Acucela ACU-4429 Emixustat Hydrochloride for Treatment of Geographic Atrophy Associated with Dry Age-Related Macular Degeneration

Overview

Status: Recruiting
Keywords: age related macular degeneration
IRB Number: 00062117
Specialty: Ophthalmology
Sub Specialties: Retinal Diseases

Brief Summary

To determine if ACU-4429 reduces the rate of progression of geographic atrophy (GA) compared to placebo in subjects with dry age-related macular degeneration (AMD).

Secondary objectives are:

1. To evaluate the safety and tolerability of ACU-4429 compared to placebo when administered orally for 24 months at fixed doses and in a step-up titration arm.

2. To assess changes in best-corrected visual acuity (BCVA) with ACU-4429 compared to placebo.

3. To evaluate the effect of ACU-4429 compared to placebo on the development of choroidal neovascularization (CNV) in the study eye.

Exploratory objectives are:

1. To investigate the relationship between the exposure of ACU-4429 and electroretinogram (ERG) results.

2. To investigate the relationship between CYP2D6 genotype and exposure to ACU-4429.

3. To investigate the relationship between AMD genotype and rate of progression of geographic atrophy.

 

Principal Investigator: Paul Bernstein
Department: Ophthalmology-Services
Co Investigator: Albert Vitale
Co Investigator: Mary Elizabeth Hartnett
Co Investigator: Mike Teske

Contact Information

Name:Susan Allman
Phone: 801-581-5142
Email: susan.allman@hsc.utah.edu

Inclusion Criteria

Subjects who meet all of the following criteria may be included in the study:

1. Males or females, age ≥55 years.

2. Clinical diagnosis of geographic atrophy associated with age-related macular degeneration (AMD) in 1 or

both eyes as determined by the Investigator and confirmed by the reading center.

3. The study eye must meet the following criteria as determined by the

central reading center’s assessment of fundus autofluorescence (FAF)

imaging at screening:

a. Total area of geographic atrophy ≥1.25 - 18 mm2 (~0.5 - 7 disc areas) in size.

b. If geographic atrophy is multifocal, at least 1 locus of geographic atrophy must be ≥1.25 mm2 (0.5

disc area) in size, with the overall aggregate area of geographic atrophy, within the

vascular arcades, ≤18 mm2 (~7 disc areas).

c. The entire lesion must be completely visualized on the macula-centered

image (Field 2 Macula Image). Geographic atrophy must be able to be

imaged in its entirety and not contiguous with any areas of

peripapillary atrophy.

4. Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity of ≥35

letters (approximately 20/200 Snellen) in the study eye.

5. Adequate clarity of ocular media and adequate pupillary dilation to

permit good quality imaging of geographic atrophy in the study eye as determined by

the Investigator.

6. Able and willing to provide written informed consent before

undergoing any study-related procedures.

7. Able to reliably administer oral medication by self or with available

assistance.

Exclusion Criteria

Subjects will be excluded from participation in the study if they meet any of

the following criteria:

1. History of, active or high risk of developing choroidal neovascularizition (CNV):

a) history of CNV associated with AMD in the study eye.

b) History of, active or high risk of developing CNV.

c) Or a spherical equivalent >8 dipters of myopia in refractive error in either eye. If the subject has previously undergone refractive surgery, including cataract surgery,  then the pre-operative refractive error can not be >8 diopters of myopia.

Note: choroidal neovascularization in the non-study eye is allowed regardless of treatment

status.

2. Geographic atrophy associated with a condition other than AMD in either eye, or macular geographic atrophy with conitguous area of peripapillary atrophy in the study eye.

3. 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, uveitis, other macular diseases or uncontrolled glaucoma/ocular hypertension (greater than or equal to 25 mm Hg with or without glaucoma medication treatment)

4. History in the study eye of macular edema, external beam radiation,

macular surgery, or transpupillary thermotherapy.

5. History of any intraocular or ocular surface surgery in either eye within

3 months of screening.

6. Previous participation in an investigational study of ACU-4429.

7. Known serious allergy to the fluorescein sodium for injection in

angiography or hypersensitivity to ACU-4429 or any of the excipients in ACU-4429 tablets (ie, silicified microcrystalline cellulose, pregelatinized starch, colloidal silicon dioscide, and stearic acid).

8. Prohibited Medications: Use of a strong inhibitor or inducer of P450 enzyme CYP3A4 or a strong inducer of or a strong or moderate inhibitor of CYP2D6 beginning 4 weeks prior to screening and throughout the duration of the study period.

9. Any of the following laboratory abnormalities at screening:

a. Aspartate transaminase (AST)/alanine transaminase (ALT)

>3.0 x upper limit of normal (ULN)

b. Total bilirubin >1.5 x ULN

c. Impaired coagulation: International Normalized Ratio (INR),

prothrombin time (PT), or activated partial thromboplastin time

(aPTT) >1.25 x ULN

d. Hemoglobin A1c 7.5%

e. Impaired hematologic function: hemoglobin <11 g/dL;

neutrophil count <2.0 x 109/L; or platelet count <100 x 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.

10. Change in a systemic prescription medication or a medication newly

prescribed within 30 days prior to screening and between screening and baseline.

11. Participation during the study period in any study using an investigational study drug (within 30 days of screening) or interventional device (within 60 days of screening). Age-related Eye Disease Study (AREDS)-formulated vitamins (which have been under investigation) are allowed during the study period.

12. History of other disease, metabolic dysfunction, chronic immunosuppression, physical examination

finding, or clinical laboratory finding that in the opinion of the

Investigator gives reasonable suspicion of a disease or condition which

contraindicates the use of an investigational drug or might have affected

interpretation of the results of the study or rendered the subject at high

risk for treatment complications.

13. Current or history of cancer (except non-metastatic in situ carcinoma or

well-controlled carcinoma, [eg, basal cell carcinoma]) within 1 year of screening.

14. Any medical condition (eg, malabsorption, inflammatory bowel

disease, or hepatic or renal disease) that could alter the absorption,

metabolism, or elimination of drugs.

15. History of myocardial infarction, stroke, unstable ischemic heart

disease, uncontrolled cardiac arrhythmia, or hospitalization for

congestive heart failure within 6 months of screening.

16. Abnormal electrocardiogram (ECG) results that are considered by the

Investigator to be clinically significant at screening.

17. Female subjects who are pregnant or lactating.

18. Female subjects of childbearing potential (ie, not postmenopausal for at

least 2 years or 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 hormonal contraceptives, nonhormonal intrauterine

contraceptive device with spermicide, condom with spermicide,

contraceptive sponge with spermicide, diaphragm with spermicide,

cervical cap with spermicide.

19. 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.

20. Unstable or poorly controlled medical or ophthalmic conditions that in

the opinion of the Investigator might interfere with the efficacy or

safety evaluation of the study drug, put the subject at any clinical risk,

negatively impact subject compliance, or jeopardize the subject’s ability

to complete the study.