Clinical trial NCT06623279: Open-laBel Dose-escalation Study for CRISPR/cas13- Rna TargetInG THerapy for the Treatment of Neovascular Age-related Macular Degeneration in Phase I Trial
Official title: A Phase 1, Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of HG202 High-fidelity CRISPR-Cas13 (hfCas13Y) RNA-targeting Therapy for Neovascular Age-related Macular Degeneration (nAMD)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Neovascular Age-Related Macular Degeneration (nAMD)
Keywords: Macular Degeneration
nAMD
wAMD
Gene-editing
CRISPR
HG202
Lead sponsor: HuidaGene Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-10-02
Enrollment: 15
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Three dosing cohort:

Low dose : 3 subjects Middle dose: 6 subjects High dose: 6 subjects
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and severity of ocular and systemic adverse events
timeFrame: 52 weeks
Secondary outcomes:
measure: Mean change from baseline in best-corrected visual acuity (BCVA)
timeFrame: 52 weeks
measure: Mean change in annualized rate of supplemental injections
timeFrame: 52 weeks
Other outcomes:
Locations:
Study officials:
affiliation: HuidaGene Therapeutics Co., Ltd.
name: Study Director
role: STUDY_DIRECTOR
References: