Natural History Study of CEP290-Related Retinal Degeneration

• ClinicalTrials.gov Identifier: NCT03396042
• Recruitment Status: Completed
• First Posted: January 10, 2018
• Last Update Posted: May 19, 2022
• Sponsor: Editas Medicine, Inc.
• Information provided by (Responsible Party): Editas Medicine, Inc.

Study Description

Brief Summary:

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.

Condition or disease
Blindness; Leber Congenital Amaurosis 10; Vision Disorders; Eye Diseases; Eye Diseases, Hereditary; Eye Disorders Congenital; Retinal Disease; Retinal Degeneration

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 Design

• Study Type: Observational
• Actual Enrollment: 26 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Natural History Study of CEP290-Related Retinal Degeneration
• Actual Study Start Date: December 17, 2017
• Actual Primary Completion Date: May 6, 2022
• Actual Study Completion Date: May 6, 2022

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Characterize CEP290-related retinal degeneration [ Time Frame: Through 12 months ]
   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

Biospecimen Retention:   Samples With DNA

Blood sampling for genetic testing of the CEP290 gene, including coding and intron 26 sequences, as part of a 280-gene retinal dystrophy gene panel.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Bascom Palmer Eye Institute

Miami, Florida, United States, 33136

United States, Massachusetts

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States, 02114

United States, Michigan

W.K. Kellogg Eye Center

Ann Arbor, Michigan, United States, 48105

United States, Oregon

Casey Eye Institute - OHSU

Portland, Oregon, United States, 97239

France

Universite Pierre et Marie Curie

Paris, France, 75252

Germany

Universitaetsklinikum Giessen and Marburg GmbH

Giessen, Germany, 35392

Netherlands

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, Netherlands, 6525

Sponsors and Collaborators

Editas Medicine, Inc.

More Information

• Responsible Party: Editas Medicine, Inc.
• ClinicalTrials.gov Identifier: NCT03396042
• Other Study ID Numbers: EDIT-NHS01
• First Posted: January 10, 2018
• Last Update Posted: May 19, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Editas Medicine, Inc.:

CEP290; LCA10; Retinal degenerative diseases (RDD); Leber congenital amaurosis (LCA); Congenital Retinal Blindness; p.Cys998X; c.2991+1655A>G; Eye Diseases Signs and Symptoms; Genetic Diseases, Inborn; Congenital Abnormalities; Eye Abnormalities

Additional relevant MeSH terms:

Blindness; Vision Disorders; Eye Diseases; Retinal Diseases; Retinal Degeneration; Leber Congenital Amaurosis; Eye Diseases, Hereditary; Eye Abnormalities; Genetic Diseases, Inborn; Disease; Pathologic Processes; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Congenital Abnormalities