Safety and Efficacy of Autologous Transplantation of iPSC-RPE in the Treatment of Macular Degeneration

Study Overview
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Brief Summary
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This project intends to perform autologous transplantation of induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE). The clinical-grade RPE will be transplanted into subretinal space to treat refractory age-related macular degeneration. The efficacy and safety of RPE transplants to treat macular degeneration will be monitored and analyzed with results from EDTRS, BCVA, OCT, ERG, microperimetry, and fluorescein angiography, before and after the treatment.

Detailed Description
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The investigators will generate iPSC lines from recruited participants and differentiate the iPSC into RPE. Autologous iPSC-derived RPE will be transplanted into participants eyes by subretinal injections. The safety and efficacy will be closely monitored and analyzed.

Official Title
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Safety and Efficacy of Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in the Treatment of Macular Degeneration

Conditions
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Macular Degeneration

Intervention / Treatment
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* Biological: Autologous iPSC-derived RPE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 50-75 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 um geographic atrophy in the fovea; Clinical diagnosis is wet AMD, but no obvious efficacy after conventional treatment; The BCVA of the target eye will be 0.05 to 0.3; Voluntary as test subjects, informed consent, regular follow-up on time. Exclusion Criteria: One-eyed subjects; Macular atrophy caused by other diseases in addition to AMD; Suffer from retinitis pigmentosa, choroidal retinitis, central serous choroiditis, 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 histories; Other intraocular surgery histories besides cataract surgery; Combined with severe systemic diseases, such as heart failure, liver disease, renal insufficiency, cor pulmonale, COPD in the previous 12 months; Combined with severe infectious diseases, such as HIV, HBV, HCV, syphilis, tuberculosis, etc; Abnormal blood coagulation function or other laboratory tests; If female and of childbearing potential, pregnant, breastfeeding, or planning to become pregnant through the study; If male, refuse to use barrier and spermicide contraception during the study; Malignant tumor and history of malignancy; Any immune deficiency; Allergy to tacrolimus or other macrolides; Any immune deficiency; Use glucocorticoids, immunosuppressive drugs, or antipsychotic drugs in the previous 3 months; Use anticoagulant, or the platelet function is still not restored to normal after stopping antiplatelet drugs for 10 days; A history of addiction to alcoholism or prohibited drugs; Be participating in other intervention clinical trials or receiving other study medications; Poor compliance, difficulty to complete the study, or refusal to informed consent; Some other situations which might increase the risks of the subjects or interfere with clinical trials, such as mental disorders, cognitive dysfunction, etc.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving intervention<br>Participants will receive autologous transplantation of induced pluripotent stem cell-derived retinal pigment epitheliums. | Biological: Autologous iPSC-derived RPE<br>* Autologous transplantation of iPSC-derived RPE<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measure | Safety will be assessed by Adverse Events (AEs) of special interest in regards to the investigational product. This will include obtaining information about Serious Adverse Events (SAEs) that are neurologic, infectious, hematologic or fatal, any AE that causes the subject to withdraw from the study, any new diagnosis of an ocular or immune-mediated disorder, cancer (irrespective of prior history), ectopic or proliferative cell growth (RPE or non-RPE) with adverse clinical consequence, unexpected, clinically significant AE possibly related to the cell transplant procedure or the investigational product (autologous iPSC-RPE), pregnancy in a female subject or the partner of a male subject and pregnancy outcome. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity (BCVA) | Change in visual acuity will be measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart. | 12 months | 
| Optical coherence tomography (OCT) imaging | The number of patients with serious retinal detachment, retinal hemorrhage, and cystoid macular edema, and the change in target treatment areas. | 12 months | 
| Color and autofluorescence imaging | Change in target treatment areas. | 12 months | 
| Fluorescein angiography | Change in target treatment areas. | 12 months | 
| Fundus autofluorescence | Change in target treatment areas. | 12 months | 
| Microperimetry | Exploratory evaluations for the change of retinal sensitivity from baseline in the region of interest. | 12 months | 
| Electroretinography (ERG) | Exploratory evaluations for the change of retinal electrophysiology responses from baseline. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinal disease, Macular degeneration, Stem Cells, RPE, Safety, Efficacy