Natural History of PRPF31 Mutation-Associated Retinal Dystrophy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to characterize the natural history through temporal systemic evaluation of subjects identified with PRPF31 mutation-associated retinal dystrophy, also called retinitis pigmentosa type 11, or RP11. Assessments will be completed to measure and evaluate structural and functional visual changes including those impacting patient quality of life associated with this inherited retinal condition and observing how these changes evolve over time.

Detailed Description
-----------------
This is a multi-center, longitudinal, prospective observational natural history study of participants with a molecularly confirmed mutation in PRPF31. Approximately 50 participants (100 eyes) at approximately 5 sites will be enrolled into a uniform protocol for follow-up and evaluations. Each participant's medical record will be reviewed for historical information, and clinical data will be recorded in a secure database. Natural history data will be collected prospectively and will include ophthalmic exams, imaging studies, electrophysiological testing, functional mobility evaluations, and questionnaires. Assessments will be conducted in a standardized protocol every 16 weeks ± 4 weeks for the first year and then every 24 weeks ± 4 weeks for up to approximately 4 years after each participant's baseline visit (Visit 2).

Official Title
-----------------
A Natural History and Outcome Measure Discovery Study of PRPF31 Mutation-Associated Retinal Dystrophy

Conditions
-----------------
Retinitis Pigmentosa, Eye Diseases, Hereditary, Retinal Dystrophies, Retinal Dystrophy Rod, Retinal Dystrophy Rod Progressive

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must meet all of the following in order to be enrolled into the study: Male or female, ≥ 10 years of age at baseline (Visit 2). Have a clinical and molecular diagnosis of PRPF31 mutation-associated retinal dystrophy. If ≥ 18 years of age, understand the language of the informed consent and are willing and able to provide written informed consent prior to any study procedures. If < 18 years of age, are willing to assent to study participation in writing and have a legally authorized representative provide written informed consent on your behalf. Are willing to comply with the instructions and attend all scheduled study visits. Exclusion Criteria: Participants or, in the case of ocular-specific criteria, individual eyes with any of the following will not be allowed to participate in this study: Have any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study (e.g., infection, uncontrolled elevated blood pressure, cardiovascular disease, or glycemic control issues) or put the participant at risk due to study procedures. Have mutations in genes that cause autosomal dominant retinitis pigmentosa (adRP), X-linked retinitis pigmentosa (XLRP), or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than PRPF31 mutations. Have used anti-vascular endothelial growth factor (VEGF) agents or corticosteroid injections or implants. Have had Ozurdex® implants placed within 3 months or Retisert® or Iluvien® implants placed within 3 years prior to Visit 2. Within 3 months prior to Visit 2, have undergone any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive procedures or multiple filtration surgeries [2 or more], etc.) or any other ocular surgery. Have ocular media opacity or poor pupillary dilation that prohibits quality ophthalmic evaluation or photography. Have used any investigational drug or device within 90 days or 5 estimated half-lives of Visit 2, whichever is longer, or plan to participate in another study of drug or device during the study period. Have received any prior cell or gene therapy for a retinal condition. Have a history of illicit drug use or alcohol dependency.

Ages Eligible for Study
-----------------
Minimum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Vision Cohort 1<br>Score of ≥ 54 ETDRS letters read and a VF diameter ≥ 10 degrees in every meridian of the central field | |
| Vision Cohort 2<br>Score of ≥ 35 ETDRS letters read and a VF diameter < 10 degrees in any meridian of the central field | |
| Vision Cohort 3<br>Score of < 35 ETDRS letters read | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Best Corrected Visual Acuity (BCVA) | BCVA letter score utilizing ETDRS (Early Treatment Diabetic Retinopathy Study) or BRVT (Berkeley Rudimentary Vision Test) for patients not able to see letters | Baseline through Year 4 | 
| Change in Best Corrected Low Luminance Visual Acuity (LLVA) | Best corrected LLVA letter score measured using the ETDRS charts and a special light filter lens | Baseline through Year 4 | 
| Change from Baseline in Retinal Thickness | Retinal thickness is measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center | Baseline through Year 4 | 
| Change from Baseline in Ellipsoid Zone (EZ) Area | Change in EZ area measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center | Baseline through Year 4 | 
| Change from Baseline in Ellipsoid Zone (EZ) Volume | Change in EZ volume measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center | Baseline through Year 4 | 
| Change from Baseline in Visual Field Sensitivity | Visual field sensitivity measured by static perimetry with topographic analysis-Hill of Vision conducted by the central reading center | Baseline through Year 4 | 
| Change from Baseline in Mean Macular Sensitivity | Mean macular sensitivity measured on guided microperimetry | Baseline through Year 4 | 
| Change from Baseline in Fixation Stability | Fixation stability as measured by Macular Integrity Assessment (MAIA) microperimeter | Baseline through Year 4 | 
| Change from Baseline in Full Field Retinal Sensitivity | Dark-adapted visual sensitivity via full-field stimulus threshold (FST) measurement | Baseline through Year 4 | 
| Change from Baseline in Electrical response | Electrical response measured using Full-field electroretinogram (ERG) with specific stimuli | Baseline through Year 4 | 
| Characterization of Changes of the Retina with Fundus Photography | Abnormalities captured by fundus photography | Baseline through Year 4 | 
| Change from Baseline in Area of Fundus Autofluorescence (FAF) | Area of hypo-autofluorescence captured by fundus autofluorescence (FAF) | Baseline through Year 4 | 
| Change from Baseline in Functional Vision | Functional vision is measured with a functional mobility course (Ora-VNC™) score | 3 times prior to Month 4 | 
| Change in Patient Reported Outcome Measures using Michigan Retinal Degeneration Questionnaire (MRDQ) | Responses on the MRDQ, a validated patient reported outcomes measure designed in accordance with U.S. FDA guidelines, specifically for conditions of inherited retinal degeneration (IRDs) | Baseline through Year 4 | 
| Change in Patient Reported Outcome Measures using Patient Global Impression of Severity (PGI-S) scale | Responses on the PGI-S to assess severity of the patient's condition | Baseline through Year 4 | 
| Change in Patient Reported Outcome Measures using Patient Global Impression of Change (PGI-C) scale | Responses on the PGI-C to assess change of the patient's condition | Baseline through Year 4 | 
| Genomic Analysis for Study Eligibility | Whole exome genomic analysis | Screening | 
| Ocular Adverse Events (AEs) | Frequency of ocular adverse events (AEs) | Screening through Year 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Retinitis Pigmentosa, Retinitis Pigmentosa Type 11, RP11, PRPF31, Retinal Dystrophy, PRPF31 Mutation-Associated Retinal Dystrophy