Stargardt DiseasePhase 3SeaSTARNCT03772665
Safety and Efficacy of Emixustat in Stargardt Disease
A Phase 3 study testing Emixustat in people with Stargardt Disease, run by Kubota Vision Inc. at 29 sites in 11 countries.
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 Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Stargardt Disease
- What is being tested?
- Emixustat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 194 participants
- Where
- 29 sitesin 11 countries
- Study dates
- 7 Jan 2019to 23 Jun 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- An abnormal electrocardiogram (ECG)
- Certain abnormalities on laboratory blood testing
- Female subjects who are pregnant or nursing
Trial locations and contacts
29 sites in 11 countries.
29 sites in 11 countries
United States11 sites
University of Michigan Kellogg Eye Center
Ann Arbor, Michigan, 48105
Emory University
Atlanta, Georgia, 30322
The Wilmer Eye Institute Johns Hopkins University
Baltimore, Maryland, 21287
Retina-Vitreous Associates Medical Group
Beverly Hills, California, 90211
Retina Foundation of the Southwest
Dallas, Texas, 75231
Duke Eye Center
Durham, North Carolina, 27710
Medical College of Wisconsin-Eye Institute
Milwaukee, Wisconsin, 53226
Casey Eye Institute - OHSU
Portland, Oregon, 97239
Mayo Clinic Rochester
Rochester, Minnesota, 55905
University of Utah John Moran Eye Center
Salt Lake City, Utah, 84132
UCSF Dept. of Ophthalmology
San Francisco, California, 94143-0730
Italy5 sites
SODC di Oculistica AOU Careggi
Florence, Tuscany, 50134
IRCCS Ospedale San Raffaele
Milan, Lombardy, 20132
UOC Oculistica Asst Fatebene Pratelli Sacco Universita delgi Studi di Milano
Milan, Lombardy, 20157
AOU Università della Campania Luigi Vanvitelli
Naples, Campania, 80131
Università Cattolica del Sacro Cuore - Fondazione Policlinico Gemelli
Rome, Lazio, 00168
Brazil2 sites
Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150-320
Hospital Sao Paulo
São Paulo, 04024-002
France2 sites
Service D'Ophtalmologie Chi Creteil
Créteil, Île-de-France Region, 94000
CHNO Quinze-Vingts - CIC
Paris, Île-de-France Region, 75012
Germany2 sites
Universitäts-Augenklinik Bonn
Bonn, 53127
Universitätsklinikum Tübingen, Department für Augenheilkunde
Tübingen, Baden-Wurttemberg, 72076
United Kingdom2 sites
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 2PD
Oxford Eye Hospital,Oxford University Hospitals NHS Foundation Trust
Oxford, Oxfordshire, OXD3 9DU
Denmark1 site
Rigshospitalet-Glostrup
Glostrup Municipality, Capital Region, DK-2600
Netherlands1 site
Radboud University Medical Center
Nijmegen, Gelderland, 6500
About this study
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
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
Read the 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
- Being tested
- Emixustat, Placebo
- Keywords
- Stargardt Disease, STGD, ABCA4
- Medical subject headings
- Stargardt Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmixustatDrug
Also called emixustat hydrochloride
Once daily oral tablet taken for 24 months
PlaceboDrug
Once daily oral tablet taken for 24 months
| Study group | Role | What they receive |
|---|---|---|
| Emixustat | Experimental | 10 mg Receives: Drug: Emixustat |
| Placebo | Placebo comparator | Includes identical tablets with only inactive ingredients (0 mg). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2018
- Study start7 Jan 2019
- Primary completion13 Jun 2022
- Study completion23 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stargardt DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kubota Vision Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Sponsor
- Investigators
- Jeff Gregory, MD, Study director, VP of Clinical Development, Acucela
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03772665
- Sponsor's protocol ID
- 4429-301
- Other IDs
- R01FD006849
- Acronym
- SeaSTAR
- Status last verified
- May 2024
- First submitted
- 30 Nov 2018
- Last updated
- 30 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03772665
- Acronym / sponsor ID
- SeaSTAR / 4429-301
- Conditions
- Stargardt Disease
- Keywords
- Stargardt Disease, STGD, ABCA4
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- Kubota Vision Inc.Industry (pharma, biotech, devices)
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 7 Jan 2019 (actual)
- Primary completion
- 13 Jun 2022 (actual)
- Study completion
- 23 Jun 2022 (actual)
- First posted
- 11 Dec 2018 (actual)
- Results
- Posted 3 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Emixustat | Experimental | Drug: Emixustat10 mg |
| Placebo | Placebo comparator | Drug: PlaceboIncludes identical tablets with only inactive ingredients (0 mg). |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmixustatAlso: emixustat hydrochlorideOnce daily oral tablet taken for 24 months | Drug | Emixustat |
| PlaceboOnce daily oral tablet taken for 24 months | Drug | Placebo |
Primary outcome
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Stargardt Disease
RecruitingObservational study
Rod and Cone Mediated Function in Retinal Disease
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RecruitingObservational study
Genotype-Phenotype Study of Patients With Plaquenil -Induced Retinal Toxicity, With Evaluation of the ABCA4 Gene
Genotype, Retinal Disease
RecruitingPhase 1
Phase 1 Study of C.001 in Retinal Degeneration
Geographic Atrophy, Stargardt Disease
RecruitingPhase 1
A Study About the Safety of a Single ASP2020 Eye Injection and if it Helps People With Vision Loss From Stargardt-type Eye Conditions
Stargardt Disease, Stargardt Macular Dystrophy
Active, not recruitingPhase 1/2
Oral Metformin for Treatment of ABCA4 Retinopathy
ABCA4 Retinopathy, Stargardt Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeff Gregory, MD study director
VP of Clinical Development, Acucela
29 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Emixustat in people with Stargardt Disease, run by Kubota Vision Inc. at 29 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Italy, Brazil, France, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2024.