Safety and Tolerability of RPE Stem Cell-derived RPE(RPESC-RPE) Transplantation in Patients With Dry Age-related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The main objective of the study is evaluation of the safety and tolerability of RPESC-RPE-4W as therapy for dry AMD.

Detailed Description
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RPESC-RPE-4W is Allogeneic RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) isolated from the RPE layer of human cadaveric eyes are transplanted under the macular. This first-in-human Phase 1/2a open-label dose-escalation interventional study plans to enroll a total of 18 subjects

Official Title
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A Phase1/2a, Open-Label Study to Evaluate the Safety and Tolerability of RPE Stem Cell-derived RPE (RPESC-RPE) Transplantation as Therapy for Dry Age-related Macular Degeneration (AMD)

Conditions
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Dry Age-related Macular Degeneration

Intervention / Treatment
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* Biological: RPESC-RPE-4W


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of dry AMD. Ability to understand and give informed consent. Adult male or female >55 years of age. Medically suitable to undergo vitrectomy and subretinal injection (>60% on Karnofsky scale). Postmenopausal if female (expected to be common for the age limitation), or the female partner of a male subject unable to father children. If male, willing to use barrier and spermicidal contraception during the study. Exclusion Criteria: Allergy or hypersensitivity to dilation drops or fluorescein. Active major medical conditions limiting ability to participate in the study. Active malignancy or treatment with chemotherapy. Systemic immunosuppressant therapy within past six months. History of toxoplasmosis, retinal histoplasmosis or tuberculosis. Receipt of investigational product (IP) in a clinical trial within prior six months. Any other medical condition, which, in the Investigator's judgment, will interfere with the subject's ability to comply with the protocol, compromises subject safety, or interferes with the interpretation of the study results. Pregnant or nursing females.

Ages Eligible for Study
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Minimum Age: 55 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50,000 cells<br>Six patients will receive single dose of 50,000 RPESC-RPE-4W cells in the eye. | Biological: RPESC-RPE-4W<br>* RPESC-RPE-4W<br>|
| Experimental: 150,000 cells<br>Six patients will receive single dose of 150,000 RPESC-RPE-4W cells in the eye. | Biological: RPESC-RPE-4W<br>* RPESC-RPE-4W<br>|
| Experimental: 250,000 cells<br>Six patients will receive single dose of 250,000 RPESC-RPE-4W cells in the eye. | Biological: RPESC-RPE-4W<br>* RPESC-RPE-4W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of RPESC-RPE-4W transplantation | The transplantation of RPESC-RPE-4W cells will be considered safe and tolerated in the absence of: Decrease in visual acuity (VA) of more than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (or to worse than counting fingers at three feet) from baseline Any Grade 2 (CTCAE version 5) or greater Adverse Events (AE) related to the cell product and investigational interventions. Any evidence that the cell are contaminated with an infectious agent or serious immune response to the cell product Any evidence that the cells show tumorigenic potential | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mean of Best Corrected Visual Acuity (BCVA) | Change in visual acuity will be measured by ETDRS chart. | 24 months | 
| Loss of ≥10 decibels of ten-degree average visual sensitivity microperimetry | Loss of ≥10 decibels of ten-degree average visual sensitivity will by measured by microperimetry. | 24 months | 
| Change in GA lesion area | Change in GA lesion area will be measured. | 24 months | 
| Evidence of structural changes | Structural evidence will be measured by OCT imaging, autofluorescence, fluorescein angiography, and fundus photography | 24 months |