The SeaSTAR Study - Amendment 1
Research type
Research Study
Full 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
IRAS ID
258748
Contact name
Angie Muller
Contact email
Sponsor organisation
Acucela Inc.
Eudract number
2018-003498-82
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
IND 101,084, IND NUMBER; 40717, NIHR
Duration of Study in the UK
2 years, 7 months, 9 days
Research summary
Summary of Research
Emixustat hydrochloride (emixustat) is under clinical development by Acucela Inc. (Acucela) for retinal diseases including Stargardt disease (STGD). This is a rare, inherited degenerative disease of the retina affecting approximately 1 in 8,000 to 10,000 individuals and is the most common type of hereditary macular dystrophy. There are no approved treatments for STGD.Stargardt disease is characterized by an excessive build-up of lipofuscin. Lipofuscin, which normally accumulates with age, consists of lipids, proteins, and toxic bis-retinoids such as A2E. Accumulation of the bis-retinoids is thought to cause retinal pigment epithelium (RPE) cell dysfunction, which leads to photoreceptor death and loss of vision.
Animal models have shown that persistent treatment with emixustat slows down the rate at which these toxins, such as A2E, accumulate. The data collected from mice with high levels of A2E suggest that the accumulation of A2E can be reversed by emixustat treatment. Nonclinical findings suggest that, orally administered emixustat may slow the progression of STGD.
This study is a multicenter, randomized, double-masked, placebo-controlled study to determine if emixustat reduces the rate of progression of macular atrophy (MA) compared to placebo in subjects with STGD. Subjects will be randomly assigned to one of two treatment arms in a 2:1 (emixustat:placebo) ratio.
Subjects will self-administer orally the study drug once a day every evening for 24 months.
This study will be conducted at approximately 30 sites in the US, Europe, and other countries. Approximately 162 subjects will be enrolled (108 emixustat and 54 placebo).
Randomization and double-masking will be used to minimize bias in subject selection and the evaluation of subjects during the study. A placebo control is included to provide an objective comparison for the safety and efficacy of emixustat.
The maximum duration of participation in the study will be 27 months,
with a total of 13 visits.
The SeaSTAR Study was 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. Stargardt disease is a rare, inherited degenerative disease of the retina. The research was carried out and funded by Acucela Inc DBA Kubota Vision.
The study design, the protocol and the Informed Consent Forms were developed by Acucela Inc., an advisory board and key opinion leaders. Patients, members of the public or service users or carers were not involved. The study took place in 29 centres in 11 countries from November 2018 to June 2022.
The study was conducted to determine if emixustat hydrochloride (emixustat) reduces the rate of progression of macular atrophy compared to placebo in subjects with Stargardt disease.
Subjects were randomly assigned to one of 2 treatment arms in a 2:1 (emixustat:placebo) ratio. Treatment arms included:
• Emixustat 10 mg
• Placebo
Subjects self-administered study drug once daily (QD) in the evening for 24 continuous months. The subjects took emixustat 5 mg QD from the evening of the Baseline visit until the evening before the Month 1 visit and 10 mg QD from the evening of the Month 1 visit until the evening before the Month 24 visit.
At any time during treatment, a dose reduction was allowed if a subject experienced a recurrent or continuous intolerable adverse event (AE) that in the opinion of the Investigator was related to study drug and would otherwise lead to discontinuation from the study drug. The dose of emixustat was reduced to 5 mg, where subjects continued on 5 mg until the evening before the Month 24 visit.
The study consisted of a screening period of up to 45 days, a 24-month dosing period, and a follow-up period of 60 days after the last dose of the study drug. During the Coronavirus Disease 19 (COVID-19) crisis, visit windows could be extended.
Subjects who discontinued from the study early underwent an Early Termination visit where safety and efficacy assessments were done when study drug was stopped, or as soon as possible after stopping study drug. Subjects who were discontinued from the treatment remained in the study and attended all clinical site visits through Month 24. The study planned to enroll approximately 189 subjects (126 subjects to emixustat and 63 subjects to placebo). A total of 194 subjects were randomized (128 subjects in the emixustat group and
66 subjects in the placebo group); all were included in the efficacy analyses (intent-to-treat set), among whom 167 subjects were included in the efficacy evaluable set, and 193 subjects (127 subjects in the emixustat group, 66 subjects in the placebo group) were included in the safety analyses. Patients’ eyes were tested in a number of ways to check for the effect of the study medication on their eyes and to evaluate the safety of the study medication.
The most commonly reported ocular treatment-emergent adverse reactions were delayed dark adaptation and visual color distortions. The most common non-ocular treatment-emergent adverse reaction was COVID-19 infection.
The primary endpoint of this study was not met. The secondary endpoint of mean retinal sensitivity showed a statistically significant difference in the study eye at Months 6, 12, 18, and 24 favoring placebo. Prompted by planned subgroup analyses suggesting that emixustat subjects with smaller atrophic lesions at baseline had a reduced rate of progression compared to placebo subjects, post hoc analyses were performed to further investigate this finding. Post-hoc analyses showed that, in subjects with smaller atrophic lesions at baseline based on DDAF, emixustat treatment resulted in a 40.5% reduction in DDAF area growth compared to placebo at Month 24. Scotopic microperimetry mean sensitivity at Month 26 showed a greater decrease from baseline in the emixustat group compared to the placebo group. Emixustat was well tolerated and demonstrated a safety profile consistent with prior studies.
Thank you to those who participated in this research study for emixustat hydrochloride. Without trial participants, drug development would not be possible. Participation in this trial has helped the researchers learn how emixustat hydrochloride works and how safe it is to use, and has provided researchers with important information about Macular Atrophy secondary to Stargardt disease and possible treatment options.
The trial information given in this summary is from one trial only and must not be used to make medical decisions. This drug is not yet approved and the outcomes of this trial may not apply to all patients. Do not change your current medical treatment without consulting your doctor.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
19/WM/0017
Date of REC Opinion
18 Mar 2019
REC opinion
Further Information Favourable Opinion