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

An Open-label, Single-arm Study to Provide Efficacy and Safety Data of Voretigene Neparvovec Administered as Subretinal Injection in Japanese Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Biallelic RPE65 Mutation-associated Retinal Dystrophy
• Intervention / Treatment: Genetic: voretigene neparvovec

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Meguro-ku, Tokyo, Japan, 152-8902
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Voretigene neparvovec; 1.5 E11 vg (0.3 mL subretinal injection in each eye, 6-18 days apart)	Genetic: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in visual field	Visual Field is assessed using the sum total degrees for VF, averaged over both eyes, as measued using Goldmann kinetic perimetry testing with a III4e target.	Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection
Change from Baseline in macular threshold	Macular threshold is assessed as averaged over both eyes, as measured using Humphrey static visual field testing.	Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection
Change from Baseline in visual acuity	Visual acuity is assessed as averaged over both eyes.	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	FST is assessed using white light, as averaged over both eyes.	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	Assessed as the presence of vector in peripheral blood or collected tear.	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
Proportion of subject with the presence of immunogenicity of voretigene neparvovec during the study period	Assessed as presence of systemic cell-mediated or humoral responses to capsid or transgene product .	Baseline, Day 30, 90, 180, 270, and Year 1 after second eye injection

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Actual): April 5, 2022
• Study Completion (Estimated): June 22, 2026

Study Registration Dates

• First Submitted: August 10, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Japanese patients; LTW888; voretigene neparvovec; Biallelic RPE65 mutation-associated retinal dystrophy
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Retinal Dystrophies
• Other Study ID Numbers: CLTW888A11301; 2019-003781-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No