Open-laBel Dose-escalation Study for CRISPR/cas13- Rna TargetInG THerapy for the Treatment of Neovascular Age-related Macular Degeneration in Phase I Trial
- Conditions
- Neovascular Age-Related Macular Degeneration (nAMD)
- Interventions
- Genetic: HG202
- Registration Number
- NCT06623279
- Lead Sponsor
- HuidaGene Therapeutics Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 15
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description HG202 HG202 The study will enroll up to 3 dose cohorts：Low dose/Middle dose/High dose
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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