Back to resultsStudy of Efficacy and Safety of Voretigene Neparvovec in Japanese Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy
Primary Purpose
Biallelic RPE65 Mutation-associated Retinal Dystrophy
Status
Active
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
voretigene neparvovec
Sponsored by
About this trial
This is an interventional treatment trial for Biallelic RPE65 Mutation-associated Retinal Dystrophy focused on measuring LTW888, voretigene neparvovec, Biallelic RPE65 mutation-associated retinal dystrophy, Japanese patients
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.
Sites / Locations
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Voretigene neparvovec
Arm Description
1.5 E11 vg (0.3 mL subretinal injection in each eye, 6-18 days apart)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Change from Baseline in macular threshold
Macular threshold is assessed as averaged over both eyes, as measured using Humphrey static visual field testing.
Change from Baseline in visual acuity
Visual acuity is assessed as averaged over both eyes.
Change from Baseline in FST for long-term period
FST is assessed using white light, as averaged over both eyes.
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.
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 .
Full Information
NCT ID
NCT04516369
First Posted
August 10, 2020
Last Updated
June 13, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04516369
Brief Title
Study of Efficacy and Safety of Voretigene Neparvovec in Japanese Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 24, 2020 (Actual)
Primary Completion Date
April 5, 2022 (Actual)
Study Completion Date
May 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Biallelic RPE65 Mutation-associated Retinal Dystrophy
Keywords
LTW888, voretigene neparvovec, Biallelic RPE65 mutation-associated retinal dystrophy, Japanese patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Voretigene neparvovec
Arm Type
Experimental
Arm Description
1.5 E11 vg (0.3 mL subretinal injection in each eye, 6-18 days apart)
Intervention Type
Genetic
Intervention Name(s)
voretigene neparvovec
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from Baseline in full-field light sensitivity threshold
Description
Full-field light sensitivity threshold (FST) is evaluated using white light, as averaged over both eyes.
Time Frame
Baseline, Day 30, 90, 180, 270, and Year 1 after second eye injection
Secondary Outcome Measure Information:
Title
Change from Baseline in visual field
Description
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.
Time Frame
Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection
Title
Change from Baseline in macular threshold
Description
Macular threshold is assessed as averaged over both eyes, as measured using Humphrey static visual field testing.
Time Frame
Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection
Title
Change from Baseline in visual acuity
Description
Visual acuity is assessed as averaged over both eyes.
Time Frame
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
Title
Change from Baseline in FST for long-term period
Description
FST is assessed using white light, as averaged over both eyes.
Time Frame
Baseline, Year 2, 3, 4 and 5 after second eye injection
Title
Proportion of subject with the presence of vector shedding of voretigene neparvovec during the study period
Description
Assessed as the presence of vector in peripheral blood or collected tear.
Time Frame
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
Title
Proportion of subject with the presence of immunogenicity of voretigene neparvovec during the study period
Description
Assessed as presence of systemic cell-mediated or humoral responses to capsid or transgene product .
Time Frame
Baseline, Day 30, 90, 180, 270, and Year 1 after second eye injection
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Meguro-ku
State/Province
Tokyo
ZIP/Postal Code
152-8902
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Learn more about this trial
Study of Efficacy and Safety of Voretigene Neparvovec in Japanese Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy
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