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

Early Phase 1

Recruiting

• Conditions: Ischemic Heart Failure; Chronic Heart Failure
• Interventions: Biological: Human (allogeneic) iPS-cell-derived cardiomyocyte

• Registration Number: NCT05566600
• Lead Sponsor: Help Therapeutics

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-22
• Study First Submitted QC: 2022-10-02
• Study First Posted: 2022-10-04
• Study Start: 2022-10-09
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-22
• Primary Completion: 2024-12-31
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose level 3	Human (allogeneic) iPS-cell-derived cardiomyocyte	400 million iPSC-CMs administration
Dose level 1	Human (allogeneic) iPS-cell-derived cardiomyocyte	100 million iPSC-CMs administration
Dose level 2	Human (allogeneic) iPS-cell-derived cardiomyocyte	200 million iPSC-CMs administration

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

The second xiangya hospital of central south university; 🇨🇳 Changsha, Hunan, China

HelpThera; 🇨🇳 Nanjing, Jiangsu, China