TEASE: a phase 2 clinical trial assessing the tolerability and effects of oral once-a-day ALK-001 on Stargardt disease

Abstract

Purpose : 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.

Methods : 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.

Results : 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).

Conclusions : 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