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

Phase 1Not Yet RecruitingNCT06623279

HuidaGene Therapeutics Co., Ltd.15 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neovascular Age-Related Macular Degeneration (nAMD)

Eligibility

Sex: ALLMin age: 50 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Incidence and severity of ocular and systemic adverse events

Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)

Time frame: 52 weeks

Secondary Outcomes

Mean change from baseline in best-corrected visual acuity (BCVA)

Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses

Time frame: 52 weeks

Mean change in annualized rate of supplemental injections

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

Time frame: 52 weeks

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts