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

Phase 1

Recruiting

• Conditions: Heart Failure
• Interventions: Drug: HiCM-188 therapy

• Registration Number: NCT06340048
• Lead Sponsor: Help Therapeutics

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.

Study Timeline

• Study Start: 2023-09-05
• Study First Submitted: 2024-01-15
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-24
• Last Update Submitted: 2024-03-24
• Study First Posted: 2024-04-01
• Last Update Posted: 2024-04-01
• Primary Completion: 2024-09-05
• Study Completion: 2025-03-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
HiCM-188 Medium dose therapy	HiCM-188 therapy	Intramyocardial injection of HiCM-188 (150 million) during CABG surgery. Interventions
HiCM-188 High dose therapy	HiCM-188 therapy	Intramyocardial injection of HiCM-188 (450 million) during CABG surgery. Interventions
HiCM-188 Low dose therapy	HiCM-188 therapy	Intramyocardial injection of HiCM-188 (50 million) during CABG surgery.

Primary Outcome Measures

Name	Time	Method
The incidence of major Serious Adverse Events (SAE)	Within the first month after surgery	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

Secondary Outcome Measures

Name	Time	Method
Myocardial viability as assessed by SPECT	Baseline, 6 and 12 months after surgery	Myocardial viability
NT-proBNP Levels	Baseline, 6 and 12 months after surgery	The changes of NT-proBNP Levels
Left ventricular geometry as assessed by cardiac magnetic resonance imaging (MRI)	Baseline, 6 and 12 months after surgery	Left ventricular wall thickness, interventricular septum thickness
Size of myocardial infarction as assessed by MRI	Baseline, 6 and 12 months after surgery	Size of myocardial infarction
Cardiac output (CO) as assessed by MRI	Baseline, 6 and 12 months after surgery	Cardiac output (CO)
Fractional shortening (FS) as assessed by Echocardiography	Baseline, 6 and 12 months after surgery	Fractional shortening
New York Heart Association (NYHA) functional classification	Baseline, 6 and 12 months after surgery	The changes of New York Heart Association (NYHA) functional classification at 6M and 12M after HiCM-188 therapy
Changes of Quality of Life(QOL) as assessed by 36-Item Short Form Survey (SF-36)	Baseline, 6 and 12 months after surgery	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.
Myocardial blood flow as assessed by SPECT	Baseline, 6 and 12 months after surgery	Myocardial blood flow
Grade 4 or above arrhythmias	Within the first month after surgery	Grade 4 or above arrhythmias associated with the HiCM-188 therapy within the first month after surgery
The incidence of tumor	12 months after surgery	assessed by PET whole-body imaging at baseline and 12 months after HiCM-188 therapy
Ventricular wall motion as assessed by MRI	Baseline, 6 and 12 months after surgery	Ventricular wall motion
Left ventricular ejection fraction as assessed by MRI	Baseline, 6 and 12 months after surgery	Left ventricular ejection fraction
Cardiac Volumes as assessed by MRI	Baseline, 6 and 12 months after surgery	Left ventricular end-diastolic volume (LVEDV), Left ventricular end-systolic volume (LVESV) and Stroke Volume (SV)
10.End-diastolic myocardial mass as assessed by MRI	Baseline, 6 and 12 months after surgery	End-diastolic myocardial mass
Left ventricular dimensions as assessed by Echocardiography	Baseline, 6 and 12 months after surgery	Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter(LVESD)and left atrial diameter
Cardiac Volumes as assessed by Echocardiography	Baseline, 6 and 12 months after surgery	Left ventricular end- diastolic volume (LVEDV) and Left ventricular end-systolic volume(LVESV)
6-minute walking distance	Baseline, 6 and 12 months after surgery	The changes of 6-minute walking distance at 6M and 12M after HiCM-188 therapy
Left ventricular ejection fraction (LVEF) as assessed by Echocardiography	Baseline, 6 and 12 months after surgery	Left ventricular ejection fraction
Mitral valve inflow spectrum(E/A) as assessed by Echocardiography	Baseline, 6 and 12 months after surgery	Mitral valve inflow spectrum (E/A)
Changes of Quality of Life (QoL) as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ)	Baseline, 6 and 12 months after surgery	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.
Longitudinal strain as assessed by Echocardiography	Baseline, 6 and 12 months after surgery	Longitudinal strain

Trial Locations

Locations (1)

TEDA International Cardiovascular Hospital; 🇨🇳 Tianjin, Tianjin, China