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Safety and Efficacy of Emixustat in Stargardt Disease (SeaSTAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03772665
Recruitment Status : Completed
First Posted : December 11, 2018
Results First Posted : August 3, 2023
Last Update Posted : August 3, 2023
Sponsor:
Collaborator:
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
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


Condition or disease Intervention/treatment Phase
Stargardt Disease Drug: Emixustat Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 194 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the efficacy and safety of emixustat compared to placebo in subjects who have Macular Atrophy secondary to Stargardt disease.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-Masked
Primary Purpose: Treatment
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
Actual Study Start Date : November 7, 2018
Actual Primary Completion Date : June 13, 2022
Actual Study Completion Date : June 23, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Emixustat
10 mg
Drug: Emixustat
Once daily oral tablet taken for 24 months
Other Name: emixustat hydrochloride

Placebo Comparator: Placebo
Includes identical tablets with only inactive ingredients (0 mg).
Drug: Placebo
Once daily oral tablet taken for 24 months




Primary Outcome Measures :
  1. Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF) [ Time Frame: 24 months ]
    Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03772665


Locations
Show Show 29 study locations
Sponsors and Collaborators
Kubota Vision Inc.
Food and Drug Administration (FDA)
Investigators
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Study Director: Jeff Gregory, MD VP of Clinical Development, Acucela
  Study Documents (Full-Text)

Documents provided by Kubota Vision Inc.:
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Responsible Party: Kubota Vision Inc.
ClinicalTrials.gov Identifier: NCT03772665    
Other Study ID Numbers: 4429-301
R01FD006849 ( U.S. FDA Grant/Contract )
First Posted: December 11, 2018    Key Record Dates
Results First Posted: August 3, 2023
Last Update Posted: August 3, 2023
Last Verified: July 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kubota Vision Inc.:
Stargardt Disease
STGD
ABCA4
Additional relevant MeSH terms:
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Stargardt Disease
Macular Degeneration
Eye Diseases, Hereditary
Eye Diseases
Retinal Degeneration
Retinal Diseases
Genetic Diseases, Inborn