UMIN-CTR Clinical Trial

Basic information
Public title	A Study of transplantation of allogenic induced pluripotent stem cell (iPSC) derived retinal pigment epithelium (RPE) cell suspension in subjects with neovascular age related macular degeneration
Acronym	Transplantation of allogenic iPSC derived RPE cell suspension in subject with neovascular AMD
Scientific Title	A Study of transplantation of allogenic induced pluripotent stem cell (iPSC) derived retinal pigment epithelium (RPE) cell suspension in subjects with neovascular age related macular degeneration
Scientific Title:Acronym	Transplantation of allogenic iPSC derived RPE cell suspension in subject with neovascular AMD
Region	Japan

Condition
Condition	Neovascular age related macular degeneration
Classification by specialty	Ophthalmology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	The objectives of this clinical study are to evaluate the safety as well as the feasibility and visual function efficacy of transplantation of RPE cells differentiated from allogenic iPS cells induced from the peripheral blood of 6 HLA locus homozygous donor for HLA haplotype matched subjects with neovascular AMD.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	The safety of the investigational treatment: the presence or absence, severity and frequency of each of the following adverse events (AE) due to the iPS cell-derived RPE cell transplantation surgery. [Adverse events associated with the iPSC-derived RPE cells] 1. Graft failure, immune rejection 2. Excessive proliferation or tumorigenesis by the graft cells [Adverse events associated with the transplantation surgery or its procedure] 1. Retinal, choroidal or vitreous hemorrhage 2. Retinal detachment
Key secondary outcomes	(1) Safety The severity and frequency of AEs other than those described above and are associated with iPSC derived RPE cells. The severity and frequency of AEs other than those described above and are associated with the transplantation surgery or its procedure. The severity, frequency, and type of all AEs (based on the CTCAE v4.0-JCOG) other than those described above. (2) Efficacy - Foveal retinal thickness, subretinal fluid, retinal edema by OCT. - Retinal sensitivity accessed by multi-local ERG and microperimetry . - Visual acuity. - The dye leakage of CNV by fluorescence angiography - The interval period until next treatment of anti-VEGF drugs because of the recurrence of CNV and the anti-VEGF drug treatment times during 1 year from the RPE cell transplantation. - Change in QOL.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Other
Interventions/Control_1	Subretinal transplantation of allogenic iPSC derived RPE cells
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	50 years-old <=
Age-upper limit	85 years-old >=
Gender	Male and Female
Key inclusion criteria	1) At least one eye has been diagnosed with wet AMD (including PCV and RAP) 2) Men and women 50 years of age and more, 85 years of age and less 3) Presence of subfoveal lesions of any of CNV, fibrotic scar, RPE atrophy or RPE tear without surgically removable lesions 4) Corrected visual acuity not less than hand motion and less than 0.3 5) The eye has relapse or incomplete resolution of exudative changes after receiving at least one additional anti-VEGF agent following 3 injections of induction therapy (total of at least 4 injections) or anti-VEGF agent is considered ineffective for exudative changes. 6) With or without dye leakage by fluorescein angiography 7) Well understood and written informed consent has been obtained from the patient. 8) Matched with HLA haplotype A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01-DPB1*09:01
Key exclusion criteria	(1)-4) applicable only in subject eye) 1) Ocular infection 2) Other retinal disease (diabetic retinopathy, hypertensive retinopathy, vascular occlusion, etc.) 3) Optic nerve atrophy 4) Glaucoma with poorly controled intraocular pressure 5) Severe liver dysfunction (AST/ALT 100 IU/L or higher) 6) Severe renal impairment that require dialysis 7) Hepatitis B virus, Hepatitis C virus, Human Immunodeficiency Virus, Adult T-cell Leukemia Virus, cases of Syphilis-positive 8) Allergic to bovine serum or antibiotics (penicillin, streptomycin) 9) Unable to quit anti-coagulants or anti-platelet medication 10) Malignant carcinoma (except for carcinoma in situ) or its history in the past 3 years 11) Allergic to fluorescein or indocyanine green angiography 12) Possible pregnancy or with the partner having a wish for pregnancy 13) Enrolled in another clinical study in the past 1 month 14) Judged unsuitable for study participation by the principal investigator or co-investigators
Target sample size	5

Research contact person
Name of lead principal investigator	1st name Yasuo Middle name Last name Kurimoto
Organization	Kobe City Eye Hospital
Division name	Department of Ophthalmology
Zip code	650-0047
Address	2-1-8, Manatojima-minamimachi, Chuo-ku, Kobe Japan
TEL	078-381-9876
Email	ykurimoto@mac.com

Public contact
Name of contact person	1st name Naoki Middle name Last name Shibatani
Organization	Kobe City Eye Hospital
Division name	Research Center
Zip code	650-0047
Address	2-1-8, Manatojima-minamimachi, Chuo-ku, Kobe Japan
TEL	078-381-9876
Homepage URL
Email	e_kenkyujimu@kcho.jp

Sponsor
Institute	Kobe City Eye Hospital
Institute
Department

Funding Source
Organization	AMED
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor	1.Osaka University Hospital 2.Center for iPS Cell Research and Application 3.RIKEN
Name of secondary funder(s)

IRB Contact (For public release)
Organization	-
Address	-
Tel	-
Email	-

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	神戸市立医療センター中央市民病院（兵庫県） 国立大学法人大阪大学医学部附属病院（大阪府）

Other administrative information
Date of disclosure of the study information	2017 Year 02 Month 06 Day

Related information
URL releasing protocol
Publication of results	Partially published

Result
URL related to results and publications	https://www.mdpi.com/2077-0383/9/7/2217
Number of participants that the trial has enrolled	5
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2017 Year 01 Month 26 Day
Date of IRB	2017 Year 01 Month 26 Day
Anticipated trial start date	2017 Year 02 Month 06 Day
Last follow-up date	2021 Year 09 Month 20 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 02 Month 04 Day
Last modified on	2021 Year 01 Month 03 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029894