NCT03772665

Safety and Efficacy of Emixustat in Stargardt Disease

A Phase 3 Multicenter, Randomized, Double-Masked Study Comparing the Efficacy and Safety of Emixustat Hydrochloride With Placebo for the Treatment of Macular Atrophy Secondary to Stargardt Disease

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 194 (actual)
• Sponsor: Kubota Vision Inc. · Industry
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine if emixustat hydrochloride reduces the rate of progression of macular atrophy compared to placebo in subjects with Stargardt disease. Funding Source -- FDA OOPD

Detailed description

Stargardt disease is a rare, inherited degenerative disease of the retina affecting approximately 1 in 8000 to 10 000 people and is the most common type of hereditary macular dystrophy. There are no approved treatments for STGD. This disease is characterized by an excessive accumulation of lipofuscin at the level of the retinal pigment epithelium (RPE). Lipofuscin is made of lipids, proteins, and toxic bis retinoids (such as N retinylidene N retinylethanolamine \[A2E\]). Accumulation of the toxic bis retinoids found in lipofuscin is thought to cause RPE cell dysfunction and eventual apoptosis, resulting in photoreceptor death and loss of vision. Stargardt disease has several sub types, where autosomal recessive STGD (STGD1) accounts for the majority (\>95%) of all cases. STGD1 is typically diagnosed in the first 3 decades of life and is caused by mutations of the adenosine triphosphate binding cassette subfamily A member 4 (ABCA4) gene. The ABCA4 gene product transports N retinylidene phosphatidylethanolamine (a precursor of toxic bis retinoids) from the lumen side of photoreceptor disc membranes to the cytoplasmic side where the retinal is hydrolyzed from phosphatidylethanolamine. Mutations of the ABCA4 gene result in accumulation of this precursor in disc membranes that are eventually phagocytized by RPE cells, where the precursors are converted into toxic bis retinoids such as A2E. In addition to being a precursor to A2E, all trans retinal has also been implicated in the pathogenesis of STGD through its role in light-mediated toxicity. Emixustat hydrochloride (emixustat) has been developed by Acucela Inc. for retinal diseases including Stargardt disease (STGD). Emixustat is a potent inhibitor of RPE65 isomerization activity and reduces visual chromophore (11 cis retinal) production in a dose-dependent and reversible manner. Because 11 cis-retinal and its photoproduct (all trans retinal) are substrates for biosynthesis of retinoid toxins (eg, A2E), chronic treatment with emixustat retards the rate at which these toxins accumulate.

Conditions

• Stargardt Disease

Interventions

Type	Name	Description
DRUG	Emixustat	Once daily oral tablet taken for 24 months
DRUG	Placebo	Once daily oral tablet taken for 24 months

Timeline

• Start date: 2019-01-07
• Primary completion: 2022-06-13
• Completion: 2022-06-23
• First posted: 2018-12-11
• Last updated: 2024-05-30
• Results posted: 2023-08-03

Locations

29 sites across 11 countries: United States, Brazil, Canada, Denmark, France, Germany, Italy, Netherlands, South Africa, Spain, United Kingdom

Regulatory

• FDA-regulated drug study