Inherited Retinal Dystrophy Due to RPE65 Mutations
Conditions
Keywords
Leber congenital amaurosis, retinitis pigmentosa
Brief summary
Multi-site, non-randomized, observational study, for up to 15 years after subretinal AAV2-hRPE65v2 administration for each subject. The study is a non-interventional, follow-up study of subjects who participated in previous AAV2-hRPE65v2 gene therapy clinical trials.
Detailed description
This is an observational follow-up study of subjects who participated in previous Phase 1 and Phase 3 clinical trials of AAV2-hRPE65v2 gene therapy (voretigene neparvovec-rzyl) to evaluate long term durability and safety for 15 years after subretinal administration.
Interventions
BIOLOGICALAAV2-hRPE65v2
Sponsors
Genentech, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1\. Subjects who participated in prior subretinal AAV2-hRPE65v2 gene therapy clinical studies
Exclusion criteria
1. Subjects who will not consent for study. 2. Subjects who the investigators believe are not capable of performing study assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mobility testing, Bilateral | 15 years | Mobility testing will be videotaped at each study visit at which it is conducted. Independent reviewers may grade subjects' mobility videos. Graders will use a defined combination of speed and accuracy to grade each course attempt at a given light intensity. The course will be re-configured between each attempt, using twelve standardized templates, to reduce the impact of a potential learning effect. Each subject will be tested, using both eyes, under at least two and sometimes three different (specified) lighting conditions. The levels of light, selected to span lighting conditions that individuals encounter in daily life, range from a studio with floodlights (400 lux) or a brightly lit office (250 lux) down to a poorly lit sidewalk at night (1 lux). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Full-field light sensitivity threshold (FST) testing | 15 years | FST testing measures the light sensitivity of the entire visual field by recording the luminance at which a subject reports seeing the dimmest flash. The test is carried out on subjects with dilated eyes in a dark-adapted state; subjects are seated in front of a Ganzfeld dome in which the light flashes are generated. The light sensitivity of each eye is measured separately by patching one eye (and then the other). A sound is generated and the subject presses one button when they see a flash or a second button if they do not see a flash. Flashes of varying luminance (in a range spanning \~80 dB) are presented in a randomized order with no flashes, except that the series starts with dim flashes. From this data, an algorithm calculates the minimum luminance (for each eye) at which the subject perceives light. |
| Mobility testing, Monocular | 15 years | Mobility testing will be videotaped at each study visit at which it is conducted. Independent reviewers may grade subjects' mobility videos. Graders will use a defined combination of speed and accuracy to grade each course attempt at a given light intensity. The course will be re-configured between each attempt, using twelve standardized templates, to reduce the impact of a potential learning effect. Each subject will be tested, using the first treated eye, under at least two and sometimes three different (specified) lighting conditions. The levels of light, selected to span lighting conditions that individuals encounter in daily life, range from a studio with floodlights (400 lux) or a brightly lit office (250 lux) down to a poorly lit sidewalk at night (1 lux). |
| Visual acuity | 15 years | Visual acuity measures central vision using the ability to resolve standard optotype images presented as letters corresponding to different visual angles, i.e., image size. This testing will include age-adapted tests, such as ETDRS testing or HOTV testing (which uses the letters H, O, T, V, which can be identified even by young children and all four of which center around a vertical axis). The level of central visual resolution is converted to a visual angle score (LogMAR). Subjects may, in some cases, need to undergo repeated testing sessions, including on successive days, to establish consistent measurements on psychophysical tests, such as visual acuity. |
Contacts
PRINCIPAL_INVESTIGATORTomas Aleman, MD
University of Pennsylvania
PRINCIPAL_INVESTIGATORStephen Russell, MD
University of Iowa
Outcome results
None listed