IPSC-CMs Combined with LVAD or CABG for the Treatment of Heart Failure

Study on the Safety and Efficacy of Human IPSC-Derived Cardiomyocytes in the Treatment of End-Stage Heart Failure

This clinical trial investigates the safety, feasibility, and therapeutic potential of a combined approach using HiCM-188 cardiomyocyte injection delivered intramyocardially alongside either LVAD implantation or CABG surgery in patients with advanced ischemic heart failure.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Heart Failure At NYHA Stage III or IV
• Intervention / Treatment: Other: CABG/LVAD+Saline; Biological: low dose CABG+iPSC-CMs; Biological: High dose CABG/LVAD+iPSC-CMs

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jiaxian Wang, MD, PhD; Phone Number: +86-18565616060; Email: wangjx@helpsci.com.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • HelpThera
      • Contact: Jiaxian Wang, MD, PhD; Phone Number: +86-18565616060; Email: wangjx@helpsci.com.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female aged 35-75 years (inclusive) at the time of signing the informed consent form.
• Capable of understanding the informed consent form, voluntarily agreeing to participate in the trial, and signing the informed consent form.
• Diagnosed with end-stage heart failure.
• Receiving optimized medical therapy for heart failure, with New York Heart Association (NYHA) functional class III-IV.
• Echocardiography demonstrating regional hypokinesia or akinesia of the ventricular wall.
• Cardiac magnetic resonance imaging (MRI) confirming left ventricular ejection fraction (LVEF) ≤35%.
• Myocardial perfusion-metabolism imaging with radionuclide indicating infarcted myocardium in the left anterior descending (LAD) artery territory.
• Meets criteria for coronary artery bypass grafting (CABG) under cardiopulmonary bypass during screening and requires CABG surgery.

• For patients enrolled in the LVAD implantation group, the following additional criteria must be met:

  1. Definitive indication for LVAD implantation due to end-stage heart failure.
  2. Anticipated significant improvement in hemodynamic stability post-LVAD implantation, with potential for further cardiac functional improvement via myocardial cell injection.
  3. Absence of significant contraindications for LVAD surgery.

Exclusion Criteria:

• History of pacemaker, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy (CRT).
• Severe valvular heart disease.
• Acute myocardial infarction or history of percutaneous coronary intervention (PCI) within 1 month prior to screening.
• Non-ischemic cardiomyopathy or acute viral myocarditis.
• Acute cerebrovascular event within 1 month prior to screening.
• History of malignancy within 5 years prior to screening.
• Autoimmune disease or chronic use of immunosuppressive agents.
• History of organ transplantation.
• Planned concurrent major surgery (excluding left ventricular aneurysm resection or left atrial appendage closure/resection).
• Malignant ventricular arrhythmia.
• Contraindications for CABG surgery.
• Positive serology for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or Treponema pallidum antibody.
• Inability to undergo cardiac MRI or PET/CT imaging.
• Contraindications to immunosuppressive therapy or inability to comply with the protocol-specified immunosuppressive regimen.
• Hypersensitivity to mycophenolate sodium, mycophenolic acid, mycophenolate mofetil, tacrolimus, macrolides, prednisone acetate/methylprednisolone, other corticosteroids, or basiliximab.
• Participation in another clinical trial within 3 months prior to screening.
• Pregnancy, lactation, or positive pregnancy test in female patients.
• Any other condition deemed by the investigator to render the patient unsuitable for trial participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control group; CABG combined with saline or LVAD combined with saline	Other: CABG/LVAD+Saline; CABG/LVAD+Saline
Experimental: Low Dose Group; CABG combined with 0.5×10^8 iPSC-CMs	Biological: low dose CABG+iPSC-CMs; CABG+0.5×10^8 iPSC-CMs
Experimental: High dose group; CABG combined with 1.5×10^8 iPSC-CMs or LVAD combined with 1.5×10^8 iPSC-CMs	Biological: High dose CABG/LVAD+iPSC-CMs; CABG+1.5×10^8 iPSC-CMs or LVAD+1.5×10^8 iPSC-CMs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute walk test		baseline, 1, 3, 6, 12 months post-operation
Major Adverse Cardiovascular Events	The composite endpoint events occurring during the prescribed postoperative follow-up period included cardiac death, non-fatal myocardial infarction, non-fatal stroke, and emergency target vessel revascularization (e.g., PCI or CABG), which was expressed as the percentage of subjects experiencing at least one of these events (%).	From enrollment to the end of study at 12 months
Survival rate		From enrollment to the end of study at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction	Improvement of left ventricular ejection fraction assessed by ECHO	baseline, 1, 3, 6, 12 months post-operation
Cardiac magnetic resonance detection index	Myocardial infarction size and Myocardial fibrosis assessed by MRI	baseline, 1, 3, 6, 12 months post-operation
BNP	BNP levels are measured by venous blood samples	baseline, 1, 3, 6, 12 months post-operation
Removal rate of LVAD	Percentage of subjects who had their Left Ventricular Assist Device (LVAD) successfully removed after surgery	From enrollment to the end of study at 12 months
SF-36	life quality assessed by SF-36 (The Short-Form-36 Health Survey). The SF-36 scale is a tool used to assess health-related quality of life, including eight dimensions: Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH). Each dimension has its unique scoring criteria, and the score range for each dimension is from 0 to 100 points. Higher scores indicate better health outcomes	baseline, 1, 3, 6, 12 months post-operation
KCCQ	Kansas City Cardiomyopathy Questionnaire, KCCQ is designed to assess the health status and quality of life of patients with heart failure. The score range is from 0 to 100 and higher scores reflect better health status and quality of life.	baseline, 1, 3, 6, 12 months post-operation

Collaborators and Investigators

• Sponsor: Help Therapeutics
• Investigators: Principal Investigator: Yongfeng Shao, MD, PhD, Jiangsu Provincial People's Hospital (First Affiliated Hospital of Nanjing Medical University); Principal Investigator: Liansheng Wang, MD, PhD, Jiangsu Provincial People's Hospital (First Affiliated Hospital of Nanjing Medical University)

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 4, 2025
• First Submitted That Met QC Criteria: March 4, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: CABG; LVAD; iPSC-CMs
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: SYF, WLS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No