Japanease

Nov. 09, 2020

Nov. 09, 2020

jRCTa032200189

Safety study of regenerative therapy with allogeneic induced pluripotent stem cell-derived cardiac spheres for severe heart failure (Regenerative cardiac spheres)

Safety study of induced pluripoteint stem cell-derived cardiac spheres transplantation (IPSCS study)

Shimizu Hideyuki

Keio University School of Medicine

35 Shinanomachi, Shinjuku-ku, Tokyo

+81-3-3353-1211

shimizu.md@gmail.com

Fujita Jun

Keio University School of Medicine

35 Shinanomachi, Shinjuku-ku, Tokyo

+81-3-3353-1211

jfujita@keio.jp

Nov. 09, 2020

3

Interventional

single arm study

open(masking not used)

active control

single assignment

treatment purpose

none

1) Patients with systolic heart failure due to dilated cardiomyopathy.
Meet the following criteria
i. Left ventricular ejection fraction (LVEF) should be 15% or more, 40% or less by modified Simpson method in echocardiography or cMRI.
2) Patients who meet all the following criteria in diagnosis of severe heart failure.
i. Patients with heart failure who have been in a state of NYHA functional classification class III or higher for at least 90 days at the time of obtaining consent, and it has been judged that improvement can not be expected by the current standard medical treatment.
ii. The standard medical treatment should be sufficiently provided for 4 weeks or more for heart failure according to Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Failure (JCS 2017/JHFS 2017).
iii. Having a history of hospitalization for heart failure in the past.
iv. Medical devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) are used appropriately.
3) Patients at the age of 20 to 75 years at the time of obtaining consent.
4) Voluntarily provide a personally-signed informed consent.
5) Patient whose HLA matches 3 or more loci (A, B, DRB1) with iPS cell line (Ff-iPSC-SCS_P10 (QHJI14) 86) provided by Center for iPS Cell Research and Application (CiRA).


1) Patients with diastolic heart failure such as hypertrophic cardiomyopathy or hypertensive heart failure, or patients with secondary cardiomyopathy whose cause is identified (e.g. amyloidosis, sarcoidosis, muscular dystrophy).
2) Patients with unstable angina.
3) Patients with co-morbidities that require simultaneous surgery.
4) Patients with combined or previous malignancy.
5) Patients with a history of cerebral infarction, transient ischemic attack, myocardial infarction, gastrointestinal hemorrhage, or patients who underwent major cardiovascular surgery such as coronary artery bypass grafting within 3 months prior to consent.
6) Patients with severe hypersensitivity to contrast media, history of side effects.
7) Patients with hypersensitivity to bovine and porcine derived proteins and a history of side effects.
8) Patients with a history of side effects, hypersensitivity to anesthetics, immunosuppressants used in this study.
9) Patients who have or have a history of interstitial pneumonia.
10) Patients with leukemia, myeloproliferative disorder, myelodysplastic syndrome, sickle cell anemia.
11) Patients with uncontrollable autoimmune disease.
12) Patients with psychiatric disorders such as depression. (including patients with mild depression, whose symptoms can be controlled by medicine)
13) Patients with splenomegaly with a major axis of 15 cm or more in the spleen on fluoro deoxy glucose positron emission tomography (FDG-PET ) CT examination.
14) Patients whose clinical laboratory test value at the time of registration falls under the following criteria.
i. Patients with hemoglobin value less than 10 g/dL
ii. Patients with ALP, ALT, AST exceeding 2.5 times the upper limit
iii. Patients with gamma-GTP exceeding 2 times the upper limit
iv. Patients with bilirubin level of 3 mg/dL or more
v. Patients with serum creatinine level of more than 1.8 mg/dL
vi. Patients with less than 40% prothrombin time (PT)
15) Patients with Hepatitis B virus surface (HBs) antigen, hepatitis B virus core (HBc) antibody, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, human T cell leukemia virus (HTLV) -1 antibody or syphilis seropositive.
16) Patients suspected of mycobacterium tuberculosis infection with Quanti-Feron TB Gold (QFT) test positive.
17) Patients with active infections (including cytomegalovirus infections).
18) Patients with systolic blood pressure more than 180 mm Hg or diastolic blood pressure more than 120 mm Hg despite appropriate antihypertensive drug treatment.
19) Patients who undergo Mini Mental State Examination and have 23 points or less
20) Patients with cardiogenic shock at the time of registration.
21) Patients who drink an average of 3 drinks a day on average for 5 years or more.
22) Pregnant women, lactating women, patients who may be pregnant, patients who can not complete contraception until the end of the study, female patients who are planning pregnancy by the end of the study.
23) Patients participating in other trials or clinical trials within 6 months prior to consent.
24) Patients who are considered to be inappropriate based on medical evidence as the target of this clinical research by principal Investigator, co-investigator or project manager.


20age old over
75age old not

Both

Severe heart failure patients with NYHA class III or higher (HFrEF by Dilated Cardiomyopathy)

Intramyocardial injection of 5x10^7 iPSC-derived cardiomyocytes by open-heart surgery

Safety
- Acute stage (~4 weeks) : evaluate the safety of cardiosphere transplantation (e.g. Frequency, severity and severity of adverse events).
- Subacute stage (~24 weeks) and chronic stage (36 and 52 weeks) : evaluate tumorigenesis and fatal arrhythmia.

Efficacy
- The recovery effect of cardiac function is evaluated by the following items.
1) NYHA functional classification
2) 6-minute walk test
3) Cardiothoracic ratio with chest roentgenography
4) BNP levels
5) left ventricular ejection function with echocardiogram and cardiac MRI
6) evaluate quality of life using KCCQ

Safety
- Tumorigenesis including teratoma caused by regenerative cardiac spheres.


Pending

Heartseed Inc.
Not applicable
Keio University Certified Committee for Regenerative Medicine
35 Shinanomachi, Shinjuku-ku, Tokyo

+81-3-5363-3503

med-saisei-jimu@adst.keio.ac.jp
Approval

June. 30, 2020