Clinical trial NCT03763136: Treating Heart Failure With hPSC-CMs
Official title: Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Lead sponsor: Help Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
First posted: 2018-12-04
Enrollment: 20
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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, feasibility 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, feasibility and efficacy.

Eligibility criteria: Inclusion criteria

1. Aged 35-75 (including 35 and 75).
2. Have signed the Informed Consent Form (ICF).
3. Patients have chronic left ventricular dysfunction.
4. Patients have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure.
5. Patients have indications for Coronary Artery Bypass Grafting.
6. 20% ≤ LVEF ≤ 45% 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).
7. Weakening or absence of segmental regional wall motion as determined by standard imaging.

Exclusion criteria

1. PRA ≥ 20% or DSA-positive.
2. Patient received ICD transplantation, CRT or similar treatment.
3. Patients with valvular heart disease or received heart valvular disease
4. Patients received treatment of percutaneous transluminal coronary intervention (PCI)
5. Patients with atrial fibrillation
6. Patients previously suffered sustained ventricular tachycardia or sudden cardiac death.
7. Baseline glomerular filtration rate \<30ml/min/1.73m2.
8. Liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
9. Hematological abnormality: A hematocrit \<25% as determined by HCT, white blood cell\<2500/ul or platelet values \<100000/ul without another explanation.
10. Known, serious radiographic contrast allergy, penicillin allergy, streptomycin allergy.
11. Coagulopathy (INR\>1.3) not due to a reversible cause.
12. Contra-indication to performance of a MRI scan.
13. Recipients of organ transplant.
14. Clinical history of malignancy within 5 years (patients with prior malignancy must be disease free for 5 years).
15. Non-cardiac condition that limits lifespan \<1 year.
16. On chronic therapy with immunosuppressant medication, such as glucocorticoid and TNFα antagonist.
17. Patients allergy to or cannot use immunosuppressant.
18. Serum positive for HIV, HBV, HCV, TP.
19. Currently enrolled other investigational therapeutic or device study.
20. Patients who are pregnant or breast feeding.
21. Other conditions that researchers consider not suitable to participate in this study.

Primary outcomes:
measure: Incidence of sustained ventricular arrhythmias
timeFrame: 1~6 Month Post-operation
measure: Incidence of newly formed tumors
timeFrame: 1~6 Month Post-operation
Secondary outcomes:
measure: Overall Left Ventricular systolic performance as assessed by MRI
timeFrame: Baseline, 1, 3, 6 and 12 Months Post-operation
measure: Overall Left Ventricular systolic performance as assessed by Echocardiogram
timeFrame: Baseline, 1, 3, 6 and 12 Months Post-operation
measure: Overall Left Ventricular systolic performance as assessed by PET/ECT Scan
timeFrame: Baseline, 6 and 12 Months Post-operation
measure: Functional status by 6 minute walk test
timeFrame: Baseline, 1, 3, 6 and 12 Months Post-operation
measure: Functional status by New York Heart Association (NYHA) Classification
timeFrame: Baseline, 1, 3, 6 and 12 Months Post-operation
measure: Minnesota Living With Heart Failure Questionnaire (MLHFQ)
timeFrame: Baseline, 1, 3, 6 and 12 Months Post-operation
measure: Incidence of Major Adverse Cardiac Events (MACE)
timeFrame: Baseline, 1~12 Months Post-operation
measure: Incidence of Serious Adverse Events (SAE)
timeFrame: Baseline, 1~12 Months Post-operation
measure: Changes in penal reactive antibodies (PRA)
timeFrame: Baseline, 1, 3, 6 and 12 Months Post-operation
measure: Changes in donor specific antibodies (DSA)
timeFrame: Baseline, 1, 3, 6 and 12 Months Post-operation
measure: Incidence of severe arrhythmia
timeFrame: First month post-operatively
measure: Changes in cytokines
timeFrame: Baseline,1, 3, 6 and 12 Months Post-operation
Other outcomes:
Locations:
city: Nanjing
country: China
facility: HelpThera
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Dongjin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang H, Xue Y, Pan T, Zhu X, Chong H, Xu C, Fan F, Cao H, Zhang B, Pan J, Zhou Q, Yang G, Wang J, Wang DJ. Epicardial injection of allogeneic human-induced-pluripotent stem cell-derived cardiomyocytes in patients with advanced heart failure: protocol for a phase I/IIa dose-escalation clinical trial. BMJ Open. 2022 May 6;12(5):e056264. doi: 10.1136/bmjopen-2021-056264.