Back to resultsTreating Heart Failure With hiPSC-CMs
Primary Purpose
Heart Failure
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
hiPSC-CM therapy
Control
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
Eligibility Criteria
Inclusion Criteria:
- Aged 35-75 (including 35 and 75).
- Have signed the Informed Consent Form (ICF).
- Patients have chronic left ventricular dysfunction.
- Patients have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure.
- Patients have indications for Coronary Artery Bypass Grafting.
- 20% ≤ LVEF ≤ 40% as determined by echocardiogram (data collected up to 3 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 TNF-α 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
hiPSC-CM therapy
Control
Arm Description
Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 100 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
Coronary artery bypass grafting surgery only.
Outcomes
Primary Outcome Measures
Incidence of serious adverse events(SAEs) within 1 month post-CABG surgery.
Incidence of serious adverse events(SAEs) within 1 month post-CABG surgery. These include death, fatal myocardial infarction, stroke, cardiac tamponade, cardiac perforation, hemodynamic ventricular arrhythmias (duration > 15s), and new allogeneic human neoplasms.
Secondary Outcome Measures
Size of infracted myocardium assessed by MRI
Size of infracted myocardium;
Left Ventricular systolic performance as assessed by MRI
left ventricular side wall thickness at diastolic; interventricular septum thickness;
Left ventricular ejection fraction assessed by MRI
left ventricular ejection fraction;
Overall Left Ventricular systolic performance as assessed by MRI
left ventricular end-systolic volume and end-diastolic volume; stroke volume;
Cardiac output assessed by MRI
cardiac output;
Myocardium density assessed by MRI
myocardium density;
Left ventricular mass assessed by MRI
left ventricular mass at diastolic;
Overall Left Ventricular systolic performance as assessed by Echocardiogram
Interventricular septum thickness at diastolic; left ventricular posterior wall thickness at diastolic;
Left Ventricular systolic performance as assessed by Echocardiogram
left ventricular end-systolic diameter and end-diastolic diameter; left atrial diameter;
Left ventricular ejection fraction assessed by Echocardiogram
left ventricular ejection fraction;
Mitral flow pattern (E/A) assessed by Echocardiogram
mitral flow pattern (E/A) ;
Overall Left Ventricular systolic performance as assessed by PET/ECT Scan
Myocardium perfusion
Functional status by 6 minute walk test
Evaluate Functional Capacity via the Six Minute Walk Test
Functional status by New York Heart Association (NYHA) Classification
Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination.
It classifies patients in one of four categories based on their limitations during physical activity; Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.
Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest.
Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.
Minnesota Living With Heart Failure Questionnaire (MLHFQ)
Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF). The Maximum possible scores being 105 and the minimum 0. Higher scores indicate a worse or worsening quality of life, while lower scores or decreasing scores indicate a better quality of life.
Incidence of Serious Adverse Events (SAE)
SAE justified (all undesirable or unintended diseases or laboratory and imaging disorders and symptoms that occur in subjects after CABG surgery and 12 months postoperative follow-up, or until the subject withdrawals from the study. AE grading will be based on Common Terminology Criteria for Adverse Events (CTCAE) V5.0.)
Incidence of severe arrhythmia
Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring
Changes in penal reactive antibodies (PRA)
Changes in penal reactive antibodies (PRA) as assessed via blooddraw
Changes in donor specific antibodies (DSA)
Changes in donor specific antibodies (DSA) as assessed via blooddraw
Changes in cytokines
Change in NT-proBNP as assessed via blooddraw
Full Information
NCT ID
NCT05223894
First Posted
December 22, 2021
Last Updated
March 23, 2022
Sponsor
Help Therapeutics
Collaborators
Shanghai East Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05223894
Brief Title
Treating Heart Failure With hiPSC-CMs
Official Title
Epicardial Injection of Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 30, 2022 (Anticipated)
Primary Completion Date
July 30, 2023 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Help Therapeutics
Collaborators
Shanghai East Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Heart failure has a high morbidity and mortality because the heart is one of the least regenerative organs in the human body. Drug treatments for heart failure manage symptoms but do not restore lost myocytes. Cellular replacement therapy is a potential approach to repair damaged myocardial tissue, restore cardiac function, which has become a new strategy for the treatment of heart failure. The purpose of this study is to assess the safety and efficacy of intramyocardial delivery of cardiomyocytes at the time of coronary artery bypass grafting in patients with chronic heart failure.
Detailed Description
Patients with heart failure will be treated with allogenic human pluripotent stem cell-derived cardiomyocytes ( hPSC-CM ) from healthy donors. The cells will be injected directly into the myocardium at time of coronary artery bypass grafting. Patients will be assessed at 1, 3, 6 and 12 months after cell transplantation for safety and efficacy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
hiPSC-CM therapy
Arm Type
Experimental
Arm Description
Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 100 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
Arm Title
Control
Arm Type
Sham Comparator
Arm Description
Coronary artery bypass grafting surgery only.
Intervention Type
Biological
Intervention Name(s)
hiPSC-CM therapy
Intervention Description
Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 100 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
Intervention Type
Other
Intervention Name(s)
Control
Intervention Description
Coronary artery bypass grafting surgery only.
Primary Outcome Measure Information:
Title
Incidence of serious adverse events(SAEs) within 1 month post-CABG surgery.
Description
Incidence of serious adverse events(SAEs) within 1 month post-CABG surgery. These include death, fatal myocardial infarction, stroke, cardiac tamponade, cardiac perforation, hemodynamic ventricular arrhythmias (duration > 15s), and new allogeneic human neoplasms.
Time Frame
1 Month Post-operation
Secondary Outcome Measure Information:
Title
Size of infracted myocardium assessed by MRI
Description
Size of infracted myocardium;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Left Ventricular systolic performance as assessed by MRI
Description
left ventricular side wall thickness at diastolic; interventricular septum thickness;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Left ventricular ejection fraction assessed by MRI
Description
left ventricular ejection fraction;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Overall Left Ventricular systolic performance as assessed by MRI
Description
left ventricular end-systolic volume and end-diastolic volume; stroke volume;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Cardiac output assessed by MRI
Description
cardiac output;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Myocardium density assessed by MRI
Description
myocardium density;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Left ventricular mass assessed by MRI
Description
left ventricular mass at diastolic;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Overall Left Ventricular systolic performance as assessed by Echocardiogram
Description
Interventricular septum thickness at diastolic; left ventricular posterior wall thickness at diastolic;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Left Ventricular systolic performance as assessed by Echocardiogram
Description
left ventricular end-systolic diameter and end-diastolic diameter; left atrial diameter;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Left ventricular ejection fraction assessed by Echocardiogram
Description
left ventricular ejection fraction;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Mitral flow pattern (E/A) assessed by Echocardiogram
Description
mitral flow pattern (E/A) ;
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Overall Left Ventricular systolic performance as assessed by PET/ECT Scan
Description
Myocardium perfusion
Time Frame
Baseline, 6 and 12 Months Post-operation
Title
Functional status by 6 minute walk test
Description
Evaluate Functional Capacity via the Six Minute Walk Test
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Functional status by New York Heart Association (NYHA) Classification
Description
Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination.
It classifies patients in one of four categories based on their limitations during physical activity; Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.
Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest.
Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Minnesota Living With Heart Failure Questionnaire (MLHFQ)
Description
Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF). The Maximum possible scores being 105 and the minimum 0. Higher scores indicate a worse or worsening quality of life, while lower scores or decreasing scores indicate a better quality of life.
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Incidence of Serious Adverse Events (SAE)
Description
SAE justified (all undesirable or unintended diseases or laboratory and imaging disorders and symptoms that occur in subjects after CABG surgery and 12 months postoperative follow-up, or until the subject withdrawals from the study. AE grading will be based on Common Terminology Criteria for Adverse Events (CTCAE) V5.0.)
Time Frame
Baseline, 1~12Months Post-operation
Title
Incidence of severe arrhythmia
Description
Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring
Time Frame
First month post-operatively
Title
Changes in penal reactive antibodies (PRA)
Description
Changes in penal reactive antibodies (PRA) as assessed via blooddraw
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Changes in donor specific antibodies (DSA)
Description
Changes in donor specific antibodies (DSA) as assessed via blooddraw
Time Frame
Baseline, 1, 3, 6 and 12 Months Post-operation
Title
Changes in cytokines
Description
Change in NT-proBNP as assessed via blooddraw
Time Frame
Baseline,1, 3, 6 and 12 Months Post-operation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 35-75 (including 35 and 75).
Have signed the Informed Consent Form (ICF).
Patients have chronic left ventricular dysfunction.
Patients have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure.
Patients have indications for Coronary Artery Bypass Grafting.
20% ≤ LVEF ≤ 40% as determined by echocardiogram (data collected up to 3 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 TNF-α 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gang Yang, MD,PhD
Phone
+86-18601406982
Email
yanggang@helpsci.com.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhongmin Liu, MD,phD
Organizational Affiliation
Shanghai East Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Treating Heart Failure With hiPSC-CMs
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