A Study of EXG102-031 in Patients With wAMD (Everest)

Study Overview
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Brief Summary
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In neovascular (wet) age-related macular degeneration (nAMD), the macula, or the part of the eye that provides the clear, detailed central vision, is being affected by abnormal blood vessel growth and leakage. This leakage affects the vision over time and can lead to severe blurriness or blinding. EXG102-031 was made to block the extra vessel formation which would lead to less leakage affecting the vision. Before EXG102-031 can be tested for its efficacy (if it makes vision better), it must be tested to see if it is safely tolerated to confirm it can continue to be studied in more patients with nAMD.

Detailed Description
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Age-related macular degeneration (AMD) is a major cause of blindness and visual impairment in older adults. The wet form of AMD, also called neovascular AMD (nAMD) usually causes faster vision loss than the dry form. The most common current treatments of nAMD are products that inhibit vascular endothelial growth factor (VEGF) (including ranibizumab (LUCENTIS®, Genentech) and aflibercept (EYLEA®, Regeneron) and are delivered by intravitreal injections at 4 to 16 week intervals and continued indefinitely. This Phase I, open-label, multiple-cohort, dose-escalation study is designed to evaluate the safety and tolerability of EXG102-031 gene therapy in subjects with previously treated nAMD. Safety will be assessed over 52 weeks after the administration of EXG102-031, and study participants will be followed for a total of five years after they receive the investigational administration of EXG102-031.

Official Title
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An Open-label, Dose-escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With EXG102-031 in Participants With Neovascular Age-related Macular Degeneration.

Conditions
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Neovascular (Wet) Age-related Macular Degeneration (nAMD)

Intervention / Treatment
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* Biological: EXG102-031


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age ≥ 50 years of age; Diagnosis of nAMD and current active lesion in the study eye at Screening; An ETDRS BCVA letter scores between 73 and 19 letters in the study eye; Response to anti-VEGF treatment during Screening; The study eye must be a pseudophakic lens (post-cataract surgery status); and Voluntarily agree to participate in the clinical trial, understand the trial procedures, and be capable of signing the informed consent form before screening. Exclusion Criteria: Presence of any ocular disease or history of disease in the study eye other than nAMD that may affect central visual acuity and/or macular detection, including retinal detachment, or in the opinion of the investigator could limit VA improvement in the study eye; Presence in the study eye of CNV or macular edema due to causes other than AMD; Presence in the study eye of scarring, fibrosis or atrophy involving the macula; Subretinal hemorrhage accumulating in the center of the macula of the test eye, with an area of hemorrhage ≥ 4 optic disc diameters; Active ocular infection in either eye; Presence of advanced glaucoma or uncontrolled glaucoma in the study eye; History of intraocular surgery in the study eye within 90 days of screening; or Prior receipt of any ocular or systemic gene therapy agent.

Ages Eligible for Study
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Minimum Age: 50 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
Intervention Model: Sequential Assignment
Interventional Model Description: Dose-escalation Study with two cohorts of three participants in each.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EXG102-031<br>Each participant will receive a single subretinal injection of EXG102-031 in the study eye. Participants will be enrolled into one of two dosage groups sequentially, and the dose administered will be determined based on which study group the participant is enrolled into. | Biological: EXG102-031<br>* EXG102-031 is a recombinant adeno-associated virus (rAAV) expressing an angiopoietin domain and VEGF receptor (ABD-VEGFR) fusion protein. EXG102-031 will be administered by subretinal injecting into one eye of each participant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety and tolerability | Frequency, type, and intensity of ocular and non-ocular adverse events (AEs) and serious adverse events (SAEs) | Throughout 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of potential efficacy | Change from baseline in best corrected visual acuity (BCVA) measured by ETDRS method | 52 weeks post administration | 
| Evaluation of potential safety | Frequency, type, and intensity of ocular and non-ocular adverse events (AEs) and serious adverse events (SAEs) | Through week 24 | 
| Evaluation of supplementary therapy injections received | Average number of doses of anti-vascular endothelial growth factor (VEGF) supplemental therapy received | Throughout 52 weeks post administration |