Study of Efficacy and Safety of Voretigene Neparvovec in Japanese Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy

NCT ID: NCT04516369

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-24
• Study Completion Date: 2026-06-22

Brief Summary

The purpose of this study is to provide safety and efficacy data for voretigene neparvovec, administered as subretinal injection, in Japanese patients with biallelic RPE65 mutation-associated retinal dystrophy.

Detailed Description

This is an open-label, single-arm study to evaluate the safety and efficacy of bilateral subretinal administration of voretigene neparvovec in Japanese patients with biallelic RPE65 mutation-associated retinal dystrophy. Assessments will include full-field light sensitivity threshold testing, visual fields, visual acuity, vector shedding, immunogenicity and adverse events. Participants will be monitored for 5 years after treatment.

Conditions

Biallelic RPE65 Mutation-associated Retinal Dystrophy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Voretigene neparvovec

1.5 E11 vg (0.3 mL subretinal injection in each eye, 6-18 days apart)

Group Type: EXPERIMENTAL

voretigene neparvovec

Intervention Type: GENETIC

Voretigene neparvovec is an adeno-associated viral type 2 (AAV2) gene therapy vector driving expression of normal human retinal pigment epithelium 65 kDa protein (hRPE65) gene.

Interventions

voretigene neparvovec

Voretigene neparvovec is an adeno-associated viral type 2 (AAV2) gene therapy vector driving expression of normal human retinal pigment epithelium 65 kDa protein (hRPE65) gene.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Japanese participants with biallelic RPE65 mutation-associated retinal dystrophy; molecular diagnosis of RPE65 mutation must be confirmed by a Novartis designated laboratory in Japan.
• Age four years or older.
• Visual acuity worse than 20/60 (both eyes) and/or visual field less than 20 degrees in any meridian as measured by a III4e isopter or equivalent (both eyes).
• Sufficient viable retinal cells as determined by non-invasive means, such as optical coherence tomography (OCT) and/ or ophthalmoscopy. Must have either:

• An area of retina within the posterior pole of > 100 µm thickness shown on OCT, or
• ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole, or
• Remaining visual field within 30 degrees of fixation as measured by a III4e isopter or equivalent

Exclusion Criteria

• Any prior participation in a study in which a gene therapy vector was administered.
• Participation in a clinical study with an investigational drug in the past 6 months from screening visit.
• Known hypersensitivity to any of the study treatments including excipients or to medications planned for use in the peri-operative period.
• Unable to reliably perform the FST assessment.
• Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme in the past 6 months from screening visit.
• Prior intraocular surgery within 6 months from screening visit.
• Prior use of any medicines that, in the opinion of the investigator, may have caused retinal damage (e.g., sildenafil or related compounds, hydroxychloroquine, chloroquine, thioridazine, any other retino-toxic compounds)
• Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery or interfere with the interpretation of study. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Meguro-ku, Tokyo, Japan

Countries

Japan

Other Identifiers

2019-003781-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLTW888A11301

Identifier Type: -

Identifier Source: org_study_id