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

Chronic Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05566600
• Other study ID #: JFYang
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 9, 2022
• Est. completion date: July 31, 2025

Study information

• Verified date: November 2023
• Source: Help Therapeutics
• Contact: Jiaxian Wang
• Phone: +86-18565616060
• Email: wangjx[@]helpsci.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: July 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

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 TNFa 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.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure
• Ischemia
• Ischemic Heart Failure

Intervention

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

Locations

Country	Name	City	State
China	The second xiangya hospital of central south university	Changsha	Hunan
China	HelpThera	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Help Therapeutics	Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of adverse events	Adverse events that require medical intervention	1~6 months post CABG surgery
Secondary	Cardiac assessment	24-hour Holter Monitoring post the CABG surgery	1~6 months post CABG surgery
Secondary	Incidence of newly formed tumor	Evaluation by chest, abdominal and pelvic CT scan and PET-CT scan	1~12 months post CABG surgery
Secondary	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
Secondary	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
Secondary	Changes in 6-minute walk test (6MWT)		from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery
Secondary	Changes in NYHA functional classification		from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery
Secondary	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
Secondary	Incidence of hospitalization for worsening heart failure		1~12 months post CABG surgery