Phase I/II Study of NGGT001 Gene Therapy for Bietti Crystalline Dystrophy

Purpose: To evaluate the safety and preliminary functional outcomes of NGGT001 gene therapy across dose cohorts in adults with Bietti crystalline dystrophy (BCD) with relatively preserved vision. Design: A phase I/II multicenter open-label dose-escalation and dose-expansion clinical trial. Participants: Twelve adults with genetically confirmed BCD. Methods: vector genomes [vg] per eye; n = 3 per cohort). Three additional participants were enrolled in a mid-dose expansion cohort. Participants were followed for 12 months. The study was conducted at 2 tertiary centers in China between March and September 2024. Main Outcome Measures: The primary outcome was safety through month 12. Secondary outcomes included changes from baseline in best-corrected visual acuity (BCVA) and macular sensitivity measured by microperimetry. Results: vg/eye). In the mid-dose cohort, mean (standard deviation) BCVA was 47.8 (13.0) ETDRS letters at baseline and improved by 13.3 (8.1) letters at month 6 and 9.1 (11.5) letters at month 12. Mean (standard deviation) microperimetry sensitivity changes from baseline were 0.86 (2.73) dB at month 6 and 0.73 (2.82) dB at month 12. Untreated fellow eyes showed mean (standard deviation) BCVA changes of 6.9 (6.6) letters and microperimetry fluctuations of 0.60 (2.2) dB at month 12. Exploratory analyses suggested greater functional improvements in eyes with more preserved outer retinal structure. Conclusions: Subretinal NGGT001 demonstrated a favorable safety profile in this phase I/II study. The mid-dose cohort showed the most consistent functional improvements, although bilateral variability was observed. These findings support further evaluation of NGGT001 in randomized controlled trials. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.