Geographic atrophy associated with dry age-related macular degeneration MedDRA version: 19.0 Level: LLT Classification code 10063947 Term: Geographic atrophy System Organ Class: 100000004853
Conditions
Interventions
Product Name: emixustat hydrochloride
Product Code: ACU-4429
Pharmaceutical Form: Tablet
INN or Proposed INN: emixustat
CAS Number: 1141934-97-5
Current Sponsor code: ACU-4429 HCl
Other descriptive na
Sponsors
Acucela Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females, age =55 years. 2. Clinical diagnosis of GA associated with 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 GA =1.25 - 18 square mm (~0.5 - 7 disc areas) in size. b. If GA is multifocal, at least 1 locus of GA must be =1.25 mm2 (0.5 disc area) in size, with the overall aggregate area of GA, 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). GA 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) BCVA 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 GA 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 48 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 432
Exclusion criteria
Exclusion criteria: 1. History of, active or high risk of developing CNV: a. History of CNV associated with AMD in the study eye b. Active CNV in the study eye as confirmed by the central reading center c. Or a spherical equivalent >8 diopters of myopia in refractive error in either eye. If the subject has previously undergone refractive surgery, including cataract surgery, then the pre-operative error cannot be >8 diopters of myopia. Note: CNV associated with AMD 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 GA with contiguous 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 (=25 mm Hg with or without glaucoma medication treatment). 4. History in study eye of macular edema, ext. beam radiat., macular surgery, or transpup. thermotherapy. 5. History of any intraocular or ocular surface surgery in either eye within 3 months of screen.. 6. Prev. particip. in an investigat. study of ACU-4429. 7. Known serious allergy to fluorescein sodium for injection in angiography or hypersensitivity to ACU-4429 or any of the excipients in ACU-4429 tablets (ie, silicif. microcrystall. cellulose, pregelatin. starch, coll. silicon dioxide and stearic acid). 8. Prohibited medications: Use of a strong inhibitor or inducer of cytochrome P450 enzyme CYP3A4 or a strong inducer of or a strong or moderate inhibitor of CYP2D6 (as listed in Appendix B) beginning 4 weeks prior to screening and throughout the duration of the study period. 9. [please see protocol] 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 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 s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: 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. ;Primary end point(s): Primary Efficacy Endpoint The primary efficacy endpoint will be the mean rate of change from baseline in the total area of the GA lesion(s) in the study eye (in mm2 per year) as imaged by FAF. Safety Endpoints Safety endpoints will include: 1. Frequency of AEs, discontinuations due to AEs, or dose modifications due to AEs; severity and seriousness of AEs. 2. Change from baseline in laboratory values, vital signs, physical examination findings, ECGs, and ophthalmic assessments. ;Timepoint(s) of evaluation of this end point: FAF will be done on Screening, Baseline (D0), Month 6, 12, 18, 24, Early Termination Visit; Frequency of AE's will be evaluated continuously at all study visits; Lab values will be evaluated at Screening, Baseline (Day 0), Month 6, 12, 24, 25 , only if safety laboratory test result(s) at the Month 24 or Early Termination visit were considered clin. sig.by Inv.; Vital Signs are evaluated at Screening, Baseline (D0), Month 6, 12, 18, 24, and Early Termin. Visit; Physical Examination is done at Screening, Month 24 and Early Termination Visit; ECG is performed at Screening, Month 6, 12, 18, 24 and Early Termination Visit; The timepoints of conduction of ophthalmic assessments depends on the kind of examination, see Schedule of Events provided in Appendix A of the protocol; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints Secondary efficacy endpoints will include: 1. Mean change from baseline in NL-BCVA score 2. Proportion of subjects who develop CNV in their study eye at any time during the study. ;Timepoint(s) of evaluation of this end point: BCVA and evaluation of CNV will be done at Screening, Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 25 and Early Termination Visit; Study exit visit: If follow-up is needed after this visit, it should occur as an unscheduled visit at the Investigator’s discretion or telephone contact. If the Early Termination visit occurs = 25 days after discontinuation of study drug, a combined Early Termination/Study Exit visit may be performed. If the Early Termination/Study Exit visits are combined, all assessments scheduled at each of the 2 visits (including ERG, if applicable) should be performed. | — |
Countries
Germany, United States
Contacts
Public ContactAcucela Clinical Trials Helpdesk
Acucela Inc.
Outcome results
None listed