Epicardial Injection of hiPSC-CMs to Treat Severe Chronic Ischemic Heart Failure

Help Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Heart Failure

Treatments: Drug: HiCM-188 therapy

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT06340048

XC Liu

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 estimated patients

Sex: All

Ages: 35 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

HiCM-188 Low dose therapy

Experimental group

Description:

Intramyocardial injection of HiCM-188 (50 million) during CABG surgery.

Treatment:

Drug: HiCM-188 therapy

HiCM-188 Medium dose therapy

Experimental group

Description:

Intramyocardial injection of HiCM-188 (150 million) during CABG surgery. Interventions

Treatment:

Drug: HiCM-188 therapy

HiCM-188 High dose therapy

Experimental group

Description:

Intramyocardial injection of HiCM-188 (450 million) during CABG surgery. Interventions

Treatment:

Drug: HiCM-188 therapy