PMID- 36246187
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221019
IS  - 2666-9145 (Electronic)
IS  - 2666-9145 (Linking)
VI  - 2
IP  - 1
DP  - 2022 Mar
TI  - Phase 1 Clinical Trial of Elamipretide in Intermediate Age-Related Macular 
      Degeneration and High-Risk Drusen: ReCLAIM High-Risk Drusen Study.
PG  - 100095
LID - 10.1016/j.xops.2021.100095 [doi]
LID - 100095
AB  - 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. DESIGN: Phase 
      1, single-center, open-label, 24-week clinical trial with preplanned HRD cohort. 
      PARTICIPANTS: Adult patients >/=55 years of age with intermediate AMD and HRD. 
      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). 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. 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. 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.
CI  - (c) 2022 Published by Elsevier Inc. on behalf of the American Academy of 
      Ophthalmology.
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 - 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 - 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 - 20211222
PL  - Netherlands
TA  - Ophthalmol Sci
JT  - Ophthalmology science
JID - 9918230896206676
PMC - PMC9560633
OTO - NOTNLM
OT  - AE, adverse event
OT  - AMD, age-related macular degeneration
OT  - BCVA, best-corrected visual acuity
OT  - DC, drusen complex
OT  - Dry age-related macular degeneration
OT  - Elamipretide
OT  - FAF, fundus autofluorescence
OT  - GA, geographic atrophy
OT  - HRD, high-risk drusen
OT  - LLQ, low-luminance questionnaire
OT  - LLRA, low-luminance binocular reading acuity
OT  - LLVA, low-luminance best-corrected visual acuity
OT  - Mitochondrial dysfunction
OT  - NCGA, noncentral, fovea-sparing geographic atrophy
OT  - NLRA, normal-luminance binocular reading acuity
OT  - Phase 1 clinical trial
OT  - RPE, retinal pigment epithelium
OT  - Retina
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- 2021/12/22
CRDT- 2022/10/17 04:27
PHST- 2021/05/20 00:00 [received]
PHST- 2021/10/29 00:00 [revised]
PHST- 2021/12/06 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- 2021/12/22 00:00 [pmc-release]
AID - S2666-9145(21)00090-7 [pii]
AID - 100095 [pii]
AID - 10.1016/j.xops.2021.100095 [doi]
PST - epublish
SO  - Ophthalmol Sci. 2021 Dec 22;2(1):100095. doi: 10.1016/j.xops.2021.100095. 
      eCollection 2022 Mar.