Neovascular Age-Related Macular Degeneration (nAMD)
Conditions
Keywords
Macular Degeneration, nAMD, wAMD, Gene-editing, CRISPR, HG202
Brief summary
Age-related macular degeneration (AMD) leads to severe and irreversible vision loss, while neovascular AMD (nAMD) accounts for 80-90% of AMD blindness. Current anti-VEGF therapies are the standard of care, but these therapies require life-long repeated intraocular injections. These frequent intravitreal injections increase the risk of complications, including submacular hemorrhage, intraocular hypertension, inflammation, and retinal detachment. Therefore, repeated treatments for nAMD place a substantial burden on healthcare systems, patients, and their caregivers. Additionally, approximately 25-35% of individuals with aggressive nAMD show suboptimal responses to the anti-VEGF therapies, experience treatment-extended failure, or require intensive, frequent intraocular injections, and do not prevent irreversible vision loss. HG202 is a CRISPR/Cas13 RNA-editing therapy delivered through one single AAV vector to partially knock down the expression of VEGFA and thus inhibit CNV formation in AMD. The long-term, stable delivery of HG202 following a one-time gene-editing therapy treatment for nAMD may potentially reduce the frequent injections and the potential risks of currently available anti-VEGF therapies since it does not rely on the long-term expression of anti-VEGF antibodies.
Interventions
GENETICHG202
Method of Administration: Once unilateral subretinal injection; The duration of the study includes a 4-week screening period, enrollment visit, treatment visit and 52 weeks follow-up period, 4 more years long term follow up as an extension study.
Sponsors
HuidaGene Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Three dosing cohort: Low dose : 3 subjects Middle dose: 6 subjects High dose: 6 subjects
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Males or females ≥ 50 and ≤ 85 years at the time of signing the ICF; * Active macular choroidal neovascularization (MNV) secondary to nAMD in the study eye; * Sentinel (1st) subject for each dose cohort must have a BCVA ≤ 20/63 and ≥ 20/400 (≤63 and ≥ 19 ETDRS letters) in the study eye. Following the sentinel subject evaluation, the rest of the subjects in the dose cohort must have a BCVA between ≤ 20/40 and ≥ 20/400 (≤ 73 and ≥ 19 ETDRS letters) in the study eye. * Able to perform visual acuity and retinal function tests and able and willing to comply with study procedures for this clinical trial.
Exclusion criteria
* Retinal or subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion in the study eye; * Other ocular diseases that may affect central vision in the study eye; * Any other cause of CNV than nAMD in the study eye * Uncontrolled glaucoma in the study eye; * History or presence of corneal transplant or corneal dystrophy in the study eye; * History of other intraocular surgery in the study eye within 3 months prior to baseline; * Prior gene therapy or oligonucleotide therapy; * Other conditions judged by the investigator as inappropriate for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of ocular and systemic adverse events | 52 weeks | Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in best-corrected visual acuity (BCVA) | 52 weeks | Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses |
| Mean change in annualized rate of supplemental injections | 52 weeks | Change from baseline in the number of anti-VEGF injections which is annualized to a per year rate in the study eye at different doses |
Contacts
Primary ContactStudy Director
Outcome results
None listed