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Hendrik P Scholl, Syed Mahmood Shah, Christine Nichols Kay, Stephen H Tsang, Kimberly E Stepien, Paul S Bernstein, Byron L Lam, Michael B Gorin, Ilyas Washington, Leonide Saad; TEASE: a phase 2 clinical trial assessing the tolerability and effects of oral once-a-day ALK-001 on Stargardt disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2685.
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© 2017 Association for Research in Vision and Ophthalmology.
Stargardt disease (STGD1) is the leading cause of inherited juvenile macular degeneration. The disease stems from mutations in ABCA4, a gene that encodes a vitamin A transport protein in the retina. Defective vitamin A transport results in accelerated formation of vitamin A dimers, thought to cause retinal degenerations including STGD1. The tolerability and effects of ALK-001 in Stargardt disease (“TEASE”) study is the first of several prospective clinical trials to test the extent to which slowing the dimerization of vitamin A prevents the progression of STGD1.
ALK-001 is a vitamin A replacement: the chemical structure of ALK-001 is similar to that of vitamin A but 3 hydrogen atoms have been exchanged by deuterium. This change prevents ALK-001 from dimerizing. However, ALK-001 keeps all known functions of vitamin A. In preclinical evaluation, ALK-001 slows the rate of vitamin A dimerization approximately 4 to 5 fold but does not affect the visual cycle. TEASE is a 24-month, multicenter, randomized, double-masked, placebo-controlled study evaluating the effects of ALK-001 in up to 50 patients diagnosed with molecularly confirmed STGD1 aged between 12 and 60 years. Study subjects may have any visual acuity to enroll and must have a lesion of well-defined decreased signal on fundus autofluorescence imaging (FAF). TEASE subjects are randomly assigned to receive one of two doses of ALK-001 (30 subjects) or placebo (20 subjects) for one year. After one year, half of the subjects receiving placebo will be randomly crossed over to receive ALK-001 for the following 12 months, while all other subjects will continue receiving their initial treatment. A Data Monitoring Committee (DMC) reviews safety and efficacy data throughout the study.
Enrollment is ongoing. As of late 2015, 15 subjects have been enrolled, with the longest treatment duration of about 3 months. The median best corrected visual acuity at baseline was 63 letters (range, 26-85) in the best eye. Median age was 44 years (range, 20-59) and median disease duration 8 years (range, 1-25). Median lesion size in the best eye on FAF was 1.80 mm2 (range, 0.25-17.74).
The TEASE study is one of the first FDA-regulated phase 2 clinical trials assessing a novel oral compound for retinal degenerative disease secondary to vitamin A dimerization, including STGD1.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
TEASE trial design
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