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Safety study using allogenic iPSC-retinal sheets for patients with retinitis pigmentosa (iRERP)

Safety Study of allogenic hiPSC-retinas in Retinitis Pigmentosa (hiRERP)

Kurimoto Yasuo

Jan. 22, 2025

2

Two subjects, a 67-year-old woman and a 42-year-old man with advanced RP who met the following conditions: (1) severe visual acuity loss (decimal visual acuity of 0.2 or less), (2) severe tunnel vision (mean deviation [MD] value =< -30 dB in the central 10-2 program of the Humphrey visual field test).

Two target cases were registered, and iPSC-derived retinal organoid sheets were transplanted in all cases. Observation and investigation were completed at 208 weeks after transplantation, and safety and efficacy were evaluated.

No adverse event related to the transplanted iPSC-derived retinal organoid sheet was observed.

Primary Endpoints 1. Increase in retinal thickness due to engraftment of allogeneic iPS cell-derived retinal sheets: Both cases showed an increase of >10% in maximum retinal thickness at 52 weeks post- transplantation compared to pre-transplantation, and was considered effective. 2. Safety of allogeneic iPSC-derived retinal sheets (at 208 weeks): No sign ofimmune rejection or unexpected overgrowth of transplanted tissue was observed in either case. Secondary Endpoints 1. Safety of allogeneic iPSC-derived retinal sheet transplantation (adverse events) No serious adverse events or adverse events related to the transplanted allogeneic iPSC-derived retinal sheet were observed in either case up to 208 weeks post-transplantation. 2. Efficacy of allogeneic iPSC-derived retinal sheet transplantation (visual function) - In both cases, no change of 3.0 dB or more was observed in the Mean Deviation (MD) value of the 10-2 program of the Humphrey visual field test. - In one case, an increase in the probability threshold of the FST test and an increase of 10% or more in the number of correctly identified letters in the table test were observed at 52 weeks post-transplantation, leading to a determination of efficacy for visual field improvement. However, no further evidence of efficacy for visual field improvement was observed in either case up to 208 weeks post-transplantation. - No improvement in visual acuity (ETDRS) was observed in either case. - In the microperimetry performed as part of the "exploration of other visual function assessment methods," retinal sensitivity across the entire measurement range was lower than pre-transplantation in both the transplanted eye and the non-transplanted eye up to 208 weeks post-transplantation. However, in one case, an increase in retinal sensitivity at the transplantation site was observed at 156 weeks and 208 weeks post-transplantation. No results suggesting graft function were obtained in other tests, including multifocal electroretinography, macular electroretinography, phosphene testing, and pupillary response measurement. 3. Efficacy of allogeneic iPS cell-derived retinal sheet transplantation (QOL) - An increase in the VFQ-25 score was observed in one case, and a decrease in another case.

In the limited number of cases, safety of iPSC-derived retinal organoid sheet transplantation was confirmed without immune reactions or unexpected overgrowth of the transplanted tissue. Furthermore, efficacy was demonstrated by confirming an increase in retinal thickness due to graft engraftment, suggesting the potential for partial improvement in visual function.

Sept. 30, 2025

Dec. 07, 2023

https://pubmed.ncbi.nlm.nih.gov/38065067/

Yes

To share clinical data obtained from cases attended to the clinical research with NRMD that has been anonymized clinical research plan after the end of the clinical research.

https://jrct.mhlw.go.jp/latest-detail/jRCTa050200027

Hirami Yasuhiko

Kobe City Eye Hospital

2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe Hyogo

e_jrct@kcho.jp

Yamasaki Shigeki

Kobe City Eye Hospital

2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe Hyogo

+81-78-381-9876

e_jrct@kcho.jp

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) clinically diagnosed as retinitis pigmentosa based on the diagnostic criteria of the designated intractable disease
2) 20 years of age or older
3) Severity grade IV by severity classification guideline under the diagnostic criteria of the designated intractable disease (corrected visual acuity less than 0.2)
4) MD values less than -30dB by Humphrey visual field test
5) Capable of understanding the documents of the research context and of informed consent and is able to provide a written informed consent

1) Ocular infection
2) Glaucoma with poorly controlled intraocular pressure
3) The affected eye was received intraocular surgeries other than cataract surgery within 3 months
4) Any of bilirubin level, albumin level, and prothrombin time is outside the normal range as a criterion for liver function.
5) Either creatinine level or eGFR (estimated glomerular filtration rate) is outside the normal range as a standard for renal function.
6) B hepatitis virus, C hepatitis virus, human immunodeficiency virus, adult T-cell leukemia virus, cases of syphilis-positive
7) Unable to quit anti-coagulants or anti-platelet medication
8) Malignant carcinoma or its history in the past 3 years
9) Family history of hereditary tumors
10) Allergic to fluorescein or indocyanine green angiography
11) Possible pregnancy or breastfeeding, or with the partner having a wish for pregnancy
12) Enrolled in another clinical study in the past 1 month
13) Judged inadequate by the principal investigator and coresearchers

Both

Retinitis pigmentosa

subretinal transplantation of allogenic iPSC-retinal sheets (up to 3 pieces)

1) Increase in retinal thickness after subretinal transplantation of allogenic iPSC-retinal sheets
2) Safety of allogenic iPSC-retinal sheets iPSC-retinal sheets (safety of cell processing product and presence or absence of immune rejection or unexpected graft proliferation)

1) Safety of therapeutic procedure of subretinal transplantation of allogenic iPSC-retinal sheets
2) Efficacy of therapeutic procedure of subretinal transplantation of allogenic iPSC-retinal sheets (visual function and quality of life assessment)

Complete

+81-6-6210-8293

Feb. 10, 2020