Natural History Study of Patients With EYS-Associated RP

Официальное название

Natural History Prospective Open Clinical and Genetic Study of Patients With EYS-Associated Retinitis Pigmentosa

Обзор

This natural history study of patients with EYS mutations from Russia and former CIS (Commonwealth of Independent States) territories will accelerate the development of outcome measures for clinical trials. Sensitive, reliable outcome measures of retinal degeneration will greatly facilitate development of treatments for retinitis pigmentosa due to EYS mutations. This approach helps to develop experimental treatment protocol, and assessing its effectiveness. The goals and expected impact of this natural history study are to: 1. Describe the natural history of retinal degeneration in patients with biallelic mutations in EYS gene in Russia and former CIS territories. 2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration in Russia and former CIS territories. 3. Identify well-defined subpopulations for future clinical trials of investigative treatments for EYS-related retinal degeneration in Russia and former CIS territories.

Подробное описание

1. Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the EYS gene over 4 years, as measured using functional, structural, and patient-reported outcome measures 2. Investigate whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the EYS gene 3. Evaluate risk factors (genotype, phenotype, environmental, and comorbidities) for progression of the outcome measures at 4 years in individuals with biallelic pathogenic mutations in the EYS gene 4. Evaluate variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the EYS gene

Вмешательства

• Диагностический тест Whole exome/genome sequencing
  Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)

Первичные конечные точки

• Change in Visual Field Sensitivity [Срок оценки: Baseline and every year until study completion (4 years)]
• Change in Retinal Function [Срок оценки: Baseline and 4 year follow-up visit.]

Вторичные конечные точки (6)

• Change in Best Corrected Visual Acuity [Срок оценки: Screening visit and every year until study completion (4 years) for cohort 1&2. Screening visit and 48 month follow-up for cohort 3.]
• Change in Mean Retinal Sensitivity [Срок оценки: Baseline and every year until study completion (4 years)]
• Change in Best Corrected Low Luminance visual acuity [Срок оценки: Screening visit and every year until study completion (4 years) for cohort 1&2. Screening visit and 48 month follow-up for cohort 3.]
• Change in Contrast Sensitivity Function [Срок оценки: Baseline and every year until study completion (4 years).]
• Change in Ellipsoid zone (EZ) area [Срок оценки: Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.]
• Explore qualitative and quantitative categorization of Fundus Autofluorescence (FAF) pattern [Срок оценки: Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.]

Критерии участия

Критерии включения

• Willing to participate in the study and able to communicate consent during the consent process
• Ability to return for all study visits over 48 months
• Age ≥ 18 years
• Must meet one of the Genetic Screening Criteria, defined below:

Screening Group A: At least 2 disease-causing variants in the EYS gene which are homozygous or heterozygous in trans, based on a report from a clinically-certified lab (or a report from a research lab that has been pre-approved by the Study Committee) Screening Group B: Only 1 disease-causing variant in the EYS gene, based on a report from a clinically-certified lab (or a report from a research lab which has been pre-approved by the Study Committee) Screening Group C: At least 2 disease-causing variants in the EYS gene which are unknown phase, based on a report from a clinically-certified lab (or a report from a research lab which has been pre-approved by the Study Committee) Note pertaining to all Screening Groups: if a participant has a variant(s) of unknown significance, he/she would still qualify as long as there is at least 1 disease-causing variant(s) on the EYS gene.

Ocular Inclusion Criteria:

Both eyes must meet all of the following:

• Clinical diagnosis of retinal dystrophy
• Clear ocular media and adequate pupil dilation to permit good quality photographic imaging

Критерии исключения

• Mutations in genes that cause autosomal dominant retinitis pigmentosa (ADRP), X-linked retinitis pigmentosa (RP), or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than EYS.
• Expected to enter experimental treatment trial at any time during this study
• History of more than 1 year of cumulative treatment, at any time, with an agent associated with pigmentary retinopathy (including hydroxychloroquine, chloroquine, thioridazine, and deferoxamine)

Ocular exclusion Criteria:

If either eye has any of the following, the participant is not eligible:

• Current vitreous hemorrhage
• Current or any history of rhegmatogenous retinal detachment
• Current or any history of (e.g., prior to cataract or refractive surgery) spherical equivalent of the refractive error worse than -8 Diopters of myopia
• History of intraocular surgery (e.g., cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within the last 3 months
• Current or any history of confirmed diagnosis of glaucoma (e.g., based on glaucomatous visual functions changes or nerve changes, or history of glaucoma filtering surgery)
• Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy
• History or current evidence of ocular disease that, in the opinion of the investigator, may confound assessment of visual function
• History or evidence of active treatment for retinitis pigmentosa that could affect the progression of retinal degeneration, including:
• Any use of ocular stem cell or gene therapy
• Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Screening Visit date)
• Treatment with any other product within five times the expected half-life of the product (time from last treatment date to Screening Visit date is at least 5 times the half-life of the given product)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Россия · 1 центр

• Oftalmic Clinical Research Center — Moscow

Идентификаторы

NCT: NCT07228793 · EYS_RUS_2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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