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

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

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.

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.

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)