Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial.
Level 2 - randomized trial
Phase II randomized, vehicle-controlled clinical trial
PubMed 37923251 · doi:10.1016/j.ophtha.2023.10.033
What was done
Twelve patients aged 18 to 50 years with genetically confirmed m.11778G>A Leber hereditary optic neuropathy (LHON) and vision loss for 1 to 10 years were enrolled in a single-center phase II trial. For the first 52 weeks, patients were randomized to receive 1% topical elamipretide ophthalmic solution in both eyes or elamipretide in one eye and vehicle in the other eye. This double-masked phase was followed by an open-label extension of up to 108 additional weeks in which all eyes received elamipretide. The primary outcomes were adverse events and change from baseline in best-corrected visual acuity (BCVA). Secondary measures included color vision, visual field mean deviation, and electrophysiological outcomes.
What was found
Elamipretide was well tolerated with no serious adverse events reported, and the majority of adverse events were mild to moderate and resolved spontaneously. Change from baseline in BCVA was not significantly different between elamipretide-treated and vehicle-treated eyes at any time point. Six of 12 subjects met criteria for clinically relevant benefit. In post hoc analysis, change from baseline in central visual field mean deviation was significantly greater in elamipretide-treated eyes versus vehicle eyes. Both treatment groups showed improvement from baseline in color discrimination and contrast sensitivity during the open-label extension.
Why it matters
This study provides initial safety and exploratory functional data for topical elamipretide in mitochondrial optic neuropathy. Although the primary visual acuity endpoint was missed, exploratory visual field and color discrimination signals may inform future trial designs.
Limits
The sample size was very small (12 patients at a single center), severely limiting statistical power. The primary efficacy endpoint was not met, and positive visual field findings derived from post hoc analyses. Data from the open-label extension lacked a concurrent control group.
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