Study of Human Central Nervous System Stem Cells (HuCNS-SC) in Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The purpose of this Phase I/II study is to investigate the safety and preliminary efficacy of unilateral subretinal transplantation of HuCNS-SC cells in subjects with geographic atrophy secondary to age-related macular degeneration.

Detailed Description
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This study is an open-label dose-escalation investigation of the safety and preliminary efficacy of unilateral subretinal transplantation of HuCNS-SC cells in subjects with Geographic Atrophy secondary to Age-Related Macular Degeneration (AMD). Subjects will be enrolled based on specific inclusion/exclusion criteria and evaluated at regular post transplant intervals. The investigation will be divided into two sequential cohorts. Subjects will be enrolled into each cohort based on best-corrected visual acuity (BCVA) visual acuity as determined by the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) acuity test. BCVA of less than or equal to 20/400 in the Study Eye will be enrolled in Cohort I. Subjects with BCVA of 20/320 to 20/100 in the Study Eye will be enrolled in Cohort II. Cohort I will consist of four subjects who will undergo transplant with 200,000 cells followed by four subjects who will undergo transplant with 1 million cells. Cohort II will consist of 7 subjects who will undergo transplant with 1 million cells. An independent Data Monitoring Committee (DMC) will review accruing safety data for all subjects. HuCNS-SC cells will be transplanted by a board-certified vitreoretinal surgeon. The transplantation will be conducted in the eye with the inferior best-corrected visual acuity (BCVA) (i.e., the Study Eye). Only the Study Eye will undergo transplantation. The HuCNS-SC cells will be administered into the subretinal space through a standard surgical approach. Immunosuppressive agents will be administered orally to all subjects for a period of three months after surgery. Subjects will be monitored frequently for a total of one year after HuCNS-SC cell transplantation. An additional four years of monitoring will be conducted in a separate follow-up study that will commence with the termination visit of the Phase I/II investigation. The follow-up study will be conducted as a separate investigation.

Official Title
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Phase I/II Study of the Safety and Preliminary Efficacy of Human Central Nervous System Stem Cells (HuCNS-SC) Subretinal Transplantation in Subjects With Geographic Atrophy of Age-Related Macular Degeneration

Conditions
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Age Related Macular Degeneration, Macular Degeneration, AMD

Intervention / Treatment
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* Drug: HuCNS-SC cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of age-related macular degeneration with geographic atrophy (GA) Only patients with a specific degree and extent of GA will be eligible Subjects with best-corrected visual acuity (BCVA) of less than or equal to 20/400 in the Study Eye will be enrolled in Cohort I. Subjects with BCVA of 20/320 to 20/100 in the Study Eye will be enrolled in Cohort II No prior or current choroidal neovascularization in either eye Must have adequate care-giver support and access to medical care in the local community Able to provide written informed consent prior to any study related procedures Agree to comply in good faith with all conditions of the study and to attend all required study visits Exclusion Criteria: Prior vitreal or retinal surgery Glaucoma Atrophic macular disease of any other cause Diabetic retinopathy or diabetic macular edema in either eye Previous organ, tissue or bone marrow transplantation Previous participation in a gene transfer or a cell transplant trial Autoimmune disease Allergy to tacrolimus, mycophenolate mofetil (MMF), scopolamine, Cyclogyl, Moxifloxacin, or Gatifloxacin Current or prior malignancy (or is on chemotherapy)

Ages Eligible for Study
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Minimum Age: 50 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: HuCNS-SC<br>HuCNS-SC cells | Drug: HuCNS-SC cells<br>* HuCNS-SC cells transplantation directly into the subretinal space of one eye (Study eye) in a single transplant procedure.<br>* Other names: Human Central Nervous System Stem Cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events | Descriptive analysis of frequency and types of adverse events experienced by each subject during the study period. | One year following transplant surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of visual function changes from baseline | Assessments will include BCVA by the E-ETDRS acuity test, fluorescein angiography and fundus photography, spectral domain ocular coherence tomography (OCT), microperimetry, multifocal electroretinography, contrast sensitivity, and a standardized questionnaire of visual function. | At frequent intervals for one year following transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-Related Macular Degeneration, Dry AMD with GA, Geographic Atrophy of Age-Related Macular Degeneration, Stem Cell Transplantation, Stem Cell transplant, Stem cells for AMD, Human neural stem cells, multipotent stem cells, Macular Degeneration, Dry AMD, Human central nervous system stemcells, dry age-related macular degeneration