Recombinant human nerve growth factor (rhNGF) eye drops for glaucoma: Results from a prospective double -masked randomized controlled trial

Abstract

Purpose : There are no therapies that target the retinal ganglion cells of the optic nerve for neuroprotection or neuroenhancement in glaucoma. rhNGF is a neurotrophin that has been shown to promote the survival, differentiation, and functionality of neurons. Here we evaluate the safety, tolerability, and effect on vision of high dose, 180 µg/ml, rhNGF eye drops versus placebo control in a cohort of glaucoma patients.

Methods : Methods: This study was designed as a monocentric, randomized, double-masked, vehicle controlled, parallel group study of 8 weeks dosing with a 24 week follow-up. At baseline, sixty (60) open-angle glaucoma patients were randomized (40:20 patients per arm) to receive either 180 µg/ml rhNGF or vehicle eye drops in both eyes, thrice daily. Subjects enrolled in the study had clinical evidence of progressive RGC dysfunction and degeneration and residual visual field preservation in at least one quadrant. Exclusion criteria included any other optic nerve or retinal degenerative disease causing significant vision loss, evidence of corneal opacification, and any current ocular inflammatory disease, diabetic macular edema, or history of ocular herpes zoster. Both eyes were dosed but one eye was officially selected as the study eye. The primary endpoints were safety, as assessed through adverse events (AEs), and tolerability, as assessed through a Visual Analog Scale (VAS). The secondary measures included BCDVA, HVF, ERG, and OCT from baseline to week 8, 12, and 32 visits.

Results : Of the 60 randomized subjects, there were 23 females (38%) and 37 males (62%). The average age was
66.5 years (range: 22 years to 89 years). The mean BCVDA in the study eye at baseline was 20/46, the median was
20/34, and the range was 20/12.5 to 20/163. In all 60 subjects, through week 32, there were no related serious
adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or eye pressure, and no drug-related local or systemic toxicities. The most common adverse events included transient ocular pain or tenderness, eye irritation or burning, photosensitivity, and headaches. Visual field progression by treatment arm was compared during and after treatment.

Conclusions : rhNGF is safe and tolerable at the 180 µg/ml concentration. Analysis for efficacy in longer administration trials is warranted.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.