Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated With Age-Related Macular Degeneration

Summary

Participation Requirements

Description

Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. There is no treatment for geographic atrophy (GA), the advanced stage of dry AMD, in which cells of the neurosensory retina and associated retinal pigment epithelium (RPE) gradually degenerate and die. Advanc...

Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. There is no treatment for geographic atrophy (GA), the advanced stage of dry AMD, in which cells of the neurosensory retina and associated retinal pigment epithelium (RPE) gradually degenerate and die. Advances in stem cell biology allowing differentiation of pluripotent cells into RPE in vitro make feasible a cell-based strategy for potential treatment of AMD, and recent methods for induced pluripotent stem cell (iPSC) generation offer promise of individualized autologous] therapy. Such an approach involves generation of iPSC from somatic cells taken from a patient with GA, differentiation of iPSC into RPE grown as a monolayer on a thin scaffold in vitro, and transplantation of the RPE/scaffold construct into a small region in the subretinal space of the same patient, with a goal of rescuing the overlying neurosensory retina from further degeneration. Objective: To evaluate the safety and feasibility of subretinal transplantation of iPSC-derived RPE, grown as a monolayer on a biodegradable poly lactic-co-glycolic acid (PLGA) scaffold, as a potential autologous cell-based therapy for GA associated with AMD. Study Population: Five participants will undergo RPE transplantation in one eye. Eligible eyes will have GA, best-corrected visual acuity (BCVA) between 20/100 and 20/500, and a fellow eye that has same or better BCVA. If the National Eye Institute (NEI) Data and Safety Monitoring Committee (DSMC) gives clearance to proceed based on review of data from the first cohort, a second cohort of up to seven additional participants with GA, BCVA between 20/80 and 20/500 in the eye being considered for RPE transplantation, and same or better visual acuity in the other eye may undergo the procedure to gather additional safety and potential efficacy data useful for planning future studies. Up to 20 participants may be enrolled to allow for screening failures or for participants withdrawing from the study prior to RPE transplantation. Design: In this phase I/IIa, prospective, single-arm, single-center clinical trial, participants will undergo subretinal transplantation of autologous iPSC-derived RPE in one eye and will be followed for five years after surgery. Outcome Measures: The primary outcome measure is the safety of RPE/PLGA transplantation, as determined by assessment of visual acuity change and summary of adverse events at 12 months after RPE/PLGA transplantation. Secondary outcome measures include visual acuity change and adverse event reporting at 24 and 60 months, and changes in the following at 12, 24 and 60 months as compared with baseline, assessed in the transplanted region, and compared where applicable with other areas in the macula, and/or with corresponding regions in the fellow eye: retinal sensitivity and fixation parameters assessed by microperimetry; multifocal electroretinography (ERG) responses; macular structure on cross-sectional and en face imaging by optical coherence tomography (OCT); macular features on color, single-wavelength reflectance, and fundus autofluorescence (FAF) photography; and fluorescein angiography (FA). Some participants may undergo imaging of photoreceptor/RPE features using adaptive-optics-assisted macular imaging under a separate protocol (e.g., 15-EI-0020).

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