Human study PLS-00104

ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.

Randomized controlled trial · 176 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.

ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.primary · Ophthalmology science · 2024-10-09 · PMID 39605874 · DOI
ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GAregistry entry · NCT03891875 (COMPLETED, results posted, planned enrollment 176)

Design and participants

Design: Randomized controlled trial
Population: Patients aged 55 years or older with at least one eye with dry age-related macular degeneration and noncentral geographic atrophy.
Conditions: Age-related macular degeneration, Geographic atrophy
Setting: Multicenter phase II trial; centers not described in the record.
Planned enrollment (registry): Not reported
Enrolled: 176
Randomized: 176
Completed follow-up: Not reported
Funding: Not stated in the record.
Authors’ conflicts: The abstract states that proprietary or commercial disclosures appear in the article's footnotes. The details are not included in the record.

Intervention and comparator

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

Elamipretide (intervention) · elamipretide · Elamipretide (MTP-131, Bendavia) given daily by subcutaneous injection through the elamipretide delivery system · subcutaneous · 48 weeks of treatment followed by a 4-week follow-up period · 117 assigned
Placebo (comparator) · Subcutaneous placebo through the elamipretide delivery system · placebo · subcutaneous · 48 weeks of treatment followed by a 4-week follow-up period · 59 assigned

What the authors reported

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

Mean change from baseline in low-luminance best-corrected visual acuity (LL BCVA)

primary outcome · patient-important · Week 48 · Low-luminance best-corrected visual acuity

Elamipretide vs Placebo: narrative — Elamipretide did not meet statistical significance versus placebo for mean change in LL BCVA

Change from baseline in square-root converted geographic atrophy area

primary outcome · surrogate · Week 48 · GA area measured by OCT, square-root transformed

Elamipretide vs Placebo: narrative — Elamipretide did not meet statistical significance versus placebo for mean change in Sqrt GA area

Progression of macular percentage of total ellipsoid zone attenuation/loss

secondary outcome · surrogate · Week 48 · OCT ellipsoid zone integrity assessment (complete loss of EZ band)

Elamipretide vs Placebo: other 43, p = 0.0034 — 43% reduction in mean progression of total EZ attenuation versus placebo (nominal P)

Progression of macular percentage of partial ellipsoid zone attenuation/degradation

secondary outcome · surrogate · Week 48 · OCT EZ-retinal pigment epithelium thickness at or below 20 microns

Elamipretide vs Placebo: other 47, p = 0.004 — 47% reduction in mean progression of partial EZ attenuation versus placebo (nominal P)

Proportion of patients with a gain of 10 or more letters in LL BCVA

secondary outcome · patient-important · Week 48 · Categorical change in low-luminance best-corrected visual acuity

Elamipretide vs Placebo: proportion 14.6, p = 0.0404 — 14.6% of elamipretide patients gained 10 or more letters versus placebo (nominal P)
Placebo: proportion 2.1 — 2.1% of placebo patients gained 10 or more letters

Incidence and severity of adverse events

primary outcome · safety · Through week 48 plus 4-week follow-up · Adverse event reporting

Elamipretide: proportion 86 — Adverse events reported in 86% of elamipretide patients
Placebo: proportion 71 — Adverse events reported in 71% of placebo patients

Adverse events

Any adverse event · Elamipretide: Not reported participants
Any adverse event · Placebo: Not reported participants
Injection site reactions (pruritus, injection site pain, bruising, erythema) · Elamipretide: Not reported participants

Monitoring: The primary safety end point was the incidence and severity of adverse events over 48 weeks of treatment plus a 4-week follow-up. Monitoring procedures are not detailed in the record.

The authors concluded (paraphrased): Primary end points were not met, but elamipretide was associated with slower ellipsoid zone degradation/loss, a surrogate for photoreceptor damage. The authors consider this clinically relevant and plan to use EZ attenuation as the phase III primary end point.

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

selective reporting: Both primary end points were not met. The positive findings are secondary EZ and responder end points reported with nominal P values, without multiplicity adjustment.
inappropriate endpoint: The favourable results rest mainly on OCT ellipsoid zone measures, which are imaging surrogates rather than vision outcomes patients experience.
inadequate blinding: Injection site reactions were more frequent with elamipretide, which may have compromised masking of participants and investigators.
small or imprecise: With 2:1 allocation, only 59 patients received placebo. The 10-letter gain difference rests on small proportions with a P near 0.04.
abstract only: Only the abstract and registry fields are available. Attrition, analysis populations, and confidence intervals are not reported.
inappropriate population: The population is dry AMD with geographic atrophy, which differs from the mitochondrial disease populations in the efficacy claims.
incomplete follow up: Completion and dropout numbers are not reported in the record, so attrition cannot be judged.
funding or conflicts: Funding and disclosures are not stated in the record; the sponsor's phase III plans suggest commercial interest.

Mean change from baseline in low-luminance best-corrected visual acuity (LL BCVA): Some concerns (Cochrane RoB 2)