The primary objectives of this study are the following:* To prospectively characterize CEP290-related retinal degeneration and the clinical phenotype of participants with light perception to 20/50 visual acuity and with either compound heterozygous…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The feasibility, test/retest variability, and changes over time of key
assessments in participants with CEP290-related retinal degeneration.
Whether the Visual Function Navigation Test as a clinically meaningful endpoint
of functional vision in participants with CEP290-related retinal degeneration.
Secondary outcome
CEP290-related retinal degeneration and the clinical phenotype of participants
with light perception to 20/50 visual acuity and with either compound
heterozygous or homozygous intron 26 c.2991+1655A>G mutations
Background summary
A deficiency in CEP290 protein in photoreceptors leads to defects in the
connecting cilium and
outer segments of photoreceptor cells (Parfitt, 2016), thereby causing
photoreceptor dysfunction,
retinal degeneration, and blindness (Yildiz, 2012). In patients with LCA10,
there is a striking
disconnect between the structure and function of the fovea, such that even
patients with little or no
vision retain a central island of photoreceptors in the fovea (cones) and
surrounding macula (cones
and rods) (Cideciyan, 2007; Boye, 2014). These and other factors suggest that
there is a window of opportunity to intervene in the
disease process to restore vision. The Sponsor is planning to conduct a
prospective natural history study with systematic
assessments and uniform follow-up that will provide a high-quality dataset for
assisting in the
design of future clinical treatment trials involving patients with
CEP290-related retinal
degeneration caused by the common intron 26 mutation.
Study objective
The primary objectives of this study are the following:
* To prospectively characterize CEP290-related retinal degeneration and the
clinical phenotype
of participants with light perception to 20/50 visual acuity and with either
compound heterozygous or homozygous intron 26 c.2991+1655A>G
mutations;
* To evaluate the feasibility, test/retest variability, and changes over time
of key assessments in
participants with CEP290-related retinal degeneration; and
* To gather information to support validation of the Visual Function Navigation
Test as a clinically meaningful
endpoint of functional vision in participants with CEP290 related retinal
degeneration.
Study design
This is an international, multicenter study to assess the natural history of
CEP290-related retinal degeneration caused by a compound heterozygous or
homozygous intron 26 c.2991+1655A>G mutation.No randomization will be
performed. Every attempt will be made to recruit 5 participants in each of
8 cohorts (6 in the Netherlands), comprising 4 age ranges (3 in the
Netherlands) and 2 visual acuity ranges. At the beginning of the study,
Principal Investigators are requested to provide the number of potential
participants based on age group and visual acuity to get a better idea of the
number of participants per cohort. Cohorts will be enrolled in parallel. The
purpose of the different cohorts is to ensure a broad spectrum of participants
for the natural history analyses and for validating the Visual Function
Navigation Test. If it is not possible to enroll the targeted number of five
participants per cohort, additional participants may be enrolled in the other
cohorts to maintain the overall sample size at 40 participants. Study visits
will occur at Screening, Baseline (test and retest), and Months 3, 6, and 12
for a total study duration of approximately 1 year. Study endpoint will be at 1
year. Both eyes of each participants will be evaluated during the course of
this natural history study. All analyses will be based on all enrolled
particpants overall and also by cohort.
Study burden and risks
Risks: Risks associated with the study procedures: blood draw, opthalmic
assessments
Burden: the invested time and filling in questionnaires about quality of life
can be experienced as burden
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Cambridge 02141
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US
Listed location countries
Age
Inclusion criteria
1. pariticipants and/or parent/legal guardian must complete/sign an informed
consent form (ICF). If
required on a per participants basis, provisions can be made for alternative
forms of consent
(eg, witnessed consent). Where required by the IRB/IEC, minors must also
verbalize or sign a
confirmation of assent. Refer to Section 11.3;
2. Male or female participants >=6 years of age at Screening;
3. Has abnormally decreased vision, defined as having light perception to 20/50
best-corrected visual acuity (BCVA) in
each eye, with examination and test results consistent with an inherited
retinal degeneration
due to mutations in the CEP290 gene;
4. Has CEP290-related retinal degeneration caused by a compound heterozygous or
homozygous
intron 26 c.2991+1655A>G mutation (ie, 1 or 2 copies of the intron 26
c.2991+1655A>G
mutation) confirmed by deoxyribonucleic acid sequencing;
5. Has ability to cooperate with assessments relative to age;
6. Has clear ocular media and adequate pupil dilation in at least 1 eye, to
permit good quality
fundus examination and optical coherence tomography (OCT) imaging; and
7. For females of childbearing potential: is not pregnant as confirmed by a
negative urine pregnancy test at Screening and is not planning to become
pregnant during the course of the study.
Exclusion criteria
1. Has history or current evidence of a medical condition (systemic or
ophthalmic disease,
metabolic dysfunction, physical examination finding, or clinical laboratory
finding) that may,
in the opinion of the Investigator, preclude adherence to the scheduled study
visits, safe
participation in the study, or affect the results of the study (eg,
uncontrolled systemic
hypertension, autoimmune disease, advanced coronary artery disease, or cerebral
vascular
disease, other unstable or progressive cardiovascular, pulmonary, Parkinson's,
liver or renal
disease, cancer, or dementia);
2. Has history or current evidence of ocular disease in either eye that, in the
opinion of the
Investigator, may confound assessment of this inherited retinal disease or the
assessments
utilized herein (eg, glaucoma, age-related macular degeneration, diabetic
retinopathy, uveitis,
or the presence of any condition that precludes adequate visualization of the
fundus such as
dense cataracts or corneal scarring);
3. Achieves a passing score for the Visual Function Navigation Test at the
maximum level of difficulty (ie. passes the most challenging Visual Function
Navigation Test under the dimmest lighting conditions) with each eye
independently and both eyes together;
4. Is currently receiving gene therapy and/or has received gene therapy or
oligonucleotide therapeutics;
5. Is currently enrolled in an investigational or interventional drug or device
study and/or has
participated in such a study within 30 days of Screening.
6. For females of childbearing potential: is pregnant (or planning to become
pregnant) or breastfeeding.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL64968.091.18 |