This is an open-label, Phase 1 single-center study in approximately 40 subjects who have 1 eye with intermediate AMD, including a high-risk drusen without geographic atrophy (GA) subgroup and a noncentral GA subgroup. Eligible subjects will receive 40 mg of elamipretide administered as a once daily 1.0 mL subcutaneous injection for 12 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
40 mg dose of elamipretide administered once daily as a 1.0mL SC injection.
Duke University School of Medicine / Dept. of Ophthalmology (Duke Eye Center)
Durham, North Carolina, United States
Change From Baseline in Mean Standard Luminance Best-corrected Visual Acuity (BCVA)
Change from Baseline in Mean Standard Luminance Best-corrected Visual Acuity (BCVA) at 4 meters, letters from Baseline to Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 28.
Time frame: Day 0 (Baseline to Day 7, and to Weeks 4, 8, 12, 16, 20, 24, and 28.
Change From Baseline in Mean Low Luminance Best-Corrected Visual Acuity (LLBCVA)
Change from Baseline in Mean Low Luminance Best-Corrected Visual Acuity (LLBCVA) from Baseline (Day 0) to Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 28.
Time frame: Baseline to Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 28.
Change From Baseline in Mean Dark Adaptometry
Change from Baseline in Mean Dark Adaptometry from Baseline to Week 24- at 0% 25%, 50%, 75% Bleach Level. Dark adaptometry, used to evaluate night blindness by measuring the absolute thresholds of rod sensitivity, was performed within 14 days before Day 0 and at all in-person visits except for Day 7. Dark adaptation is the delayed recovery of light sensitivity in darkness following prior light exposure (photobleaching). The observed and change from baseline recovery scores (in minutes) for each bleach level (0%, 25%, 50%, and 75%) were summarized descriptively for each eye at each visit and were presented in a listing. Shorter recovery times are better than longer recovery times.
Time frame: Baseline (Day 0) and Week 24
Mean Treatment Compliance (%) of Administration of Subcutaneous Elamipretide
Mean percentage of treatment compliance of administration of subcutaneous elamipretide. The number of injections (diary) and vials used was used to compute % compliance over the duration of the subject's participation in the trial. Percentage can range from 0-100%, where 0% means the participant followed the correct dosing 0% of the time, and 100% compliance means the participant followed the correct dosing 100% of the time, with a higher % meaning a better outcome.
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Time frame: Baseline through Week 28
Mean Number of Home Health Visits to Administer Elamipretide
Mean Number of Home Health Visits Necessary for Participant or Caregiver to Learn How to Administer Elamipretide
Time frame: Baseline (Day 0) through Week 24
Change From Baseline in Mean Area of Geographic Atrophy by Fundus Autofluorescence
Change from Baseline in Mean Area of Geographic Atrophy (GA) by Fundus Autofluorescence (FAF) at Week 24. Fluorescein angiography (FA) was used to examine the circulation of the retina and choroid using fluorescein dye and a specialized camera to trace the dye. Fundus autofluorescence imaging of the retinal pigment epithelium and neurosensory retina was performed within 14 days of Day 0 and at every visit with the exception of Day 0 and Day 7. Atrophy is characterized by loss of the retinal pigment epithelium (RPE), overlying photoreceptors and underlying choriocapillaris. Greater area affected means a worse outcome than smaller area affected.
Time frame: Baseline (Day 0) to Week 24
Change From Baseline in Mean Area of Geographic Atrophy as Measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)
Change from Baseline in Mean Area of Geographic Atrophy by Sector as measured by Spectral-Domain Optical Coherence Tomography (SD-OCT) at Week 24
Time frame: Baseline to Week 24
Change From Baseline in Mean Reading Acuity Test: With Standard Luminance
Change from Baseline in Mean Reading Acuity Test: Mean Critical Print Size with Standard Luminance in Weeks 4, 8, 12, 16, 20, 24 and 28 as measured by the Logarithm of the Minimum Angle of Resolution LogMAR chart. Scores range from -0.3 to 1.0, where higher number means worse acuity/worse outcome, a lower number means better acuity/better outcome.
Time frame: Baseline and Weeks 4, 8, 12, 16 20, 24 and 28
Change From Baseline in Mean Reading Acuity Test: Low Luminance
Change from Baseline in Mean Reading Acuity Test: Mean Critical Print Size with Low Luminance in Weeks 4, 8, 12, 16, 20, 24 and 28 as measured by the Logarithm of the Minimum Angle of Resolution LogMAR chart. Scores range from -0.3 to 1.0, where higher number means worse acuity/worse outcome, a lower number means better acuity/better outcome.
Time frame: Assessed at screening, baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 28
Change From Baseline in National Eye Institute Visual Function Questionnaire-39 (VFQ-39) Score Standard Luminance
Change from baseline (Day 0) at Week 12, 24 and 28. National Eye Institute Visual Function Questionnaire-39 (VFQ-39) score measures health-related quality of life of subjects with visual impairment, in 12 domains: general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, color vision, and peripheral vision and 1 composite score. Each domain is converted to a 0 to 100 scale; the lowest and highest possible scores are set at 0 and 100 points, respectively. Higher score means higher functioning. Scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score. For the composite score, the vision-targeted sub-scale scores are averaged, excluding the general health questions. Domain scores from each cohort are averaged and the change from baseline per domain is calculated.
Time frame: Assessed at baseline (Day 0), Week 12, Week 24 and Week 28
Change From Baseline in Mean Low Luminance Questionnaire (LLQ) Score
Change from baseline (Day 0) at Week 12, Week 24, and Week 28 in LLQ score. The LLQ is a 32-item questionnaire with six subscales related to low luminance settings: driving, mobility, extreme lighting, general dim lighting, and peripheral vision. Each question is scored on a scale ranging from 0, or maximal difficulty, to 100, or no difficulty in low luminance settings. Higher scores mean better functioning. The questions are assigned to different subscales and are averaged to generate one score per subscale. After weighting each subscale for the number of questions, the weighted subscales are averaged to generate a composite LLQ score.
Time frame: Baseline (Day 0), Week 12, and Week 24 and Week 28
Change From Baseline in Mean Mesopic Light Sensitivity
Change from baseline in mean mesopic light sensitivity for Weeks, 4, 8, 12, 16, 20, and 24 as assessed by microperimetry for number of loci \<25dB and \<14dB. Mesopic microperimetry, used to measure retinal sensitivity, was performed within 14 days before Day 0 and at all in-person visits except for Day 7.
Time frame: Baseline (Day 0) and Weeks 4,8,12,16,20,and 24
Change From Baseline in Mean Retinal Pigment Epithelium - Drusen Complex (RPEDC) Thickness as Measured by SD-OCT
Change from baseline in mean retinal pigment epithelium - drusen complex (RPEDC) thickness as Measured by SD-OCT by sector at Week 24
Time frame: Baseline (Day 0) and Week 24
Change From Baseline in Mean Retinal Pigment Epithelium-Drusen Complex Volume
Change from baseline in mean Retinal Pigment Epithelium-Drusen Complex volume at Week 24 by sector
Time frame: Baseline (Day 0) to Week 24