapy.

          -  Hepatic dysfunction as evidenced by elevated AST or ALT levels > 2.5 x ULN.

          -  Any previous transplant requiring immunosuppression.

          -  Disease state requiring chronic immunosuppression.