UMIN-CTR Clinical Trial

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

Condition
Condition	Exudative age related macular degeneration
Classification by specialty	Ophthalmology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	In this trial of retinal pigment epithelium (RPE) replacement, the aim will be to evaluate the safety and feasibility/efficacy of treating subjects with exudative age-related macular degeneration (AMD) by transplanting autologous iPSC derived RPE sheets
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Safety of the proposed treatment protocol: incidence and severity of adverse events related to the use of autologous iPSC derived RPE sheet. <Adverse events related to iPSC derived RPE sheet> 1 Poor survival of the graft, immune rejection 2 Tumor formation <Adverse events related to surgical procedure> 1. Retinal detachment, choroidal hemorrhage, vitreous hemorrhage 2 Retinal tear and retinal detachment
Key secondary outcomes

Base
Study type	Interventional

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

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Device,equipment Maneuver Other
Interventions/Control_1	The size of the RPE sheet used in the first 3 cases will be 1.3 mm x 3 mm
Interventions/Control_2	In the 3 following cases, the use of RPE sheets of a larger size, or of in multiple number with the same size, will be allowed. In case of using multiple sheets, maximum of 3 sheets will be used.
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	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Diagnosis of exudative AMD including non-typical subtypes in at least one eye. 2) Male and female subjects aged 50 year and older at the time of acquired consent 3) Presence of subfoveal CNV, fibrotic scar, or RPE tear related to exudative AMD 4) The visual acuity of less than 0.3 but better than hand motion. 5) Treatment history of standard anti-VEGF therapy with limited effects such as poor response or persistent recurrence (minimum treatment with anti-VEGF induction therapy followed by at least one additional injection) 6) The mean Central 4-degree retinal sensitivity of less than 5 db on MicroPerimeter1 (MP-1) examination 7) Able to understand and willing to sign the informed consent
Key exclusion criteria	1) Presence of ocular infection 2) Presence of other retinal diseases such as diabetic retinopathy, hypertensive retinopathy, retinal vessel occlusions. 3) Presence of optic nerve atrophy 4) Presence of glaucoma of uncontrolled ocular pressure 5) Presence of significant hepatic failure (with either AST or ALT higher than 100 IU/L) 6) Presence of renal failure 7) Negative serum tests for human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) or syphilis. 8)No history of allergic reaction to antibiotics or bovine serum 9) No medical requirements for a continuous treatment of anti-coagulants or anti-platelets 10) Medically suitable for general anesthesia 11) No presence of or history of malignancy in past 5 years 12) No history of allergic reaction to ICG or Fluorescein 13) Pregnant females; breastfeeding females; and females of childbearing potential. 14) No participation in other clinical trials that involve the last one month before informed consent is obtained 15) Medically judged inadequate by the docters responsible for this study
Target sample size	6

Research contact person
Last name of lead principal investigator	1st name Middle name Last name Masayo Takahashi
Organization	RIKEN
Division name	Laboratory for Retinal Regeneration
Zip code
Address	2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo
TEL	078-306-3305
Email	retinalab@cdb.riken.jp

Public contact
1st name of contact person	1st name Middle name Last name Yasuhiko Hirami
Organization	Kobe City Medical Center General Hospital
Division name	Department of Ophthalmology
Zip code
Address	2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo
TEL	078-302-4321
Homepage URL	http://www.riken-ibri.jp/AMD/
Email	hirami@fbri.org

Sponsor
Institute	RIKEN
Institute
Department

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

Other related organizations
Co-sponsor	Foundation for Biomedical Research and Innovation Kobe City Medical Center general Hospital
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	先端医療センター病院（兵庫県） 理化学研究所　多細胞システム形成研究センター（兵庫県）

Other administrative information
Date of disclosure of the study information	2013 Year 10 Month 02 Day

Related information
URL releasing protocol
Publication of results	Partially published

Result
URL related to results and publications	https://www.nejm.org/doi/full/10.1056/NEJMoa1608368
Number of participants that the trial has enrolled	1
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	2013 Year 07 Month 29 Day
Date of IRB	2013 Year 07 Month 29 Day
Anticipated trial start date	2013 Year 10 Month 02 Day
Last follow-up date	2019 Year 02 Month 28 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	The trial was halted after two patients because of Japan's Regenerative Medicine Law of 2014

Management information
Registered date	2013 Year 10 Month 01 Day
Last modified on	2019 Year 04 Month 05 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013279