Acucela 4429-204 Stargardt Disease

Principal Investigator: Paul Bernstein
Keywords: Retinal eye disease , Drug dose comparison Department: Ophthalmology-Services
IRB Number: 00098518 Co Investigator:  
Specialty: Ophthalmology
Sub Specialties: Retinal Diseases
Recruitment Status: Recruiting

Contact Information

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

Brief Summary

Primary Objective:  To characterize the pharmacodynamics (PD) of emixustat hydrochloride (emixustat) in subjects with macular atrophy (MA) secondary to Stargardt Disease (STGD).

Secondary Objective:  To evaluate the safety and tolerability of emixustat when administered orally for 1 month.

Inclusion Criteria

1. Males or females, age ≥18 years.
2. Clinical diagnosis of MA secondary to STGD in one or both eyes as determined by the Investigator and confirmed by the central image reading center.
3. At least 2 pathogenic mutations of the ABCA4 gene. If only one ABCA4 allele has a pathogenic mutation, the subject must have a typical STGD phenotype (ie, at least one eye has flecks at the level of the RPE typically seen in STGD) and be approved for enrollment by the Sponsor.
4. Total area of definitely decreased autofluorescence MA in the study eye equal to 1.25 -26 mm2 (~0.5 - 10.25 disc areas) in size as determined by the central image reading center’s assessment of fundus autofluorescence (FAF) imaging at Screening.
5. The entire lesion must be completely visualized on the macula-centered image (Field 2 - Macula Image).
6. Early Treatment Diabetic Retinopathy Study BCVA of ≥ 20 letters (approximately ≥ 20/400 Snellen) in the study eye.
7. Adequate clarity of ocular media and adequate pupillary dilation to permit good quality imaging of MA in the study eye as determined by the Investigator.
8. Able and willing to provide written informed consent before undergoing any study related procedures.
9. Able to reliably administer oral medication by self or with available assistance.

Exclusion Criteria

1. Macular atrophy associated with a condition other than STGD in either eye.
2. 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.
3. History of any intraocular or ocular surface surgery in either eye within 3 months of Screening.
4. Current or previous participation in an interventional study to treat STGD using gene therapy or stem cell therapy at any time, or participation in an interventional study of a vitamin A derivative ≤3 months prior to screening.
5. 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).
6. Prohibited medications: Systemic use of a strong inducer of, or a strong or moderate inhibitor of, cytochrome P450 2D6 (CYP2D6) beginning within 4 weeks prior to Screening or between Screening and Baseline, or planned use during the study period.
7. Any of the following laboratory abnormalities at Screening:
a. Aspartate transaminase (AST)/alanine transaminase (ALT) > 2.5 × upper limit of normal (ULN).
b. Total bilirubin > 1.5 × ULN.
c. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2.
d. Impaired hematologic function: hemoglobin < 10 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 30-day period from Screening to Baseline.
 
8. Participation in any study using an investigational drug within 5 half-lives (of the investigational drug) of Screening, or, if the half-life is not known, within 30 days of Screening.
9. Participation in any study of an investigational device within 60 days of Screening.
10. Anticipated participation during the study period in any other study using an investigational study drug or interventional device.
11. 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 PD 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.
12. Current or history of cancer (except for adequately treated basal cell or squamous cell carcinoma of the skin) within 1 year of Screening.
13. History of myocardial infarction, stroke, unstable ischemic heart disease, uncontrolled cardiac arrhythmia, or hospitalization for congestive heart failure within 6 months of Screening.
14. Anticipated hospitalization for a medical/surgical procedure(s) that could result in interruption/premature cessation of study treatment or participation.
15. Electrocardiogram with a clinically significant abnormal finding (eg, acute ischemia, bundle branch block) or a QT interval, corrected for heart rate by Bazett’s formula (QTcB) or Fridericia’s formula (QTcF), of > 460 milliseconds (msec) for men and > 470 msec for women at Screening.
16. Female subjects who are pregnant or lactating.
17. Female subjects of childbearing potential (ie, not postmenopausal for at least 2 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 after the final dose of study drug. 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.
18. 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 the final dose of study drug.