Rate of Progression in EYS Related Retinal Degeneration

Retinitis Pigmentosa Clinical Trial

— Pro-EYS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04127006
• Other study ID #: Pro-EYS
• Status: Active, not recruiting
• Start date: February 25, 2020
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 107
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Eye Diseases
• Retinal Degeneration
• Retinitis
• Retinitis Pigmentosa

Locations

Country	Name	City	State
Canada	Hospital for Sick Children	Toronto
Finland	Helsinki University Hospital	Helsinki
France	Centre hospitalier National d'Ophtalmologie des Quinze-Vingts	Paris
Germany	University of Tubingen	Tübingen
Israel	Hadassah Medical Center	Jerusalem
Netherlands	Radboud University	Nijmegen
United States	Kellogg Eye Center, University of Michigan	Ann Arbor	Michigan
United States	Emory Eye Center	Atlanta	Georgia
United States	Wilmer Eye Institute at Johns Hopkins	Baltimore	Maryland
United States	Massachusetts Eye and Ear	Boston	Massachusetts
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Colorado Retina Associates	Denver	Colorado
United States	Duke University Eye Center	Durham	North Carolina
United States	Vitreo-Retinal Associates	Gainesville	Florida
United States	University of Wisconsin-Madison: McPherson Eye Research Institute	Madison	Wisconsin
United States	University of Miami: Neuro-ophthalmology Department	Miami	Florida
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health Science University Casey Eye Institute	Portland	Oregon
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	Foundation Fighting Blindness

Countries where clinical trial is conducted

United States,  Canada,  Finland,  France,  Germany,  Israel,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient Reported Outcomes for Vision Cohorts 1 and 2 (Vision Visual Functioning)	Measured by Veterans Affairs Low Vision Visual Functioning Questionnaire (VA LV VFQ-48)	Baseline, 2 year follow-up, and 4 year follow-up visit
Other	Patient Reported Outcomes for Vision Cohorts 1 and 2	Measured by Patient-Reported Outcomes Measurement Information System (PROMIS®-29)	Baseline, 2 year follow-up, and 4 year follow-up visit
Other	Patient Reported Outcomes for Vision Cohort 3 (Vision Visual Functioning)	Measured by Ultra-Low Vision Visual Functioning Questionnaire (ULV-VFQ-50)	Baseline and 4 year follow-up visit
Other	Patient Reported Outcomes for Vision Cohort 3	Measured by Patient-Reported Outcomes Measurement Information System (PROMIS®-29)	Baseline and 4 year follow-up visit
Primary	Change in Visual Field Sensitivity	Measured by static perimetry with topographic analysis (Hill of Vision) and assessed by a central reading center for cohorts 1 and 2.	Baseline and every year until study completion (4 years)
Primary	Change in Best Corrected Visual Acuity	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.	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.
Primary	Change in Mean Retinal Sensitivity	Measured by fundus-guided microperimetry (MP) and assessed by a central reading center at selected sites with requisite equipment for cohorts 1 and 2.	Baseline and every year until study completion (4 years).
Primary	Change in Full-field Retinal Sensitivity	Measured by full-field stimulus threshold (FST) testing to blue, white, and red stimuli	Baseline and every year until study completion (4 years) for cohort 1 and 2. Baseline and 4 year follow-up for cohort 3.
Primary	Change in Best Corrected Low Luminance visual acuity	Measured by letter score	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.
Primary	Change in Contrast Sensitivity Function	Measured by the CSV-1000E VectorVision chart for cohorts 1 and 2.	Baseline and every year until study completion (4 years).
Primary	Change in Retinal Function	Measured by full-field electroretinogram (ERG) amplitudes and timing in response to rod- and cone-specific stimuli for cohorts 1 and 2.	Baseline and 4 year follow-up visit.
Primary	Change in Ellipsoid zone (EZ) area	Measured by spectral domain optical coherence tomography (SD-OCT) and assessed by a central reading center	Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
Secondary	Explore Qualitative categorization of Fundus Autofluorescence (FAF) pattern	Assessed by a central reading center	Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.
Secondary	Explore quantitative measures of FAF	assessed by a central reading center	Baseline and every year until study completion (4 years) for cohorts 1 and 2. Baseline and 4 year follow-up for cohort 3.

External Links

•   Foundation Fighting Blindness Public Website