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Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy

Rath, Eitan Z. MD; Hazan, Zadik MD; Adamsky, Konstantin PhD; Solomon, Arieh MD, PhD; Segal, Zvi I. MD, MBA; Levin, Leonard A. MD, PhD

Section Editor(s): E. Moss, Heather MD, PhD; L. Pineles, Stacy MD

doi: 10.1097/WNO.0000000000000786
Clinical Research: Epidemiology Meets Neuro-Ophthalmology

Background: No proven treatment exists for nonarteritic anterior ischemic optic neuropathy (NAION), either in the acute or late phase.

Objective: To assess safety and changes in visual function and structure after RPh201/placebo treatment in participants with previous NAION.

Design and Setting: Phase 2a, single-site, prospective, randomized, placebo-controlled, double-masked trial (registration NCT02045212).

Main Outcomes Measures: Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), visual fields, retinal nerve fiber layer, and visual evoked potential at weeks 13, 26, and after a 13-week wash-out (“off-drug”) period; and safety.

Study Population: Twenty-two participants aged 18 years or older with previous NAION.

Intervention(s): RPh201 (20 mg) or placebo (cottonseed oil vehicle) administered subcutaneously twice weekly at the study site.

Results: Thirteen men and 9 women were randomized, of which 20 completed all visits. The mean (±SD) age was 61.0 ± 7.6 years. In a post hoc analysis, after 26 weeks of treatment, BCVA improved by ≥15 letters in 4/11 (36.4%) eyes with RPh201, compared to 1/8 (12.5%) eyes with placebo (P = 0.24). Overall, 7/11 (63.6%) of participants on RPh201 showed some improvement in BCVA, compared with 3/8 (37.5%) on placebo (P = 0.26). Improvement in BCVA from a calculated baseline was 14.8 ± 15.8 letters for RPh201 and 6.6 ± 15.3 for placebo (P = 0.27). Of the 154 adverse effects (AEs), 52 were considered related to the study procedures/treatment. Across the study and 1,017 injections, the most frequently reported AE was injection site pain (23 events in 5 participants). There were no clinically significant changes in vital signs or laboratory values.

Conclusions: This Phase 2a was designed to assess safety, feasibility, and explore potential efficacy signals in treating previous NAION with RPh201. No safety concerns were raised. The results support a larger trial in patients with previous NAION.

Ophthalmology Department (EZR, ZIS), Galilee Medical Center, Nahariya; and Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; Regenera Pharma Ltd (ZH, KA), Israel; Goldschleger Eye Research Institute (AS), Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel; and Departments of Ophthalmology and Visual Sciences, Neurology and Neurosurgery (LAL), McGill University, Montreal, Canada.

Address correspondence to Leonard A. Levin, MD, PhD, Department of Ophthalmology and Visual Sciences, McGill University, 5252 Boul de Maisonneuve West, Montreal, QC H4A 3S5, Canada; E-mail:

The study was funded by Regenera Pharma Limited. L. A. Levin received funding from the Canadian Foundation for Innovation, Canadian Research Chairs program, and National Institutes of Health (R21 EY025074 and P30 EY016665), and is the Canada Research Chair in Translational Visual Science.

Z. I. Segal and E. Z. Rath were PIs of the study. Z. Hazan and K. Adamsky are employees of Regenera Pharma Limited, which funded the study. L. A. Levin is a consultant to Regenera, as well as to Aerie, Eyevensys, Galimedix, and Quark.

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© 2019 by North American Neuro-Ophthalmology Society