A Study of iPS Cell-derived Cardiomyocyte Spheroids (HS-001) in Patients With Heart Failure (LAPiS Study)

Study Overview
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Brief Summary
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The purpose of this clinical study is to evaluate the safety and efficacy of HS-001 CS transplanted into severe heart failure patients with underlying ischemic heart disease for 26 weeks after transplantation.

Detailed Description
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This is a multicenter, open-label, two-group dose-escalation, phase I/II study in 10 severe heart failure patients (five in the low-dose group and five in the high-dose group) with underlying ischemic heart disease. After screening period is completed, subjects undergo HS-001 CS transplantation. After transplantation, subjects take immunosuppressant and have efficacy/safety assessments.

Official Title
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A Phase I/II Study of Human Induced Pluripotent Stem (iPS) Cell-derived Cardiomyocyte Spheroids (HS-001) in Patients With Severe Heart Failure, Secondary to Ischemic Heart Disease

Conditions
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Heart Failure, Ischemic Heart Disease

Intervention / Treatment
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* Biological: HS-001 CS
* Device: HS-001-D needle, HS-001-D Adaptor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with resting left ventricular ejection fraction (LVEF) ≦40% based on institutional assessment on either screening cardiac MRI or echocardiographic assessment New York Heart Association (NYHA) cardiac function classification of grade II or higher at screening Other Criteria apply, please contact the investigator Exclusion Criteria: Patients screened less than 1 month after the onset of myocardial infarction Patients with congenital heart disease, or cardiac sarcoidosis Other Criteria apply, please contact the investigator

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-001 Low dose<br>HS-001 Low dose Administration | Biological: HS-001 CS<br>* Human (allogeneic) iPS-cell-derived cardiomyocyte spheroids suspension<br>Device: HS-001-D needle, HS-001-D Adaptor<br>* Cardiomyocyte spheroids Dedicated Needles for Implantation and Guided Adaptors<br>|
| Experimental: HS-001 High dose<br>HS-001 High dose Administration | Biological: HS-001 CS<br>* Human (allogeneic) iPS-cell-derived cardiomyocyte spheroids suspension<br>Device: HS-001-D needle, HS-001-D Adaptor<br>* Cardiomyocyte spheroids Dedicated Needles for Implantation and Guided Adaptors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Adverse events and safety in the 26 weeks after HS-001 CS transplantation | 26 weeks post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Ejection Fraction in Cardiac MRI scan & Echocardiography | Left Ventricular Ejection Fraction in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 
| Myocardial wall motion evaluation in Echocardiography | Myocardial wall motion evaluation (Index of myocardial strain) in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 
| Myocardial blood flow in SPECT | Myocardial blood flow in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 
| Myocardial viability in SPECT | Myocardial viability in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 
| 6-minute walk distance | 6-minute walk distance in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | Kansas City Cardiomyopathy Questionnaire in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 
| 5-level EQ-5D version (EQ-5D-5L) | 5-level EQ-5D version (EQ-5D-5L) in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 
| N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) in the 26 weeks and 52 weeks after HS-001 CS transplantation | 26 weeks and 52 weeks post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Ischemic Heart Disease