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

eyeDNA Therapeutics

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Retinitis Pigmentosa

Treatments: Biological: AAV2/5-hPDE6B

Study type: Interventional

Funder types: Industry

Identifiers

NCT03328130

2016-001429-16 (EudraCT Number)

HORA-PDE6B-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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19 participants in 5 patient groups

Cohort 1 - Low Dose

Experimental group

Description:

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the lowest dose. Dose-escalation will be performed after DSMC assessment.

Treatment:

Biological: AAV2/5-hPDE6B

Cohort 2a - Medium Dose

Experimental group

Description:

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the medium dose. Confirmatory dose will be determined after DSMC assessment.

Treatment:

Biological: AAV2/5-hPDE6B

Cohort 2b - High Dose

Experimental group

Description:

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the highest dose. Confirmatory dose will be determined after DSMC assessment.

Treatment:

Biological: AAV2/5-hPDE6B

Cohort 3 - High Dose (confirmatory cohort)

Experimental group

Description:

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.

Treatment:

Biological: AAV2/5-hPDE6B

Cohort 4 - High Dose - 13 years old or older population

Experimental group

Description:

Biological: AAV2/5-hPDE6B Unilateral (one eye), subretinal, administration of the confirmatory dose.

Treatment:

Biological: AAV2/5-hPDE6B