Phase 3 Study of ALK-001 in Geographic Atrophy

Study Overview
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Brief Summary
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This is a double-masked, multicenter, randomized, placebo-controlled clinical trial, evaluating the efficacy and safety of ALK-001 in participants with Geographic Atrophy (GA) secondary to age-related macular degeneration (AMD). Up to 200 participants will receive ALK-001 while up to 100 participants will receive a placebo.

Detailed Description
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There is no treatment available for Geographic Atrophy secondary to AMD. AMD is characterized by an age-related degeneration of the retina. The root cause for this degeneration or why some people develop AMD while others do not, is unknown. Over 20 years ago, it was hypothesized that the dimerization of vitamin A may be a significant contributor to the etiology of AMD. The eye indeed uses vitamin A as a cofactor to sense light, and a striking chemical signature of the aging and degenerating retina is the accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and the underlying Bruch's membrane. In rodent models, high levels of vitamin A dimers correlate with poor retinal health, and a variety of mechanisms have been proposed by which vitamin A dimers may induce retinal toxicity. It has been argued that these mechanisms participate in the development and progression of AMD. ALK-001, the study drug, is a modified form of vitamin A. When taken once a day as a capsule, it replaces natural vitamin A in the body with one that forms vitamin A dimers more slowly. This study will measure the extent to which treatment with ALK-001 slows the progression of Geographic Atrophy.

Official Title
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A Phase 2/3 Multicenter, Randomized, Double-masked, Parallel-group, Placebo-controlled Study to Investigate the Safety, Pharmacokinetics, Tolerability, and Efficacy of ALK-001 in Geographic Atrophy Secondary to Age-related Macular Degeneration

Conditions
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Geographic Atrophy, Age Related Macular Degeneration, AMD, Atrophy, Geographic

Intervention / Treatment
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* Drug: ALK-001 oral capsule
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: - At least one eye with geographic atrophy secondary to dry age-related macular degeneration (AMD) Major Exclusion Criteria: - Medical condition, which may interfere with the progression of GA, prevent performance of study procedures, compliance with protocol, or continuous participation in the study

Ages Eligible for Study
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Minimum Age: 60 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: ALK-001<br>Capsule | Drug: ALK-001 oral capsule<br>* Daily administration for 24 months<br>* Other names: C20 Deuterated vitamin A;|
| Placebo Comparator: Placebo<br>Capsule | Drug: Placebo oral capsule<br>* Daily administration for 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth rate of GA lesions, as assessed by Fundus Autofluorescence (FAF) |  | Baseline to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability, as assessed by evaluation of adverse events |  | Baseline to 24 months | 
| Pharmacokinetics, as assessed by plasma concentrations of ALK-001 and metabolites |  | Baseline to 24 months | 
| Incidence of choroidal neovascularization (CNV) |  | Baseline to 24 months | 
| Changes in Visual Acuity |  | Baseline to 24 months | 
| Changes in Reading Speed |  | Baseline to 24 months |