Allogeneic iPSC-derived Cardiomyocyte Therapy in Patients With Worsening Ischemic Heart Failure

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

This study is designed to evaluate the safety and efficacy of allogeneic induced pluripotent cell derived cardiomyocytes (iPSC-CMs) in treating patients with worsening ischemic heart failure undergoing coronary artery bypass graft surgery.

After screening, iPSC-CMs will be administrated intramyocardially in consented and eligible patients undergoing open-chest CABG surgery and the estimated population size for the study will be 32 patients.

Study Overview

• Status: Recruiting
• Conditions: Chronic Heart Failure; Ischemic Heart Failure
• Intervention / Treatment: Biological: Human (allogeneic) iPS-cell-derived cardiomyocyte

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Early Phase 1

Contacts and Locations

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

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • The second Xiangya hospital of central south university
      • Contact: Chengming Fan; Phone Number: +86-18390945539
      • Principal Investigator: Jinfu Yang, MD
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Not yet recruiting
      • HelpThera
      • Contact: Jiaxian Wang; Phone Number: +86-18565616060; Email: wangjx@helptx.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 35-75 (including 35 and 75).
• Signed the Informed Consent Form (ICF).
• Have chronic left ventricular dysfunction.
• Have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure.
• Have indications for Coronary Artery Bypass Grafting.
• LVEF < 40% as determined by echocardiogram (data collected up to 6 months prior to inclusion evaluation are valid; data collected within 1 month since a myocardial infarction are invalid).
• Weakening or absence of segmental regional wall motion as determined by standard imaging

Exclusion Criteria:

• PRA ≥ 20% or DSA-positive
• Patient received ICD transplantation, CRT or similar treatment.
• Patients with valvular heart disease or received heart valvular disease
• Patients received treatment of percutaneous transluminal coronary intervention (PCI)
• Patients with atrial fibrillation
• Patients previously suffered sustained ventricular tachycardia or sudden cardiac death.
• Baseline glomerular filtration rate <30ml/min/1.73m2.
• Liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
• Hematological abnormality: A hematocrit <25% as determined by HCT, white blood cell<2500/ul or platelet values <100000/ul without another explanation.
• Known, serious radiographic contrast allergy, penicillin allergy, streptomycin allergy.
• Coagulopathy (INR>1.3) not due to a reversible cause.
• Contra-indication to performance of a MRI scan.
• Recipients of organ transplant.
• Clinical history of malignancy within 5 years (patients with prior malignancy must be disease free for 5 years).
• Non-cardiac condition that limits lifespan <1 year.
• On chronic therapy with immunosuppressant medication, such as glucocorticoid and TNFα antagonist.
• Patients allergy to or cannot use immunosuppressant.
• Serum positive for HIV, HBV, HCV, TP.
• Currently enrolled other investigational therapeutic or device study.
• Patients who are pregnant or breast feeding.
• Other conditions that researchers consider not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose level 1; 100 million iPSC-CMs administration	Biological: Human (allogeneic) iPS-cell-derived cardiomyocyte; 10-20 epicardial injections (0.25 mL each) of iPSC-CMs will be delivered in the border zone of the infarcted myocardium
Experimental: Dose level 2; 200 million iPSC-CMs administration	Biological: Human (allogeneic) iPS-cell-derived cardiomyocyte; 10-20 epicardial injections (0.25 mL each) of iPSC-CMs will be delivered in the border zone of the infarcted myocardium
Experimental: Dose level 3; 400 million iPSC-CMs administration	Biological: Human (allogeneic) iPS-cell-derived cardiomyocyte; 10-20 epicardial injections (0.25 mL each) of iPSC-CMs will be delivered in the border zone of the infarcted myocardium
No Intervention: Control; Participants will received CABG surgery only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety in terms of the incidence and severity of adverse events	Number of participants with death, fatal myocardial infarction, stroke, ventricular tachycardia sustained for >15 seconds and newly formed tumor	within 1 month post CABG surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Adverse events that require medical intervention	1~6 months post CABG surgery
Cardiac assessment	24-hour Holter Monitoring post the CABG surgery	1~6 months post CABG surgery
Incidence of newly formed tumor	Evaluation by chest, abdominal and pelvic CT scan and PET-CT scan	1~12 months post CABG surgery
Immunogenic assessments	Donor specific antibody (DSA), serum anti-human leukocyte antigens (anti-HLA) antibody/panel-reactive antibody (PRA) serology monitoring	1 month, 3 months and 6 months post CABG surgery
Changes in left ventricle function evaluation by echocardiogram (ECHO) or cardiac MRI	Changes in cardiac function will be assessed by left ventricular end-systolic volume (LVESV, mL) changes from baseline to 12 months post surgery	from baseline to 12 months at 3, 6, and 12 months post CABG surgery
Changes in 6-minute walk test (6MWT)		from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery
Changes in NYHA functional classification		from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery
Changes in quality of life (QoL)	Quality of life changes as measured by Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores	from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery
Incidence of hospitalization for worsening heart failure		1~12 months post CABG surgery

Collaborators and Investigators

• Sponsor: Help Therapeutics
• Collaborators: Central South University

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: October 2, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Failure; Ischemia
• Other Study ID Numbers: JFYang

Drug and device information, study documents

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