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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06340048
• Other study ID #: XC Liu
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 5, 2023
• Est. completion date: March 5, 2025

Study information

• Verified date: March 2024
• Source: Help Therapeutics
• Contact: Xiaocheng Liu
• Phone: +86-022-65208030
• Email: liuxc[@]tedaich.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: March 5, 2025
• Est. primary completion date: September 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• HiCM-188 therapy
Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes (HiCM-188) during coronary artery bypass grafting surgery

Locations

Country	Name	City	State
China	TEDA International Cardiovascular Hospital	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Help Therapeutics	TEDA International Cardiovascular Hospital

Country where clinical trial is conducted

China, 

Outcome

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