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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/NCT05589714




Registration number
NCT05589714
Ethics application status
Date submitted
18/10/2022
Date registered
21/10/2022
Date last updated
3/06/2024

Titles & IDs
Public title
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants
Scientific title
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants
Secondary ID [1] 0 0
Uni-Rare
Universal Trial Number (UTN)
Trial acronym
Uni-Rare
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inherited Retinal Degeneration 0 0
Retinitis Pigmentosa 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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Younger Age Cohort - Participants ages = 4 years and < 8 years old will be designated as the Younger Age Cohort.
Participants in this cohort will not be assigned a Vision Cohort.
Registry/Screening Visit and Natural History Study Visits will have an abbreviated testing schedule, detailed in the Schedule of Study Visits and Procedures table.

Vision Cohort 1 - Participants who are aged = 8 years old will be designated into a Vision Cohort based on data in the better eye, at the Registry/Screening Visit. Criteria that must be met in the better eye* at the Registry/Screening Visit: visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field** diameter 10 degrees or more in every meridian of the central field

Vision Cohort 2 - Participants who are aged = 8 years old will be designated into a Vision Cohort based on data in the better eye, at the Registry/Screening Visit. Criteria that must be met in the better eye* at the Registry/Screening Visit: visual acuity ETDRS letter score of 19-53 (approximate Snellen equivalent 20/100 to 20/400) or visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field** diameter less than 10 degrees in any meridian of the central field

Vision Cohort 3 - Participants who are aged = 8 years old will be designated into a Vision Cohort based on data in the better eye, at the Registry/Screening Visit. Criteria that must be met in the better eye* at the Registry/Screening Visit: visual acuity ETDRS letter score of 18 or less (approximate Snellen equivalent 20/500 or worse)
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Functional Outcome: Characterize change using Visual field sensitivity measured with quantitative topographic analysis (hill of vision [HOV])
Timepoint [1] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [2] 0 0
Functional Outcome: Characterize Change Using Early Treatment of Diabetic Retinopathy Study (ETDRS) / HOTV Best Corrected Visual Acuity (BCVA) letter score
Timepoint [2] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [3] 0 0
Functional Outcome: Characterize Change Using Low visual acuity test - for participants unable to see ETDRS letters
Timepoint [3] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [4] 0 0
Functional Outcome: Characterize Change Using ETDRS/HOTV best corrected low luminance visual acuity letter score
Timepoint [4] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [5] 0 0
Functional Outcome: Characterize Change in Mean retinal sensitivity
Timepoint [5] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [6] 0 0
Functional Outcome: Characterize Change in Contrast sensitivity function
Timepoint [6] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [7] 0 0
Functional Outcome: Characterize Change in Retinal function using amplitudes and timing in response to rod- and cone-specific stimuli
Timepoint [7] 0 0
Baseline and at study completion (4 years)
Primary outcome [8] 0 0
Functional Outcome: Characterize Change in Full-field retinal sensitivity
Timepoint [8] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [9] 0 0
Functional Outcome: Characterize Change in Color vision function
Timepoint [9] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [10] 0 0
Structural Outcome: Characterize Change in Ellipsoid zone (EZ) area; outer nuclear layer and ganglion cell layer thicknesses
Timepoint [10] 0 0
Baseline and every year until study completion (4 years)
Primary outcome [11] 0 0
Structural Outcome: Characterize Change Using Qualitative and quantitative assessments of autofluorescence pattern
Timepoint [11] 0 0
Baseline and every year until study completion (4 years)

Eligibility
Key inclusion criteria
Participants must meet all the following inclusion criteria at the
Registry/Screening Visit to be eligible to enroll into the genetic screening phase:

1. Willing to participate in the study and able to communicate consent during the consent
process

2. Willing and able to complete all applicable Registry/Screening Visit assessments

3. Age = 4 years

4. Must have a single gene on the RD Rare Gene List which meets one of the Genetic
Screening Criteria below based on a genetic report* from a clinically certified lab
(or from a research lab which has been approved by the study Genetics Committee):

Inheritance Pattern is Recessive and has at least 2 disease-causing variants which are
homozygous or heterozygous in trans

OR

Inheritance Pattern is Recessive and has 2 disease-causing variants with unknown phase and
meets all the following additional informatic criteria that is consistent with likely
segregation in trans:

1. Investigator confirms genotype and phenotype are consistent with autosomal recessive
inheritance

2. The 2 disease-causing variants have not been reported in cis in variant databases

3. No additional potentially pathogenic variants were found on the gene (and the
sequencing data for the gene were sufficiently robust to detect any additional
potentially pathogenic variants)

4. No potentially pathogenic variants were found in other common, likely candidate genes
for the proposed condition

OR

Inheritance Pattern is Dominant, X-linked, or Mitochondrial and has at least 1
disease-causing variant

Both eyes must meet the following criteria at the Registry/Screening Visit to enroll into
the genetic screening phase:

1. Both eyes must have a clinical diagnosis of retinal dystrophy

2. Both eyes must permit good quality photographic imaging (e.g., but not limited to,
clear ocular media, adequate pupil dilation, stable fixation)
Minimum age
4 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants must not meet any of the following exclusion criteria at the
Registry/Screening Visit to be eligible to enroll into the genetic screening phase:

1. History of more than 1 year of cumulative treatment, at any time, with an agent
associated with pigmentary retinopathy including amiodarone, chloroquine, deferoxamine,
hydroxychloroquine, pentosan polysulfate, tamoxifen, and deferoxamine Note: Since this is
an observational study, pregnant women will not be specifically excluded from
participation. However, minors that are pregnant shall be precluded from participation
until they become the age of majority.

Ocular

If either eye has any of the following ocular exclusion criteria at the Registry/Screening
Visit, then the participant is not eligible to enroll into the genetic screening phase:

1. Current vitreous hemorrhage

2. Current complications of pathological myopia (for example, but not limited to, myopic
maculopathy including atrophy, scar, choroidal neovascularization, schisis) that could
inhibit ability to obtain good quality photographic imaging

3. History of intraocular surgery (for example, but not limited to, cataract surgery,
vitrectomy, penetrating keratoplasty, or LASIK) within 3 months of Registry/Screening
Visit

4. Current or any history of confirmed diagnosis of glaucoma (for example, but not
limited to, glaucomatous VF changes or nerve changes, or history of glaucoma filtering
surgery)

5. Current or any history of retinal vascular occlusion or proliferative diabetic
retinopathy

6. History or current evidence of ocular disease that, in the opinion of the
Investigator, may confound assessment of visual function (for example, but not limited
to, tractional or rhegmatogenous retinal detachment, any vitreoretinal surgery,
retinal vascular occlusion, proliferative diabetic retinopathy)

7. The following medications and treatments are prohibited as they can affect progression
of retinitis pigmentosa (RP). The participant must not have received the following
treatments:

Any use of ocular stem cell or gene therapy Any treatment with ocriplasmin Treatment
with Ozurdex (dexamethasone), Iluvien, or Yutiq (fluocinolone acetonide) intravitreal
implant

8. The following medications and treatments are excluded within the specified timeframe:

Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date
is less than 9 months prior to Registry/Screening Visit date)

Treatment with any other product within five times the expected half-life of the product
(time from last treatment date to Registry/Screening Visit date is at least 5 times the
half-life of the given product)

Study design
Purpose
Duration
Cross-sectional
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/12/2026
Actual
Sample size
Target
1500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Centre for Eye Research Australia - East Melbourne
Recruitment postcode(s) [1] 0 0
- East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Brazil
State/province [16] 0 0
Minas Gerais
Country [17] 0 0
Brazil
State/province [17] 0 0
São Paulo Province
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Finland
State/province [20] 0 0
Helsinki
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
Israel
State/province [22] 0 0
Jerusalem
Country [23] 0 0
Mexico
State/province [23] 0 0
Merida
Country [24] 0 0
Netherlands
State/province [24] 0 0
Nijmegen
Country [25] 0 0
Switzerland
State/province [25] 0 0
Basel-Stadt
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Jaeb Center for Health Research
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Foundation Fighting Blindness
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is an international, multicenter study with two components:

Registry

- A standardized genetic screening and a prospective, standardized, cross-sectional
clinical data collection

- Enrollment is open to all genes on the RD Rare Gene List

Natural History Study

- A prospective, standardized, longitudinal Natural History Study

- Enrollment opens gene-by-gene, based on funding and within-gene Registry enrollment The
study objectives are as follows.

Registry Objectives

1. Genotype Characterization

2. Cross-Sectional Phenotype Characterization (within gene)

3. Establish a Link to My Retina Tracker Registry (MRTR)

4. Ancillary Exploratory Studies - Pooling of Genes

Natural History Study Objectives

1. Natural History (within gene)

2. Structure-Function Relationship (within gene)

3. Risk Factors for Progression (within gene)

4. Ancillary Exploratory Studies - Pooling of Genes
Trial website
https://clinicaltrials.gov/ct2/show/NCT05589714
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
José-Alain Sahel, MD
Address 0 0
Director, UPMC Eye Center University of Pittsburgh School of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Coordinating Center
Address 0 0
Country 0 0
Phone 0 0
813-975-8690
Fax 0 0
Email 0 0
ffb@jaeb.org
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05589714