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

Biallelic RPE65 Mutation-associated Retinal Dystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04516369
• Other study ID #: CLTW888A11301
• Secondary ID: 2019-003781-41
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 24, 2020
• Est. completion date: May 31, 2026

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4
• Est. completion date: May 31, 2026
• Est. primary completion date: April 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Biallelic RPE65 Mutation-associated Retinal Dystrophy
• Retinal Dystrophies

Intervention

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.

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Meguro-ku	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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