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

Abstract Purpose To assess safety, tolerability, and feasibility of subcutaneous administration of 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 Adult patients, age ≥ 55 years, with dry AMD and NCGA. Methods Participants received subcutaneous elamipretide 40 mg daily, with safety and tolerability assessed throughout the study. Ocular assessments included normal luminance best-corrected visual acuity (BCVA), low-luminance best-corrected visual acuity (LLVA), normal luminance binocular reading acuity (NLRA), low luminance binocular reading acuity (LLRA), spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF), and patient self-reported function by low luminance questionnaire (LLQ). Main Outcome Measures The primary endpoint was safety and tolerability. Prespecified exploratory endpoints included changes in BCVA, LLVA, NLRA, LLRA, GA area, and LLQ. Results Subcutaneous administration of elamipretide was highly feasible. All participants (n=19) experienced ≥ 1 non-ocular 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 due to AEs (conversion to neovascular AMD (n=1); intolerable injection site reaction (n=1)), one participant discontinued due to self-perceived lack of efficacy, and one participant chose not to continue with study visits. Among participants completing the study (n=15), mean change (standard deviation (SD)) in BCVA from baseline to week 24 was +4.6 (5.1) letters (P=0.0032), while mean change (SD) in LLVA was +5.4 (7.9) letters (P=0.0245). While there was minimal change in NLRA, mean change (SD) in LLVA was -0.52 (0.75) logMAR units (P=0.005). Mean change (SD) in GA area (SQRT) from baseline to week 24 was 0.14 (0.08) mm by FAF and 0.13 (0.14) mm by OCT. Improvement was observed in LLQ for dim light reading and general dim light vision. Conclusions Elamipretide appears to be well tolerated without serious AEs in patients with dry AMD and NCGA. Exploratory analyses demonstrate possible positive effect on visual function, particularly under low luminance. A Phase 2b trial is underway to further evaluate elamipretide in dry AMD and NCGA.