Neuroprotection clinical trials

Novel study designs shorten study times, moving therapies closer to reality

Howard Larkin

Posted: Sunday, March 1, 2020

Jeffrey L Goldberg MD, PhD

Innovative study designs and integrating therapeutic testing with biomarkers have advanced several neuroprotective and neuroenhancement compounds to clinical trials, which could advance glaucoma therapy beyond prevention through IOP control, Jeffrey L Goldberg MD, PhD, told the AAO 2019 Glaucoma Subspecialty Day in San Francisco, USA.

Preliminary analysis of a phase II randomised controlled trial of a Ciliary Neurotrophic Factor implant shows a statistically significant increase in nerve fibre layer (RNFL) thickness with no serious or treatment-limiting adverse effects after one year, said Dr Goldberg, who is professor and chair of ophthalmology at Stanford University, Palo Alto, California, USA. The trial involves 54 patients in three sites randomised 1:1 to sham surgery with no implant, with opportunity for the control group to cross over to treatment in an open-label extension.

Dr Goldberg presented a case from the study in which a female patient in the treatment group experienced significant thickening of the RNFL, which is typical of both the current treatment group as well as in 11 patients treated in an earlier phase I study. This patient also showed improvement in Humphrey visual field tests more than the treatment group as a whole. The sham design of the current trial will help filter out variability and any learning effects influencing these results, he noted.

A further trial extension is planned to add an arm with two implants in treated eyes, Dr Goldberg said.

“We are asking the question: would two implants, or double the dose, have a more detectable effect?”

A parallel phase II trial of the same implant was positive for photoreceptor neuroprotection for patients with macular telangiectasia type II at two and three years, and is in phase III development under the FDA, he added.

An eight-week phase I/II randomised clinical trial of nerve growth factor eye drops for glaucoma using a stronger formulation of Oxervate (Dompe), which is approved for neurotrophic keratitis, has also been conducted. An anti-C1q intravitreal injection for glaucoma has completed a phase Ib randomised study, removing the inflammatory factor that is strongly associated with glaucoma and other neurodegenerative diseases, Dr Goldberg noted. A phase Ib randomised study of virtual reality visual stimulation approach using VR goggles to stimulate RGC cells or balancing inter-eye competition is also in the works.

These studies can produce results in a shorter time than previous neuroprotection studies by focusing on rapidly progressing patients and clustering visual field tests to hedge against variability in 12- to 18-month tests, and by studying sick, but not dead, RGCs in shorter neuroenhancement studies, Dr Goldberg said. Both types incorporate new exploratory biomarkers to cross validate results.

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