Study to Evaluate Sub-retinal Transplantation of Retinal Pigmented Epithelial Cells in Patients With Dry AMD

Study Overview
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Brief Summary
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To evaluate the safety of 3 regimens of short-term, low-dose systemic IMT as rejection prophylaxis prior to and/or following transplant of MA09-hRPE cells.

Detailed Description
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This study will be a Phase 2, double-masked, randomized, parallel group, sham surgery/placebo control, multi-center trial. Subjects will be randomized in a 3:1 ratio to either the treatment or control group respectively. Subjects randomized to the treatment group will receive transplantation with 200,000 MA09-hRPE (human embryonic stem cell derived retinal pigmented epithelial)cells in one eye. Subjects randomized to the control group will have a sham surgery without transplantation of MA09-hRPE cells. The study eye must meet all eligibility criteria. If both eyes meet all eligibility criteria, then the study eye will be the eye with the worst Best Corrected Visual Acuity (BCVA) score at screening. If both eyes have identical BCVA scores, then the study eye will be chosen by the Investigator and the subject. There will be 3 cohorts, each with a different regimen of low-dose IMT [tacrolimus and mycophenolate mofetil (MMF)]. Subjects will be randomized to treatment or control within cohorts, defined by severity of BCVA in the study eye at Screening. Enrollment in Cohort 1 and 2 will be concurrent. Enrollment into Cohort 3 will begin once Cohort 2 is fully enrolled.

Official Title
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Ph 2, Double-Masked, Randomized, Parallel, Sham Surgery/Placebo Control, Multi-Center Study to Evaluate Systemic IMT Regimens as Graft Rejection Prophylaxis Following Transplantation of hESC Derived RPE Cells in Patients With AMD

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Biological: Sub-retinal transplantation of MA09-hRPE cells
* Drug: tacrolimus and mycophenolate mofetil
* Drug: Placebo tacrolimus and mycophenolate mofetil
* Procedure: Sham Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Geographic atrophy (GA) secondary to AMD with no evidence of prior to active choroidal neovascularization (CNV) in the study eye. BCVA in the study eye must be between 4 and 58 Early Treatment of Diabetic Retinopathy Study (EDTRS) letters (20/800 to 20/80; 0.025-0.25) Subjects must be willing to take IMT and willing to discontinue any medication that has a known strong interaction with tacrolimus or mycophenolate mofetil (MMF) Exclusion Criteria: Macular atrophy due to causes other than AMD Other sight-threatening ocular disease Current or prior history of optic neuropathy, retinal dystrophy, retinitis pigmentosa, chorioretinitis, vasoocclusive disease, retinal vascular disease or retinal degenerative disease OTHER than AMD History of uveitis History of allergic reaction to sulfa drugs Solid organ or bone marrow transplant recipient History of malignancy within the previous 5 years (except for BCC (basal cell carcinoma), SCC (squamous cell carcinoma) or in-situ cervical) History of myocardial infarction with past 12 months History of clinically significant cardiac dysrhythmia History of diabetes mellitus, bowel disease, tuberculosis Prior treatment for non-exudative AMD Intraocular, refractive or cataract surgery in the last 12 weeks Prior retinal surgery, vitrectomy, macular laser photocoagulation, external beam radiation therapy, transpupillary thermotherapy, glaucoma filtration surgery or corneal surgery (except cataract surgery) Receipt of gene transfer of cell transplant therapy in a prior clinical trial Participation in any other interventional clinical trial within the last 12 weeks

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control group<br>Sham surgery and placebo immunosuppressive therapy (IMT) | Drug: Placebo tacrolimus and mycophenolate mofetil<br>* placebo<br>Procedure: Sham Surgery<br>* Sham surgery<br>|
| Active Comparator: Active Group<br>Sub-retinal transplantation of MA09-hRPE cells and IMT | Biological: Sub-retinal transplantation of MA09-hRPE cells<br>* transplantation<br>Drug: tacrolimus and mycophenolate mofetil<br>* Immunosuppressive Agents<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with evidence of graft failure or rejection. |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in area of geographic atrophy by Optical coherence tomography | Change from baseline to Week 78 | 18 months | 
| Change in area of geographic atrophy by Autofluorescence | Change from baseline to Week 78 | 18 months | 
| Change in average Best Corrected Visual Acuity (BCVA) | Change from baseline to Week 78 | 18 months |