Natural History of PRPF31 Mutation-Associated Retinal Dystrophy

NCT05573984 | Active Not Recruiting

• 1 other identifier: VP001-CL001
• Study Type: observational
• Target: 50
• Locations: 2 countries
• Sites: 7

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.

Conditions

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

Keywords

Retinitis Pigmentosa; Retinitis Pigmentosa Type 11; RP11; PRPF31; Retinal Dystrophy; PRPF31 Mutation-Associated Retinal Dystrophy

Outcome Measures

Primary Outcomes (18)

• 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

Study Arms (3)

Vision Cohort 1

Score of ≥ 54 ETDRS letters read and a VF diameter ≥ 10 degrees in every meridian of the central field

Vision Cohort 2

Score of ≥ 35 ETDRS letters read and a VF diameter \< 10 degrees in any meridian of the central field

Vision Cohort 3

Score of \< 35 ETDRS letters read

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of approximately 50 participants (100 eyes) with a genetically confirmed PRPF31 mutation.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PYC Therapeutics: lead

Study Sites (7)

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Florida Health

Jacksonville, Florida, 32209, United States

Location

University of Michigan Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

Oregon Health and Science University - Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75321, United States

Location

Lions Eye Institute

Nedlands, Western Australia, 6009, Australia

Location

Centre For Eye Research Australia (CERA) - Retinal Gene Therapy Unit

East Melbourne, Australia

Location

Related Publications (8)

• Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795-809. doi: 10.1016/S0140-6736(06)69740-7.

  PMID: 17113430 BACKGROUND

• Ferrari S, Di Iorio E, Barbaro V, Ponzin D, Sorrentino FS, Parmeggiani F. Retinitis pigmentosa: genes and disease mechanisms. Curr Genomics. 2011 Jun;12(4):238-49. doi: 10.2174/138920211795860107.

  PMID: 22131869 BACKGROUND

• Rio Frio T, Wade NM, Ransijn A, Berson EL, Beckmann JS, Rivolta C. Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay. J Clin Invest. 2008 Apr;118(4):1519-31. doi: 10.1172/JCI34211.

  PMID: 18317597 BACKGROUND

• Sullivan LS, Bowne SJ, Seaman CR, Blanton SH, Lewis RA, Heckenlively JR, Birch DG, Hughbanks-Wheaton D, Daiger SP. Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4579-88. doi: 10.1167/iovs.06-0440.

  PMID: 17003455 BACKGROUND

• Venturini G, Rose AM, Shah AZ, Bhattacharya SS, Rivolta C. CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance. PLoS Genet. 2012;8(11):e1003040. doi: 10.1371/journal.pgen.1003040. Epub 2012 Nov 8.

  PMID: 23144630 BACKGROUND

• Vithana EN, Abu-Safieh L, Allen MJ, Carey A, Papaioannou M, Chakarova C, Al-Maghtheh M, Ebenezer ND, Willis C, Moore AT, Bird AC, Hunt DM, Bhattacharya SS. A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11). Mol Cell. 2001 Aug;8(2):375-81. doi: 10.1016/s1097-2765(01)00305-7.

  PMID: 11545739 BACKGROUND

• Wheway G, Douglas A, Baralle D, Guillot E. Mutation spectrum of PRPF31, genotype-phenotype correlation in retinitis pigmentosa, and opportunities for therapy. Exp Eye Res. 2020 Mar;192:107950. doi: 10.1016/j.exer.2020.107950. Epub 2020 Jan 31.

  PMID: 32014492 BACKGROUND

• Food and Drug Administration. Rare Diseases: Natural History Studies for Drug Development. Draft Guidance for Industry 2019. https://www.fda.gov/media/122425/download

  BACKGROUND

MeSH Terms

Conditions

Retinitis Pigmentosa; Eye Diseases, Hereditary; Retinal Dystrophies

Condition Hierarchy (Ancestors)

Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Sreenivasu Mudumba, PhD

  PYC Therapeutics

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: October 10, 2022
• Study Start: July 7, 2022
• Primary Completion (Estimated): September 9, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); AU (2)