Treating Congestive HF With hiPSC-CMs Through Endocardial Injection

Treating Congestive Heart Failure Patients With Human iPSC-derived Cardiomyocytes Through Catheter-based Endocardial Injection

Heart failure is the primary cause of morbidity and mortality worldwide. Currently drug treatments for heart failure manage the symptoms, but not restore the loss cardiomyocytes due to the very limited regenerative capability in the adult heart. Novel reparative therapies that replace the cardiomyocytes loss are highly demanded to restore the cardiac function. The main purposes of this explanatory study is to investigate the safety and efficacy of the catheter-based endocardial delivery of human iPSC-derived cardiomyocytes in patients with congestive heart failure.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Dilated Cardiomyopathy; Congestive Heart Failure
• Intervention / Treatment: Biological: hiPSC-CM therapy

Detailed Description

Patients with severe congestive heart failure will be treated with allogeneic human iPSC-derived cardiomyocytes (HiCM-188) through the catheter-based injections. HiCM188, produced by Help therapeutics with cGMP condition, will be transplanted into the myocardium through a transcatheter endocardial injection system with two dosage (100 million cells or 400 million cells). The safety and efficacy assessments will be conducted at1, 3, 6 and 12 months after the cell transplantation.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jiaxian Wang, MD, PhD; Phone Number: +86-18565616060; Email: wangjx@helptx.com.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • HELP Therapeutics
      • Contact: Jiaxian Wang, MD,PhD; Phone Number: +8618565616060; Email: wangjx@helpsci.com.cn
      • Principal Investigator: Ling Tao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged 18-75 years (including 18 and 75).
2. Signed the informed consent.
3. Patients with congestive heart failure who have received regular treatment for heart failure.
4. New York Heart Association (NYHA) Class III or IV despite optimal standard of care
5. Left Ventricular Ejection Fraction (LVEF)<40% as assessed by echocardiography ( measure in the 3 months of recruit is included, excluding the measured values within 1 month of myocardial infarction ）
6. The thickness of left ventricular ≥8mm
7. Female patient who is not pregnant or nursing during the clinical trial

Exclusion Criteria:

1. PRA ≥ 20% or DSA positive.
2. Patients received treatments such as pacemakers, ICD or CRT device.
3. Patient with severe valvular disease or presence of a mechanical valve replacement, such as PCI implantation, or patients requiring simultaneous radiofrequency ablation of atrial fibrillation.
4. Patient with any therapeutic traumatic heart surgery within 30 days.
5. Hemodynamic instability or cardiogenic shock.
6. Right heart failure.
7. Restrictive cardiomyopathy such as amyloidosis, sarcoidosis or hematochromia, constrictive pericarditis.
8. Myocardial infarction occurred within 30 days or stroke occurred within 60 days before enrollment.
9. Thickness at left ventricular free wall infarction < 6 mm.
10. Severe ventricular arrhythmias (persistent ventricular tachycardia or other conditions that the investigator considers necessary to exclude).
11. Baseline glomerular filtration rate < 30 ml/min / 1.73 m2.
12. Abnormal liver function: ALT or AST 3 times higher than the normal value.
13. Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cells count <2,500/ul or platelet count <100000 / ul.
14. Known allergies to penicillin, streptomycin or radiocontrast agent.
15. Abnormal coagulation function, INR > 1.3, which cannot be corrected.
16. Contra-indication to performance of a magnetic resonance imaging scan and PET/ECT examinations.
17. Organ transplant recipient
18. Patients with other malignant disease within 5 years prior to enrollment.
19. Non-cardiac condition that limits lifespan to < 1 year
20. On chronic therapy with immunosuppressant medication such as glucocorticoid or TNFα antagonist
21. Contra-indication to take immunosuppressant medication.
22. Serum positive for infectious diseases (HIV, HBV, HCV, TP).
23. Participated in other clinical trials within the previous 3 months .
24. Female patient who is pregnant or nursing.
25. Other condition that the investigator considers inappropriate for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hiPSC-CM therapy low dosage	Biological: hiPSC-CM therapy; 20 patients with congestive heart failure who met the inclusion and exclusion criteria will be recruited. After being fully informed and signed the informed consent, the patients will be randomly divided into two dosage groups: 100 million cells (10 patients) and 400 million cells (10 patients). Human iPSC-derived cardiomyocytes will be injected into the myocardium through a transcatheter endocardial injection system.
Experimental: hiPSC-CM therapy high dosage	Biological: hiPSC-CM therapy; 20 patients with congestive heart failure who met the inclusion and exclusion criteria will be recruited. After being fully informed and signed the informed consent, the patients will be randomly divided into two dosage groups: 100 million cells (10 patients) and 400 million cells (10 patients). Human iPSC-derived cardiomyocytes will be injected into the myocardium through a transcatheter endocardial injection system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of major serious adverse events (SAEs)	Incidence of SAEs is defined as the composite of: death, fatal myocardial infarction, stroke, tamponade, cardiac perforation, ventricular arrhythmias affecting hemodynamics (> 15s), and tumorigenicity related to the hiPSC-CM .	First month post-catheterization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe arrhythmia	Clinically significant arrhythmias will be recorded by 24-hour ambulatory electrocardiogram	1-6 months post-catheterization
Incidence of newly formed tumors	by comparing chest, abdominal and pelvic CT scan and PET-CT scan	Baseline, 1,3,6 and 12 months post-catheterization
Changes in penal reactive antibodies (PRA)	Changes in penal reactive antibodies (PRA) as assessed via blooddraw	Baseline, 1, 3 and 6 months post-catheterization
Changes in donor specific antibodies (DSA)	Changes in donor specific antibodies (DSA) as assessed via blooddraw	Baseline, 1, 3 and 6 months post-catheterization
Overall Left Ventricular systolic performance as assessed by MRI	Left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDV), left ventricular end-systolic dimension (LVESV), evaluated and compared to baseline values.	Baseline, 1, 3, 6 and 12 months post-catheterization
Overall Left Ventricular systolic performance as assessed by PET/ECT Scan	Myocardial contraction and relaxation and myocardial perfusion, evaluated and compared to baseline values.	Baseline, 6 and 12 months post-catheterization
Functional status by 6 minute walk test	valuate Functional Capacity via the Six Minute Walk Test	Baseline, 1,3,6 and 12 months post-catheterization
Functional status by New York Heart Association (NYHA) Classification	Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination	Baseline, 1,3,6 and 12 months post-catheterization
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.	Baseline, 1,3,6 and 12 months post-catheterization

Collaborators and Investigators

• Sponsor: Help Therapeutics
• Collaborators: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): July 31, 2023

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 19, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 22, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: dilated cardiomyopathy; Regenerative medicine; Congestive heart failure; induced pluripotent stem cell
• Additional Relevant MeSH Terms: Heart Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Heart Failure; Cardiovascular Diseases; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: LTao (Registry Identifier: AnhuiZhifei)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No