Clinical trial NCT06340048: Epicardial Injection of hiPSC-CMs to Treat Severe Chronic Ischemic Heart Failure
Official title: Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Ischemic Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Lead sponsor: Help Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: TEDA International Cardiovascular Hospital
First posted: 2024-04-01
Enrollment: 36
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical study is to evaluate the feasibility, safety and efficacy of intramyocardial injection of human induce pluripotent stem cell-derived cardiomyocytes (HiCM-188) during coronary artery bypass grafting (CABG) surgery in patients with severe chronic ischemic heart failure.

Detailed description: This is a single center, open-label, three-group dose-escalation (phase I) study followed by dose-extension (phase IIa) study in up to 36 severe ischemic heart failure patients. It is estimated that up to 18 phase I patients will be received HiCM-188 intramyocardial injection during CABG surgery. The maximum number of subjects after dose escalation and dose extension studies in each dose group is 12. All the subjects need take immunosuppressant after transplantation.

Eligibility criteria: Inclusion Criteria:

1. 35-75 years of age (including 35 and 75 years)
2. Willingness and ability to give written informed consent
3. Patients with severe chronic ischemic heart failure
4. New York Heart Association (NYHA) Class III or IV under optimal medical therapy
5. Weakening or absence of segmental regional wall motion as determined by standard imaging.
6. LVEF≤40% as assessed by MRI
7. Nuclide-myocardial metabolic perfusion imaging revealed infarcted myocardium in the left anterior descending branch (LAD) coronary artery supply area
8. Patients have indications for Coronary Artery Bypass Grafting

Exclusion Criteria:

1. Patient with pacemaker, implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy (CRT) treatment.
2. Patients with severe valvular heart disease
3. Patients had acute myocardial infarction or underwent percutaneous coronary intervention (PCI) surgery within 1 month
4. Patients with non-ischemic heart failure, acute viral myocarditis.
5. Patients had acute cerebrovascular events within 1 month before screening.
6. Diagnosed with malignancy within 5 years
7. Autoimmune disease or long-term therapy with immunosuppressant
8. Recipients of organ transplant.
9. Patients undergoing other surgical operations (excluding resection of ventricular aneurysm).
10. Severe ventricular arrhythmia
11. Contraindication to CABG surgery
12. Serum-positive for HIV, hepatitis BsAg, HCV and TP.
13. Contraindication to performance of MRI or PET/CT scan.
14. Contraindication to use immunosuppressant
15. Be allergic to immunosuppressant
16. Patients who had participated in other clinical trials within 3 months
17. Women are pregnant, breastfeeding or blood pregnancy test positive
18. Patients with other conditions are not eligible to participate in this clinical trial

Primary outcomes:
measure: The incidence of major Serious Adverse Events (SAE)
timeFrame: Within the first month after surgery
Secondary outcomes:
measure: Grade 4 or above arrhythmias
timeFrame: Within the first month after surgery
measure: The incidence of tumor
timeFrame: 12 months after surgery
measure: Left ventricular geometry as assessed by cardiac magnetic resonance imaging (MRI)
timeFrame: Baseline, 6 and 12 months after surgery
measure: Size of myocardial infarction as assessed by MRI
timeFrame: Baseline, 6 and 12 months after surgery
measure: Ventricular wall motion as assessed by MRI
timeFrame: Baseline, 6 and 12 months after surgery
measure: Left ventricular ejection fraction as assessed by MRI
timeFrame: Baseline, 6 and 12 months after surgery
measure: Cardiac Volumes as assessed by MRI
timeFrame: Baseline, 6 and 12 months after surgery
measure: Cardiac output (CO) as assessed by MRI
timeFrame: Baseline, 6 and 12 months after surgery
measure: 10.End-diastolic myocardial mass as assessed by MRI
timeFrame: Baseline, 6 and 12 months after surgery
measure: Left ventricular ejection fraction (LVEF) as assessed by Echocardiography
timeFrame: Baseline, 6 and 12 months after surgery
measure: Fractional shortening (FS) as assessed by Echocardiography
timeFrame: Baseline, 6 and 12 months after surgery
measure: Left ventricular dimensions as assessed by Echocardiography
timeFrame: Baseline, 6 and 12 months after surgery
measure: Cardiac Volumes as assessed by Echocardiography
timeFrame: Baseline, 6 and 12 months after surgery
measure: Mitral valve inflow spectrum(E/A) as assessed by Echocardiography
timeFrame: Baseline, 6 and 12 months after surgery
measure: Longitudinal strain as assessed by Echocardiography
timeFrame: Baseline, 6 and 12 months after surgery
measure: Myocardial viability as assessed by SPECT
timeFrame: Baseline, 6 and 12 months after surgery
measure: Myocardial blood flow as assessed by SPECT
timeFrame: Baseline, 6 and 12 months after surgery
measure: NT-proBNP Levels
timeFrame: Baseline, 6 and 12 months after surgery
measure: 6-minute walking distance
timeFrame: Baseline, 6 and 12 months after surgery
measure: New York Heart Association (NYHA) functional classification
timeFrame: Baseline, 6 and 12 months after surgery
measure: Changes of Quality of Life (QoL) as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ)
timeFrame: Baseline, 6 and 12 months after surgery
measure: Changes of Quality of Life(QOL) as assessed by 36-Item Short Form Survey (SF-36)
timeFrame: Baseline, 6 and 12 months after surgery
Other outcomes:
Locations:
city: Tianjin
country: China
facility: TEDA International Cardiovascular Hospital
state: Tianjin
Study officials:
References: