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

NCT06623279 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: HG20202
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Neovascular Age-Related Macular Degeneration (nAMD)

Keywords

Macular Degeneration; nAMD; wAMD; Gene-editing; CRISPR; HG202

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of ocular and systemic adverse events

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

  52 weeks

Secondary Outcomes (2)

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

  52 weeks

• Mean change in annualized rate of supplemental injections

  52 weeks

Study Arms (1)

HG202

EXPERIMENTAL

The study will enroll up to 3 dose cohorts：Low dose/Middle dose/High dose

Genetic: HG202

Interventions

HG202 GENETIC

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.

HG202

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• HuidaGene Therapeutics Co., Ltd.: lead

MeSH Terms

Conditions

Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Officials

• Study Director

  HuidaGene Therapeutics Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Study Director

CONTACT

732-318-9873; HG20202@huidagene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Three dosing cohort: Low dose : 3 subjects Middle dose: 6 subjects High dose: 6 subjects

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 2, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2031
• Last Updated: October 2, 2024

Record last verified: 2024-09