Back to resultsClinical Trial of Human (Allogeneic) iPS Cell-derived Cardiomyocytes Sheet for Ischemic Cardiomyopathy
Primary Purpose
Myocardial Ischemia
Status
Unknown status
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Human (allogeneic) iPS cell derived-cardiomyocyte sheet
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Ischemia focused on measuring ischemic cardiomyopathy, D017202
Eligibility Criteria
Inclusion Criteria:
- Patients with chronic ischemic heart disease
- Patients with Grade III-IV NYHA Functional Classification heart failure
- Patients who are in the state of heart failure despite maximal oral medications including digitalis, diuretics, ACE inhibitors, ARBs, beta-blockers, anti-aldosterone drugs, and oral cardiotonics
- Patients who are 20 years of age or older at the point of consent
- Patients at risk of worsening heart failure despite being under standard surgical treatment (coronary artery bypass surgery, mitral valve angioplasty, left ventricular angioplasty, cardiac resynchronization therapy, and percutaneous coronary intervention) for more than 3 months
- Patients with LVEF (Echocardiography) at rest of 35% or less
- Patients whose informed consent for clinical trial participation can be obtained from the subject himself/herself in writing
- Patients who can continue to visit to the clinical trial site for 52 weeks after obtaining consent, continue to live in Japan, and can be expected to have data collected by NRMD/PMS
Exclusion Criteria:
- Patients with autoimmune diseases
- Patients with allergies or hypersensitivity to the immunosuppressant used
- Patients with active infections
- Patients who remain in shock due to worsening heart failure
- Patients with irreversible organ failure other than heart
- Patients with malignant tumors
- Patients who are or may be pregnant
- Patients with history of alcoholism or drug addiction within six months from the day of consent
- Patients with allergies or hypersensitivity to animals such as cattle from which the raw materials are derived
- Patients with severe pulmonary hypertension
- Patients within 6 months of completion of other clinical trials at the time of enrollment
- In addition, patients with other cardiovascular abnormalities who are determined to be unfit for this study as per the judgment of the patient enrollment study committee of physicians
Sites / Locations
- Osaka University HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Group of subjects undergoing cell transplantation
Arm Description
Human (allogeneic) iPS cell derived-cardiomyocyte sheet transplantation (only once)
Outcomes
Primary Outcome Measures
The number of patients with improved LVEF
The number of patients with improved LVEF by echocardiography 26 weeks postoperatively compared with preoperatively.
Incidence of adverse events and defects [Safety and Tolerability]
Regarding adverse events and side effects (of the adverse events, those whose causal relationship with the clinical trial product is determined to be other than "not related" will be treated as side effects.) the number of occurrences and the number of occurrence examples by event and severity will be obtained.
Incidence of serious adverse events [Safety and Tolerability]
Regarding serious adverse events, the number of occurrences and the number of occurrence examples by event and severity will be obtained.
Incidence of abnormal vital signs [Safety and Tolerability]
Regarding changes in vital signs(Body temperature, blood pressure (systolic, diastolic), and pulse rate), summary statistics and changes at each measurement time point will be obtained.
Incidence of abnormal general blood tests [Safety and Tolerability]
Regarding changes in general blood tests(WBC, RBC, Hb, Ht, PLT), summary statistics and changes at each measurement time point will be obtained.
Incidence of abnormal blood biochemical tests [Safety and Tolerability]
Regarding changes in blood biochemistry tests(AST(GOT), ALT(GPT), LDH, ALP, BUN, Cre, UA, TG, T-Cho, LDL-Cho, Alb, CK, CK-MB, electrolytes (Na, K, Cl, Ca, iP, Mg), CRP, blood sugar), summary statistics and changes at each measurement time point will be obtained.
Incidence of abnormal tumor marker tests [Safety and Tolerability]
Regarding changes in tumor marker tests(AFP, CA19-9, CEA, hCG), summary statistics and changes at each measurement time point will be obtained.
Incidence of cardiac function clinical events such as death and hospitalization [Safety and Tolerability]
With respect to the incidence of cardiac function clinical events such as death and hospitalization, the number of cases in which the causes of death are related to heart disease and those unrelated to heart disease will be determined for cases of death.
Secondary Outcome Measures
Number of Responder patients 26 and 52 weeks after transplantation of this product
To comprehensively evaluate the efficacy of this product transplantation
Contraction function of the entire left ventricle
To comprehensively evaluate the efficacy of this product transplantation
Left ventricular remodeling (LVESVI)
Changes in left ventricular end systolic volume index (LVESVI) (echocardiography, CT (if available))
Left ventricular remodeling (LVEDVI)
Changes in left ventricular end-diastolic volume index (LVEDVI) (echocardiography, CT (if available))
New York Heart Association functional classification
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Class I to Class IV, the more severe, the higher the number.
Specific Activity Scale (SAS)
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. This is a quantitative evaluation of the subjective symptoms of heart failure from the viewpoint of exercise tolerance. List various daily activities for which exercise intensity [oxygen uptake or metabolic equivalents (METs)] is almost known in advance, ask whether they are possible, and exercise with the lowest activity level that was not possible is evaluated value. The higher the number, the better the condition.
The Minnesota Living with Heart Failure Questionnaire
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. The lower the number, the better the condition.
36-Item Short Form Survey (SF-36)
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. The higher the number, the better the condition.
6-minute walking distance
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. The higher the number, the better the condition.
Brain natriuretic peptide (BNP)
Evaluation of the following changes and transitions.
N-terminal pro-brain natriuretic peptide (NT-proBNP)
Evaluation of the following changes and transitions.
Exercise tolerance (VO2max)
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Measure the maximum oxygen uptake (VO2max) using the bicycle ergometer.
Exercise tolerance (AT)
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Measure the anaerobic metabolism threshold (AT) using the bicycle ergometer.
Exercise tolerance (VE/VCO2)
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Measure the expiratory minute volume (VE)/the CO2 uptake (VCO2) using the bicycle ergometer.
Cumulative number of rejections that occurred during the observation period
Cumulative number of rejections from transplant up to 26 weeks after surgery
Full Information
NCT ID
NCT04696328
First Posted
December 11, 2020
Last Updated
April 19, 2021
Sponsor
Osaka University
Collaborators
Cuorips Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04696328
Brief Title
Clinical Trial of Human (Allogeneic) iPS Cell-derived Cardiomyocytes Sheet for Ischemic Cardiomyopathy
Official Title
Clinical Trial of Human (Allogeneic) iPS Cell-derived Cardiomyocytes Sheet for Ischemic
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 2, 2019 (Actual)
Primary Completion Date
May 30, 2022 (Anticipated)
Study Completion Date
May 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Osaka University
Collaborators
Cuorips Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Targeting patients with severe ischemic cardiomyopathy, the purpose of this study is as follows: to confirm short-term efficacy by observing changes and transitions in cardiac function and clinical symptoms compared with each patient's baseline (before and after comparison) by human iPS cell-derived cardiomyocyte sheet transplantation, and to evaluate the safety and tolerability including the combined use of immunosuppressants.
Detailed Description
The objective of this study is to confirm the efficacy and safety of a human (allogeneic) iPS cell-derived cardiomyocyte sheet in combination with an immunosuppressant for ischemic cardiomyopathy patients. The primary evaluation items will be improvement of left ventricular systolic function (LVEF) for efficacy, and safety will be assessed by blood tests, general laboratory tests, and other safety-related evaluations. Secondary evaluation items are NYHA functional evaluation, left ventricular remodeling evaluation by echocardiography, hemodynamic evaluation, physical activity function evaluation such as 6MWD and SAS, QOL, and exercise tolerance evaluation by questionnaires.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Ischemia
Keywords
ischemic cardiomyopathy, D017202
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group of subjects undergoing cell transplantation
Arm Type
Experimental
Arm Description
Human (allogeneic) iPS cell derived-cardiomyocyte sheet transplantation (only once)
Intervention Type
Biological
Intervention Name(s)
Human (allogeneic) iPS cell derived-cardiomyocyte sheet
Intervention Description
Transplantation
Primary Outcome Measure Information:
Title
The number of patients with improved LVEF
Description
The number of patients with improved LVEF by echocardiography 26 weeks postoperatively compared with preoperatively.
Time Frame
26 weeks
Title
Incidence of adverse events and defects [Safety and Tolerability]
Description
Regarding adverse events and side effects (of the adverse events, those whose causal relationship with the clinical trial product is determined to be other than "not related" will be treated as side effects.) the number of occurrences and the number of occurrence examples by event and severity will be obtained.
Time Frame
From postoperative to the end of the observation period (52 weeks)
Title
Incidence of serious adverse events [Safety and Tolerability]
Description
Regarding serious adverse events, the number of occurrences and the number of occurrence examples by event and severity will be obtained.
Time Frame
From postoperative to the end of the observation period (52 weeks)
Title
Incidence of abnormal vital signs [Safety and Tolerability]
Description
Regarding changes in vital signs(Body temperature, blood pressure (systolic, diastolic), and pulse rate), summary statistics and changes at each measurement time point will be obtained.
Time Frame
Before surgery, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Title
Incidence of abnormal general blood tests [Safety and Tolerability]
Description
Regarding changes in general blood tests(WBC, RBC, Hb, Ht, PLT), summary statistics and changes at each measurement time point will be obtained.
Time Frame
Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Title
Incidence of abnormal blood biochemical tests [Safety and Tolerability]
Description
Regarding changes in blood biochemistry tests(AST(GOT), ALT(GPT), LDH, ALP, BUN, Cre, UA, TG, T-Cho, LDL-Cho, Alb, CK, CK-MB, electrolytes (Na, K, Cl, Ca, iP, Mg), CRP, blood sugar), summary statistics and changes at each measurement time point will be obtained.
Time Frame
Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Title
Incidence of abnormal tumor marker tests [Safety and Tolerability]
Description
Regarding changes in tumor marker tests(AFP, CA19-9, CEA, hCG), summary statistics and changes at each measurement time point will be obtained.
Time Frame
Screening, 13 weeks, 26 weeks, 52 weeks
Title
Incidence of cardiac function clinical events such as death and hospitalization [Safety and Tolerability]
Description
With respect to the incidence of cardiac function clinical events such as death and hospitalization, the number of cases in which the causes of death are related to heart disease and those unrelated to heart disease will be determined for cases of death.
Time Frame
From postoperative to the end of the observation period (52 weeks)
Secondary Outcome Measure Information:
Title
Number of Responder patients 26 and 52 weeks after transplantation of this product
Description
To comprehensively evaluate the efficacy of this product transplantation
Time Frame
26 and 52 weeks
Title
Contraction function of the entire left ventricle
Description
To comprehensively evaluate the efficacy of this product transplantation
Time Frame
26 weeks
Title
Left ventricular remodeling (LVESVI)
Description
Changes in left ventricular end systolic volume index (LVESVI) (echocardiography, CT (if available))
Time Frame
26 weeks
Title
Left ventricular remodeling (LVEDVI)
Description
Changes in left ventricular end-diastolic volume index (LVEDVI) (echocardiography, CT (if available))
Time Frame
26 weeks
Title
New York Heart Association functional classification
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Class I to Class IV, the more severe, the higher the number.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
Specific Activity Scale (SAS)
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. This is a quantitative evaluation of the subjective symptoms of heart failure from the viewpoint of exercise tolerance. List various daily activities for which exercise intensity [oxygen uptake or metabolic equivalents (METs)] is almost known in advance, ask whether they are possible, and exercise with the lowest activity level that was not possible is evaluated value. The higher the number, the better the condition.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
The Minnesota Living with Heart Failure Questionnaire
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. The lower the number, the better the condition.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
36-Item Short Form Survey (SF-36)
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. The higher the number, the better the condition.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
6-minute walking distance
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. The higher the number, the better the condition.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
Brain natriuretic peptide (BNP)
Description
Evaluation of the following changes and transitions.
Time Frame
Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Title
N-terminal pro-brain natriuretic peptide (NT-proBNP)
Description
Evaluation of the following changes and transitions.
Time Frame
Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Title
Exercise tolerance (VO2max)
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Measure the maximum oxygen uptake (VO2max) using the bicycle ergometer.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
Exercise tolerance (AT)
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Measure the anaerobic metabolism threshold (AT) using the bicycle ergometer.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
Exercise tolerance (VE/VCO2)
Description
Evaluation of the following changes and transitions before and 26 and 52 weeks after surgery. Measure the expiratory minute volume (VE)/the CO2 uptake (VCO2) using the bicycle ergometer.
Time Frame
Before surgery, 26 weeks, 52 weeks
Title
Cumulative number of rejections that occurred during the observation period
Description
Cumulative number of rejections from transplant up to 26 weeks after surgery
Time Frame
26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with chronic ischemic heart disease
Patients with Grade III-IV NYHA Functional Classification heart failure
Patients who are in the state of heart failure despite maximal oral medications including digitalis, diuretics, ACE inhibitors, ARBs, beta-blockers, anti-aldosterone drugs, and oral cardiotonics
Patients who are 20 years of age or older at the point of consent
Patients at risk of worsening heart failure despite being under standard surgical treatment (coronary artery bypass surgery, mitral valve angioplasty, left ventricular angioplasty, cardiac resynchronization therapy, and percutaneous coronary intervention) for more than 3 months
Patients with LVEF (Echocardiography) at rest of 35% or less
Patients whose informed consent for clinical trial participation can be obtained from the subject himself/herself in writing
Patients who can continue to visit to the clinical trial site for 52 weeks after obtaining consent, continue to live in Japan, and can be expected to have data collected by NRMD/PMS
Exclusion Criteria:
Patients with autoimmune diseases
Patients with allergies or hypersensitivity to the immunosuppressant used
Patients with active infections
Patients who remain in shock due to worsening heart failure
Patients with irreversible organ failure other than heart
Patients with malignant tumors
Patients who are or may be pregnant
Patients with history of alcoholism or drug addiction within six months from the day of consent
Patients with allergies or hypersensitivity to animals such as cattle from which the raw materials are derived
Patients with severe pulmonary hypertension
Patients within 6 months of completion of other clinical trials at the time of enrollment
In addition, patients with other cardiovascular abnormalities who are determined to be unfit for this study as per the judgment of the patient enrollment study committee of physicians
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Takuji Kawamura, Ph.D
Phone
+81-6-6879-3154
Email
saisentan@tissue.med.osaka-u.ac.jp
First Name & Middle Initial & Last Name or Official Title & Degree
Shigeru Miyagawa, PhD
Phone
+81-6-6879-3154
Email
miyagawakenkyu@surg1.med.osaka-u.ac.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yoshiki Sawa, Ph.D
Organizational Affiliation
Osaka University
Official's Role
Study Director
Facility Information:
Facility Name
Osaka University Hospital
City
Suita
State/Province
Osaka
ZIP/Postal Code
5650871
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Satoshi Kainuma, Ph.D
Phone
+81-6-6879-3154
Email
saisentan@tissue.med.osaka-u.ac.jp
First Name & Middle Initial & Last Name & Degree
Masao Sasai, Ph.D
Phone
+81-6-6105-5240
Email
sasai-masao@tissue.med.osaka-u.ac.jp
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Not planned at this time.
Learn more about this trial
Clinical Trial of Human (Allogeneic) iPS Cell-derived Cardiomyocytes Sheet for Ischemic Cardiomyopathy
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