Back to Search Start Over

Phase 1 Clinical Trial of Elamipretide in Intermediate Age-Related Macular Degeneration and High-Risk Drusen: ReCLAIM High-Risk Drusen Study.

Phase 1 Clinical Trial of Elamipretide in Intermediate Age-Related Macular Degeneration and High-Risk Drusen: ReCLAIM High-Risk Drusen Study.

Authors :
Allingham MJ
Mettu PS
Cousins SW
Source :
Ophthalmology science [Ophthalmol Sci] 2021 Dec 22; Vol. 2 (1), pp. 100095. Date of Electronic Publication: 2021 Dec 22 (Print Publication: 2022).
Publication Year :
2021

Abstract

Purpose: To assess safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with intermediate age-related macular degeneration (AMD) and high-risk drusen (HRD) and to perform exploratory analyses of change in visual function.<br />Design: Phase 1, single-center, open-label, 24-week clinical trial with preplanned HRD cohort.<br />Participants: Adult patients ≥55 years of age with intermediate AMD and HRD.<br />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 OCT, fundus autofluorescence (FAF), mesopic microperimetry, dark adaptation, and low-luminance questionnaire (LLQ).<br />Main Outcome Measures: The primary end point was safety and tolerability. Prespecified exploratory end points included changes from baseline in BCVA, LLVA, NLRA, LLRA, retinal pigment epithelium (RPE)-drusen complex (DC) volume by OCT, FAF, mesopic microperimetry, dark adaptation, and LLQ results.<br />Results: Subcutaneous administration of elamipretide was highly feasible. All participants with HRD (n = 21) experienced 1 or more adverse events (AEs), but all were mild (57%) or moderate (43%), with the most common events related to injection site reactions. No serious systemic AEs occurred. One participant discontinued because of injection site reaction, 1 participant withdrew because they did not wish to continue study visits, and 1 participant withdrew after experiencing transient visual impairment. Among the 18 participants who completed the study, mean change in BCVA from baseline to 24 weeks was +3.6 letters ( P = 0.014) and LLVA was +5.6 letters ( P = 0.004). Compared with baseline, mean NLRA improved by -0.11 logarithm of the minimum angle of resolution (logMAR) units ( P = 0.001), and LLRA by -0.28 logMAR units ( P < 0.0001). Significant improvements were found in 6 of 7 subscales of the LLQ ( P < 0.0015). No significant changes were observed for RPE-DC volume, FAF, mesopic microperimetry, or dark adaptation.<br />Conclusions: Elamipretide appeared to be generally safe and well tolerated in treating intermediate AMD and HRD. Exploratory analyses demonstrate a positive effect on visual function, particularly under low-luminance conditions. Further study of elamipretide for treatment of intermediate AMD with HRD is warranted.<br /> (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Details

Language :
English
ISSN :
2666-9145
Volume :
2
Issue :
1
Database :
MEDLINE
Journal :
Ophthalmology science
Publication Type :
Academic Journal
Accession number :
36246187
Full Text :
https://doi.org/10.1016/j.xops.2021.100095