ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA

Study Overview
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Brief Summary
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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.

Detailed Description
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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 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.

Official Title
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A Phase 2 Randomized, Double-Masked, Placebo-Controlled Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Elamipretide in Subjects With Age-Related Macular Degeneration With Non-central Geographic Atrophy

Conditions
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Age-related Macular Degeneration

Intervention / Treatment
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* Combination Product: Subcutaneous elamipretide through the elamipretide delivery system
* Combination Product: Subcutaneos placebo through the elamipretide delivery system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 55 years of age with at least 1 eye with AMD with non-central GA as determined by FAF. Ocular conditions-study eye GA in the study eye at the Screening Visit may be multi-focal, but the cumulative GA lesion and size must: be ≥ 0.05 mm2 and ≤ 10.16 mm2 and reside completely within the FAF 30 or 35 degree image. must be at least 150 μm from foveal center with preserved outer retinal structural details No evidence of CNV by history, OCT or FA in the study eye. BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) score of ≥ 55 letters (Snellen equivalent ≥ 20/70) in the study eye at the Screening Visit and Baseline Visit. LL BCVA by ETDRS score of ≥ 10 letters in the study eye at the Screening Visit and Baseline Visit. LL VA deficit (defined as difference the between BCVA and LL BCVA) of > 5 letters in the study eye at Screening and Baseline Visits. The fellow eye may have any of the following: no AMD, AMD without GA, AMD with GA, CNV AMD, or central GA. Ongoing treatment with anti-angiogenic therapies in the fellow eye is allowable. Sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and ability to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment in the study eye. Systemic and general criteria Exclusion Criteria: Ocular conditions-study eye The absence of observable hyper-FAF at the margins of the GA in the study eye(only for lesions ≥ 0.25mm2) Atrophic retinal disease of causality other than AMD including myopia-related maculopathy and monogenetic macular dystrophies including pattern dystrophy and adult-onset Stargardt disease in the study eye. Presence or diagnosis of exudative AMD or CNV in the study eye. Presence of retinal vein occlusion in the study eye. Presence of diabetic retinopathy (a history of diabetes mellitus without retinopathy is not a criterion for exclusion) in either eye. Presence of vitreous hemorrhage in the study eye. History of retinal detachment in the study eye. History of macular hole (stages 2 to 4) in the study eye. Presence of an epiretinal membrane that causes distortion of the retinal contour in the study eye. Presence of vitreomacular traction in the study eye. At the Screening Visit, advanced glaucoma resulting in a cup to disc ratio of > 0.8 in the study eye. History of glaucoma filtration surgery or uncontrolled glaucoma defined as IOP > 22 mmHg at baseline despite anti-glaucoma treatment with or without topical anti-hypertensive eye drops in the study eye OR currently using > 2 medications (note: combination medications count as 2 medications). Presence of visually significant cataract OR presence of significant posterior capsular opacity in the setting of pseudophakia. Significant cataract is defined as > +2 nuclear sclerosis based upon the scale below or any Posterior Subcapsular Cataract in the study eye. The Sponsor, or its designee, will supply the trial sites with a copy of the standard photographs. Presence of significant keratopathy or any other media or corneal opacity that would cause scattering of light or alter visual function, especially in LL conditions in the study eye. Ocular incisional or laser surgery (including cataract surgery) in the study eye within 90 days before Day 1. Yag laser capsulotomy in the study eye within 30 days before Day 1. Aphakia in the study eye. History of vitrectomy surgery, submacular surgery, or any vitreoretinal surgery in the study eye. Prior treatment with Visudyne® (verteporfin) ocular photodynamic therapy, external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy in the study eye. History of subthreshold laser treatment or other forms of photobiomodulation for AMD in the study eye. Intravitreal drug delivery in the past 60 days or 5-half-lives of the injected drug whichever is longer (e.g., intravitreal corticosteroid injection, anti angiogenic drugs, or device implantation) in the study eye. Current use of medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine [Plaquenil®], tamoxifen, phenothiazines, ethambutol, digoxin, and aminoglycosides) from the Screening Visit through the completion of the trial. Ocular conditions--either eye History of herpetic infection in either eye. Concurrent disease in either the study eye or fellow control eye that could require medical or surgical intervention during the study period. Active uveitis and/or vitritis (grade trace or above) in either eye. History of idiopathic or autoimmune-associated uveitis in either eye. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. Systemic conditions. Known to be immunocompromised or receiving systemic immunosuppression for ≥ 4 consecutive weeks prior to screening. Any disease or medical condition that in the opinion of the Investigator would prevent the subject from successfully participating in the study or might confound study results. General Participation in other investigational drug or device clinical studies within 30 days of enrollment and/or planning to participate in any other investigational drug or device clinical studies within 30 days of study completion. History of allergy to fluorescein that is not amenable to treatment. Creatinine clearance of ≤ 30 mL/min at the Screening Visit (using Modification of Diet in Renal Disease Study formula). Inability to comply with study or follow-up procedures. Inability to obtain color fundus photograph, FAF, and FA of sufficient quality to be analyzed and interpreted. Active malignancy or any other cancer from which the subject has been cancer-free for < 2 years. History of allergic reaction to the investigational drug or any of its components. Prior treatment with Elamipretide.

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elamipretide<br>40 mg subcutaneous injection of elamipretide using the elamipretide delivery system for 48 weeks followed by a 4 week follow-up period. | Combination Product: Subcutaneous elamipretide through the elamipretide delivery system<br>* 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.<br>* Other names: Bendavia;|
| Placebo Comparator: Placebo<br>subcutaneous injection of placebo using the elamipretide delivery system for 48 weeks followed by a 4 week follow-up period. | Combination Product: Subcutaneos placebo through the elamipretide delivery system<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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) | Baseline and Weeks 12, 24, 36, 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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). | 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. | Baseline and Weeks 12, 24, 36, 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Macular degeneration, non-central geographic atrophy, MTP-131, elamipretide