Safety and Efficacy Study of Novel Gene Therapy AGX-08 for Geographic Atrophy

Official title

Prospective, Dose-Escalating, Investigator Initiated Trial to Evaluate the Safety and Efficacy of AGX-08 in Geographic Atrophy

Overview

This is AGX-08's safety, tolerability, and efficacy in Geographic Atrophy first-in-human study. This trial is meant to evaluate the safety and efficacy of AGX-08 in Geographic Atrophy patients. Unilateral intravitreal injections (IVT) will be given into the subject's Study Eye.

Detailed description

Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population. Patients with GA experience progressive degeneration of retinal cells, resulting in gradual and permanent visual decline. Currently, there are limited effective treatment options available. We have developed an innovative adeno-associated virus (AAV)-based gene therapy for patients with GA, regardless of underlying genetic background. Approximately 8 to 24 subjects with GA will be recruited, among whom a subset will receive a single unilateral intravitreal injection of AGX-08 at ascending doses, while a proportion of subjects will receive sham injections as the control group.

Interventions

• Drug AGX-08-L
  rAAV2.AG-eNCRV intravitreal injection of low dose
• Drug AGX-08-H
  rAAV2.AG-eNCRV intravitreal injection of high dose
• Procedure AGX-08-S
  sham intravitreal injection of AGX-08 (not actual injection)

Primary outcome measures

• Incidence of treatment-emergent adverse events,adverse events, serious adverse events and dose-limiting toxicities [Time frame: baseline to Week 52]

Secondary outcome measures (2)

• Change in Fundus Autofluorescence (FAF) [Time frame: baseline to Week 52]
• Change in best corrected visual acuity (BCVA) [Time frame: baseline to Week 52]

Eligibility criteria

Inclusion criteria

• Clinically confirmed diagnosis of geographic atrophy (GA) secondary to age-related macular degeneration (AMD);
• Age ≥ 50 years, regardless of sex;
• Best-corrected visual acuity (BCVA) in the study eye measured using the ETDRS chart at a starting distance of 4 meters must be ≤35 letters (Snellen equivalent ≤20/200), with vision no worse than light perception; the fellow eye must not have better visual acuity than the study eye;
• GA lesion size between 2.5 and 17.5 mm² with clearly defined borders. For multifocal GA, at least one lesion must be ≥1.25 mm² (0.5 disc area) to ensure measurable efficacy assessment;
• Presence of choroidal neovascularization (CNV) in the fellow eye is allowed;
• Women of childbearing potential must have a negative pregnancy test (blood or urine);
• Women of childbearing potential and male participants must agree to use effective contraception during the study and for 3 months after completion, with no plans for reproduction;
• Willing and able to provide written informed consent and comply fully with the study protocol.

Exclusion criteria

• GA caused by conditions other than AMD (e.g., Stargardt disease, cone-rod dystrophy, or other inherited macular dystrophies);
• Aphakia in the study eye, or cataract surgery/YAG capsulotomy within 3 months prior to screening;
• Refractive status or axial length outside the following range: spherical equivalent between -6.00D and +5.00D, and axial length between 21 mm and 26 mm;
• Two baseline BCVA measurements (ETDRS) taken at least 14 days apart during screening differ by >30%;
• Current or prior evidence of exudative (wet) AMD in the study eye, including retinal pigment epithelium tear, retinal vascular occlusions, history of corneal transplantation, or any neovascularization confirmed by fluorescein angiography;
• Active ocular diseases in the study eye, including inflammation, other macular diseases, glaucoma, ocular hypertension, or acute/chronic ocular infections;
• Major ocular surgery within 3 months prior to screening;
• History of retinal detachment or other fundus diseases unsuitable for study participation;
• Prior macular laser photocoagulation with irreversible retinal damage;
• Pregnant or lactating women, or participants unwilling to use effective contraception for 12 months before and after study intervention;
• Narrow anterior chamber angle or other contraindications to pupil dilation;
• Any ocular condition that may interfere with visual acuity assessment, OCT, or other ophthalmic evaluations;
• History of hypersensitivity to contrast agents, study drugs, or excipients;
• Allergy to corticosteroids, intolerance to protocol-required corticosteroid therapy, or contraindicated active infections;
• Severe systemic diseases, psychiatric disorders, uncontrolled chronic conditions, or other medical conditions that may increase study risk (e.g., malignancy, metabolic or autoimmune diseases);
• articipants with a prior history of malignancy must have completed curative treatment ≥5 years before enrollment and must have no evidence of active disease, recurrence, or metastasis. Participants whose prior malignancy is considered unlikely to affect life expectancy may be eligible based on Investigator assessment in consultation with an oncology specialist. The 5-year disease-free interval requirement may be waived for adequately treated cervical carcinoma in situ or non-melanoma skin cancer with minimal risk of recurrence.;
• Receiving or likely to receive immunosuppressive therapy outside this study;
• Participation in another investigational drug study within 3 months prior to screening;
• Prior gene therapy other than this study;
• Any condition that may compromise scientific evaluation of the study;
• Any contraindication to intravitreal (IVT) injection;
• Any other condition deemed unsuitable by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07602127 · AGX-08

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗