Human study PLS-00105

Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial.

Randomized controlled trial · 12 participants enrolled

Version 1 · published November 7, 2026 · evidence through November 7, 2026 · research snapshot 2026.1.1 · methodology ev-1 · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

Only the abstract was available. Essential methods may be missing, which limits what can be judged.

Reports of this study

Every publication, registration and abstract describing this one study. Participants are counted once.

Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial.primary · Ophthalmology · 2023-11-03 · PMID 37923251 · DOI

Design and participants

Design: Randomized controlled trial
Population: Not reported
Setting: Single-center clinical trial; 52-week double-masked treatment period followed by an open-label extension of up to 108 additional weeks.
Planned enrollment (registry): Not reported
Enrolled: 12
Randomized: 12
Completed follow-up: Not reported
Funding: PubMed lists 'Research Support, Non-U.S. Gov't'; the funder is not named in the abstract.
Authors’ conflicts: The abstract's financial disclosure states the authors have no proprietary or commercial interest in any materials discussed.

Intervention and comparator

What each group received. Related peptides, analogs and combinations are never treated as the compound itself.

Elamipretide-treated eyes (intervention) · elamipretide · Elamipretide topical ophthalmic solution. Patients were randomized to 1 of 3 groups: elamipretide in both eyes, elamipretide in the left eye only, or elamipretide in the right eye only, with vehicle in the other eye. · topical ophthalmic · 52-week double-masked treatment period · Not reported assigned
Vehicle-treated eyes (comparator) · Vehicle eye drops in the fellow eye of patients randomized to single-eye elamipretide treatment. · placebo · topical ophthalmic · 52-week double-masked treatment period · Not reported assigned
Open-label extension (both eyes elamipretide) (intervention) · elamipretide · Elamipretide topical ophthalmic solution given to both eyes during the open-label extension. · topical ophthalmic · Up to 108 additional weeks after the 52-week masked period · Not reported assigned

What the authors reported

As stated in the sources. This is the authors’ account, not Peptide Library’s assessment.

Adverse events

primary outcome · safety · Throughout the masked period and the open-label extension · Assessment of adverse events from topical elamipretide administration

Elamipretide-treated eyes: narrative — Well tolerated; most AEs mild to moderate and resolved spontaneously; no serious AEs reported

Change from baseline in best-corrected visual acuity (BCVA)

primary outcome · patient-important · All time points of the 52-week masked period · Best-corrected visual acuity change from baseline

Elamipretide-treated eyes vs Vehicle-treated eyes: narrative — BCVA change not significantly different from vehicle eyes at any time point

Clinically relevant benefit (CRB)

unclear outcome · patient-important · Not stated · Proportion of subjects meeting criteria for clinically relevant benefit (criteria not described in abstract)

Elamipretide-treated eyes: proportion — Six of 12 subjects met the criteria for clinically relevant benefit

Visual field mean deviation

secondary outcome · patient-important · Not stated · Change in visual field mean deviation

No results reported.

Central visual field mean deviation (Humphrey automated visual field central region)

post hoc outcome · patient-important · Not stated · Change from baseline in mean deviation in the central visual field

Elamipretide-treated eyes vs Vehicle-treated eyes: narrative — Post hoc: central field mean deviation change significantly greater in elamipretide-treated than vehicle eyes

Color vision (color discrimination)

secondary outcome · patient-important · Open-label extension · Change in color discrimination from baseline

Open-label extension (both eyes elamipretide): narrative — Both treatment groups showed improvement in color discrimination versus baseline in the OLE

Contrast sensitivity

unclear outcome · patient-important · Open-label extension · Change in contrast sensitivity from baseline

Open-label extension (both eyes elamipretide): narrative — Both treatment groups showed improvement in contrast sensitivity versus baseline in the OLE

Electrophysiological outcomes

secondary outcome · surrogate · Not stated · Changes in electrophysiological measures (not specified)

No results reported.

Adverse events

Adverse events (majority mild to moderate, resolving spontaneously): Not reported participants
Serious adverse events (serious): 0 participants

Monitoring: Adverse event assessment was the primary outcome measure; the abstract gives no further details of monitoring procedures.

The authors concluded (paraphrased): Topical elamipretide was generally well tolerated with no serious AEs. The trial missed its primary BCVA efficacy endpoint, but visual function improvements in the open-label extension and the post hoc central visual field findings were encouraging and warrant further study.

Peptide Library’s assessment

An automated assessment, made by AI separately from the authors’ conclusions and not reviewed by a person. How risk of bias is assessed.

Limitations

small or imprecise: Only 12 patients were enrolled, so efficacy and safety estimates are imprecise and rare adverse events could be missed.
selective reporting: The favorable central visual field result comes from a post hoc analysis, while the prespecified primary BCVA endpoint was not met.
no control group: Color discrimination and contrast sensitivity improvements were reported against baseline during the open-label extension, without a concurrent control.
inadequate blinding: The open-label extension was unmasked, so subjective visual function tests in that phase are at risk of expectation bias.
other: Fellow-eye vehicle control within the same patient cannot separate systemic or contralateral effects and gives no between-patient comparison for systemic adverse events.
abstract only: Only the abstract was available: no numeric effect estimates, AE counts, dropout data or randomization details are reported.
inappropriate population: The population is LHON patients receiving topical eye drops, unlike the Barth syndrome or mitochondrial myopathy populations in the claims.

Adverse events: Some concerns (Cochrane RoB 2)

Risk of bias in one result of a randomized trial, judged in five domains.

Domain judgments
Randomization process	Some concerns	The abstract says patients were randomized to 3 groups but gives no details on sequence generation or allocation concealment.
Deviations from intended interventions	Some concerns	The masked period was double-masked, but adherence is not described and the within-patient eye design means systemic AEs cannot be attributed to one eye.
Missing outcome data	Some concerns	Completion and dropout numbers are not reported in the abstract.
Measurement of the outcome	Some concerns	AE ascertainment methods are not described, and AEs in the open-label extension were assessed unmasked.
Selection of the reported result	Some concerns	AEs are summarized only narratively, with no counts by arm; the full report and protocol were not available.

Randomized and double-masked, but abstract-only reporting leaves concerns across all domains, especially the absence of per-arm AE data.

Version 1 · published November 7, 2026 · evidence through November 7, 2026 · research snapshot 2026.1.1 · methodology ev-1 · RoB 2 (2019-08-22) · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

Change from baseline in best-corrected visual acuity (BCVA): Some concerns (Cochrane RoB 2)

Risk of bias in one result of a randomized trial, judged in five domains.

Domain judgments
Randomization process	Some concerns	Randomization to eye-treatment groups is stated, but the method and concealment are not described in the abstract.
Deviations from intended interventions	Some concerns	Double-masked vehicle control is stated, but adherence and possible fellow-eye effects are not addressed.
Missing outcome data	Some concerns	The number of eyes or patients analyzed at each time point is not reported.
Measurement of the outcome	Some concerns	BCVA was measured during a double-masked period, but assessor masking procedures are not described.
Selection of the reported result	Some concerns	BCVA was the prespecified primary efficacy endpoint, but only a narrative non-significant result is given and no protocol was available.

Prespecified, masked comparison, but key methodological details are missing from the abstract.

Central visual field mean deviation (Humphrey automated visual field central region): High risk of bias (Cochrane RoB 2)

Risk of bias in one result of a randomized trial, judged in five domains.

Domain judgments
Randomization process	Some concerns	Sequence generation and allocation concealment are not described in the abstract.
Deviations from intended interventions	Some concerns	The masked design is stated, but adherence and contralateral-eye effects are not reported.
Missing outcome data	Some concerns	The number of eyes analyzed and any missing visual field tests are not reported.
Measurement of the outcome	Some concerns	Automated perimetry is reasonably objective, but masking during testing is not described.
Selection of the reported result	High risk of bias	The abstract states this central-region analysis was post hoc, chosen after the primary endpoint failed.

A post hoc subregion analysis carries high risk of selective reporting of the result.

Claims this study informs

Improves function in Barth syndrome: not eligible (wrong population) for “Muscle strength, exercise capacity and fatigue”
Improves exercise capacity in primary mitochondrial myopathy: not eligible (wrong population) for “Six-minute walk distance and fatigue”
Is safe for human administration: eligible for “Adverse events, including injection-site reactions, and discontinuations”, indirect evidence

Insufficient information to assess Adverse events, including injection-site reactions, and discontinuations

Where each value comes from

adverse_events: PMID 37923251, abstract (Results section, sentence 1; Conclusions section, sentence 1) · extracted by AI (automated, not verified by a person) · abstract only
arms: PMID 37923251, abstract (Methods section, sentence 1; Design section, sentence 1) · extracted by AI (automated, not verified by a person) · abstract only
author_conclusion: PMID 37923251, abstract (Conclusions section, sentences 1-2) · extracted by AI (automated, not verified by a person) · abstract only
design: PMID 37923251, abstract (Design section, sentence 1) · extracted by AI (automated, not verified by a person) · abstract only
funding: PMID 37923251, abstract (Financial disclosure section, sentence 1) · extracted by AI (automated, not verified by a person) · abstract only
limitations: PMID 37923251, abstract (Participants section, sentence 1; Results section, sentences 4-5) · extracted by AI (automated, not verified by a person) · abstract only
outcomes: PMID 37923251, abstract (Main outcome measures section, sentences 1-2) · extracted by AI (automated, not verified by a person) · abstract only
participants: PMID 37923251, abstract (Participants section, sentences 1-2) · extracted by AI (automated, not verified by a person) · abstract only
population: PMID 37923251, abstract (Participants section, sentence 2) · extracted by AI (automated, not verified by a person) · abstract only
results: PMID 37923251, abstract (Results section, sentences 2-5) · extracted by AI (automated, not verified by a person) · abstract only

Version 1 · published November 7, 2026 · evidence through November 7, 2026 · research snapshot 2026.1.1 · methodology ev-1 · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

These assessments describe published research. Records marked automated were produced by AI under the published methodology and have not been reviewed by a person; they can contain errors. None of this is medical advice, not a statement about any product’s safety for human use, and not a regulatory approval. Peptide Library’s vendor and partner relationships play no part in them (editorial independence).