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Safety and Efficacy of Emixustat in Stargardt Disease (SeaSTAR)

Primary Purpose

Stargardt Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Emixustat
Placebo
Sponsored by
Kubota Vision Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stargardt Disease focused on measuring Stargardt Disease, STGD, ABCA4

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Retina-Vitreous Associates Medical Group
  • UCSF Dept. of Ophthalmology
  • Emory University
  • The Wilmer Eye Institute Johns Hopkins University
  • University of Michigan Kellogg Eye Center
  • Mayo Clinic Rochester
  • Duke Eye Center
  • Casey Eye Institute - OHSU
  • Retina Foundation of the Southwest
  • University of Utah John Moran Eye Center
  • Medical College of Wisconsin-Eye Institute
  • Santa Casa de Misericórdia de Belo Horizonte
  • Hospital Sao Paulo
  • The Hospital for Sick Children
  • Rigshospitalet-Glostrup
  • Service D'Ophtalmologie Chi Creteil
  • CHNO Quinze-Vingts - CIC
  • Universitätsklinikum Tübingen, Department für Augenheilkunde
  • Universitäts-Augenklinik Bonn
  • AOU Università della Campania Luigi Vanvitelli
  • Università Cattolica del Sacro Cuore - Fondazione Policlinico Gemelli
  • IRCCS Ospedale San Raffaele
  • UOC Oculistica Asst Fatebene Pratelli Sacco Universita delgi Studi di Milano
  • SODC di Oculistica AOU Careggi
  • Radboud University Medical Center
  • Pretoria Eye Institute
  • Fundacion Jimenez Diaz University Hospital
  • Oxford Eye Hospital,Oxford University Hospitals NHS Foundation Trust
  • Moorfields Eye Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Emixustat

Placebo

Arm Description

10 mg

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

First Posted
November 30, 2018
Last Updated
July 13, 2023
Sponsor
Kubota Vision Inc.
Collaborators
Food and Drug Administration (FDA)
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1. Study Identification

Unique Protocol Identification Number
NCT03772665
Brief Title
Safety and Efficacy of Emixustat in Stargardt Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
November 7, 2018 (Actual)
Primary Completion Date
June 13, 2022 (Actual)
Study Completion Date
June 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kubota Vision Inc.
Collaborators
Food and Drug Administration (FDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stargardt Disease
Keywords
Stargardt Disease, STGD, ABCA4

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-Masked
Allocation
Randomized
Enrollment
194 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Emixustat
Arm Type
Experimental
Arm Description
10 mg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Includes identical tablets with only inactive ingredients (0 mg).
Intervention Type
Drug
Intervention Name(s)
Emixustat
Other Intervention Name(s)
emixustat hydrochloride
Intervention Description
Once daily oral tablet taken for 24 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Once daily oral tablet taken for 24 months
Primary Outcome Measure Information:
Title
Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF)
Description
Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeff Gregory, MD
Organizational Affiliation
VP of Clinical Development, Acucela
Official's Role
Study Director
Facility Information:
Facility Name
Retina-Vitreous Associates Medical Group
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
UCSF Dept. of Ophthalmology
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0730
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
The Wilmer Eye Institute Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Michigan Kellogg Eye Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Duke Eye Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Casey Eye Institute - OHSU
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Retina Foundation of the Southwest
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Utah John Moran Eye Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Medical College of Wisconsin-Eye Institute
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Santa Casa de Misericórdia de Belo Horizonte
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30150-320
Country
Brazil
Facility Name
Hospital Sao Paulo
City
São Paulo
ZIP/Postal Code
04024-002
Country
Brazil
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
MSG 1X8
Country
Canada
Facility Name
Rigshospitalet-Glostrup
City
Glostrup
State/Province
Hovedstaden
ZIP/Postal Code
DK-2600
Country
Denmark
Facility Name
Service D'Ophtalmologie Chi Creteil
City
Créteil
State/Province
Île-de-France
ZIP/Postal Code
94000
Country
France
Facility Name
CHNO Quinze-Vingts - CIC
City
Paris
State/Province
Île-de-France
ZIP/Postal Code
75012
Country
France
Facility Name
Universitätsklinikum Tübingen, Department für Augenheilkunde
City
Tübingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
Universitäts-Augenklinik Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
AOU Università della Campania Luigi Vanvitelli
City
Naples
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Università Cattolica del Sacro Cuore - Fondazione Policlinico Gemelli
City
Rome
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
Facility Name
IRCCS Ospedale San Raffaele
City
Milan
State/Province
Lombardy
ZIP/Postal Code
20132
Country
Italy
Facility Name
UOC Oculistica Asst Fatebene Pratelli Sacco Universita delgi Studi di Milano
City
Milan
State/Province
Lombardy
ZIP/Postal Code
20157
Country
Italy
Facility Name
SODC di Oculistica AOU Careggi
City
Florence
State/Province
Tuscany
ZIP/Postal Code
50134
Country
Italy
Facility Name
Radboud University Medical Center
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6500
Country
Netherlands
Facility Name
Pretoria Eye Institute
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0082
Country
South Africa
Facility Name
Fundacion Jimenez Diaz University Hospital
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Oxford Eye Hospital,Oxford University Hospitals NHS Foundation Trust
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OXD3 9DU
Country
United Kingdom
Facility Name
Moorfields Eye Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Safety and Efficacy of Emixustat in Stargardt Disease

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