Advanced Heart Failure, Ischemic Heart Failure
Conditions
Keywords
HiCM-188, iPSC-derived cardiomyocytes, Allogeneic cell therapy, Advanced heart failure, Ischemic heart failure, Intramyocardial injection, Coronary artery bypass grafting, CABG, Dose escalation, NYHA Class III-IVa
Brief summary
This clinical study will evaluate the safety and tolerability of HiCM-188, an investigational allogeneic induced pluripotent stem cell (iPSC)-derived cardiomyocyte therapy, in adults with advanced heart failure who are undergoing coronary artery bypass grafting (CABG) surgery. Participants who meet the study eligibility criteria will receive a single dose intramyocardial injection of HiCM-188 during CABG surgery. The study will evaluate two dose levels of HiCM-188 using an open-label dose-escalation design. Participants will be followed for up to 12 months after treatment to monitor safety and preliminary signs of clinical effect.
Detailed description
This is a Phase I/IIa, open-label, dose-escalation study of HiCM-188 in adult participants with advanced heart failure. HiCM-188 is an investigational cell therapy product consisting of allogeneic human iPSC-derived cardiomyocytes intended for intramyocardial administration. Eligible participants will receive HiCM-188 during coronary artery bypass grafting (CABG) surgery. The study uses a 3+3 dose-escalation design to evaluate two dose levels of HiCM-188: 0.5 × 10\^8 cells and 1.5 × 10\^8 cells. The primary objective is to evaluate the safety and tolerability of intramyocardial injection of HiCM-188. Secondary objectives include evaluation of preliminary efficacy based on cardiac function, myocardial perfusion, exercise capacity, NYHA functional classification, quality of life, and major adverse cardiac events. Participants will be monitored during the in-hospital period after CABG surgery and HiCM-188 administration, and then followed for up to 12 months after treatment.
Interventions
DRUGHiCM-188 Cells
HiCM-188 is an investigational allogeneic human induced pluripotent stem cell (iPSC)-derived cardiomyocyte therapy administered as intramyocardial injection during CABG surgery.
Sponsors
HELP Therapeutics Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label 3+3 dose-escalation study. Eligible participants with advanced heart failure will be enrolled sequentially and will receive a single dose intramyocardial injection of HiCM-188 during CABG surgery. Two dose levels are planned: 0.5 × 10\^8 cells and 1.5 × 10\^8 cells. Dose escalation will proceed based on dose-limiting toxicity (DLT) criteria.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Able to sign informed consent and comply with the study protocol * 18 to 75 years old at the time of signing informed consent * Advanced heart failure patients with New York Heart Association (NYHA) class III to IVa despite receiving guideline-directed medical therapy (GDMT) * Patients with an indication for coronary artery bypass grafting (CABG) per 2011 ACCF/AHA Guideline meeting a Class of Recommendation (COR) of Class I or Class IIa * Minimum left ventricular wall thickness of ≥ 8 mm in the areas of injection, as confirmed on the screening echocardiogram (ECHO) or cardiac MRI * Left ventricular ejection fraction (LVEF) of 20% to 45%, as confirmed on the screening echocardiogram (ECHO) or cardiac MRI * Other criteria apply. Please contact the investigator for more information.
Exclusion criteria
* Viral myocarditis * Amyloidosis * Pericardial disorders or pericarditis * Left ventricular aneurysm or thrombus, except a small laminar thrombus at the site of previous myocardial infarction (MI) in a different area * Primary significant organic valvular heart disease, with specified dimensions * Untreated congenital heart disease * Complete atrioventricular (AV) conduction block * History of left ventricular assist device surgery * Other criteria apply. Please contact the investigator for more information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Serious Adverse Events | Up to 12 months post-transplant | Incidence of serious adverse events (SAEs) at 12 months post-transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Ventricular Ejection Fraction by Cardiac MRI | Baseline, 6 months, and 12 months | Change from baseline in left ventricular ejection fraction (LVEF, %) assessed by cardiac magnetic resonance imaging (MRI). Echocardiogram may be used as an alternative if cardiac MRI is not medically appropriate or per institutional practice. |
| Change From Baseline in Left Ventricular End-Diastolic Volume by Cardiac MRI | Baseline, 6 months, and 12 months | Change from baseline in left ventricular end-diastolic volume (LVEDV, mL) assessed by cardiac MRI. Echocardiogram may be used as an alternative if cardiac MRI is not medically appropriate or per institutional practice. |
| Change From Baseline in Left Ventricular End-Systolic Volume by Cardiac MRI | Baseline, 6 months, and 12 months | Change from baseline in left ventricular end-systolic volume (LVESV, mL) assessed by cardiac MRI. Echocardiogram may be used as an alternative if cardiac MRI is not medically appropriate or per institutional practice. |
| Change From Baseline in Infarct Size by Cardiac MRI | Baseline, 6 months, and 12 months | Change from baseline in myocardial infarct size assessed by cardiac MRI. |
| Change From Baseline in Myocardial Tissue Perfusion by PET/CT or SPECT | Baseline, 6 months, and 12 months | Change from baseline in myocardial tissue perfusion assessed by positron emission tomography/computed tomography (PET/CT) or single-photon emission computed tomography (SPECT). |
| Change From Baseline in 6-Minute Walk Distance | Baseline, 6 months, and 12 months | Change from baseline in exercise capacity as assessed by the 6-minute walk distance (6MWD). The 6-Minute Walk Distance is measured as the distance walked in 6 minutes, with longer distances reflecting better functional exercise capacity. |
| Change From Baseline in New York Heart Association Functional Classification | Baseline, 6 months, and 12 months | Change from baseline in New York Heart Association (NYHA) functional classification. The New York Heart Association Functional Classification ranges from Class I to Class IV, with higher classes reflecting more severe limitation of physical activity and worse heart failure symptoms. |
| Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score | Baseline, 6 months, and 12 months | Change from baseline in quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The Minnesota Living With Heart Failure Questionnaire score ranges from 0 to 105, with higher scores reflecting worse heart failure-related quality of life. |
| Incidence of Major Adverse Cardiac Events | Up to 12 months post-transplant | Incidence of major adverse cardiac events (MACE) during the study follow-up period. |
Countries
United States
Contacts
CONTACTAlex Zhang
Outcome results
None listed