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)
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)
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 Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Study Director
- Phone Number: 732-318-9873
- Email: HG20202@huidagene.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: HG202
The study will enroll up to 3 dose cohorts：Low dose/Middle dose/High dose
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence and severity of ocular and systemic adverse events
Time Frame: 52 weeks
|
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
|
52 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Mean change from baseline in best-corrected visual acuity (BCVA)
Time Frame: 52 weeks
|
Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses
|
52 weeks
|
|
Mean change in annualized rate of supplemental injections
Time Frame: 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
|
52 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Study Director, HuidaGene Therapeutics Co., Ltd.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HG20202
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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