Preliminary safety and efficacy of DB-OTO gene therapy in pediatric patients with profound deafness due to otoferlin variants: The CHORD phase 1/2 open-label trial

Abstract

Otoferlin is critical for inner hair cell (IHC) signal transmission to auditory nerve fibers. Biallelic otoferlin gene (OTOF) variants typically cause severe-to-profound deafness. As per preclinical data, DB-OTO gene therapy promotes IHC-selective otoferlin expression from the human OTOF gene, which may instate high-quality hearing. In this first-in-human multicenter, phase 1/2 open-label clinical trial with DB-OTO (CHORD, NCT05788536), safety, tolerability and preliminary efficacy of DB-OTO is evaluated in pediatric patients with profound OTOF-related deafness.