PMID- 36246181
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230918
IS  - 2666-9145 (Electronic)
IS  - 2666-9145 (Linking)
VI  - 2
IP  - 1
DP  - 2022 Mar
TI  - Phase 1 Clinical Trial of Elamipretide in Dry Age-Related Macular Degeneration 
      and Noncentral Geographic Atrophy: ReCLAIM NCGA Study.
PG  - 100086
LID - 10.1016/j.xops.2021.100086 [doi]
LID - 100086
AB  - 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 (P = 0.0032), while mean change (SD) in LLBCVA was +5.4 +/- 7.9 
      letters (P = 0.0245). Although minimal change in NLBRA occurred, mean +/- SD change 
      in LLBCVA was -0.52 +/- 0.75 logarithm of the minimum angle of resolution units (P 
      = 0.005). Mean +/- SD change in GA area (square root transformation) 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 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.
CI  - (c) 2022 Published by Elsevier Inc. on behalf of the American Academy of 
      Ophthalmology.
FAU - Mettu, Priyatham S
AU  - Mettu PS
AD  - Duke Center for Macular Diseases, Department of Ophthalmology, Duke Eye Center, 
      Duke University School of Medicine, Durham, North Carolina.
FAU - Allingham, Michael J
AU  - Allingham MJ
AD  - Duke Center for Macular Diseases, Department of Ophthalmology, Duke Eye Center, 
      Duke University School of Medicine, Durham, North Carolina.
FAU - Cousins, Scott W
AU  - Cousins SW
AD  - Duke Center for Macular Diseases, Department of Ophthalmology, Duke Eye Center, 
      Duke University School of Medicine, Durham, North Carolina.
LA  - eng
PT  - Journal Article
DEP - 20211127
PL  - Netherlands
TA  - Ophthalmol Sci
JT  - Ophthalmology science
JID - 9918230896206676
PMC - PMC9560640
OTO - NOTNLM
OT  - AE, adverse event
OT  - AMD, age-related macular degeneration
OT  - BCVA, best-corrected visual acuity
OT  - Dry age-related macular degeneration
OT  - ETDRS, Early Treatment Diabetic Retinopathy Study
OT  - Elamipretide
OT  - FAF, fundus autofluorescence
OT  - GA, geographic atrophy
OT  - Geographic atrophy
OT  - LLBCVA, low-luminance best-corrected visual acuity
OT  - LLBRA, low-luminance binocular reading acuity
OT  - LLQ, low-luminance questionnaire
OT  - Mitochondrial dysfunction
OT  - NCGA, noncentral geographic atrophy
OT  - NLBRA, normal-luminance binocular reading acuity
OT  - Phase 1 clinical trial
OT  - RPE, retinal pigment epithelium
OT  - SD, standard deviation
OT  - logMAR, logarithm of the minimum angle of resolution
EDAT- 2022/10/18 06:00
MHDA- 2022/10/18 06:01
PMCR- 2021/11/27
CRDT- 2022/10/17 04:27
PHST- 2021/04/08 00:00 [received]
PHST- 2021/11/01 00:00 [revised]
PHST- 2021/11/23 00:00 [accepted]
PHST- 2022/10/17 04:27 [entrez]
PHST- 2022/10/18 06:00 [pubmed]
PHST- 2022/10/18 06:01 [medline]
PHST- 2021/11/27 00:00 [pmc-release]
AID - S2666-9145(21)00088-9 [pii]
AID - 100086 [pii]
AID - 10.1016/j.xops.2021.100086 [doi]
PST - epublish
SO  - Ophthalmol Sci. 2021 Nov 27;2(1):100086. doi: 10.1016/j.xops.2021.100086. 
      eCollection 2022 Mar.