A randomized, double-masked, placebo-controlled study to evaluate the safety, efficacy and pharmacokinetics of elamipretide in subjects with Age-Related Macular Degeneration with non-central Geographic Atrophy.
This was a randomized, double-masked, placebo controlled study using three periods to evaluate the safety, efficacy and pharmacokinetics of elamipretide in subjects with Age-Related Macular Degeneration with non-central Geographic Atrophy. The total duration of subject participation was up to 54 weeks, including a Screening Period (≤2 weeks), Treatment Period (48 weeks), and Follow-up (4 weeks). 176 eligible subjects were randomized in a 2:1 ratio (elamipretide:placebo) to receive 40 mg elamipretide or placebo. The study drug (i.e., elamipretide or placebo) was administered once daily via SC injection using the elamipretide delivery system during the 48 week Treatment Period. After completion of the 48-week Treatment Period subjects continued to be monitored for safety during the 4-week Follow-up Period and an end of study (EOS) Follow-up Visit was conducted at Week 52.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
176
Subjects will be randomized in a 2:1 ratio to receive either elamipretide or placebo through the elamipretide delivery system. Subjects will dose daily for up to 48 weeks.
Subjects will be randomized in a 2:1 ratio to receive either elamipretide or placebo through the elamipretide delivery system. Subjects will dose daily for up to 48 weeks.
LL BCVA Score Change From Baseline
Change in low luminance best corrected visual acuity (LL BCVA) score from Baseline to the end of treatment (EOT; Week 48) assessment measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. ETDRS charts present a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows; there is a total of 14 lines (70 letters), with letter size increasing further geometrically and equivalently in every line by a factor of 1.2589 (or 0.1 log unit), moving up the chart. Minimum score of zero, maximum score of 100. Change from baseline: a more negative score is worse outcome, a more positive score is better outcome. A lower score means less letters were read correctly (worse outcome) and a higher score means more letters were read correctly (better outcome).
Time frame: Baseline and Weeks 4, 8, 12, 24, 36, 48
GA Area Change From Baseline by OCT
Geographic atrophy (GA) area: change from baseline as measured by optical coherence tomography (OCT) from Baseline to the end of treatment (EOT; Week 48)
Time frame: Baseline and Weeks 12, 24, 36, 48
LL RA Change From Baseline
Low-luminance ready acuity (LL RA) score change from baseline to the EOT (Week 48). Mean Critical Print Size with Low Luminance in Weeks 4, 12, 36, 48 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 4,12, 36, 48
BCVA Change From Baseline
Best-corrected visual acuity (BCVA) change from Baseline Change in best corrected visual acuity (BCVA) score from Baseline to the end of treatment (EOT; Week 48) assessment measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. ETDRS charts present a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows; there is a total of 14 lines (70 letters), with letter size increasing further geometrically and equivalently in every line by a factor of 1.2589 (or 0.1 log unit), moving up the chart. Minimum score of zero, maximum score of 100. Change from baseline: a more negative score is worse outcome, a more positive score is better outcome. A lower score means less letters were read correctly (worse outcome) and a higher score means more letters were read correctly (better outcome).
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Time frame: Baseline and Weeks 4, 8, 12, 24, 36, 48
GA Area as Measured by Fundus Autofluorescence (FAF) Change From Baseline
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 and Weeks 12, 24, 36, 48