Treating Heart Failure With hPSC-CMs (HEAL-CHF)

• ClinicalTrials.gov Identifier: NCT03763136
• Recruitment Status: Recruiting
• First Posted: December 4, 2018
• Last Update Posted: April 5, 2022
• Sponsor: Help Therapeutics
• Collaborator: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Information provided by (Responsible Party): Help Therapeutics

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, feasibility and efficacy of intramyocardial delivery of cardiomyocytes at the time of coronary artery bypass grafting in patients with chronic heart failure.

Condition or disease	Intervention/treatment	Phase
Heart Failure	Biological: hPSC-CM Therapy	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: The study adopts a "single-blind design plus double-blind management" principle. To ensure the study results are evaluated without bias, participants and outcomes assessors will not be informed the randomization details.
• Primary Purpose: Treatment
• Official Title: Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Heart Failure
• Actual Study Start Date: October 8, 2021
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: July 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: hPSC-CM Therapy; Procedure: Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.	Biological: hPSC-CM Therapy; Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
Sham Comparator: Control; Procedure: Coronary artery bypass grafting surgery only.	Biological: hPSC-CM Therapy; Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.

Outcome Measures

Primary Outcome Measures :

1. Incidence of sustained ventricular arrhythmias [ Time Frame: 1~6 Month Post-operation ]
   defined as the proportion of patients experiencing ventricular arrhythmias lasting more than 30 seconds
2. Incidence of newly formed tumors [ Time Frame: 1~6 Month Post-operation ]
   by comparing chest, abdominal and pelvic CT scan and PET-CT scan

Secondary Outcome Measures :

1. Overall Left Ventricular systolic performance as assessed by MRI [ Time Frame: Baseline, 1, 3, 6 and 12 Months Post-operation ]
   Size of infracted myocardium, left ventricular side wall thickness at diastolic, interventricular septum thickness, left ventricular ejection fraction, left ventricular end-systolic volume and end-diastolic volume, stroke volume, cardiac output, myocardium density and left ventricular mass at diastolic will be evaluated and compared to baseline values.
2. Overall Left Ventricular systolic performance as assessed by Echocardiogram [ Time Frame: Baseline, 1, 3, 6 and 12 Months Post-operation ]
   Interventricular septum thickness at diastolic, left ventricular end-systolic diameter and end-diastolic diameter, left ventricular posterior wall thickness at diastolic, left atrial diameter, left ventricular ejection fraction, mitral flow pattern (E/A) will be evaluated and compared to baseline values.
3. Overall Left Ventricular systolic performance as assessed by PET/ECT Scan [ Time Frame: Baseline, 6 and 12 Months Post-operation ]
   Myocardium perfusion
4. Functional status by 6 minute walk test [ Time Frame: Baseline, 1, 3, 6 and 12 Months Post-operation ]
   Evaluate Functional Capacity via the Six Minute Walk Test
5. Functional status by New York Heart Association (NYHA) Classification [ Time Frame: Baseline, 1, 3, 6 and 12 Months Post-operation ]
   Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination
6. Minnesota Living With Heart Failure Questionnaire (MLHFQ) [ Time Frame: Baseline, 1, 3, 6 and 12 Months Post-operation ]
   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.
7. Incidence of Major Adverse Cardiac Events (MACE) [ Time Frame: Baseline, 1~12 Months Post-operation ]
   Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) non-lethal myocardial infraction, and (3) hospitalization for worsening HF
8. Incidence of Serious Adverse Events (SAE) [ Time Frame: Baseline, 1~12 Months Post-operation ]
   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.)
9. Changes in penal reactive antibodies (PRA) [ Time Frame: Baseline, 1, 3, 6 and 12 Months Post-operation ]
   Changes in penal reactive antibodies (PRA) as assessed via blooddraw
10. Changes in donor specific antibodies (DSA) [ Time Frame: Baseline, 1, 3, 6 and 12 Months Post-operation ]
    Changes in donor specific antibodies (DSA) as assessed via blooddraw
11. Incidence of severe arrhythmia [ Time Frame: First month post-operatively ]
    Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring
12. Changes in cytokines [ Time Frame: Baseline,1, 3, 6 and 12 Months Post-operation ]
    Change in NT-proBNP as assessed via blooddraw

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Jiaxian Wang, MD, PhD; +86-18565616060; wangjx@helpsci.com.cn

Locations

China, Jiangsu

HelpThera; Recruiting

Nanjing, Jiangsu, China, 210000

Contact: Jiaxian Wang, Phd +86-18565616060 wangjx@helpsci.com.cn

Sponsors and Collaborators

Help Therapeutics

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Investigators

• Principal Investigator: Dongjin Wang, MD; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Help Therapeutics
• ClinicalTrials.gov Identifier: NCT03763136
• Other Study ID Numbers: JWang
• First Posted: December 4, 2018
• Last Update Posted: April 5, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Results of the trial will be disseminated to study participants through direct consultation with a trial clinician at completion of the trial, as well as through the publication of results.
• Supporting Materials: Study Protocol; Clinical Study Report (CSR)
• Time Frame: One year after study completed
• Access Criteria: Results of the trial will be disseminated to study participants through direct consultation with a trial clinician at completion of the trial, as well as through the publication of results.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases