Pro-EYS: Rate of Progression in EYS Related Retinal Degeneration

Sponsor

Jaeb Center for Health Research (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04127006

Collaborator

Foundation Fighting Blindness (Other)

107

Enrollment

Locations

69.2

Anticipated Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall goal of this project funded by the Foundation Fighting Blindness is to characterize the natural history of disease progression in patients with EYS mutations in order to accelerate the development of outcome measures for clinical trials.

Condition or Disease	Intervention/Treatment	Phase
Retinitis Pigmentosa Eye Diseases

Detailed Description

This natural history study of patients with EYS mutations 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. Together these approaches are expected to have an impact on understanding EYS-related retinal degeneration, developing experimental treatment protocols, and assessing their effectiveness.

The goals and expected impact of this natural history study are to:

Describe the natural history of retinal degeneration in patients with biallelic mutations in the EYS gene
Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration
Identify well-defined subpopulations for future clinical trials of investigative treatments for EYS-related retinal degeneration

Study Objectives

The primary objectives of the natural history study are to:

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
Investigate whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the EYS gene
Evaluate possible risk factors (genotype, phenotype, environmental, and comorbidities) for progression of the outcome measures at 4 years in individual with biallelic pathogenic mutations in the EYS gene
Evaluate variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the EYS gene

Study Design

Study Type:

Observational

Anticipated Enrollment :

107 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Rate of Progression in EYS Related Retinal Degeneration (Pro-EYS)

Actual Study Start Date :

Feb 25, 2020

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Vision Cohort 1 Participants with the better eye Screening Visit visual acuity ETDRS letter score of 54 or more [approximate Snellen equivalent 20/80 or better] and visual field diameter 10 degrees or more in every meridian of the central field
Vision Cohort 2 Participants with the better eye Screening Visit visual acuity ETDRS letter score of 19-53 [approximate Snellen equivalent 20/100 - 20/400] or (visual acuity ETDRS letter score of 54 or more [approximate Snellen equivalent 20/80 or better] and visual field diameter less than 10 degrees in any meridian of the central field)
Vision Cohort 3 Participants with the better eye Screening Visit visual acuity ETDRS letter score of 18 or less [approximate Snellen equivalent 20/500 or worse]

Outcome Measures

Primary Outcome Measures

Change in Visual Field Sensitivity [Baseline and every year until study completion (4 years)]
Measured by static perimetry with topographic analysis (Hill of Vision) and assessed by a central reading center for cohorts 1 and 2.
Change in Best Corrected Visual Acuity [Screening visit and every year until study completion (4 years) with the exception of baseline for cohorts 1 and 2. Screening visit and 48 month follow-up for cohort 3.]
Measured on the Electronic Visual Acuity (EVA) system or ETDRS charts. Berkeley Rudimentary Vision Test (BRVT) will be used for patients unable to see letters.
Change in Mean Retinal Sensitivity [Baseline and every year until study completion (4 years).]
Measured by fundus-guided microperimetry (MP) and assessed by a central reading center at selected sites with requisite equipment for cohorts 1 and 2.
Change in Full-field Retinal Sensitivity [Baseline and every year until study completion (4 years) for cohort 1 and 2. Baseline and 4 year follow-up for cohort 3.]
Measured by full-field stimulus threshold (FST) testing to blue, white, and red stimuli
Change in Best Corrected Low Luminance visual acuity [Screening visit and every year until study completion (4 years) with the exception of baseline for cohorts 1 and 2. Screening visit and 48 month follow-up for cohort 3.]
Measured by letter score
Change in Contrast Sensitivity Function [Baseline and every year until study completion (4 years).]
Measured by the CSV-1000E VectorVision chart for cohorts 1 and 2.
Change in Retinal Function [Baseline and 4 year follow-up visit.]
Measured by full-field electroretinogram (ERG) amplitudes and timing in response to rod- and cone-specific stimuli for cohorts 1 and 2.
Change in Ellipsoid zone (EZ) area [Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.]
Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center

Secondary Outcome Measures

Explore Qualitative categorization of Fundus Autofluorescence (FAF) pattern [Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.]
Assessed by a central reading center
Explore quantitative measures of FAF [Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.]
assessed by a central reading center

Other Outcome Measures

Patient Reported Outcomes for Vision Cohorts 1 and 2 (Vision Visual Functioning) [Baseline, 2 year follow-up, and 4 year follow-up visit]
Measured by Veterans Affairs Low Vision Visual Functioning Questionnaire (VA LV VFQ-48)
Patient Reported Outcomes for Vision Cohorts 1 and 2 [Baseline, 2 year follow-up, and 4 year follow-up visit]
Measured by Patient-Reported Outcomes Measurement Information System (PROMIS®-29)
Patient Reported Outcomes for Vision Cohort 3 (Vision Visual Functioning) [Baseline and 4 year follow-up visit]
Measured by Ultra-Low Vision Visual Functioning Questionnaire (ULV-VFQ-50)
Patient Reported Outcomes for Vision Cohort 3 [Baseline and 4 year follow-up visit]
Measured by Patient-Reported Outcomes Measurement Information System (PROMIS®-29)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 Genetics 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 Genetics 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 Genetics 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

Exclusion Criteria:

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 VF 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
Any treatment with ocriplasmin
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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143-0344
2	Colorado Retina Associates	Denver	Colorado	United States	80230
3	Vitreo-Retinal Associates	Gainesville	Florida	United States	32607
4	University of Miami: Neuro-ophthalmology Department	Miami	Florida	United States	33136
5	Emory Eye Center	Atlanta	Georgia	United States	30322
6	University of Kentucky	Lexington	Kentucky	United States	40508
7	Wilmer Eye Institute at Johns Hopkins	Baltimore	Maryland	United States	21287-9277
8	Massachusetts Eye and Ear	Boston	Massachusetts	United States	02114
9	Kellogg Eye Center, University of Michigan	Ann Arbor	Michigan	United States	48105
10	Duke University Eye Center	Durham	North Carolina	United States	27710
11	Oregon Health Science University Casey Eye Institute	Portland	Oregon	United States	97239
12	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
13	Retina Foundation of the Southwest	Dallas	Texas	United States	75231
14	University of Wisconsin-Madison: McPherson Eye Research Institute	Madison	Wisconsin	United States	53705
15	Hospital for Sick Children	Toronto		Canada
16	Helsinki University Hospital	Helsinki		Finland
17	Centre hospitalier National d'Ophtalmologie des Quinze-Vingts	Paris		France	75012
18	University of Tubingen	Tübingen		Germany
19	Hadassah Medical Center	Jerusalem		Israel
20	Radboud University	Nijmegen		Netherlands