Phase 1 Clinical Trial of Elamipretide in Dry Age-Related Macular Degeneration and Noncentral Geographic Atrophy: ReCLAIM NCGA Study.

Purpose: Assess the safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with dry age-related macular degeneration (AMD) and noncentral geographic atrophy (NCGA) and to perform exploratory analyses of change in visual function. Design: Phase 1, single-center, open-label, 24-week clinical trial with preplanned NCGA cohort. Participants: Adults ≥ 55 years of age with dry AMD and NCGA. Methods: Participants received subcutaneous elamipretide 40-mg daily; safety and tolerability assessed throughout. Ocular assessments included normal-luminance best-corrected visual acuity (BCVA), low-luminance BCVA (LLBCVA), normal-luminance binocular reading acuity (NLBRA), low-luminance binocular reading acuity (LLBRA), spectral-domain OCT, fundus autofluorescence (FAF), and patient self-reported function by low-luminance questionnaire (LLQ). Main Outcome Measures: Primary end point was safety and tolerability. Prespecified exploratory end-points included changes in BCVA, LLBCVA, NLBRA, LLBRA, geographic atrophy (GA) area, and LLQ. Results: Subcutaneous elamipretide was highly feasible. All participants (n = 19) experienced 1 or more nonocular adverse events (AEs), but all AEs were either mild (73.7%) or moderate (26.3%); no serious AEs were noted. Two participants exited the study because of AEs (conversion to neovascular AMD, n = 1; intolerable injection site reaction, n = 1), 1 participant discontinued because of self-perceived lack of efficacy, and 1 participant chose not to continue with study visits. Among participants completing the study (n = 15), mean ± standard deviation (SD) change in BCVA from baseline to week 24 was +4.6 (5.1) letters ( Conclusions: Elamipretide seems to be well tolerated without serious AEs in patients with dry AMD and NCGA. Exploratory analyses demonstrated possible positive effect on visual function, particularly under low luminance. A Phase 2b trial is underway to evaluate elamipretide further in dry AMD and NCGA.