Natural History of PRPF31 Mutation-Associated Retinal Dystrophy

Active, not recruiting

• Conditions: Eye Diseases, Hereditary; Retinal Dystrophy Rod; Retinal Dystrophy Rod Progressive; Retinal Dystrophies; Retinitis Pigmentosa

• Registration Number: NCT05573984
• Lead Sponsor: PYC Therapeutics

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).

Study Timeline

• Study Start: 2022-07-07
• Study First Submitted: 2022-09-08
• Study First Submitted QC: 2022-10-05
• Study First Posted: 2022-10-10
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-14
• Primary Completion: 2026-02-28
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Participants must meet all of the following in order to be enrolled into the study:

1. Male or female, ≥ 10 years of age at baseline (Visit 2).
2. Have a clinical and molecular diagnosis of PRPF31 mutation-associated retinal dystrophy.
3. 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.
4. 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:

1. 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.
2. 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.
3. Have used anti-vascular endothelial growth factor (VEGF) agents or corticosteroid injections or implants.
4. Have had Ozurdex® implants placed within 3 months or Retisert® or Iluvien® implants placed within 3 years prior to Visit 2.
5. 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.
6. Have ocular media opacity or poor pupillary dilation that prohibits quality ophthalmic evaluation or photography.
7. 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.
8. Have received any prior cell or gene therapy for a retinal condition.
9. Have a history of illicit drug use or alcohol dependency.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Trial Locations

Locations (7)

University of California San Francisco; 🇺🇸 San Francisco, California, United States

University of Florida Health; 🇺🇸 Jacksonville, Florida, United States

University of Michigan Kellogg Eye Center; 🇺🇸 Ann Arbor, Michigan, United States

Oregon Health and Science University - Casey Eye Institute; 🇺🇸 Portland, Oregon, United States

Retina Foundation of the Southwest; 🇺🇸 Dallas, Texas, United States

Lions Eye Institute; 🇦🇺 Nedlands, Western Australia, Australia

Centre For Eye Research Australia (CERA) - Retinal Gene Therapy Unit; 🇦🇺 East Melbourne, Australia