Safety and Efficacy of Emixustat in Stargardt Disease
- Registration Number
- NCT03772665
- Lead Sponsor
- Kubota Vision Inc.
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 194
- A clinical diagnosis of macular atrophy secondary to Stargardt disease (STGD)
- Macular atrophy measured to fall within a defined size range
- Two mutations of the ABCA4 gene. If only one mutation, a typical STGD appearance of the retina.
- Visual acuity in the study eye of at least 20/320
- Macular atrophy secondary to a disease other than STGD
- Mutations of genes, other than ABCA4, that are associated with retinal degeneration
- Surgery in the study eye in the past 3 months
- Prior participation in a gene therapy or stem cell clinical trial for STGD
- Recent participation in a clinical trial for STGD evaluating a complement inhibitor or vitamin A derivative
- Use of certain medications in the past 4 weeks that might interfere with emixustat
- An abnormal electrocardiogram (ECG)
- Certain abnormalities on laboratory blood testing
- Female subjects who are pregnant or nursing
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Includes identical tablets with only inactive ingredients (0 mg). Emixustat Emixustat 10 mg
- Primary Outcome Measures
Name Time Method Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF) 24 months Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (29)
The Wilmer Eye Institute Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
University of Michigan Kellogg Eye Center
🇺🇸Ann Arbor, Michigan, United States
Casey Eye Institute - OHSU
🇺🇸Portland, Oregon, United States
Retina Foundation of the Southwest
🇺🇸Dallas, Texas, United States
Medical College of Wisconsin-Eye Institute
🇺🇸Milwaukee, Wisconsin, United States
Hospital Sao Paulo
🇧🇷São Paulo, Brazil
Service D'Ophtalmologie Chi Creteil
🇫🇷Créteil, Île-de-France, France
CHNO Quinze-Vingts - CIC
🇫🇷Paris, Île-de-France, France
Università Cattolica del Sacro Cuore - Fondazione Policlinico Gemelli
🇮🇹Rome, Lazio, Italy
UOC Oculistica Asst Fatebene Pratelli Sacco Universita delgi Studi di Milano
🇮🇹Milan, Lombardy, Italy
Fundacion Jimenez Diaz University Hospital
🇪🇸Madrid, Spain
Radboud University Medical Center
🇳🇱Nijmegen, Gelderland, Netherlands
Pretoria Eye Institute
🇿🇦Pretoria, Gauteng, South Africa
Moorfields Eye Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Oxford Eye Hospital,Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, Oxfordshire, United Kingdom
IRCCS Ospedale San Raffaele
🇮🇹Milan, Lombardy, Italy
SODC di Oculistica AOU Careggi
🇮🇹Florence, Tuscany, Italy
UCSF Dept. of Ophthalmology
🇺🇸San Francisco, California, United States
Duke Eye Center
🇺🇸Durham, North Carolina, United States
University of Utah John Moran Eye Center
🇺🇸Salt Lake City, Utah, United States
Santa Casa de Misericórdia de Belo Horizonte
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Universitätsklinikum Tübingen, Department für Augenheilkunde
🇩🇪Tübingen, Baden-Württemberg, Germany
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Rigshospitalet-Glostrup
🇩🇰Glostrup, Hovedstaden, Denmark
Universitäts-Augenklinik Bonn
🇩🇪Bonn, Germany
AOU Università della Campania Luigi Vanvitelli
🇮🇹Naples, Campania, Italy