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

J Neuroophthalmol. 2019 Sep;39(3):291-298. doi: 10.1097/WNO.0000000000000786.


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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Evoked Potentials, Visual / drug effects*
  • Evoked Potentials, Visual / physiology
  • Female
  • Humans
  • Male
  • Mastic Resin / adverse effects
  • Mastic Resin / pharmacology
  • Mastic Resin / therapeutic use*
  • Middle Aged
  • Optic Neuropathy, Ischemic / drug therapy*
  • Optic Neuropathy, Ischemic / physiopathology
  • Plant Extracts / adverse effects
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Retina / drug effects
  • Retina / physiopathology
  • Treatment Outcome
  • Visual Acuity / drug effects*
  • Visual Acuity / physiology


  • Mastic Resin
  • Plant Extracts

Associated data

  • ClinicalTrials.gov/NCT02045212