Principal Investigator: Paul Bernstein
Keywords: Retinal disease Department: Ophthalmology-Services
IRB Number: 00119725
Specialty: Ophthalmology
Sub Specialties: Retinal Diseases
Recruitment Status: Not yet recruiting

Contact Information

Kimberley Wegner
kimberley.wegner@hsc.utah.edu
801-581-6265

Simple Summary

To determine if the study drug, emixustat hydrochloride (emixustat), reduces the rate of progression of macular atrophy (MA) compared to placebo in subjects with Stargardt disease (STGD).

Inclusion Criteria

1. Males or females, age ≥ 16 years; female partner of a male participant who becomes pregnant, and her child; child of a female participant who became pregnant.

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.

Exclusion Criteria

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 serious 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:
a. Systemic use of a strong inducer of or a strong or moderate inhibitor of cytochrome P450 2D6 (CYP2D6) (as listed in Table 1) beginning 4 weeks prior to Screening or between Screening and Baseline, or planned use during the study period.
b. Systemic use of a Vitamin A or beta-carotene supplement beginning 4 weeks prior to Screening or between Screening and Baseline, or planned use during the study period.
c. As determined by the Investigator, use of medications known to affect vision (eg, hydroxychloroquine) or that might interfere with the evaluation of the efficacy or safety of emixustat, beginning 4 weeks prior to Screening or between Screening and Baseline, or planned use during the study period.

12. Any of the following laboratory abnormalities at Screening:
a. Aspartate transaminase (AST) or alanine transaminase (ALT) > 3.0 × upper limit of normal (ULN)
b. Total bilirubin > 1.5 × ULN
c. Serum creatinine > 2.0 mg/dL
d. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2
e. Impaired hematologic function: hemoglobin < 11 g/dL; neutrophil count < 1.6 × 109/L; or platelet count < 100 × 109/L.
Any laboratory screening test that meets the abnormality criteria stated above can be repeated once within the 45-day period from Screening to Baseline.

13. Participation in any study using an investigational drug within 30 days 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.

9. Abnormal 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 for at least two years and not surgically sterile) 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 abstinence, hormonal contraceptives, nonhormonal intrauterine contraceptive device with spermicide, condom with spermicide, contraceptive sponge with spermicide, diaphragm with spermicide, or cervical cap with spermicide.

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.

Participant Reimbursement

Participants will be paid $54 for each of the 11 protocol-specified visits over 26 months, up to a total maximum of $540 for study completion.