Preliminary results in 18 patients undergoing retinal gene therapy for X-linked retinitis pigmentosa with codon-optimized AAV8-RPGR

Abstract

Purpose: To investigate the safety and efficacy of adeno-associated viral vector (AAV8) encoding retinitis pigmentosa GTPase regulator (RPGR) for X-linked retinitis pigmentosa (XLRP).Methods: This study (ClinicalTrials. gov ID NCT03116113) is being conducted in 2 Parts: Part I is a Phase 1 dose-escalation study to identify the maximum tolerated dose (MTD); Part II is a Phase 2/3, assessor-masked, dose-expansion study. In Part I, subjects with genetically confirmed RPGR-associated XLRP were administered a sub-retinal dose of AAV8-RPGR. The vector used a rhodopsin kinase promoter to drive expression of a codon-optimized sequence that generated the correct full length RPGR protein. A 3+ 3 escalation scheme was used, with 3 subjects/dose (5× 10 9, 1× 10 10, 5× 10 10, 1× 10 11, 2.5× 10 11, and 5× 10 11 gp). Part I endpoints were safety (adverse events [AEs], dose-limiting toxicities [DLTs], ophthalmic