Safety and Efficacy of Emixustat in Stargardt Disease

NCT ID: NCT03772665

Last Updated: 2024-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-07
• Study Completion Date: 2022-06-23

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.

Conditions

Stargardt Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Emixustat

10 mg

Group Type: EXPERIMENTAL

Emixustat

Intervention Type: DRUG

Once daily oral tablet taken for 24 months

Placebo

Includes identical tablets with only inactive ingredients (0 mg).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Once daily oral tablet taken for 24 months

Interventions

Emixustat

Once daily oral tablet taken for 24 months

Intervention Type: DRUG

Placebo

Once daily oral tablet taken for 24 months

Intervention Type: DRUG

Other Intervention Names

emixustat hydrochloride

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

Kubota Vision Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeff Gregory, MD

Role: STUDY_DIRECTOR

VP of Clinical Development, Acucela

Locations

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States

UCSF Dept. of Ophthalmology

San Francisco, California, United States

Emory University

Atlanta, Georgia, United States

The Wilmer Eye Institute Johns Hopkins University

Baltimore, Maryland, United States

University of Michigan Kellogg Eye Center

Ann Arbor, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Duke Eye Center

Durham, North Carolina, United States

Casey Eye Institute - OHSU

Portland, Oregon, United States

Retina Foundation of the Southwest

Dallas, Texas, United States

University of Utah John Moran Eye Center

Salt Lake City, Utah, United States

Medical College of Wisconsin-Eye Institute

Milwaukee, Wisconsin, United States

Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Hospital Sao Paulo

São Paulo, , Brazil

The Hospital for Sick Children

Toronto, Ontario, Canada

Rigshospitalet-Glostrup

Glostrup Municipality, Capital Region, Denmark

Service D'Ophtalmologie Chi Creteil

Créteil, Île-de-France Region, France

CHNO Quinze-Vingts - CIC

Paris, Île-de-France Region, France

Universitätsklinikum Tübingen, Department für Augenheilkunde

Tübingen, Baden-Wurttemberg, Germany

Universitäts-Augenklinik Bonn

Bonn, , Germany

AOU Università della Campania Luigi Vanvitelli

Naples, Campania, Italy

Università Cattolica del Sacro Cuore - Fondazione Policlinico Gemelli

Rome, Lazio, Italy

IRCCS Ospedale San Raffaele

Milan, Lombardy, Italy

UOC Oculistica Asst Fatebene Pratelli Sacco Universita delgi Studi di Milano

Milan, Lombardy, Italy

SODC di Oculistica AOU Careggi

Florence, Tuscany, Italy

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Pretoria Eye Institute

Pretoria, Gauteng, South Africa

Fundacion Jimenez Diaz University Hospital

Madrid, , Spain

Oxford Eye Hospital,Oxford University Hospitals NHS Foundation Trust

Oxford, Oxfordshire, United Kingdom

Moorfields Eye Hospital NHS Foundation Trust

London, , United Kingdom

Countries

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

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01FD006849

Identifier Type: FDA

Identifier Source: secondary_id

View Link

4429-301

Identifier Type: -

Identifier Source: org_study_id