Wet age-related macular degeneration resistant to anti-VEGF therapy
Conditions
Interventions
Treatment group:Subretinal injection of 7.5×10^10 vg/eye of AAV-nCas9 and AAV-DIDA-CBE
Sponsors
Shenzhen Eye Hospital
Eligibility
Sex/Gender
All
Age
50 Years to 89 Years
Inclusion criteria
Inclusion criteria: 1. Patients diagnosed with neovascular age-related macular degeneration, regardless of gender. 2. Aged between 50 and 89 years old. 3. Following prior anti-VEGF therapy in the study eye, SD-OCT assessment indicated a prior therapeutic response (defined as a reduction in central retinal thickness of =5 letters in best-corrected visual acuity (BCVA) relative to baseline or the highest BCVA achieved during treatment). 5. Recruited subjects had best-corrected visual acuity (BCVA) ranging from 20/400 to 20/63 (Snellen chart, corresponding to ETDRS letters 19 to 63). 6. Both eyes meet the inclusion criteria; the eye with poorer vision is selected for inclusion. 7. The study must clearly diagnose subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). The CNV lesion area must be less than 10 disc areas, and the haemorrhagic area must constitute less than 50% of the total lesion area. 8. The degree of cataract formation does not affect the assessment of the fundus or the fitting of an intraocular lens. 9. Able to comply with all research procedures and follow-up appointments during the study period. 10. Female subjects of childbearing potential must have a negative urine pregnancy test at the screening visit, a negative serum pregnancy test result on day 8, and must consent to additional pregnancy testing during the study period. 11. Participants who are sexually active must agree to use contraception from the date of recruitment until 24 weeks after carrier administration. Should contraception need to be discontinued thereafter, this should be decided following discussion with the responsible physician. 12. Subjects must be willing and able to sign a written informed consent form.
Exclusion criteria
Exclusion criteria: 1. Investigate the presence of choroidal neovascularisation or macular oedema caused by factors other than age-related macular degeneration. 2. The haemorrhagic area within the AMD lesion is >=50%, or the haemorrhagic area beneath the fovea centralis in the study eye exceeds 1.0 mm². 3. Any pathological condition that may impede the improvement of visual acuity, such as fibrosis, atrophy, or retinal pigment epithelial detachment in the foveal region. 4. The eye under investigation exhibits active retinal detachment or a history of retinal detachment. 5. The eye exhibits signs of advanced glaucoma. 6. Investigate any existing conditions that may increase subject risk, necessitate pharmacological or surgical intervention during the study to prevent or treat vision loss, or interfere with study procedures or assessments (as determined by the investigator). 7. Subjects who had undergone intraocular surgery within the 12 weeks preceding recruitment, or who had received YAG laser posterior capsulotomy within the preceding 10 weeks. 8. Within the six months preceding recruitment, the study eye had received intravitreal treatment other than anti-VEGF therapy (such as intravitreal corticosteroid injections or investigational products). 9. At the time of recruitment, the eye under investigation must already have an implant (excluding intraocular lenses). 10. Recruitment excludes individuals who have had malignant tumours requiring chemotherapy and/or radiotherapy within the preceding five years. Excludes localised basal cell carcinoma. 11. Received the investigational product within 30 days prior to study entry or within five half-lives of the investigational product. 12. Has previously participated in other gene therapy research. 13. Previously received treatment known to cause retinal toxicity, or currently receiving medication that may affect vision or has known retinal toxicity (e.g., chloroquine or hydroxychloroquine). 14. Investigate whether any ocular or periorbital infections may interfere with surgical procedures. 15. Myocardial infarction, cerebrovascular accident, or transient ischaemic attack within the past six months. 16. Uncontrolled hypertension is present (systolic blood pressure > 180 mmHg, diastolic blood pressure > 100 mmHg). 17. Currently undergoing treatment concurrently that may interfere with ocular surgical procedures or postoperative healing (as determined by the investigator). 18. Known hypersensitivity to rituximab or any of its constituents, or a history of allergic reactions to AAV-based medicinal products (as determined by the investigator). 19. Suffering from severe, chronic, or unstable medical or psychiatric conditions which, in the investigator's judgement, may jeopardise the subject's safety or impair their ability to complete all assessments and follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events within 24 weeks of subretinal injection; | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety of subretinal injections at 48 weeks follow-up;Best-corrected visual acuity;The necessity of supplementary anti-VEGF-A injections during the 48-week follow-up period;Concentration of VEGF protein in the anterior chamber aqueous;Central retinal thickness; | — |
Countries
China
Contacts
Public ContactChi Wei
Shenzhen Eye Hospital
Outcome results
None listed