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

Phase 1

Recruiting

• Conditions: Retinitis Pigmentosa
• Interventions: Biological: AAV2/5-hPDE6B

• Registration Number: NCT03328130
• Lead Sponsor: eyeDNA Therapeutics

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.

Then at least four patients 13 years of age or older, within a fifth cohort, 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 Timeline

• Study First Submitted: 2017-10-05
• Study First Submitted QC: 2017-10-31
• Study First Posted: 2017-11-01
• Study Start: 2017-11-06
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-07
• Primary Completion: 2029-12
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• Clinical and molecular diagnosis of retinitis pigmentosa caused by defect in PDE6B gene without other syndromic manifestations
• Aged above 13 years
• Ability to give informed consent

Key

Exclusion Criteria

• Previous ocular surgery or thermal laser within 6 months before the surgery
• Lens opacities or obscured ocular media upon recruitment such reliable evaluation or grading of the posterior segment cannot be performed
• Known serious allergies to the fluorescein dye used in angiography, to the mydriatic, steroidal and non-steroidal eye drops
• Participation in another clinical trial with an investigational agent
• Enrolled or being enrolled in another gene therapy clinical trial
• Active, extraocular infection requiring the prolonged or chronic use of antimicrobial agents
• Chronic medical conditions, cancer
• Abnormal laboratory values
• On immunosuppressive therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 3 - High Dose (confirmatory cohort)	AAV2/5-hPDE6B	Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.
Cohort 2b - High Dose	AAV2/5-hPDE6B	Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the highest dose. Confirmatory dose will be determined after DSMC assessment.
Cohort 4 - High Dose - 13 years old or older population	AAV2/5-hPDE6B	Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.
Cohort 1 - Low Dose	AAV2/5-hPDE6B	Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the lowest dose. Dose-escalation will be performed after DSMC assessment.
Cohort 2a - Medium Dose	AAV2/5-hPDE6B	Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the medium dose. Confirmatory dose will be determined after DSMC assessment.

Primary Outcome Measures

Name	Time	Method
Incidence of ocular and non-ocular adverse events	1 year + 4 years follow-up

Secondary Outcome Measures

Name	Time	Method
Improvement in visual function	1 year + 4 years follow-up	Improvement in visual function as assessed by reading speed
Improvement in visual fields	1 year + 4 years follow-up	Improvement in visual fields as assessed by visual fields measurements
Improvement in Quality of Life	1 year + 4 years follow-up	Quality of life will be measured by Quality of Life questionnaire National Eye Institute Visual Function Questionnaire (NEI VFQ-25)

Trial Locations

Locations (1)

Clinique Ophtalmologique, CHU de Nantes; 🇫🇷 Nantes, France