Open-laBel Dose-escalation Study for CRISPR/cas13- Rna TargetInG THerapy for the Treatment of Neovascular Age-related Macular Degeneration in Phase I Trial (BRIGHT)

HuidaGene Therapeutics

Status and phase

Not yet enrolling

Phase 1

Conditions

Neovascular Age-Related Macular Degeneration (nAMD)

Treatments

Genetic: HG202

Study type

Interventional

Funder types

Industry

Identifiers

NCT06623279

HG20202

Details and patient eligibility

About

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.

Enrollment

15 estimated patients

Sex

All

Ages

50 to 85 years old

Volunteers

No Healthy Volunteers

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.