An Exploratory Clinical Trial Evaluating LX109 Gene Therapy in Patients With nAMD

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of intravitreal injection of LX109 in patients with nAMD.

Detailed Description
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In this study, 9 to 12 participants were enrolled in an open monocular, single dose escalation study design. Two dose groups were set up: low dose group (7×109 VG/ eye, 0.05ml) and high dose group (3.5×1010 VG/ eye, 0.05ml). Among them, 3 to 6 subjects were enrolled in low-dose group and 6 subjects were enrolled in high-dose group.

Official Title
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An Exploratory Clinical Trial Evaluating LX109 Gene Therapy in Patients With Neovascular Age-related Macular Degeneration (nAMD)

Conditions
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To Evaluate the Safety and Tolerability of Intravitreal Injection of LX109 in Patients With nAMD

Intervention / Treatment
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* Drug: LX109


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Informed consent must be signed before all assessments; 2) Male or female patients ≥50 years of age; 3) To investigate the presence of active CNV secondary to nAMD (occult or micromenorrhea) in the eye 4) When studying the baseline of the eye, use the ETDRS eye chart to test the BCVA of 19 to 73 letters (approximately equivalent to decimal notation) Recorded visual acuity 0.05-0.5); 5) Study eyes received at least 2 anti-VEGF treatments within 6 months. Note: For all subjects, only one eye was used as the study eye (i.e. the study eye receiving treatment). If both eyes of the subject meet the inclusion criteria, the eye with poor baseline vision will be selected as the study eye, or the eye with better vision may be selected for medical reasons or ethical requirements. Exclusion Criteria: 1. In the investigator's judgment, concomitant eye diseases of the study eye at screening or baseline may cause subjects to fail to respond to study therapy or confuse the interpretation of study findings. For example, diabetic retinopathy, retinal vein obstruction, retinal retinal detachment, macular hiatus (stage 3 or 4), uveitis, vitreous macular traction affecting central vision, macular anterior membrane involving macular fovea or damaging macular structure, equivalent spherical lens ≤-8.00D of the study eye, etc. 2. To investigate the presence of subretinal hyperreflective substance (SHRM) involving the fovea except CNV lesions; 3. Central serous chorioretinopathy (CSC) was confirmed in the study eyes at any time; 4. Study retinal detachment in the eye at any time; 5. Non-study eye BCV A less than decimal recorded visual acuity 0.05(<19 ETDRS letters); 6. The presence of uncontrolled glaucoma (defined as intraocular pressure ≥25mmHg after standard treatment) in the study eye; 7. Active intraocular or periocular inflammation or infection in the study eye or non-study eye; 8. To investigate the presence of CNV or macular edema secondary to causes other than AMD; 9. In the study, the refractive medium of the eye is seriously cloudy or the pupil cannot be sufficiently dilated, affecting BCVA or causing insufficient acquisition Clear eye imaging data, such as OCT, FFA, and fundus photography, affect researchers' observation of safety and efficacy. Eye Treatment： 10. Internal eye surgery, such as vitrectomy, cataract phacoemulsification, trabeculectomy, or other filtering surgery, was performed within 3 months prior to baseline screening or study eye screening; 11. Study eyes screened or treated with intravitreal drug injections or drug-containing intraocular implants other than anti-VEGF drugs, such as intraocular corticosteroids, within 6 months prior to baseline; 12. Research eye or systemic have received gene therapy; 13. Study eyes screened or treated with macular laser photocoagulation or photodynamic therapy (PDT) or full vision membrane laser photocoagulation within 3 months prior to baseline; 14. Study eyes were screened or underwent YAG laser posterior capsulectomy or laser trabeculectomy or laser periiridectomy within 1 month prior to baseline

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LX109<br> | Drug: LX109<br>* LX109 gene injection Specification: 0.2ml/bottle, 1.4×1012VG/ml Administration route: intravitreal injection, injection volume 0.05ml/eye<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of mean BCVA score on the ETDRS visual acuity scale from baseline. | Changes of BCVA scores on the ETDRS visual acuity chart of the study eye from baseline at 4, 24 and 52 weeks after treatment with LX109. | 4 weeks、24 weeks、52 weeks | 
| Changes in mean eye CST from baseline at 4, 24 and 52 weeks after LX109 treatment were studied. |  | 4 weeks、24 weeks、52 weeks | 
| The time after LX109 treatment to the first salvage treatment. |  | 52 weeks | 
| Proportion of subjects receiving salvage treatment in the study eye at 24 weeks and 52 weeks after treatment with LX109. |  | 24 weeks、52 weeks | 
| The number of times the eye received salvage treatment at 24 weeks and 52 weeks after treatment with LX109 was studied. |  | 24 weeks、52 weeks |