Single Ascending Dose Study in Participants With LCA10

Retinal Disease Clinical Trial

Official title:

Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Efficacy of EDIT-101 in Adult and Pediatric Participants With Leber Congenital Amaurosis Type 10 (LCA10), With Centrosomal Protein 290 (CEP290)-Related Retinal Degeneration Caused by a Compound Heterozygous or Homozygous Mutation Involving c.2991+1655A>G in Intron 26 (IVS26) of the CEP290 Gene ("LCA10-IVS26")

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03872479
• Other study ID #: 1991-201-008
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 26, 2019
• Est. completion date: May 23, 2025

Study information

• Verified date: December 2022
• Source: Editas Medicine, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of EDIT-101 administered via subretinal injection in participants with LCA10 caused by a homozygous or compound heterozygous mutation involving c.2991+1655A>G in intron 26 of the CEP290 gene ("LCA10-IVS26").

Description:

This is an open-label, single ascending dose study of EDIT-101 in adult and pediatric (ie, ages 3 to 17) participants with LCA10-IVS26. Up to 34 participants will be enrolled in up to 5 cohorts to evaluate up to 3 dose levels of EDIT-101 in this study. EDIT-101 is a novel gene editing product designed to eliminate the mutation on the CEP290 gene that results in the retinal degeneration that defines LCA10-IVS26.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 34
• Est. completion date: May 23, 2025
• Est. primary completion date: May 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

Inclusion Criteria:

• Male or female

• At least 3 years of age at screening with CEP290-related retinal degeneration caused by a homozygous or compound heterozygous mutation involving c.2991+1655A>G in IVS26 of the CEP290 gene.

• Visual Acuity:

• Sentinel participant will have severe vision loss with a logMAR BCVA of =1.6 to 3.9 (20/800 or worse to LP) in the study eye

• Non-sentinel participants must have BCVA between 1.0 - 3.0 logMAR in the study eye

Exclusion Criteria:

• Other known disease-causing mutations

• Achieves a passing score for the mobility course at the most difficult level

• In either eye, active systemic or ocular/intraocular infection or inflammation

• In either eye, history of steroid-responsive intraocular pressure with increases > 25 mm Hg following corticosteroid exposure

• Any vaccination/immunization in the last 28 days before screening

• Inability or unwillingness to take oral prednisone

• Prior gene therapy or oligonucleotide treatment

Related Conditions & MeSH terms

• Blindness
• Disease
• Eye Abnormalities
• Eye Diseases
• Eye Diseases, Hereditary
• Eye Disorders Congenital
• Genetic Diseases, Inborn
• Inherited Retinal Dystrophies
• Leber Congenital Amaurosis
• Leber Congenital Amaurosis 10
• Retinal Degeneration
• Retinal Disease
• Retinal Diseases
• Retinal Dystrophies
• Vision Disorders

Intervention

Drug:
• EDIT-101
Participants will receive a single dose of EDIT-101 administered via subretinal injection in the study eye. Up to 5 cohorts across 3 doses will be enrolled in this study.

Locations

Country	Name	City	State
United States	W.K. Kellogg Eye Center - University of Michigan	Ann Arbor	Michigan
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Casey Eye Institute - OSHU	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Editas Medicine, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Adverse Events related to EDIT-101		1 year
Primary	Number of participants experiencing procedural related adverse events		1 year
Primary	Incidence of dose limiting toxicities		1 year
Secondary	Maximum tolerated dose as determined by occurrence of dose limiting toxicities		1 year
Secondary	Change from baseline in Mobility course score	Testing the subjects visual function by having the subject walk through obstacle courses. Courses will have different levels of difficulty depending on the light levels of the room and the contrast of the objects in the room.	1 year
Secondary	Change from baseline in LogMAR measurement of BCVA	The test will evaluate visual acuity in ranges from light perception to normal vision.	1 year
Secondary	Change from baseline in pupillary response	Measuring the change in pupil diameter in response to a light stimulus.	1 year
Secondary	Change from baseline in dark adapted visual sensitivity using Full field light sensitivity threshold (FST)	Flashes of light of varying luminance are presented to the eye and the subject reports is the flash was seen.	1 year
Secondary	Change from baseline in macula thickness		1 year
Secondary	Change from baseline in contrast sensitivity	The Lea symbols chart will be used for subjects under age 6 and the Pelli-Robson chart for all other subjects. The images or letters on the charts are in decreasing contrast.	1 year
Secondary	Change from baseline in macular sensitivity as measured by microperimetry	Visual field test measuring the amount of light perceived in specific parts of the macula.	1 year
Secondary	Change from baseline in color vision score using the Farnsworth 15 score	The Farnsworth D15 tests for congenital and acquired color vision defects. Fifteen color discs will be arranged by the subject. Scoring is accomplished by recording the sequence selected by the patient on a copy of the score sheet. A patient with a color vision deficiency will arrange the color discs in a different order than a person with normal color vision.	1 year
Secondary	Change from baseline in QOL score for Age <8 years using the Children's Visual Function Questionnaire		1 year
Secondary	Change from baseline in QOL score for Age 8 to <18 years using the Impact of Vision Impairment for Children		1 year
Secondary	Change from baseline in QOL score for Age >18 years if BCVA is worse than 1.0 logMAR in both eyes using the Impact of Vision Impairment for Very Low Vision		1 year
Secondary	Change from baseline in QOL score for Age >18 years if BCVA is 1.0 logMAR or better in both eyes using the Impact of Vision Impairment		1 year
Secondary	Change from baseline in visual field using kinetic perimetry	Kinetic perimetry looks as the visual field to identify regions of normal and abnormal sensitivity to light	1 year
Secondary	Change from baseline in Patient Global Impressions of Change score	This QOL has 5 non-numeric choices for the subject to select how they believe their condition has changed.	1 year
Secondary	Change from baseline in gaze tracking	Video clips of the eyes are used to measure eye position and stability over time.	1 year

External Links

•   Clinical Trial Informational Website