臨床研究等提出・公開システム

Regenerative medicine for spinal cord injury at subacute stage using human induced pluripotent stem cell-derived neural stem/progenitor cells

Regenerative medicine for spinal cord injury at subacute stage using human induced pluripotent stem cell-derived neural stem/progenitor cells

Matsumoto Morio

Nov. 19, 2024

4

spinal cord injury at subacute stage

Clinical research began on December 1, 2020. Actual patient recruitment began from June 2021, due to COVID-19 pandemic. The 1st patient was enrolled in December 2021. The trial period was extended for one year in September 2022. The one-year observation period for all four cases ended in November 2024.

There were 24 adverse events for which a causal relationship with clinical research could not be ruled out (hereafter abbreviated as side effects), in 4 out of 4 patients. Of these, 14 cases of non-infectious diseases were observed in 4 cases (100%), and 10 cases of infectious diseases were observed in 4 cases (100%). No serious side effects were observed. Among the side effects, events observed in 2 or more out of 4 patients were 'hypomagnesemia' in 100% (4/4) , 'urinary tract infection' in 100% (4/4), 'hyperkalemia' in 50% (2/4), 'tinea pedis' in 50% (2/4), and 'tinea cruris' in 50% (2/4). Of the 24 side effects, 3 events occurred multiple times in the same patient. One patient had 'hepatic function abnormalities' twice. All 4 cases had 'urinary tract infections' 3 to 5 times, and 1 case had 'pneumonia' twice. Regarding the causal relationship of side effects, no side effect was caused by the cell processing products. There were two side effects that could not be ruled out to be related to the transplant surgery of the cell processing products ('increase of upper respiratory tract secretion' and 'leakage of cerebrospinal fluid'), and both were non-serious. The other 22 side effects (12 non-infectious events, and 10 infectious events) were determined to be related to tacrolimus, which was used to suppress rejection of transplanted cells.

Safety (Primary Endpoint): No adverse events were determined to be attributable to the specified cell-processed product. Two adverse events were identified for which a causal relationship with the transplant surgery of the specified cell-processed product could not be excluded. Additionally, 22 adverse events were observed for which a causal relationship with the immunosuppressive agent tacrolimus could not be ruled out. All of these events were assessed as non-serious. Efficacy (Secondary Endpoint): With respect to efficacy, a comparative analysis of the change from baseline to Week 52 in the ASIA motor score and the ASIA Impairment Scale (AIS), relative to external control data, demonstrated results suggestive of a potential therapeutic benefit.

All observed adverse events were non-serious. Two events may have been related to surgery, and 22 were potentially associated with tacrolimus. No events were attributed to the transplanted cells. Efficacy analysis showed greater median improvements in ASIA motor score and AIS grade from baseline to Week 52, compared to external control data. These results indicate that the cell product and its transplantation method may be safe and potentially effective for subacute spinal cord injury.

Sept. 18, 2025

Yes

Data on the safety and efficacy of this clinical study will be published in the database of the Japanese Society for Regenerative Medicine (National Regenerative Medicine Database:NRMD) under the responsibility of the study manager.

https://jrct.mhlw.go.jp/latest-detail/jRCTa031190228

Nakamura Masaya

Keio University School of Medicine

35 Shinanomachi, Shinjuku-ku Tokyo

okanolab2020sci@gmail.com

Kozuki Tsuneo

Keio University School of Medicine

35 Shinanomachi, Shinjuku-ku Tokyo

+81-3-5363-3747

okanolab2020sci@gmail.com

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Complete spinal cord injury (ASIA impairment scale A) at C3/4-Th10 level, within predetermined days after spinal cord injury at acquiring consent. 2) Possible to transplant cells between predetermined days after the injury. 3) Possible to be hospitalized first to Keio University Hospital after the transplantation, then to the Murayama Medical Center up to predetermined months after cell transplantation.Also able to visit Keio University Hospital up to predetermined weeks after cell transplant surgery. 4) 18 years old, or older. 5) Sufficient informed consent.

1)Multiple or transection injury of spinal cord, or combined damage of dural membrane by preoperative MRI imaging 2)Past diseases Primary neurodegenerative diseases Unable to take MRI Intoxication Other diseases which make it difficult to comply with protocol treatment 3)Comorbidity Major respiratory complications. Trauma, or organ injuries to make the assessments difficult Other severe medical complications including heart failure, diabetes mellitus, hypertension, interstitial pneumonia, renal failure, autoimmune disease, and cancer. Active infectious diseases that contraindicate surgery. 4)Significant abnormality in clinical laboratory values 5)Allergy to immunosuppressant 6)Combination therapy Participation in another clinical trial Medication with predetermined drugs 7)Pregnancy

Both

spinal cord injury at subacute stage

Transplantation of iPSC derived neural stem/progenitor cells between predetermined day after spinal cord injury

Safety

Effectiveness

Complete

+81-3-5363-3503

Nov. 27, 2018