Subretinal Transplantation of Retinal Pigment Epitheliums in Treatment of Age-related Macular Degeneration Diseases

Study Overview
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Brief Summary
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This project intends to transplant human embryonic stem cells derived retinal pigment epitheliums into subretinal space of patients to treat dry age-related macular degeneration(dry-AMD).And we will assess the safety and efficacy of RPE transplants to treat dry AMD.

Detailed Description
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This project intends to transplant human embryonic stem cells derived retinal pigment epitheliums into subretinal space to treat age-related macular degeneration(AMD). Through the statistical analysis EDTRS, BCVA, OCT, ERG, Fluorescein angiography, Ophthalmic AB ultrasound changes between before and after the treatment to assess the efficacy and safety of RPE transplants to treat AMD disease.

Official Title
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Safety and Efficacy of Subretinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigment Epitheliums in Treatment of Age-related Macular Degeneration Diseases

Conditions
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Dry Age-related Macular Degeneration

Intervention / Treatment
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* Biological: retinal pigment epithelium transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 55-80 years; Clinical diagnosis is consistent with the definition of late dry AMD in the age-related eye disease study (AREDS) (with one or more >250 micron geographic atrophy in the fovea; No CNV; The BCVA of target eye will not be better than 20/200; -8.00D<diopter<+8.00D，21mm<axis oculi≤28mm; voluntary as test subjects, signed informed consent, regular follow-up on time. Exclusion Criteria: The macular atrophy caused by other diseases in addition to AMD; Suffer from retinitis pigmentosa, choroidal retinitis, central serous chorositis, diabetic retinopathy or other retinal vascular and degenerative diseases besides AMD; Lens opacities (affecting the central vision), glaucoma, uveitis, retinal detachment, optic neuropathy and other ocular history; Other intraocular surgery history besides cataract surgery; In the last 6 months, there were severe heart failure (New York Heart Association grade III and IV) or the left ventricular ejection fraction <35% in any examinations One of the following circumstances: (1) dialysis or eGFR<20ml/min/1.73m2; (2) urinary protein / urinary creatinine is ≥1g/g; (3) creatinine or albumin / urinary creatinine is ≥600mg/g; Chronic liver disease, ALT increased >3 times normal value of the upper limit; Combined with other serious systemic diseases, such as cor pulmonale, severe COPD (FEV1%<50%) and so on; Combined with severe infectious diseases (such as HIV, syphilis antibody positive, etc; The quantitative detection of HCV-RNA was positive, the quantitative detection of HBV-DNA was greater than 103 IU/ml, and tuberculosis was in the contagious period, etc; Patients who are using anticoagulant, or the platelet function is still not restored to normal after stopping antiplatelet drugs for 10 days（The results of VerifyNow test show that AUC is greater than 470 and PRU is more than 208）; Abnormal blood coagulation function or other obvious abnormal laboratory test results; Malignant tumor and history of malignant tumor; Women who are pregnant，prepare to be pregnant during the trial, be lactating；men who prepare to have baby during the trial; Any immune deficiency; Glucocorticoids or immunosuppressive drugs have been used in the last 3 months; Antipsychotic drugs have been used in the last 3 months, such as antidepressants, antipsychotic drugs, and so on; With hypersensitivity to tacrolimus or other macrolides; The history of addiction to alcoholism or prohibited drugs; Being participating in any intervention clinical trials; Poor compliance, difficult to complete the study; The person who did not receive the informed consent; Some researchers believe that there may be situations that can increase risks of the subjects or interfere clinical trials (for example, patients are prone to mental stress, depression, mental disorders, cognitive dysfunction, etc.).

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: retinal pigment epithelium transplantation<br>Subretinal transplantation of human embryonic stem cell derived retinal pigment epitheliums. | Biological: retinal pigment epithelium transplantation<br>* Transplant retinal pigment epithelium derived from human embryonic stem cells into subretinal space of patients with dry age-related macular degeneration(dry AMD).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerance of transplantation | The safety and tolerance of transplantation of clinical grade hESC-derived RPE will be considered safe: no above moderate adverse events or severe adverse events which related to transplantation of retinal pigment epithelial cells ; Cells without infectious; No tumorigenicity. Through the clinical signs of subjects and laboratory examination to judge the tolerance, integrity, repellency of RPE cells, and monitoring the presence of local or systemic infection, and presence of metastatic tumor cells. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy:Early treatment of diabetic retinopathy eye chart (ETDRs) | Visual function measure: change in visual acuity | one year | 
| Efficacy：Best corrected visual acuity（BCVA） | Visual function measure: change in visual acuity | one year | 
| Efficacy：Optical coherent tomography (OCT) | Transplant and host retina integrity and survival | one year | 
| Efficacy：fundus autofluorescence | Transplant and host retina integrity and survival | one year |