Clinical trial NCT04127006: Rate of Progression in EYS Related Retinal Degeneration
Official title: Rate of Progression in EYS Related Retinal Degeneration (Pro-EYS)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Retinitis Pigmentosa
Eye Diseases
Keywords: EYS mutation
Retinitis Pigmentosa
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Foundation Fighting Blindness
First posted: 2019-10-15
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Potential eligibility may be assessed as part of a routine care examination by an investigator prior to obtaining informed consent, as part of usual care, by referral from another physician, or self-referral.

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.

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:

1. Describe the natural history of retinal degeneration in patients with biallelic mutations in the EYS gene
2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials in EYS-related retinal degeneration
3. 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:

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 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
4. Evaluate variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the EYS gene

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 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:

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)

Ocular exclusion Criteria:

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

1. Current vitreous hemorrhage
2. Current or any history of rhegmatogenous retinal detachment
3. 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
4. History of intraocular surgery (e.g., cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within the last 3 months
5. 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)
6. Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy
7. History or current evidence of ocular disease that, in the opinion of the investigator, may confound assessment of visual function
8. History or evidence of active treatment for retinitis pigmentosa that could affect the progression of retinal degeneration, including:

   1. Any use of ocular stem cell or gene therapy
   2. Any treatment with ocriplasmin
   3. Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Screening Visit date)
   4. 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)

Primary outcomes:
measure: Change in Visual Field Sensitivity
timeFrame: Baseline and every year until study completion (4 years)
measure: Change in Best Corrected Visual Acuity
timeFrame: 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.
measure: Change in Mean Retinal Sensitivity
timeFrame: Baseline and every year until study completion (4 years).
measure: Change in Full-field Retinal Sensitivity
timeFrame: Baseline and every year until study completion (4 years) for cohort 1 and 2. Baseline and 4 year follow-up for cohort 3.
measure: Change in Best Corrected Low Luminance visual acuity
timeFrame: 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.
measure: Change in Contrast Sensitivity Function
timeFrame: Baseline and every year until study completion (4 years).
measure: Change in Retinal Function
timeFrame: Baseline and 4 year follow-up visit.
measure: Change in Ellipsoid zone (EZ) area
timeFrame: Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
Secondary outcomes:
measure: Explore Qualitative categorization of Fundus Autofluorescence (FAF) pattern
timeFrame: Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
measure: Explore quantitative measures of FAF
timeFrame: Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
Other outcomes:
measure: Patient Reported Outcomes for Vision Cohorts 1 and 2 (Vision Visual Functioning)
timeFrame: Baseline, 2 year follow-up, and 4 year follow-up visit
measure: Patient Reported Outcomes for Vision Cohorts 1 and 2
timeFrame: Baseline, 2 year follow-up, and 4 year follow-up visit
measure: Patient Reported Outcomes for Vision Cohort 3 (Vision Visual Functioning)
timeFrame: Baseline and 4 year follow-up visit
measure: Patient Reported Outcomes for Vision Cohort 3
timeFrame: Baseline and 4 year follow-up visit
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Gainesville
country: United States
facility: Vitreo-Retinal Associates
state: Florida
city: Miami
country: United States
facility: University of Miami: Neuro-ophthalmology Department
state: Florida
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Baltimore
country: United States
facility: Wilmer Eye Institute at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center, University of Michigan
state: Michigan
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health Science University Casey Eye Institute
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
city: Madison
country: United States
facility: University of Wisconsin-Madison: McPherson Eye Research Institute
state: Wisconsin
city: Toronto
country: Canada
facility: Hospital for Sick Children
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Paris
country: France
facility: Centre hospitalier National d'Ophtalmologie des Quinze-Vingts
city: Tübingen
country: Germany
facility: University of Tubingen
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University
Study officials:
affiliation: Division Chief, Ophthalmic Genetics Oregon Health & Science University
name: Mark Pennesi, MD, PhD
role: STUDY_CHAIR
References: