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Clinical trial of human (allogeneic) iPS cell-derived cardiomyocytes sheet for ischemic cardiomyopathy

Clinical trial of human (allogeneic) iPS cell-derived cardiomyocytes sheet for ischemic cardiomyopathy

8

Patients with ischemic cardiomyopathy who met the inclusion criteria and did not fall under the exclusion criteria were enrolled. At the time of obtaining consent, the age (mean +- standard deviation, hereinafter the same) was 61.1 +- 7.3 years, the weight was 70.00 +- 11.70 kg, the systolic blood pressure was 110.8 +- 14.2 mmHg, the diastolic blood pressure was 62.5 +- 6.3 mmHg, the pulse rate was 69.0 +- 8.1 beats/min, the BNP was 126.51 +- 120.64 pg/mL, and the LVEF was 30.49 +- 7.56%. All eight patients had a history of coronary revascularization surgery, and their NYHA classification was III. Seven patients (87.5%) were male.

Three patients were enrolled in cohort A and five in cohorts B-I. All patients received the investigational product and were observed and examined for up to 52 weeks. All eight patients were included in the efficacy and safety analysis sets.

Adverse events were observed in 7 of 8 subjects (87.5%) in the safety analysis population combining Cohort A and Cohort B-I. No side effects were observed. Adverse events observed in 2 or more of the 8 subjects and their incidence rates were increased white blood cell count in 4 subjects (50.0%), hyperglycemia in 3 subjects (37.5%), anemia, wound complications, and renal dysfunction in 2 subjects each (25.0%). One subject (12.5%) experienced adverse events of "severe" severity. No adverse events led to death. Ten serious adverse events were observed in 5 of the 8 subjects. The outcomes of all observed events were "recovered," and a causal relationship to the investigational product was denied for all of them.

The primary endpoint was "the number of subjects whose LVEF measured by echocardiogram improved 26 weeks after implantation of the investigational product compared to before implantation," and the result was 2 out of 8 subjects in both Cohort A and Cohort B-I. Of the 8 subjects in both Cohort A and Cohort B-I, 6 were determined to be responders based on the progress up to 26 weeks after implantation, and all 8 were determined to be responders based on the progress up to 52 weeks after implantation.

This clinical trial evaluated the efficacy and safety of the investigational product in patients with ischemic cardiomyopathy, including when used in combination with immunosuppressants. The data analysis and results of the primary and secondary outcomes, as well as the results listed in the summary of disease occurrence status, demonstrated the efficacy and safety of the investigational product for ischemic cardiomyopathy.

May. 02, 2025

Aug. 16, 2022

https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.950829/full

Yes

The deidentified individual subject data will be used for conference presentations, research article,or both.If it is provided to the sponsor, it will be shared based on the contract.

https://jrct.mhlw.go.jp/latest-detail/jRCT2053190081

Miyagawa Shigeru

Osaka university hospital

2-15, Yamadaoka, Suita, Osaka

saisentan@tissue.med.osaka-u.ac.jp

Kawamura Takuji

Osaka university hospital

2-15, Yamadaoka, Suita, Osaka

+81-6-6879-3154

saisentan@tissue.med.osaka-u.ac.jp

Complete

Dec. 11, 2019

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Ischemic cardiomyopathy
2) NYHA class III, IV
3) Patients who can not expect symptomatic improvement with standard treatment for target disease. To be recognized by the third party committee with experts.
4) Ejection fraction <= 35%

1) Autoimmune disease
2) Allergic or hypersensitive to the immunosuppressant
3) Severe infection
4) Persistent shock due to worsening heart failure
5) Irreversible organ failure other than heart
6) Maignancy
7) Pregnancy
8) Alcoholic or drug addiction in recent six months
9) Allergies or hypersensitivity to animals from which raw materials used
10) Severe pulmonary hypertension

Both

Ischemic cardiomyopathy

Human (allogeneic) iPS cell derived-cardiomyocyte sheet transplantation

D017202

D017690

Number of patients with improved LVEF compared with preoperative at 26 weeks after transplantation

1) Number of responders at 26 and 52 weeks after transplantation
2) Evaluation of the following changes before 26 and 52 weeks after transplantation
(1) LVEF
(2) Left ventricular remodeling
(3) Severity of heart failure
(4) Rejections
(5) Others

+81-6-6210-8290

Sept. 28, 2019

+81-92-642-5774

Sept. 28, 2019

+81-3-3353-8111

Sept. 28, 2019

none