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Allogeneic iPSC-derived Cardiomyocyte Therapy in Patients With Worsening Ischemic Heart Failure

Primary Purpose

Ischemic Heart Failure, Chronic Heart Failure

Status

Not yet recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

Human (allogeneic) iPS-cell-derived cardiomyocyte

About this trial

This is an interventional treatment trial for Ischemic 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).
Signed the Informed Consent Form (ICF).
Have chronic left ventricular dysfunction.
Have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure.
Have indications for Coronary Artery Bypass Grafting.
LVEF < 40% 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

The second xiangya hospital of central south university
HelpThera

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

No Intervention

Arm Label

Dose level 1

Dose level 2

Dose level 3

Control

Arm Description

100 million iPSC-CMs administration

200 million iPSC-CMs administration

400 million iPSC-CMs administration

Participants will received CABG surgery only

Outcomes

Primary Outcome Measures

Safety in terms of the incidence and severity of adverse events

Number of participants with death, fatal myocardial infarction, stroke, ventricular tachycardia sustained for >15 seconds and newly formed tumor

Secondary Outcome Measures

Incidence of adverse events

Adverse events that require medical intervention

Cardiac assessment

24-hour Holter Monitoring post the CABG surgery

Incidence of newly formed tumor

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

Immunogenic assessments

Donor specific antibody (DSA), serum anti-human leukocyte antigens (anti-HLA) antibody/panel-reactive antibody (PRA) serology monitoring

Changes in left ventricle function evaluation by echocardiogram (ECHO) or cardiac MRI

Changes in cardiac function will be assessed by left ventricular end-systolic volume (LVESV, mL) changes from baseline to 12 months post surgery

Changes in 6-minute walk test (6MWT)

Changes in NYHA functional classification

Changes in quality of life (QoL)

Quality of life changes as measured by Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores

Incidence of hospitalization for worsening heart failure

Full Information

NCT ID

NCT05566600

First Posted

September 22, 2022

Last Updated

October 12, 2022

Sponsor

Help Therapeutics

Collaborators

Central South University

1. Study Identification

Unique Protocol Identification Number

NCT05566600

Brief Title

Allogeneic iPSC-derived Cardiomyocyte Therapy in Patients With Worsening Ischemic Heart Failure

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

October 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 30, 2022 (Anticipated)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

July 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Help Therapeutics

Collaborators

Central South University

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

This study is designed to evaluate the safety and efficacy of allogeneic induced pluripotent cell derived cardiomyocytes (iPSC-CMs) in treating patients with worsening ischemic heart failure undergoing coronary artery bypass graft surgery. After screening, iPSC-CMs will be administrated intramyocardially in consented and eligible patients undergoing open-chest CABG surgery and the estimated population size for the study will be 32 patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Heart Failure, Chronic Heart Failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose level 1

Arm Type

Experimental

Arm Description

100 million iPSC-CMs administration

Arm Title

Dose level 2

Arm Type

Experimental

Arm Description

200 million iPSC-CMs administration

Arm Title

Dose level 3

Arm Type

Experimental

Arm Description

400 million iPSC-CMs administration

Arm Title

Control

Arm Type

No Intervention

Arm Description

Participants will received CABG surgery only

Intervention Type

Biological

Intervention Name(s)

Human (allogeneic) iPS-cell-derived cardiomyocyte

Intervention Description

10-20 epicardial injections (0.25 mL each) of iPSC-CMs will be delivered in the border zone of the infarcted myocardium

Primary Outcome Measure Information:

Title

Safety in terms of the incidence and severity of adverse events

Description

Number of participants with death, fatal myocardial infarction, stroke, ventricular tachycardia sustained for >15 seconds and newly formed tumor

Time Frame

within 1 month post CABG surgery

Secondary Outcome Measure Information:

Title

Incidence of adverse events

Description

Adverse events that require medical intervention

Time Frame

1~6 months post CABG surgery

Title

Cardiac assessment

Description

24-hour Holter Monitoring post the CABG surgery

Time Frame

1~6 months post CABG surgery

Title

Incidence of newly formed tumor

Description

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

Time Frame

1~12 months post CABG surgery

Title

Immunogenic assessments

Description

Donor specific antibody (DSA), serum anti-human leukocyte antigens (anti-HLA) antibody/panel-reactive antibody (PRA) serology monitoring

Time Frame

1 month, 3 months and 6 months post CABG surgery

Title

Changes in left ventricle function evaluation by echocardiogram (ECHO) or cardiac MRI

Description

Changes in cardiac function will be assessed by left ventricular end-systolic volume (LVESV, mL) changes from baseline to 12 months post surgery

Time Frame

from baseline to 12 months at 3, 6, and 12 months post CABG surgery

Title

Changes in 6-minute walk test (6MWT)

Time Frame

from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery

Title

Changes in NYHA functional classification

Time Frame

from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery

Title

Changes in quality of life (QoL)

Description

Quality of life changes as measured by Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores

Time Frame

from baseline to 12 months at 1, 3, 6, and 12 months post CABG surgery

Title

Incidence of hospitalization for worsening heart failure

Time Frame

1~12 months post CABG surgery

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). Signed the Informed Consent Form (ICF). Have chronic left ventricular dysfunction. Have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure. Have indications for Coronary Artery Bypass Grafting. LVEF < 40% 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

Phone

+86-18565616060

wangjx@helpsci.com.cn

Facility Information:

Facility Name

The second xiangya hospital of central south university

City

Changsha

State/Province

Hunan

ZIP/Postal Code

410000

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chengming Fan

Phone

+86-18390945539

First Name & Middle Initial & Last Name & Degree

Jinfu Yang, MD

Facility Name

HelpThera

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210000

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiaxian Wang

Phone

+86-18565616060

wangjx@helptx.com.cn

12. IPD Sharing Statement

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Allogeneic iPSC-derived Cardiomyocyte Therapy in Patients With Worsening Ischemic Heart Failure

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