Treating Congestive Heart Failure Patients With Human iPSC-derived Cardiomyocytes Through Catheter-based Endocardial Injection
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Cardiovascular Diseases
- Sponsor
- Help Therapeutics
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Incidence of major serious adverse events (SAEs)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
Heart failure is the primary cause of morbidity and mortality worldwide. Currently drug treatments for heart failure manage the symptoms, but not restore the loss cardiomyocytes due to the very limited regenerative capability in the adult heart. Novel reparative therapies that replace the cardiomyocytes loss are highly demanded to restore the cardiac function. The main purposes of this explanatory study is to investigate the safety and efficacy of the catheter-based endocardial delivery of human iPSC-derived cardiomyocytes in patients with congestive heart failure.
Detailed Description
Patients with severe congestive heart failure will be treated with allogeneic human iPSC-derived cardiomyocytes (HiCM-188) through the catheter-based injections. HiCM188, produced by Help therapeutics with cGMP condition, will be transplanted into the myocardium through a transcatheter endocardial injection system with two dosage (100 million cells or 400 million cells). The safety and efficacy assessments will be conducted at1, 3, 6 and 12 months after the cell transplantation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients aged 18-75 years (including 18 and 75).
- •Signed the informed consent.
- •Patients with congestive heart failure who have received regular treatment for heart failure.
- •New York Heart Association (NYHA) Class III or IV despite optimal standard of care
- •Left Ventricular Ejection Fraction (LVEF)\<40% as assessed by echocardiography ( measure in the 3 months of recruit is included, excluding the measured values within 1 month of myocardial infarction ）
- •The thickness of left ventricular ≥8mm
- •Female patient who is not pregnant or nursing during the clinical trial
Exclusion Criteria
- •PRA ≥ 20% or DSA positive.
- •Patients received treatments such as pacemakers, ICD or CRT device.
- •Patient with severe valvular disease or presence of a mechanical valve replacement, such as PCI implantation, or patients requiring simultaneous radiofrequency ablation of atrial fibrillation.
- •Patient with any therapeutic traumatic heart surgery within 30 days.
- •Hemodynamic instability or cardiogenic shock.
- •Right heart failure.
- •Restrictive cardiomyopathy such as amyloidosis, sarcoidosis or hematochromia, constrictive pericarditis.
- •Myocardial infarction occurred within 30 days or stroke occurred within 60 days before enrollment.
- •Thickness at left ventricular free wall infarction \< 6 mm.
- •Severe ventricular arrhythmias (persistent ventricular tachycardia or other conditions that the investigator considers necessary to exclude).
Outcomes
Primary Outcomes
Incidence of major serious adverse events (SAEs)
Time Frame: First month post-catheterization
Incidence of SAEs is defined as the composite of: death, fatal myocardial infarction, stroke, tamponade, cardiac perforation, ventricular arrhythmias affecting hemodynamics (\> 15s), and tumorigenicity related to the hiPSC-CM .
Secondary Outcomes
- Overall Left Ventricular systolic performance as assessed by MRI(Baseline, 1, 3, 6 and 12 months post-catheterization)
- Incidence of severe arrhythmia(1-6 months post-catheterization)
- Incidence of newly formed tumors(Baseline, 1,3,6 and 12 months post-catheterization)
- Changes in donor specific antibodies (DSA)(Baseline, 1, 3 and 6 months post-catheterization)
- Changes in penal reactive antibodies (PRA)(Baseline, 1, 3 and 6 months post-catheterization)
- Overall Left Ventricular systolic performance as assessed by PET/ECT Scan(Baseline, 6 and 12 months post-catheterization)
- Functional status by 6 minute walk test(Baseline, 1,3,6 and 12 months post-catheterization)
- Functional status by New York Heart Association (NYHA) Classification(Baseline, 1,3,6 and 12 months post-catheterization)
- Minnesota Living With Heart Failure Questionnaire (MLHFQ)(Baseline, 1,3,6 and 12 months post-catheterization)