Advancing methods for evaluating therapeutic response have fostered a new era in glaucoma neuroprotection in which promising candidates are already being investigated in clinical trials and others are poised to begin phase I testing, said Jeffrey L. Goldberg, MD, PhD.
“There has been a real reticence to engage in development programs for neuroprotective interventions because of the long timeline necessary to bring a product to market,” said Dr. Goldberg, professor and chair, Byers Eye Institute, Stanford University, Palo Alto, CA.
“Many researchers . . . have identified treatments that could maintain the viability of retinal ganglion cells (RGCs) or even augment or enhance the function of residual RGCs, and the threshold has been lowered to bring these modalities into clinical testing,” he said.
Clinical trial update
Implant of the ciliary neurotrophic factor (CNTF)-secreting intravitreal device (NT-501 Encapsulated Cell Therapy, Neurotech) for glaucoma neuroprotection and vision restoration is currently being evaluated in a phase II trial. The study has a planned enrollment of 60 patients, is under way at three centers (Stanford University; Columbia University, New York; Glaucoma Associates of Texas, Dallas), and may begin recruiting patients at New York University.
A phase I study investigating the safety of the CNTF-secreting implant was already completed with favorable results and promising evidence of biological activity. The technology has been studied in other diseases, including age-related macular degeneration, retinitis pigmentosa, and ischemic optic neuropathy.
In the phase II study, patients are being randomly assigned to receive the implant or to undergo sham surgery. The planned study duration is 2 years with the primary analysis at 6 months.
Change in visual field is being analyzed as the primary outcome measure. Secondary outcome structural measures include change in RGC layer thickness, retinal nerve fiber layer thickness, and optic nerve topography.
Topical treatment with recombinant human nerve growth factor (rhNGF, Dompé Farmaceutici) is being evaluated in a phase I single center study. This trial also plans to enroll 60 patients who are being randomly assigned to use the experimental drop or vehicle placebo for 2 months, and then followed for an additional 6 months.
Safety evaluation is the primary objective of the study and biological activity using newer structure and function modalities are being measured as secondary and exploratory endpoints.
Recruitment is expected to be completed by September 2017. Small clinical series investigating the rhNGF drops as treatment for neurotrophic keratitis, ischemic optic neuropathy, and optic glioma have already been completed.
Building on laboratory research led by Andrew Huberman, PhD, associate professor of ophthalmology and neurobiology, Stanford University, a clinical trial investigating visual stimulation for neuroprotection or as a means for enhancing vision is also being initiated.
In this study, stimuli optimized from vision neurosciences will be delivered to the retina using non-invasive, virtual reality-based technology, with the hope of improving the structure and activity of dysfunctional RGCs.