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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05573984




Registration number
NCT05573984
Ethics application status
Date submitted
8/09/2022
Date registered
10/10/2022
Date last updated
31/05/2024

Titles & IDs
Public title
Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
Scientific title
A Natural History and Outcome Measure Discovery Study of PRPF31 Mutation-Associated Retinal Dystrophy
Secondary ID [1] 0 0
VP001-CL001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Retinitis Pigmentosa 0 0
Eye Diseases, Hereditary 0 0
Retinal Dystrophies 0 0
Retinal Dystrophy Rod 0 0
Retinal Dystrophy Rod Progressive 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in Best Corrected Visual Acuity (BCVA)
Timepoint [1] 0 0
Baseline through Year 4
Primary outcome [2] 0 0
Change in Best Corrected Low Luminance Visual Acuity (LLVA)
Timepoint [2] 0 0
Baseline through Year 4
Primary outcome [3] 0 0
Change from Baseline in Retinal Thickness
Timepoint [3] 0 0
Baseline through Year 4
Primary outcome [4] 0 0
Change from Baseline in Ellipsoid Zone (EZ) Area
Timepoint [4] 0 0
Baseline through Year 4
Primary outcome [5] 0 0
Change from Baseline in Ellipsoid Zone (EZ) Volume
Timepoint [5] 0 0
Baseline through Year 4
Primary outcome [6] 0 0
Change from Baseline in Visual Field Sensitivity
Timepoint [6] 0 0
Baseline through Year 4
Primary outcome [7] 0 0
Change from Baseline in Mean Macular Sensitivity
Timepoint [7] 0 0
Baseline through Year 4
Primary outcome [8] 0 0
Change from Baseline in Fixation Stability
Timepoint [8] 0 0
Baseline through Year 4
Primary outcome [9] 0 0
Change from Baseline in Full Field Retinal Sensitivity
Timepoint [9] 0 0
Baseline through Year 4
Primary outcome [10] 0 0
Change from Baseline in Electrical response
Timepoint [10] 0 0
Baseline through Year 4
Primary outcome [11] 0 0
Characterization of Changes of the Retina with Fundus Photography
Timepoint [11] 0 0
Baseline through Year 4
Primary outcome [12] 0 0
Change from Baseline in Area of Fundus Autofluorescence (FAF)
Timepoint [12] 0 0
Baseline through Year 4
Primary outcome [13] 0 0
Change from Baseline in Functional Vision
Timepoint [13] 0 0
3 times prior to Month 4
Primary outcome [14] 0 0
Change in Patient Reported Outcome Measures using Michigan Retinal Degeneration Questionnaire (MRDQ)
Timepoint [14] 0 0
Baseline through Year 4
Primary outcome [15] 0 0
Change in Patient Reported Outcome Measures using Patient Global Impression of Severity (PGI-S) scale
Timepoint [15] 0 0
Baseline through Year 4
Primary outcome [16] 0 0
Change in Patient Reported Outcome Measures using Patient Global Impression of Change (PGI-C) scale
Timepoint [16] 0 0
Baseline through Year 4
Primary outcome [17] 0 0
Genomic Analysis for Study Eligibility
Timepoint [17] 0 0
Screening
Primary outcome [18] 0 0
Ocular Adverse Events (AEs)
Timepoint [18] 0 0
Screening through Year 4

Eligibility
Key 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.
Minimum age
10 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2027
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Lions Eye Institute - Nedlands
Recruitment hospital [2] 0 0
Centre For Eye Research Australia (CERA) - Retinal Gene Therapy Unit - East Melbourne
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment postcode(s) [2] 0 0
- East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
PYC Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05573984
Trial related presentations / publications
Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795-809. doi: 10.1016/S0140-6736(06)69740-7.
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.
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.
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.
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.
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.
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.
Food and Drug Administration. Rare Diseases: Natural History Studies for Drug Development. Draft Guidance for Industry 2019. https://www.fda.gov/media/122425/download
Public notes

Contacts
Principal investigator
Name 0 0
Sreenivasu Mudumba, PhD
Address 0 0
PYC Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Lexitas Pharma Services, Inc.
Address 0 0
Country 0 0
Phone 0 0
1-510-423-2680
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05573984