Clinical trial NCT04696328: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Myocardial Ischemia
Keywords: ischemic cardiomyopathy, D017202
Lead sponsor: Osaka University
Sponsor class: OTHER
Collaborators: name: Cuorips Inc.
First posted: 2021-01-06
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The number of patients with improved LVEF
timeFrame: 26 weeks
measure: Incidence of adverse events and defects [Safety and Tolerability]
timeFrame: From postoperative to the end of the observation period (52 weeks)
measure: Incidence of serious adverse events [Safety and Tolerability]
timeFrame: From postoperative to the end of the observation period (52 weeks)
measure: Incidence of abnormal vital signs [Safety and Tolerability]
timeFrame: Before surgery, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
measure: Incidence of abnormal general blood tests [Safety and Tolerability]
timeFrame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
measure: Incidence of abnormal blood biochemical tests [Safety and Tolerability]
timeFrame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
measure: Incidence of abnormal tumor marker tests [Safety and Tolerability]
timeFrame: Screening, 13 weeks, 26 weeks, 52 weeks
measure: Incidence of cardiac function clinical events such as death and hospitalization [Safety and Tolerability]
timeFrame: From postoperative to the end of the observation period (52 weeks)
Secondary outcomes:
measure: Number of Responder patients 26 and 52 weeks after transplantation of this product
timeFrame: 26 and 52 weeks
measure: Contraction function of the entire left ventricle
timeFrame: 26 weeks
measure: Left ventricular remodeling (LVESVI)
timeFrame: 26 weeks
measure: Left ventricular remodeling (LVEDVI)
timeFrame: 26 weeks
measure: New York Heart Association functional classification
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: Specific Activity Scale (SAS)
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: The Minnesota Living with Heart Failure Questionnaire
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: 36-Item Short Form Survey (SF-36)
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: 6-minute walking distance
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: Brain natriuretic peptide (BNP)
timeFrame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
measure: N-terminal pro-brain natriuretic peptide (NT-proBNP)
timeFrame: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
measure: Exercise tolerance (VO2max)
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: Exercise tolerance (AT)
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: Exercise tolerance (VE/VCO2)
timeFrame: Before surgery, 26 weeks, 52 weeks
measure: Cumulative number of rejections that occurred during the observation period
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
Study officials:
affiliation: Osaka University
name: Yoshiki Sawa, Ph.D
role: STUDY_DIRECTOR
References: