Clinical trial NCT03845582: Phase 3 Study of ALK-001 in Geographic Atrophy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Geographic Atrophy
Age Related Macular Degeneration
AMD
Atrophy, Geographic
Lead sponsor: Alkeus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-02-19
Enrollment: 200
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Growth rate of GA lesions, as assessed by Fundus Autofluorescence (FAF)
timeFrame: Baseline to 24 months
Secondary outcomes:
measure: Safety and tolerability, as assessed by evaluation of adverse events
timeFrame: Baseline to 24 months
measure: Pharmacokinetics, as assessed by plasma concentrations of ALK-001 and metabolites
timeFrame: Baseline to 24 months
measure: Incidence of choroidal neovascularization (CNV)
timeFrame: Baseline to 24 months
measure: Changes in Visual Acuity
timeFrame: Baseline to 24 months
measure: Changes in Reading Speed
timeFrame: Baseline to 24 months
Other outcomes:
Locations:
city: Somerville
country: United States
facility: Coordinating Center
state: Massachusetts
Study officials:
affiliation: Alkeus Pharmaceuticals, Inc.
name: Leonide Saad, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.