Natural History Study of CEP290-Related Retinal Degeneration

A prospective natural history study with systematic assessments and uniform follow-up to 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 Overview

• Status: Completed
• Conditions: Eye Diseases; Retinal Degeneration; Eye Diseases, Hereditary; Vision Disorders; Blindness; Leber Congenital Amaurosis 10; Retinal Disease; Eye Disorders Congenital

Detailed Description

The purpose of the study is to describe the natural history of CEP290-related retinal degeneration caused by a compound heterozygous or homozygous intron 26 c.2991+1655A>G mutation and to better understand the best assessments for evaluation of patients with this condition in a future interventional trial. Patients meeting the entry criteria will be enrolled in the study. Visits will occur at Screening, Baseline, and Months 3, 6, and 12, for a total duration of 1 year.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• France
  • Paris, France, 75252
    • Universite Pierre et Marie Curie
• Germany
  • Giessen, Germany, 35392
    • Universitaetsklinikum Giessen and Marburg GmbH
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525
      • Radboud Universitair Medisch Centrum
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • W.K. Kellogg Eye Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute - OHSU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 97 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The indication for this study is CEP290-related retinal degeneration caused by a compound heterozygous or homozygous intron 26 c.2991+1655A>G mutation.

Description

Inclusion Criteria:

• Patient and/or parent/legal guardian must complete/sign an informed consent form (ICF). If required on a per patient 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.
• At least 3 years of age at screening.
• Has abnormally decreased vision, defined as having light perception to 20/50 visual acuity in each eye, with examination and test results consistent with an inherited retinal degeneration due to mutations in the CEP290 gene.
• 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.
• Has ability to cooperate with assessments relative to age.
• 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.

Exclusion Criteria:

• 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).
• 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).
• 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.
• Is currently receiving gene therapy and/or has received gene therapy.
• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort
Group 1; 5 Patient target, ages 3 to 5 yr, with visual acuity Light Perception (LP) to <=20/200
Group 2; 5 Patient target, ages 3 to 5 yr, with visual acuity >20/200 to <=20/50
Group 3; 5 Patient target, ages 6 to 11 yr, with visual acuity LP to <=20/200
Group 4; 5 Patient target, ages 6 to 11 yr, with visual acuity >20/200 to <=20/50
Group 5; 5 Patient target, ages 12 to 17 yr, with visual acuity LP to <=20/200
Group 6; 5 Patient target, ages 12 to 17 yr, with visual acuity >20/200 to <=20/50
Group 7; 5 Patient target, ages 18yr and older, with visual acuity LP to <=20/200
Group 8; 5 Patient target, ages 18yr and older, with visual acuity >20/200 to <=20/50

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize CEP290-related retinal degeneration	To prospectively characterize CEP290-related retinal degeneration and the clinical phenotype of patients with either compound heterozygous or homozygous intron 26 c.2991+1655A>G mutations	Through 12 months

Collaborators and Investigators

• Sponsor: Editas Medicine, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2017
• Primary Completion (Actual): May 6, 2022
• Study Completion (Actual): May 6, 2022

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: January 4, 2018
• First Posted (Actual): January 10, 2018

Study Record Updates

• Last Update Posted (Actual): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Congenital Abnormalities; Genetic Diseases, Inborn; CEP290; LCA10; Retinal degenerative diseases (RDD); Leber congenital amaurosis (LCA); Congenital Retinal Blindness; p.Cys998X; c.2991+1655A>G; Eye Diseases Signs and Symptoms; Eye Abnormalities
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Sensation Disorders; Disease; Retinal Diseases; Eye Diseases; Genetic Diseases, Inborn; Blindness; Vision Disorders; Retinal Degeneration; Leber Congenital Amaurosis; Eye Diseases, Hereditary; Eye Abnormalities
• Other Study ID Numbers: EDIT-NHS01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No