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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

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

Maruyama Hideki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

rinshoshiken.toroku@novartis.com

Maruyama Hideki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

+81-120-003-293

rinshoshiken.toroku@novartis.com

completed

Nov. 30, 2020

Interventional

Intervention Model: Single Group Assignment Masking: None (Open Label)

treatment purpose

3

-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 micrometre 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

-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.

Both

Biallelic RPE65 Mutation-associated Retinal Dystrophy

investigational material(s)
Generic name etc :
INN of investigational material : Voretigene neparvovec
Therapeutic category code : 131 Agents for ophthalmic use
Dosage and Administration for Investigational material :

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material :

efficacy
-Change from Baseline in full-field light sensitivity threshold [ Time Frame: Baseline, Day 30, 90, 180, 270, and Year 1 after second eye injection ]

safety
efficacy
other
-Change from Baseline in visual field [ Time Frame: 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 [ Time Frame: 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 [ 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 ]
Visual acuity is assessed as averaged over both eyes.
-Change from Baseline in FST for long-term period [ Time Frame: 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 [ 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 ]
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 [ Time Frame: 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 .

+81-3-3411-0111

Jan. 21, 2020