Study of human central nervous system stem cells in age-related macular degeneration

Institution: Retina Foundation of the Southwest, Dallas

Author/principal investigator: David G. Birch, PhD

Abstract/statement of the trial’s goals

The purpose of this phase 1/2 study is to investigate the safety and preliminary efficacy of unilateral subretinal transplantation of human central nervous system stem cells (HuCNS-SC) in subjects with geographic atrophy secondary to age-related macular degeneration.

ClinicalTrials.gov identifier: NCT01632527

Study population: 16

Inclusion criteria

Diagnosis of AMD with geographic atrophy
Only patients with a specific degree and extent of geographic atrophy will be eligible
No prior or current choroidal neovascularization in either eye
Must have adequate caregiver support and access to medical care in the local community
Able to provide written informed consent before 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 cell transplant trial
Autoimmune disease
Allergy to tacrolimus, monomethyl fumarate, scopolamine, moxifloxacin or gatifloxacin
Current or prior malignancy, or on chemotherapy

Enrollment status: Currently recruiting participants

A note from the institution regarding the value of this trial

This study is an open-label dose-escalation investigation of the safety and preliminary efficacy of unilateral subretinal transplantation of HuCNS-SC in subjects with geographic atrophy secondary to 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 as determined by the electronic Early Treatment Diabetic Retinopathy Study acuity test. Subjects with BCVA of 20/400 or less will be enrolled in cohort 1. Subjects with BCVA of 20/200 to 20/100 will be enrolled in cohort 2. Cohort 1 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 2 will consist of eight subjects who will undergo transplant with 1 million cells. An independent data monitoring committee will review accruing safety data for all subjects.

The cells have been shown effective in preserving photoreceptors in an animal model of retinal degeneration, the Royal College of Surgeons (RCS) rat. As in AMD, photoreceptor loss in the RCS rat is thought to be secondary to retinal pigment epithelium damage. HuCNS-SC transplanted to the subretinal space are thought to provide a neuroprotective effect that preserves photoreceptor survival.

The cells are transplanted by Rand Spencer, MD, a board-certified vitreoretinal surgeon. The transplantation is conducted in the eye with the worse BCVA. Only one eye will undergo transplantation. The 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 3 months after surgery.

Subjects will be monitored frequently for a total of 1 year after transplantation. An additional 4 years of monitoring will be conducted in a separate follow-up study that will commence with the termination visit of the phase 1/2 investigation. The follow-up study will be conducted as a separate investigation.