Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated With Age-Related Macular Degeneration
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|ClinicalTrials.gov Identifier: NCT04339764|
Recruitment Status : Recruiting
First Posted : April 9, 2020
Last Update Posted : September 22, 2021
Age-related macular degeneration is a common eye disease in people over 50. The "dry" form of the disease can worsen into geographic atrophy, causing blind spots. Researchers want to learn if replacing older eye cells with younger ones can help treat this disease.
To test the safety of putting cells inside the eye as a possible future treatment for dry age-related macular degeneration.
People ages 55 and older who have geographic atrophy with loss of vision. People who have had "wet" macular degeneration in either eye are NOT eligible.
Participants will be screened with:
- Medical history
- Physical exam
- Blood and urine tests
- Eye exam
- Eye photos
- Fluorescein angiography. An intravenous (IV) line is placed in an arm vein. A dye is injected. A camera takes pictures of the dye as it flows through the eyes' blood vessels.
- Electroretinography. An electrode is taped to participants' forehead. They sit in the dark. After 30 minutes, numbing eye drops and contact lenses are placed in their eyes. They watch flashing lights.
- Tuberculosis test
- Chest X-ray
- Electrocardiography. Sticky pads are placed on participants' chest to record the heart's electrical activity.
Participants will have at least 14 study visits over 5 and a half years. They will repeat screening tests.
Participants will have retinal pigment epithelium (RPE) transplantation surgery in one eye. For this, cells from participants' blood are turned into RPE cells. These cells are placed in their eye through a cut in their retina. They will get dilating eye drops, an IV line, and anesthesia that may make them sleep. A gas bubble will be put in their eye to help it heal.
Participants will be contacted yearly for up to 15 years.
|Condition or disease||Intervention/treatment||Phase|
|Age-Related Macular Degeneration||Device: iPSC-derived RPE/PLGA transplantation Biological: Atuologous iPSC-derived RPE on PGLA||Phase 1 Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/IIa Trial for Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated With Age-Related Macular Degeneration|
|Actual Study Start Date :||September 23, 2020|
|Estimated Primary Completion Date :||May 31, 2029|
|Estimated Study Completion Date :||May 31, 2029|
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.
Device: iPSC-derived RPE/PLGA transplantation
iPSC-derived RPE/PGLA transplantation
Biological: Atuologous iPSC-derived RPE on PGLA
Administered in one eye and followed for 5 years.
- Visual acuity change [ Time Frame: 12, 24, and 60 month ]safety measure
- Summary of adverse events [ Time Frame: 12, 24 and 60 month ]safety measure
- Retinal Structure (optical coherence tomography) [ Time Frame: 12, 24, and 60 month ]Safety and efficacy measure
- Retinal sensitivity and fixation (microperimetry) [ Time Frame: 12, 24, and 60 month ]Safety and efficacy measure
- Multifocal electroretinography responses [ Time Frame: 12, 24, and 60 month ]Safety and efficacy measure
- Retinal Structure (color and autofluorescence imaging) [ Time Frame: 12, 24, and 60 month ]Safety and efficacy measure
- Retinal structure (fluorescein angiography) [ Time Frame: 12, 24, and 60 month ]Safety and efficacy measure
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04339764
|Contact: Angel H Garced, R.N.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Henry E Wiley, M.D.||National Eye Institute (NEI)|