{"doi":"10.1016/j.xops.2025.100970","title":"Intravitreal Gene Therapy with LX102-C01 in Neovascular Age-Related Macular Degeneration: A Phase I Dose-Escalation Study of 12-Month Safety and Efficacy Outcomes","abstract":"Purpose To assess the safety, tolerability, and preliminary efficacy of a single intravitreal injection of LX102-C01 in eyes with neovascular age-related macular degeneration (nAMD) followed up to 52 weeks. Design Open-label, single-center, dose-escalation investigator-initiated trial (IIT; NCT05831007) with two cohorts (3E10 vg and 1E11 vg per eye). Subjects Eyes with choroidal neovascularization secondary to nAMD, subretinal or intraretinal fluid, and a history of more than two anti-VEGF treatments in the past six months with a good response. Methods and Measures All patients received one injection of aflibercept two weeks before LX102-C01. Dose escalation started with 3E10 vector genomes (vg) and increased to 1E11 vg per eye. Visual acuity, anatomy, and adverse events were assessed. Macular choroidal thickness and vascularity were measured using a 6 × 6 mm scan on swept-source optical coherence tomography angiography (SS-OCTA) imaging. The primary endpoint was adverse events (AEs) at one year. Secondary endpoints were best-corrected visual acuity (BCVA), central subfield thickness (CST) and incidence of rescue treatment. Exploratory endpoints included the macular hypoautofluorescent area, choroidal thickness, and choroidal vascularity index. Results Six eyes of 6 patients were included. There was no LX102-C01-related non-ocular adverse events. All LX102-C01-related ocular AEs were mild, predominantly anterior inflammation. No evidence of vasculitis, retinitis, choroiditis, vascular occlusions or endophthalmitis. Two eyes from 2 patients developed recurrent subretinal fluid or hemorrhages that did not meet rescue criteria, and resolved spontaneously after 1 to 2 months. All patients were free of rescue anti-VEGF treatments till the latest visit. Compared to baseline, BCVA maintained and CST decreased up to 12 months in both cohorts. The area of hypo-autofluorescence remained stable in both groups. Mean choroidal thickness (MCT) decreased from 162.1 μm to 147.1 μm (P=0.03), but the choroidal vascularity index (CVI) measurement showed no significant change (P=0.6) up to 12 months. Changes in MCT and CVI showed no statistically significant differences compared to the control group receiving standard aflibercept treatment. Conclusions LX102-C01 showed a favorable safety profile and potential efficacy in this preliminary 52-week study, with no observed macular atrophy, suggesting short-term tolerability of gene therapy associated anti-VEGF expression.","journal":"Ophthalmology Science","year":2025,"id":577596,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":687992,"name":"Mengxi Shen","orcid":"0000-0002-1336-1695","position":1,"is_corresponding":false},{"id":1487124,"name":"Jieqiong Chen","orcid":"0000-0003-1673-6517","position":2,"is_corresponding":false},{"id":1487125,"name":"Yidong Wu","orcid":"0000-0003-0803-657X","position":3,"is_corresponding":false},{"id":1408460,"name":"Yongsheng Zhou","orcid":"0000-0002-8503-4669","position":4,"is_corresponding":false},{"id":1487126,"name":"Jingyang Feng","orcid":"0000-0001-6031-7980","position":5,"is_corresponding":false},{"id":364504,"name":"Yuxuan Cheng","orcid":"0000-0003-1200-727X","position":6,"is_corresponding":false},{"id":1487127,"name":"Huixun Jia","orcid":"0000-0001-9341-5587","position":7,"is_corresponding":false},{"id":1487128,"name":"Xiaolu Yang","orcid":"0000-0002-9823-0458","position":8,"is_corresponding":false},{"id":1487129,"name":"Yuanyuan Gong","orcid":"0000-0002-9250-8957","position":9,"is_corresponding":false},{"id":314002,"name":"Yan Liu","orcid":"0000-0003-4242-4840","position":10,"is_corresponding":false},{"id":105025,"name":"Hong Wang","orcid":"0000-0003-0477-2908","position":11,"is_corresponding":false},{"id":284472,"name":"Ruikang K. Wang","orcid":"0000-0001-5169-8822","position":12,"is_corresponding":false},{"id":304779,"name":"Philip J. Rosenfeld","orcid":"0000-0002-4068-6671","position":13,"is_corresponding":false},{"id":1487130,"name":"Tong Li","orcid":"0000-0002-2544-1254","position":14,"is_corresponding":false},{"id":1083588,"name":"Xiaodong Sun","orcid":"0000-0001-5015-0945","position":16,"is_corresponding":false},{"id":1487123,"name":"Junran Sun","orcid":"0000-0001-6545-5223","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:58:16.148027Z","pmid":"41552660","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}