Clinical Trial of Human (Allogeneic) iPS Cell-derived Cardiomyocytes Sheet for Ischemic Cardiomyopathy

• ClinicalTrials.gov Identifier: NCT04696328
• Recruitment Status: Unknown
• First Posted: January 6, 2021
• Last Update Posted: April 20, 2021
• Sponsor: Osaka University
• Collaborator: Cuorips Inc.
• Information provided by (Responsible Party): Koichi Toda, Osaka University

Tracking Information

• First Submitted Date: December 11, 2020
• First Posted Date: January 6, 2021
• Last Update Posted Date: April 20, 2021
• Actual Study Start Date: December 2, 2019
• Estimated Primary Completion Date: May 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 4, 2021)

• The number of patients with improved LVEF [ Time Frame: 26 weeks ]
  The number of patients with improved LVEF by echocardiography 26 weeks postoperatively compared with preoperatively.
• Incidence of adverse events and defects [Safety and Tolerability] [ Time Frame: From postoperative to the end of the observation period (52 weeks) ]
  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] [ Time Frame: From postoperative to the end of the observation period (52 weeks) ]
  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] [ Time Frame: Before surgery, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks ]
  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] [ Time Frame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks ]
  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] [ Time Frame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks ]
  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] [ Time Frame: Screening, 13 weeks, 26 weeks, 52 weeks ]
  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] [ Time Frame: From postoperative to the end of the observation period (52 weeks) ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 4, 2021)

• Number of Responder patients 26 and 52 weeks after transplantation of this product [ Time Frame: 26 and 52 weeks ]
  To comprehensively evaluate the efficacy of this product transplantation
• Contraction function of the entire left ventricle [ Time Frame: 26 weeks ]
  To comprehensively evaluate the efficacy of this product transplantation
• Left ventricular remodeling (LVESVI) [ Time Frame: 26 weeks ]
  Changes in left ventricular end systolic volume index (LVESVI) (echocardiography, CT (if available))
• Left ventricular remodeling (LVEDVI) [ Time Frame: 26 weeks ]
  Changes in left ventricular end-diastolic volume index (LVEDVI) (echocardiography, CT (if available))
• New York Heart Association functional classification [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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) [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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 [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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) [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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 [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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) [ Time Frame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks ]
  Evaluation of the following changes and transitions.
• N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks ]
  Evaluation of the following changes and transitions.
• Exercise tolerance (VO2max) [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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) [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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) [ Time Frame: Before surgery, 26 weeks, 52 weeks ]
  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 [ Time Frame: 26 weeks ]
  Cumulative number of rejections from transplant up to 26 weeks after surgery

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Myocardial Ischemia

Intervention

Biological: Human (allogeneic) iPS cell derived-cardiomyocyte sheet

Transplantation

Study Arms

Experimental: Group of subjects undergoing cell transplantation

Human (allogeneic) iPS cell derived-cardiomyocyte sheet transplantation (only once)

Intervention: Biological: Human (allogeneic) iPS cell derived-cardiomyocyte sheet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 4, 2021): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 30, 2023
• Estimated Primary Completion Date: May 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients with chronic ischemic heart disease
2. Patients with Grade III-IV NYHA Functional Classification heart failure
3. 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
4. Patients who are 20 years of age or older at the point of consent
5. 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
6. Patients with LVEF (Echocardiography) at rest of 35% or less
7. Patients whose informed consent for clinical trial participation can be obtained from the subject himself/herself in writing
8. 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:

1. Patients with autoimmune diseases
2. Patients with allergies or hypersensitivity to the immunosuppressant used
3. Patients with active infections
4. Patients who remain in shock due to worsening heart failure
5. Patients with irreversible organ failure other than heart
6. Patients with malignant tumors
7. Patients who are or may be pregnant
8. Patients with history of alcoholism or drug addiction within six months from the day of consent
9. Patients with allergies or hypersensitivity to animals such as cattle from which the raw materials are derived
10. Patients with severe pulmonary hypertension
11. Patients within 6 months of completion of other clinical trials at the time of enrollment
12. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04696328
• Other Study ID Numbers: CVSC0005
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Not planned at this time.

• Current Responsible Party: Koichi Toda, Osaka University
• Original Responsible Party: Same as current
• Current Study Sponsor: Osaka University
• Original Study Sponsor: Same as current
• Collaborators: Cuorips Inc.

Investigators

• Study Director: Yoshiki Sawa, Ph.D; Osaka University

• PRS Account: Osaka University
• Verification Date: April 2021