Natural History Study in Subjects With Usher Syndrome

Study Overview
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Brief Summary
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The objective of the study is to evaluate the natural progression of disease over time in USHIB patients

Detailed Description
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This natural history study (NHS) is being conducted to understand the progression of disease in USH1B patients as measured by a number of vision-related assessments. Disease progression will be evaluated as change over time in these measures, and associations between the endpoints will be examined.

Official Title
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A Multicentre Longitudinal, Observational Natural History Study to Evaluate Disease Progression in Subjects With Usher Syndrome Type 1B (USH1B)

Conditions
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Usher Syndrome, Type 1B

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be willing to adhere to protocol for long-term follow-up as evidenced by written informed consent or parental permission and subject assent. Subjects diagnosed with USH1. Molecular diagnosis of USH1B due to MYO7A mutations (homozygotes or compound heterozygotes). Age eight years old or older at the time of baseline. Visual acuity ≥ 20/640 in at least one eye Exclusion Criteria: Unable or unwilling to meet requirements of the study. Unable to communicate with suitable verbal/auditory and/or tactile sign language (in the opinion of the investigator) Participation in a clinical study with an investigational drug in the past six months. Pre-existing eye conditions that would interfere with the interpretation of study endpoints (for example, glaucoma, corneal or significant lenticular opacities, cystoid macular oedema, macular hole). Complicating systemic diseases in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example, radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Also excluded would be subjects with immuno- compromising diseases, as there could be susceptibility to opportunistic infection [such as cytomegalovirus (CMV) retinitis]. Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes). Prior ocular surgery within three months. Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual acuity | Refraction and Best Corrected Visual Acuity | 1 year | 
| visual acuity | Refraction and Best Corrected Visual Acuity | 2 years | 
| visual field testing | kinetic perimetry and a full field static perimetry | 1 year | 
| visual field testing | kinetic perimetry and a full field static perimetry | 2 years | 
| Clinical ophthalmic examination | External Ocular Examination to assess the motility of the extraocular muscles and the appearance and function | 1 year | 
| Clinical ophthalmic examination | External Ocular Examination to assess the motility of the extraocular muscles and the appearance and function | 2 years | 
| Clinical ophthalmic examination | Slit Lamp Examination to assess eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber | 1 year | 
| Clinical ophthalmic examination | Slit Lamp Examination to assess eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber | 2 years | 
| Clinical ophthalmic examination | Intraocular Pressure measurement | 1 year | 
| Clinical ophthalmic examination | Intraocular Pressure measurement | 2 years | 
| Clinical ophthalmic examination | Dilated Fundus Ophthalmoscopy to assess the retina, macula, choroid and optic nerve head. | 1 year | 
| Clinical ophthalmic examination | Dilated Fundus Ophthalmoscopy to assess the retina, macula, choroid and optic nerve head. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microperimetry | central visual field | 1 year | 
| Microperimetry | central visual field | 2 years | 
| Safety and Tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Safety and Tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 1 year | 
| Safety and Tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Safety and Tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 2 years |