Safety and Efficacy of Emixustat in Stargardt Disease

Stargardt Disease Clinical Trial

— SeaSTAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03772665
• Other study ID #: 4429-301
• Secondary ID: R01FD006849
• Status: Completed
• Phase: Phase 3
• Start date: January 7, 2019
• Est. completion date: June 23, 2022

Study information

• Verified date: May 2024
• Source: Kubota Vision Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: June 23, 2022
• Est. primary completion date: June 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Macular Degeneration
• Stargardt Disease

Intervention

Drug:
• Emixustat
Once daily oral tablet taken for 24 months
• Placebo
Once daily oral tablet taken for 24 months

Locations

Country	Name	City	State
Brazil	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	Hospital Sao Paulo	São Paulo
Canada	The Hospital for Sick Children	Toronto	Ontario
Denmark	Rigshospitalet-Glostrup	Glostrup	Hovedstaden
France	Service D'Ophtalmologie Chi Creteil	Créteil	Île-de-France
France	CHNO Quinze-Vingts - CIC	Paris	Île-de-France
Germany	Universitäts-Augenklinik Bonn	Bonn
Germany	Universitätsklinikum Tübingen, Department für Augenheilkunde	Tübingen	Baden-Württemberg
Italy	SODC di Oculistica AOU Careggi	Florence	Tuscany
Italy	IRCCS Ospedale San Raffaele	Milan	Lombardy
Italy	UOC Oculistica Asst Fatebene Pratelli Sacco Universita delgi Studi di Milano	Milan	Lombardy
Italy	AOU Università della Campania Luigi Vanvitelli	Naples	Campania
Italy	Università Cattolica del Sacro Cuore - Fondazione Policlinico Gemelli	Rome	Lazio
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland
South Africa	Pretoria Eye Institute	Pretoria	Gauteng
Spain	Fundacion Jimenez Diaz University Hospital	Madrid
United Kingdom	Moorfields Eye Hospital NHS Foundation Trust	London
United Kingdom	Oxford Eye Hospital,Oxford University Hospitals NHS Foundation Trust	Oxford	Oxfordshire
United States	University of Michigan Kellogg Eye Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	The Wilmer Eye Institute Johns Hopkins University	Baltimore	Maryland
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Duke Eye Center	Durham	North Carolina
United States	Medical College of Wisconsin-Eye Institute	Milwaukee	Wisconsin
United States	Casey Eye Institute - OHSU	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Utah John Moran Eye Center	Salt Lake City	Utah
United States	UCSF Dept. of Ophthalmology	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Kubota Vision Inc.	Food and Drug Administration (FDA)

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Denmark,  France,  Germany,  Italy,  Netherlands,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF)	Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)	24 months