Unilateral subretinal administration of HORA-PDE6β in patients with retinitis pigmentosa harbouring mutations in the PDE6β gene: study protocol of HORA-PDE6β-001 phase I/II clinical trial.

INTRODUCTION

This phase I/II clinical trial, titled HORA-PDE6β-001, investigates the safety, tolerability and preliminary efficacy of HORA-PDE6β, a gene therapy for patients with retinitis pigmentosa (RP) caused by mutations in the PDE6β gene. The primary objective is to assess the safety profile of a unilateral subretinal injection of HORA-PDE6β, while secondary objectives include evaluating immune responses, vector shedding and visual function improvements.

METHODS AND ANALYSIS: This trial is conducted at a single centre, the CHU de Nantes, and involves five cohorts, including patients aged 13 years and older. This first-in-human study was approved by the French regulatory authorities on 28 July 2017. With a total of 19–21 patients enrolled across the cohorts, the study will monitor patients over 5 years, conducting assessments at regular intervals. The investigational product is an adeno-associated virus vector containing the human PDE6β gene, delivered to the retina to address the gene defect that causes RP. This trial aims to identify the optimal dosage for future clinical applications and to explore the therapeutic potential of gene therapy in halting or reversing retinal degeneration.

ETHICS AND DISSEMINATION: The ethics committee gave its approval on 20 July 2017. The results of this study could significantly impact the development of gene therapies for inherited retinal diseases and will be disseminated in scientific conferences and peer-reviewed indexed journals.

TRIAL REGISTRATION NUMBER: NCT03328130.