Biallelic RPE65 Mutation-associated Retinal Dystrophy
Conditions
Keywords
LTW888, voretigene neparvovec, Biallelic RPE65 mutation-associated retinal dystrophy, Japanese patients
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.
Interventions
GENETICvoretigene 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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in full-field light sensitivity threshold | Baseline, Day 30, 90, 180, 270, and Year 1 after second eye injection | Full-field light sensitivity threshold (FST) is evaluated using white light, as averaged over both eyes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in visual field | Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection | 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 | Baseline, Day 14, 30, 90, 180, 270, and Year 1, 2, 3, 4, 5 after second eye injection | Macular threshold is assessed as averaged over both eyes, as measured using Humphrey static visual field testing. |
| 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 | Visual acuity is assessed as averaged over both eyes. |
| Change from Baseline in FST for long-term period | Baseline, Year 2, 3, 4 and 5 after second eye injection | 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 | 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 | 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 | Baseline, Day 30, 90, 180, 270, and Year 1 after second eye injection | Assessed as presence of systemic cell-mediated or humoral responses to capsid or transgene product . |
Countries
Japan
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed