Natural History Study of Patients With EYS-Associated RP

NCT ID: NCT07228793

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 45 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-11-07
• Study Completion Date: 2030-03-30

Brief Summary

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.

Detailed Description

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

Conditions

Retinitis Pigmentosa; Eye Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Vision Cohort 1

Participants with the better eye Screening Visit decimal visual acuity of 0.4 or more and visual field diameter 10 degrees or more in every meridian of the central field.

Whole exome/genome sequencing

Intervention Type: DIAGNOSTIC_TEST

Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)

Vision Cohort 2

Participants with the better eye Screening Visit decimal visual acuity 0.15 - 0.35 and visual field diameter less than 10 degrees in any meridian of the central field)

Whole exome/genome sequencing

Intervention Type: DIAGNOSTIC_TEST

Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)

Vision Cohort 3

Participants with the better eye Screening Visit decimal visual acuity 0.14 or less.

Whole exome/genome sequencing

Intervention Type: DIAGNOSTIC_TEST

Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)

Interventions

Whole exome/genome sequencing

Next generation sequencing and segregation analysis or long read sequencing for confirmation of biallelic mutations (in trans-position)

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Willing to participate in the study and able to communicate consent during the consent process

2. Ability to return for all study visits over 48 months

3. Age ≥ 18 years

4. 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.

Both eyes must meet all of the following:

1. Clinical diagnosis of retinal dystrophy

2. Clear ocular media and adequate pupil dilation to permit good quality photographic imaging

Exclusion Criteria

1. 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.

2. Expected to enter experimental treatment trial at any time during this study

3. 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)

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)

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Russian RetinaFond

UNKNOWN

Sponsor Role: collaborator

Sensor Technology for Deafblind

INDUSTRY

Sponsor Role: lead

Responsible Party

Marianna E. Weener

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marianna Weener, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oftalmic

Locations

Oftalmic Clinical Research Center

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Olga Luneva

Role: CONTACT

info@oftalmic.com

+7 903 758 66 19

Facility Contacts

Marianna E Weener, MD, PhD

Role: primary

info@oftalmic.com

+7 903 758 66 19

Other Identifiers

EYS_RUS_2025

Identifier Type: -

Identifier Source: org_study_id