Phase 2/3 Study of ALK-001 in Geographic Atrophy

There is no oral 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.

• ALK-001 oral capsule (Drug), also known as C20-D3-Retinyl Acetate, C20 Deuterated vitamin A: Daily administration for 24 months
• Placebo oral capsule (Drug): Daily administration for 24 months

Primary outcomes

• Growth Rate of GA Lesions, as Assessed by Fundus Autofluorescence (FAF) [Baseline to 24 months]

Secondary outcomes

• Number of Participants With Adverse Events [Baseline to 24 months]
• Changes in Visual Acuity [Baseline to 24 months]: Changes in LLVA and BCVA

Sex: All, ages: 60 Years to any

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

Participant flow

Outcome results

• Growth Rate of GA Lesions, as Assessed by Fundus Autofluorescence (FAF) (Primary), Least squares mean, mm2/year: ALK-001 1.62 +/- 0.081; Placebo 1.87 +/- 0.116
• Number of Participants With Adverse Events (Secondary), Count of participants, Participants: ALK-001 97; Placebo 52
• Changes in Visual Acuity (Secondary), Least squares mean, letters: ALK-001 -3.896 +/- 1.316; Placebo -8.298 +/- 1.835

Adverse events

Time frame: Two years

Serious adverse events by term

Other adverse events by term

• Kaufman Y, Ma L, Washington I. Deuterium enrichment of vitamin A at the C20 position slows the formation of detrimental vitamin A dimers in wild-type rodents. J Biol Chem. 2011 Mar 11;286(10):7958-7965. doi: 10.1074/jbc.M110.178640. Epub 2010 Nov 12. PMID 21075840
• Mihai DM, Jiang H, Blaner WS, Romanov A, Washington I. The retina rapidly incorporates ingested C20-D(3)-vitamin A in a swine model. Mol Vis. 2013 Jul 25;19:1677-83. Print 2013. PMID 23914132
• Saad L, Washington I. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies? Adv Exp Med Biol. 2016;854:355-61. doi: 10.1007/978-3-319-17121-0_47. PMID 26427432
• Results publication: Boyer DS, Saad L, Washington I, Melamud A, Graham KB, O'Malley AE, DeBartolomeo GM, Jiang H, Harris LD, Kay CN, Ferrone PJ, Khan S; SAGA Study Team. Gildeuretinol Acetate versus Placebo for Geographic Atrophy Secondary to Age-Related Macular Degeneration: The Study of ALK-001 in Geographic Atrophy Randomized Clinical Trial. Ophthalmol Retina. 2026 Jun 3:S2468-6530(26)00268-X. doi: 10.1016/j.oret.2026.05.018. Online ahead of print. PMID 42242606
• Results publication: Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2023 Sep 13;9(9):CD000254. doi: 10.1002/14651858.CD000254.pub5. PMID 37702300

• Study Protocol (PDF, 2019-02-01)
• Statistical Analysis Plan (PDF, 2024-06-20)