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

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.

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.

Study Overview

• Status: Completed
• Conditions: Neovascular (Wet) Age-related Macular Degeneration (nAMD)
• Intervention / Treatment: Biological: EXG102-031

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retina Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, age ≥ 50 years of age;
2. Diagnosis of nAMD and current active lesion in the study eye at Screening;
3. An ETDRS BCVA letter scores between 73 and 19 letters in the study eye;
4. Response to anti-VEGF treatment during Screening;
5. The study eye must be a pseudophakic lens (post-cataract surgery status); and
6. 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:

1. 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;
2. Presence in the study eye of CNV or macular edema due to causes other than AMD;
3. Presence in the study eye of scarring, fibrosis or atrophy involving the macula;
4. Subretinal hemorrhage accumulating in the center of the macula of the test eye, with an area of hemorrhage ≥ 4 optic disc diameters;
5. Active ocular infection in either eye;
6. Presence of advanced glaucoma or uncontrolled glaucoma in the study eye;
7. History of intraocular surgery in the study eye within 90 days of screening; or
8. Prior receipt of any ocular or systemic gene therapy agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXG102-031; Each participant will receive a single subretinal injection of EXG102-031 in the study eye. Participants will be enrolled into one of four dosage groups sequentially, and the dose administered will be determined based on which study group the participant is enrolled into.	Biological: EXG102-031; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Exegenesis Bio
• Investigators: Principal Investigator: Arshad Khanani, MD, Sierra Eye Associates

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2023
• Primary Completion (Actual): February 16, 2026
• Study Completion (Actual): February 16, 2026

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration
• Other Study ID Numbers: EXG102-031 (211)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No