Epicardial Injection of hiPSC-CMs to Treat Severe Chronic Ischemic Heart Failure (HEAL-AHF)

Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Ischemic Heart Failure

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: HiCM-188 therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300457
      • Teda International Cardiovascular Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years
2. Willingness and ability to give written informed consent
3. Nuclide-myocardial metabolic perfusion imaging or Magnetic Resonance Imaging (MRI) revealed infarcted myocardium in the left anterior descending branch (LAD) coronary artery supply area
4. LVEF<50% as assessed by Echocardiography or LVEF≤40% as assessed by MRI
5. Patients have indications for Coronary Artery Bypass Grafting

Exclusion Criteria:

1. Presence of a pacemaker, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy device (CRT)
2. Diagnosed with malignancy within 5 years
3. Autoimmune disease
4. Recipients of organ transplant.
5. Patients undergoing other surgical operations (excluding resection of ventricular aneurysm and left atrial appendage excision/occlusion).
6. Severe ventricular arrhythmia
7. Contraindication to CABG surgery
8. Contraindication to cardiac MRI or PET/CT scan.
9. Contraindication to immunosuppressants
10. Participation in another clinical trial within 3 months prior to screening
11. Pregnancy, lactation, or a positive serum pregnancy test
12. Any other condition considered by the investigator to be inappropriate for inclusion in this clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HiCM-188 Low dose therapy; Intramyocardial injection of HiCM-188 (50 million) during CABG surgery.	Drug: HiCM-188 therapy; Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes (HiCM-188) during coronary artery bypass grafting surgery
Experimental: HiCM-188 Medium dose therapy; Intramyocardial injection of HiCM-188 (150 million) during CABG surgery.	Drug: HiCM-188 therapy; Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes (HiCM-188) during coronary artery bypass grafting surgery
Experimental: HiCM-188 High dose therapy; Intramyocardial injection of HiCM-188 (450 million) during CABG surgery.	Drug: HiCM-188 therapy; Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes (HiCM-188) during coronary artery bypass grafting surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of major Serious Adverse Events (SAE)	The incidence of major Serious Adverse Events (SAE) within the first month after surgery, including pericardial tamponade, nonfatal myocardial infarction, stroke, and all-cause death	Within the first month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of tumor	assessed by PET whole-body imaging at baseline and 12 months after HiCM-188 therapy	12 months after surgery
Left ventricular geometry as assessed by cardiac magnetic resonance imaging (MRI)	Left ventricular wall thickness, interventricular septum thickness	Baseline, 6 and 12 months after surgery
Size of myocardial infarction as assessed by MRI	Size of myocardial infarction	Baseline, 6 and 12 months after surgery
Ventricular wall motion as assessed by MRI	Ventricular wall motion	Baseline, 6 and 12 months after surgery
Left ventricular ejection fraction as assessed by MRI	Left ventricular ejection fraction	Baseline, 6 and 12 months after surgery
Cardiac Volumes as assessed by MRI	Left ventricular end-diastolic volume (LVEDV), Left ventricular end-systolic volume (LVESV) and Stroke Volume (SV)	Baseline, 6 and 12 months after surgery
Cardiac output (CO) as assessed by MRI	Cardiac output (CO)	Baseline, 6 and 12 months after surgery
Left ventricular ejection fraction (LVEF) as assessed by Echocardiography	Left ventricular ejection fraction	Baseline, 6 and 12 months after surgery
Fractional shortening (FS) as assessed by Echocardiography	Fractional shortening	Baseline, 6 and 12 months after surgery
Left ventricular dimensions as assessed by Echocardiography	Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter(LVESD)and left atrial diameter	Baseline, 6 and 12 months after surgery
Cardiac Volumes as assessed by Echocardiography	Left ventricular end- diastolic volume (LVEDV) and Left ventricular end-systolic volume(LVESV)	Baseline, 6 and 12 months after surgery
Mitral valve inflow spectrum(E/A) as assessed by Echocardiography	Mitral valve inflow spectrum (E/A)	Baseline, 6 and 12 months after surgery
Longitudinal strain as assessed by Echocardiography	Longitudinal strain	Baseline, 6 and 12 months after surgery
Myocardial viability as assessed by SPECT	Myocardial viability	Baseline, 6 and 12 months after surgery
Myocardial blood flow as assessed by SPECT	Myocardial blood flow	Baseline, 6 and 12 months after surgery
NT-proBNP Levels	The changes of NT-proBNP Levels	Baseline, 6 and 12 months after surgery
6-minute walking distance	The changes of 6-minute walking distance at 6M and 12M after HiCM-188 therapy	Baseline, 6 and 12 months after surgery
New York Heart Association (NYHA) functional classification	The changes of New York Heart Association (NYHA) functional classification at 6M and 12M after HiCM-188 therapy	Baseline, 6 and 12 months after surgery
Changes of Quality of Life (QoL) as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ)	The MLHFQ is a self-administered disease-specific outcome measure instrument for patients with heart failure (HF), comprising 21 items rated on Likert scales, representing different degrees of impact of HF on QoL. The MLHFQ scores are on a range of 0-105, in which higher scores reflect better health status.	Baseline, 6 and 12 months after surgery
Changes of Quality of Life(QOL) as assessed by 36-Item Short Form Survey (SF-36)	The 36-Item Short Form Survey(SF-36) is a self-administered outcome measure instrument that comprises 36 items grouped into 8 dimensions: limitations in physical activities because of health problems, limitations in social activities because of physical or emotional problems, limitations in usual role activities because of physical health problems, bodily pain, general mental health, limitations in usual role activities because of emotional problems, vitality, general health perceptions. The SF-36 scores are on a range of 0-100, in which higher scores reflect better health status.	Baseline, 6 and 12 months after surgery
Grade 4 or above arrhythmias Related to HiCM-188 Cell Therapy	Grade 4 or above arrhythmias associated with the HiCM-188 therapy within the first month after surgery	Within the first month after surgery
End-diastolic myocardial mass as assessed by MRI	End-diastolic myocardial mass	Baseline, 6 and 12 months after surgery

Collaborators and Investigators

• Sponsor: Help Therapeutics
• Collaborators: TEDA International Cardiovascular Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): May 10, 2027

Study Registration Dates

• First Submitted: January 15, 2024
• First Submitted That Met QC Criteria: March 24, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: XC Liu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No