Study to Evaluate Safety and Efficacy of EG-301 in Patients With Nonfocal Geographic Atrophy Secondary to dAMD

Study Overview
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Brief Summary
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This is a parallel, randomized, open-label, controlled study to evaluate the efficacy and safety of oral EG-301 in patients with intermediate non-exudative (dry) age-related macular degeneration (dAMD). Ninety patients will be randomly allocated in a 2:1 ratio to one of two treatment arms for at least 6 months duration. The two treatment arms are: AREDS2 supplements (Control Group, N=30) AREDS2 supplements plus EG-DPMP-01 150 mg daily (Experimental Group, N=60)

Official Title
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A Phase 2, Parallel, Randomized, Open-label, Controlled Study of EG-301 150 mg Daily in Patients With Nonfocal Geographic Atrophy Secondary to dAMD

Conditions
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Non-Exudative (Dry) Age-related Macular Degeneration (dAMD)

Intervention / Treatment
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* Drug: EG-301
* Dietary Supplement: AREDS2 supplements


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, 50 to 75 years of age at screening visit Subject has signed the Informed Consent form Subjects with intermediate nonfocal geographic atrophy secondary to Non-Exudative (dry) AMD having ETDRS BCVA between 35 and 80 letters read (equivalent to 20/25 - 20/200 on Snellen Chart) with the level of vision caused by the non-exudative AMD and no other factor/s Subjects with symptomatic decrease in visual acuity in the last 12 months Subjects with confirmed diagnosis of geographic atrophy (GA) secondary to dAMD in the study eye* as evidenced by the following characteristics: Non-center involving GA lesions that reside completely within the FAF imaging field (field 2, 30 degree image centered on the fovea) Total GA area is ≥2.5 and ≤ 17.5 mm2 (1 and 7 disk areas [DA]) If GA is multifocal, at least one focal lesion must be >1.25 mm2 (0.5 DA) Combination of areas of RPE disturbances described as a pattern of hyper or hypo-pigmentation in the junctional zone of GA. Absence of hyper-autofluorescence is exclusionary Subjects with evidence of reasonably well-preserved areas of RPE by clinical examination and well-defined RPE and outer segment ellipsoid line by OCT examination in the central 1 mm of the macula as confirmed by the central reading center. More specifically, reasonably well- preserved central 1 mm of the macula means: The RPE and outer retinal layers throughout the central 1 mm are intact No signs of NVAMD such as intraretinal or sub retinal fluid, or sub retinal hyper-reflective material No serous pigment epithelium detachments >100 microns in height Sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and able to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment Exclusion Criteria: Females who are pregnant, nursing, planning a pregnancy during the study or who are of childbearing potential not using a reliable method of contraception and/or not willing to maintain a reliable method of contraception during their participation in the study. Women of childbearing potential with a positive urine pregnancy test administered at baseline are not eligible to receive study drug Prior cataract surgery is allowed up to 90 days before the baseline visit, but refractive surgery in either eye may not be conducted during the study. Subject with exudative AMD or choroidal neovascularization (CNV), including any evidence of retinal pigment epithelium rips, detachments or evidence of neovascularization anywhere in either eye based on SD-OCT imaging and/or fluorescein angiography as assessed by the Reading Center Subjects who had anti-VEGF IVT in either eye in the past 90 days Subjects who have received any drug or herbal medicine known to inhibit CYP2D6 enzyme activity prior to the first dose of the investigational drug (the patient can be enrolled if the washout period is ≥5 half-lives of the CYP2D6 inhibitor), or subjects who need to continue receiving these medications during the study period. (Refer to Appendix 1 for a list of CYP2D6 inhibitors) Subjects with moderate or severe renal impairment as indicated by an estimated glomerular filtration rate (eGFR) <60 mL/min, calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Subjects with moderate or severe hepatic impairment as indicated by a score on the Child-Pugh scale at screening as follows: Child-Pugh C (Severe hepatic impairment): ≥ 10 and ≤ 15 Child-Pugh B (Moderate hepatic impairment): ≥ 7 and ≤ 9 Subject has any active ocular disease or condition that in the opinion of the Investigator could confound visual function or assessment of the macula, or be a contraindication to oral drugs with anticholinergic side effects (e.g., angle closure glaucoma, uncontrolled open-angle glaucoma, corneal opacification) Subject who had any intra-ocular surgery (except for intraocular lens replacement surgery) of fewer than 3 months prior to consent Subject who participated in an investigational drug or device study within 90 days of screening Subjects with neurological conditions that can impair vision or who take medications that affect the metabolism of EG-DPMP-01 (e.g., Parkinson's disease, multiple sclerosis, Alzheimer's disease) Subjects with comorbid cardiovascular and metabolic disease Subjects with a family history of congenital long QT syndrome Subjects with concomitant use of metabolic inhibitors and agents associated with QT interval prolongation and hypokalaemia Subject with history or presence of pro-arrhythmic conditions, including a marked baseline prolongation of QTc interval (i.e., repeated demonstration of a QTc interval >450 milliseconds) or a history of additional significant risk factors for torsade de pointes (e.g., family history of long QT syndrome), including any evidence of QTc prolongation at screening Subjects with a family history of sudden death, cardiac dysrhythmias, or cardiac conduction disturbances Subjects with a history of seizure disorder Subjects who are taking bupropion (because risk of seizure may be increased) Subjects who are in the acute recovery period following myocardial infarction Subjects with any disease or medical condition that in the opinion of the Investigator would prevent the subject from successfully participating in the study or might confound study results

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm: AREDS2 supplements (SOC)<br>All patients assigned to this Control Group will receive standard of care to include AREDS2 supplements daily throughout the study. | Dietary Supplement: AREDS2 supplements<br>* AREDS2 supplement is the stand of care<br>|
| Experimental: Experomental Arm: AREDS2 supplements (SOC) plus EG-301<br>Patients assigned to the Experimental Group will receive a standard of care equivalent to that of the Control Group plus EG-DPMP-01 (150 mg daily, given at bedtime with a light snack). | Drug: EG-301<br>* The investigation drug, EG-301 Tablets 150mg, is for oral use.<br>Dietary Supplement: AREDS2 supplements<br>* AREDS2 supplement is the stand of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events Assessment using CTCAE v5.0 | Number of Participants With Treatment-Related Adverse Events as Assessed by NCI CTCAE v5.0, toxicities will be characterized in terms including seriousness, causality, toxicity grading, and action taken with regard to trial treatment. | Evaluation in 26 weeks treatment period, and 4 weeks safety follow up period. | 
| GA lesion size change | The mean change in GA lesion size as measured by a) fundus autofluorescence (FAF) by an independent central reading center (CRC), and b) SD-OCT | From baseline to Week 26 treatment period | 
| Overall retinal sensitivity | Change in overall retinal sensitivity as measured by microperimetry using macular integrity assessment (MAIA) | From baseline to Week 26 treatment period | 
| BCVA in number of letters | The mean change in BCVA in the number of letters as assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol | From baseline to Week 26 treatment period, and 4 weeks safety follow up period. | 
| Low luminance visual acuity (LLVA) | The mean change in low luminance visual acuity (LLVA) in number of letters as assessed by the ETDRS protocol | From baseline to Week 26 treatment period | 
| Binocular reading speed | Binocular reading speed as assessed by the Minnesota Low-Vision Reading Test (MNRead) Charts | From baseline to Week 26 treatment period | 
| Binocular critical print size | Binocular critical print size as assessed by the Minnesota Low-Vision Reading Test (MNRead) Charts | From baseline to Week 26 treatment period | 
| NEI-VFQ score | Change in NEI-VFQ score | From baseline to Week 26 treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of bioactive lipids | Changes in plasma levels of bioactive lipids, including sphingolipids, ceramides, and lysophosphatidic acids | From baseline to Week 26 treatment period | 
| Plasma levels of beclin-1 levels | Changes in plasma levels of beclin-1 levels as measured by the enzyme-linked immunosorbent assay (ELISA) method with a human beclin-1 ELISA kit | From baseline to Week 26 treatment period | 
| Complement factor levels | Changes in complement factor levels, including plasma concentrations of activation products C3d, Ba, C3a, C5a, and SC5b-9. | From baseline to Week 26 treatment period |