Gene-editing therapy for treating neovascular age-related macular degeneration

A Trial to Evaluate the Safety, Tolerability, and Efficacy of CRISPR-Cas13 RNA-editing Therapy Targeting Knockdown of Vascular Endothelial Growth Factor a (HG202) in the Treatment of Neovascular Age-related Macular Degeneration (nAMD)

This study is testing a new gene-editing treatment to see if it can help people with neovascular age-related macular degeneration improve their vision and reduce the need for frequent injections.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 50 Years to 80 Years
• Sex: All
• Sponsor: HuidaGene Therapeutics Co., Ltd. (Industry-sponsored)
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT06031727 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of CRISPR/Cas13-mediated RNA targeting therapy, specifically HG202, to treat neovascular age-related macular degeneration (nAMD), a condition that leads to severe vision loss. The trial aims to address the limitations of current anti-VEGF therapies, which often require frequent injections and may lead to complications or reduced efficacy over time. Participants will be evaluated based on their visual acuity and responsiveness to previous anti-VEGF treatments. The goal is to provide a more effective and long-lasting treatment option for patients suffering from nAMD.

Who should consider this trial

Good fit: Ideal candidates are males or females aged 50 to 80 with diagnosed choroidal neovascularization secondary to AMD and a history of responsiveness to anti-VEGF therapy.

Not a fit: Patients who have shown resistance to anti-VEGF therapy and have not responded to initial treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve vision preservation and reduce the need for frequent injections in patients with nAMD.

How similar studies have performed: While gene-editing approaches are relatively novel in this context, there is growing interest and preliminary success in similar studies targeting genetic factors in AMD.

Eligibility criteria

Inclusion Criteria:

* Males or females ≥ 50 and ≤ 80 years at the time of signing the ICF
* Diagnosed of choroidal neovascularization (CNV) secondary to AMD in the study eye;
* Best-corrected visual acuity (BCVA) ranged from 73 to 23 early treatment diabetic retinopathy study (ETDRS)letter score (corresponding to 20/32 to 20/320 of Snellen visual acuity) in the study eye;
* BCVA in the non-study eye had an ETDRS letter score of 19(equivalent to Snellen visual acuity20/400) and above;
* Able to perform visual acuity and retinal function tests and able and willing to comply with study procedures for this clinical trial;

RESPONSIVE SUBJECTS:

* History of need for and responsive to anti-VEGF therapy in the study eye

NON-RESPONSIVE SUBJECTS:

* History of receiving anti-VEGF therapy but is resistant to treatment, which is defined as: a. complete or near-complete remission of subretinal fluid after the initial 3 doses of anti-VEGF agents and thenno improvement (less than 50um reduction) or deterioration of CRT by OCT

Exclusion Criteria:

* Subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion in the study eye;
* Any condition in the Investigator's opinion that could limit visual improvement in the study eye;
* Other ocular diseases that may affect central vision in the study eye (e.g., retinal vein occlusion, retinal detachment, macular hole, optic nerve disease, etc.);
* Presence of CNV not due to nAMD in the study eye,
* Uncontrolled glaucoma in the study eye;
* Active intraocular inflammation or a history of uveitis in either eye;
* History or presence of corneal dystrophy in the study eye;
* Subjects with immunodeficiency diseases prone to opportunistic infections;
* History of other intraocular surgery in the study eye within 3 months prior to baseline that in the Investigator's opinion could impact healing or study outcome interpretation;
* Prior gene therapy or oligonucleotide therapy;
* History of acute coronary syndrome, myocardial infarction, coronary revascularization, cerebrovascular accident, or transient ischemic attack within 6 months prior to the Screening Visit;
* Other conditions judged by the investigator as inappropriate for the study.

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Eye & ENT Hospital of Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
• Tianjin Medical University Eye Hospital — Tianjin, Tianjing, China (Recruiting)

Study contacts

• Study coordinator: Study Director

Conditions Neovascular Age-related Macular Degeneration; Macular Degeneration/nAMD/wAMD/Gene-editing/CRISPR/HG202