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

NCT04516369 | Active Not Recruiting Phase 3

• 2 other identifiers: CLTW888A113012019-003781-41
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Biallelic RPE65 Mutation-associated Retinal Dystrophy

Keywords

LTW888; voretigene neparvovec; Biallelic RPE65 mutation-associated retinal dystrophy; Japanese patients

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in full-field light sensitivity threshold

  Full-field light sensitivity threshold (FST) is evaluated using white light, as averaged over both eyes.

  Baseline, Day 30, 90, 180, 270, and Year 1 after second eye injection

Secondary Outcomes (6)

• Change from Baseline in visual field

  Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection

• Change from Baseline in macular threshold

  Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection

• Change from Baseline in visual acuity

  Baseline, Day 1, and 3 after first eye injection; Day 1, 3, 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection

• Change from Baseline in FST for long-term period

  Baseline, Year 2, 3, 4 and 5 after second eye injection

• Proportion of subject with the presence of vector shedding of voretigene neparvovec during the study period

  Baseline, Day 0, 1 and 3 after first eye injection; Day 0, 1, 3, 14, 30, 90, 180, 270, and Year 1 after second eye injection

Study Arms (1)

Voretigene neparvovec

EXPERIMENTAL

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

Genetic: voretigene neparvovec

Interventions

voretigene neparvovec 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.

Voretigene neparvovec

Eligibility Criteria

• Age: 4 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Meguro-ku, Tokyo, 152-8902, Japan

Location

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2020
• First Posted: August 18, 2020
• Study Start: November 24, 2020
• Primary Completion: April 5, 2022
• Study Completion (Estimated): June 22, 2026
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (1)