Safety and Efficacy Study in Patients With Retinitis Pigmentosa Due to Mutations in PDE6B Gene

Safety and Efficacy Study in Patients With Retinitis Pigmentosa Due to Mutations in PDE6B Gene

Brief Summary:
The study is a Phase I/II, monocentric, open-label, dose-ranging safety and efficacy gene therapy intervention by subretinal administration of AAV2/5-hPDE6B. At least twelve patients 18 years of age or older, within four consecutive cohorts of patients, will be recruited.

Detailed Description:
Retinitis pigmentosa (RP) is a disease where part of the eye (the retina) is degenerating over time. Patients initially present with night blindness, and later in life experience loss of central vision which leads to blindness. RP is a highly variable disorder with some patients developing symptomatic visual loss in childhood whereas others remain asymptomatic until mid-adulthood. There are no treatments available.

This study focuses on the form of RP caused by mutations (modifications) in the genetic information necessary to make the protein called rod cGMP phosphodiesterase 6 β subunit (or PDE6β). Clinical diagnosis is made by function tests of the eye and confirmed using a specific method called molecular testing to verify that the PDE6B gene is not correct.

This study uses a gene therapy vector inspired from an adeno-associated virus (AAV) called AAV2/5-hPDE6B. This vector intends to supply to the target cells the PDE6B therapeutic gene that is not functioning properly in the cell. The AAV parts of the gene therapy vector work as a vehicle to deliver the normal human PDE6B gene into the cells of the retina.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 15 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Four successive cohorts separated by DSMC assessments
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of a Unilateral Subretinal Administration of HORA-PDE6B in Patients With Retinitis Pigmentosa Harbouring Mutations in the PDE6B Gene Leading to a Defect in PDE6ß Expression
Actual Study Start Date: November 6, 2017
Estimated Primary Completion Date: September 2022
Estimated Study Completion Date: September 2026

Arm:
- Experimental: Cohort 1 - Low Dose
- Experimental: Cohort 2a - Medium Dose
- Experimental: Cohort 2b - High Dose
- Experimental: Cohort 3 - High Dose (confirmatory cohort)

View full details