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

Subjects who meet all of the following criteria at Screening and Baseline
(unless otherwise indicated) may be eligible for inclusion in the study:
1. Males or females, age * 16 years.
2. Clinical diagnosis of MA secondary to STGD in one or both eyes as determined
by the Investigator.
3. The subject must have 1 or more pathogenic mutation(s) of the ABCA4 (ATP
binding cassette subfamily A member 4) gene. If only one ABCA4 pathogenic
mutation is identified or if two ABCA4 pathogenic mutations that typically
occur on the same allele (ie, *in cis*) are identified, the subject must have a
typical STGD phenotype (at least one eye has flecks at the level of the retinal
pigmented epithelium [RPE] typically seen in STGD) and be approved by the
Sponsor. If 2 or more pathogenic mutations that do not typically occur on the
same allele are identified, a typical STGD phenotype and separate Sponsor
approval are not required. Segregation analysis is not required. The
pathogenicity of all mutations will be determined by the Sponsor working with
experts in ophthalmic genetics.
4. The study eye must meet the following criteria as determined by the central
reading center*s assessment of FAF imaging at Screening:
a. Total area of DDAF
i. If the lesion is unifocal: * 3.0 * 22.0 mm2 (~1.2 * 8.7 disc areas) in size.
ii. If the lesion is multifocal: * 1.0 * 22.0 mm2 (~0.4 * 8.7 disc areas) in
size.
b. The entire lesion must be completely visualized on the macula-centered image
(Field 2 * Macula Image). The DDAF lesion must be able to be imaged in its
entirety, and all lesion borders must be * 300 microns from all image edges.
5. Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA letter score of * 25
letters (approximately * 20/320 Snellen) in the study eye at Screening.
6. Adequate clarity of ocular media and adequate pupillary dilation to permit
good quality imaging of macular atrophy in the study eye as determined by the
Investigator.
7. Able to reliably administer oral medication by self or with available
assistance.
8. Able and willing to provide written informed consent/assent
a. For subjects * 18 years of age: able and willing to provide written informed
consent before undergoing any study-related procedures.
b. For subjects * 16 and 18 years of age: able and willing to provide written
informed assent, and has a parent or legal guardian able and willing to provide
written informed consent for the minor before the subject undergoes any
study-related procedures. Where required by local regulations, both parents
must consent to the subject*s participation in the study, if both have legal
custody.

Subjects will be excluded from participation in the study if they meet any of
the following criteria at Screening or Baseline (unless otherwise indicated):,
1. Macular atrophy associated with a condition other than STGD in either eye.,
2. DDAF with contiguous area of peripapillary atrophy in the study eye, as
determined by the reading center.
3. Mutation(s) in any of the following genes * elongation of very long chain
fatty acids-like 4 (ELOVL4), prominin 1 (PROM1), or peripherin 2
(PRPH2)/retinal degeneration slow (RDS) * determined by the Sponsor working
with experts in ophthalmic genetics to likely be disease-causing.
4. If tested, any mutation(s):
a. In a gene(s) encoding a visual cycle protein [e.g., retinal pigment
epithelium 65 (RPE65), lecithin:retinol acyltransferase (LRAT), retinol
dehydrogenase 12 (RDH12), RDH5, and retinaldehyde binding protein 1 (RLBP1)],
confirmed by the Sponsor working with experts in ophthalmic genetics to likely
be disease-causing. Testing for these mutations is not required.,
b. Associated with a non-STGD retinal dystrophy/degeneration, confirmed by the
Sponsor working with experts in ophthalmic genetics to likely be
disease-causing. Testing is not required.,
5. Presence in either eye of an active ocular disease that in the opinion of
the Investigator compromises or confounds visual function, including, but not
limited to, choroidal neovascularization, diabetic retinopathy, uveitis, other
macular diseases, or uncontrolled glaucoma/ocular hypertension.,
6. History of any intraocular or ocular surface surgery in either eye * 3
months prior to Screening., 7. Current or previous participation in an
interventional study to treat STGD using gene therapy or stem cell therapy.
8. Current or previous participation in a study to treat STGD using a vitamin A
derivative * 6 months prior to Screening.
9. Current or previous participation in a study to treat STGD using a
complement inhibitor * 6 months prior to Screening.
10. Known hypersensitivity to emixustat or any of the excipients in emixustat
tablets (ie, silicified microcrystalline cellulose, pregelatinized starch,
colloidal silicon dioxide, and stearic acid).,
11. Prohibited medications: Please refer to page 29 of the protocol.,
12. Any of the following laboratory abnormalities at Screening: Please refer to
page 30 of the protocol,
13. Participation in any study using an investigational drug within 30 days or
5 half-lives (of the investigational drug) of Screening.
14. Participation in any study of an interventional, investigational device
within 60 days of Screening.,
15. Anticipated participation during the study period in any study using an
investigational drug or an interventional, investigational device.
16. Presence of other medical or ophthalmic disease, physical examination
finding, or clinical laboratory finding that in the opinion of the Investigator
contraindicates the use of an investigational drug, places the subject at risk
by participating in the study, might interfere with the evaluation of the
efficacy or safety of emixustat, negatively impacts subject compliance with the
protocol, confounds the ability to interpret data from the study, or
jeopardizes the subject*s ability to complete the protocol.
17. Current or history of cancer (except for adequately treated basal cell or
squamous cell carcinoma of the skin) within 1 year of Screening.,
18. History of myocardial infarction, stroke, unstable ischemic heart disease,
uncontrolled cardiac arrhythmia, or hospitalization for congestive heart
failure within 6 months of Screening.,
19. Abnormal electrocardiogram (ECG) results that are considered by the
Investigator to be clinically significant at Screening.,
20. Female subjects who are pregnant or lactating.,
21. Female subjects of childbearing potential [(ie, not postmenopausal (without
menses for 12 months without an alternative medical cause) for at least two
years and not surgically sterile via hysterectomy, bilateral salpingectomy, or
bilateral oophorectomy)] who are not willing to practice a medically accepted
method of birth control with their non-surgically sterile male sexual partner
from Screening through 30 days following the completion of the study.
Medically accepted methods of birth control include true abstinence,
estrogen+progestogen hormonal hormonal contraceptives, progestogen-only
hormonal contraceptives, nonhormonal or hormonal intrauterine contraceptive
device with spermicide, bilateral tubal occlusion, male or female condom with
spermicide, contraceptive sponge with spermicide, diaphragm with spermicide, or
cervical cap with spermicide. True abstinence is when abstinence from
heterosexual intercourse is in line with the preferred and usual lifestyle of
the subject and is not just limited to the duration of this study.,
22. Male subjects who are not surgically sterile and are not willing to
practice a medically accepted method of birth control with their female partner
of childbearing potential (as listed above) from Screening through 30 days
after completion of the study.