Natural History of PRPF31 Mutation-Associated Retinal Dystrophy

NCT ID: NCT05573984

Last Updated: 2025-03-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-07-07

Study Completion Date

2026-02-28

Brief Summary

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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

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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).

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Vision Cohort 1

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

No interventions assigned to this group

Vision Cohort 2

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

No interventions assigned to this group

Vision Cohort 3

Score of \< 35 ETDRS letters read

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PYC Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sreenivasu Mudumba, PhD

Role: STUDY_CHAIR

PYC Therapeutics

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status

University of Florida Health

Jacksonville, Florida, United States

Site Status

University of Michigan Kellogg Eye Center

Ann Arbor, Michigan, United States

Site Status

Oregon Health and Science University - Casey Eye Institute

Portland, Oregon, United States

Site Status

Retina Foundation of the Southwest

Dallas, Texas, United States

Site Status

Lions Eye Institute

Nedlands, Western Australia, Australia

Site Status

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

East Melbourne, , Australia

Site Status

Countries

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United States Australia

References

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

Reference Type BACKGROUND
PMID: 17113430 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22131869 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18317597 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17003455 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23144630 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11545739 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32014492 (View on PubMed)

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

Reference Type BACKGROUND

Other Identifiers

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VP001-CL001

Identifier Type: -

Identifier Source: org_study_id

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