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: Participants received a single subretinal injection of NGGT001 at 3 dose levels (7.5 × 10 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: NGGT001 was well tolerated with no treatment-related serious adverse events and no evidence of intraocular inflammation or retinal toxicity. One participant developed choroidal neovascularization associated with a pre-existing lesion. No dose-limiting toxicities were observed across dose cohorts. Across treated eyes, modest improvements in functional outcomes were observed, with the most consistent changes in the mid-dose cohort (1.5 × 10 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.