PMID- 37923251
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240325
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Linking)
VI  - 131
IP  - 4
DP  - 2024 Apr
TI  - Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber 
      Hereditary Optic Neuropathy: A Randomized Trial.
PG  - 422-433
LID - S0161-6420(23)00802-3 [pii]
LID - 10.1016/j.ophtha.2023.10.033 [doi]
AB  - PURPOSE: This study aimed to assess the safety, tolerability, and potential 
      efficacy of topical elamipretide in patients affected with Leber hereditary optic 
      neuropathy (LHON). DESIGN: This phase II, prospective, randomized, 
      vehicle-controlled, single-center clinical trial involved administration of 
      elamipretide 1% topical ophthalmic solution to patients with LHON over a 52-week 
      double-masked treatment period, followed by an open-label extension (OLE) for up 
      to 108 additional weeks of treatment. PARTICIPANTS: Twelve patients with LHON 
      were included in this study. Patients aged 18 to 50 years with decreased vision 
      for at least >/= 1 year and </= 10 years, and a genetically confirmed diagnosis of 
      m.11778G>A LHON were eligible for this trial. METHODS: For the first 52 weeks of 
      the study, patients were randomized to 1 of 3 groups: elamipretide in both eyes 
      or elamipretide in 1 eye (left eye and right eye were considered separate groups) 
      and vehicle in the other eye, followed by an OLE in which both eyes were treated 
      with elamipretide. MAIN OUTCOME MEASURES: The primary outcome measure was 
      assessment of adverse events (AEs) from the administration of topical 
      elamipretide, and the primary efficacy end point was change in best-corrected 
      visual acuity (BCVA). Secondary outcome measures included changes in color 
      vision, visual field mean deviation, and electrophysiological outcomes. RESULTS: 
      Elamipretide was well tolerated with the majority of AEs being mild to moderate 
      and resolving spontaneously. The change from baseline in BCVA in 
      elamipretide-treated eyes was not significantly different from the vehicle eyes 
      at any time point. Six of 12 subjects met the criteria for clinically relevant 
      benefit (CRB). In the post hoc analysis, change from baseline in mean deviation 
      in the central visual field was significantly greater in elamipretide-treated 
      eyes versus the vehicle eyes. Compared with baseline, both treatment groups 
      showed improvement in color discrimination and contrast sensitivity in the OLE. 
      CONCLUSIONS: Elamipretide treatment was generally well tolerated, with no serious 
      AEs reported. Although this study did not meet its primary BCVA efficacy end 
      point, improvements across assessments on visual function during the OLE and the 
      post hoc findings of the Humphrey automated visual field central region were 
      encouraging and require further exploration. FINANCIAL DISCLOSURE(S): The 
      author(s) have no proprietary or commercial interest in any materials discussed 
      in this article.
CI  - Copyright (c) 2023 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Karanjia, Rustum
AU  - Karanjia R
AD  - Doheny Eye Centers UCLA, Department of Ophthalmology, David Geffen School of 
      Medicine at UCLA, Los Angeles, California; Doheny Eye Institute, Los Angeles, 
      California; Department of Ophthalmology, Universtiy of Ottawa, Ottawa, Canada; 
      Ottawa Eye Institute, The Otawa Hospital, Ottawa, Canada. Electronic address: 
      Rkaranjia@toh.ca.
FAU - Sadun, Alfredo A
AU  - Sadun AA
AD  - Doheny Eye Centers UCLA, Department of Ophthalmology, David Geffen School of 
      Medicine at UCLA, Los Angeles, California; Doheny Eye Institute, Los Angeles, 
      California.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20231103
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
RN  - 0 (arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Oligopeptides)
SB  - IM
MH  - Humans
MH  - *Optic Atrophy, Hereditary, Leber/diagnosis
MH  - Prospective Studies
MH  - Ophthalmic Solutions/therapeutic use
MH  - Visual Acuity
MH  - *Oligopeptides
OTO - NOTNLM
OT  - Elamipretide
OT  - LHON
OT  - Optic neuropathy
OT  - Visual acuity
EDAT- 2023/11/06 03:54
MHDA- 2024/03/25 06:42
CRDT- 2023/11/03 20:20
PHST- 2023/08/03 00:00 [received]
PHST- 2023/10/03 00:00 [revised]
PHST- 2023/10/17 00:00 [accepted]
PHST- 2024/03/25 06:42 [medline]
PHST- 2023/11/06 03:54 [pubmed]
PHST- 2023/11/03 20:20 [entrez]
AID - S0161-6420(23)00802-3 [pii]
AID - 10.1016/j.ophtha.2023.10.033 [doi]
PST - ppublish
SO  - Ophthalmology. 2024 Apr;131(4):422-433. doi: 10.1016/j.ophtha.2023.10.033. Epub 
      2023 Nov 3.