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

Primary Purpose

Heart Failure

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

hPSC-CM Therapy

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 ≤ 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).
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 TNFα 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

HelpTheraRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

hPSC-CM Therapy

Control

Arm Description

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.

Procedure: Coronary artery bypass grafting surgery only.

Outcomes

Primary Outcome Measures

Incidence of sustained ventricular arrhythmias

defined as the proportion of patients experiencing ventricular arrhythmias lasting more than 30 seconds

Incidence of newly formed tumors

by comparing chest, abdominal and pelvic CT scan and PET-CT scan

Secondary Outcome Measures

Overall Left Ventricular systolic performance as assessed by MRI

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.

Overall Left Ventricular systolic performance as assessed by Echocardiogram

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.

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

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 Major Adverse Cardiac Events (MACE)

Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) non-lethal myocardial infraction, and (3) hospitalization for worsening HF

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.)

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

Incidence of severe arrhythmia

Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring

Changes in cytokines

Change in NT-proBNP as assessed via blooddraw

Full Information

NCT ID

NCT03763136

First Posted

November 9, 2018

Last Updated

March 24, 2022

Sponsor

Help Therapeutics

Collaborators

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

1. Study Identification

Unique Protocol Identification Number

NCT03763136

Brief Title

Treating Heart Failure With hPSC-CMs

Acronym

HEAL-CHF

Official Title

Epicardial Injection of Allogeneic 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

Recruiting

Study Start Date

October 8, 2021 (Actual)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

July 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Help Therapeutics

Collaborators

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

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, 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.

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

ParticipantOutcomes 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.

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

hPSC-CM Therapy

Arm Type

Experimental

Arm Description

Arm Title

Control

Arm Type

Sham Comparator

Arm Description

Procedure: Coronary artery bypass grafting surgery only.

Intervention Type

Biological

Intervention Name(s)

hPSC-CM Therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of sustained ventricular arrhythmias

Description

defined as the proportion of patients experiencing ventricular arrhythmias lasting more than 30 seconds

Time Frame

1~6 Month Post-operation

Title

Incidence of newly formed tumors

Description

by comparing chest, abdominal and pelvic CT scan and PET-CT scan

Time Frame

1~6 Month Post-operation

Secondary Outcome Measure Information:

Title

Overall Left Ventricular systolic performance as assessed by MRI

Description

Time Frame

Baseline, 1, 3, 6 and 12 Months Post-operation

Title

Overall Left Ventricular systolic performance as assessed by Echocardiogram

Description

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

Time Frame

Baseline, 1, 3, 6 and 12 Months Post-operation

Title

Minnesota Living With Heart Failure Questionnaire (MLHFQ)

Description

Time Frame

Baseline, 1, 3, 6 and 12 Months Post-operation

Title

Incidence of Major Adverse Cardiac Events (MACE)

Description

Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) non-lethal myocardial infraction, and (3) hospitalization for worsening HF

Time Frame

Baseline, 1~12 Months Post-operation

Title

Incidence of Serious Adverse Events (SAE)

Description

Time Frame

Baseline, 1~12 Months Post-operation

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

Incidence of severe arrhythmia

Description

Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring

Time Frame

First month post-operatively

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

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 ≤ 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). 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 TNFα 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

Jiaxian Wang, MD, PhD

Phone

+86-18565616060

wangjx@helpsci.com.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dongjin Wang, MD

Organizational Affiliation

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Official's Role

Principal Investigator

Facility Information:

Facility Name

HelpThera

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiaxian Wang, Phd

Phone

+86-18565616060

wangjx@helpsci.com.cn

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

One year after study completed

IPD Sharing 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.

Citations:

PubMed Identifier

35523485

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.

Results Reference

derived

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Treating Heart Failure With hPSC-CMs

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