Single Ascending Dose Study in Participants With LCA10

Phase 1

Active, not recruiting

• Conditions: Leber Congenital Amaurosis 10; Inherited Retinal Dystrophies; Eye Diseases, Hereditary; Retinal Disease; Vision Disorders; Retinal Degeneration; Eye Disorders Congenital
• Interventions: Drug: EDIT-101

• Registration Number: NCT03872479
• Lead Sponsor: Editas Medicine, Inc.

Brief 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").

Detailed 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.

Study Timeline

• Study First Submitted: 2018-10-12
• Study First Submitted QC: 2019-03-11
• Study First Posted: 2019-03-13
• Study Start: 2019-09-26
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-02
• Last Update Posted: 2022-12-05
• Primary Completion: 2025-05-23
• Study Completion: 2025-05-23

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 34

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Adults Low Dose	EDIT-101	Single dose of EDIT-101 administered by subretinal injection surgery
Adults Middle Dose	EDIT-101	Single dose of EDIT-101 administered by subretinal injection surgery
Pediatric Middle Dose	EDIT-101	Single dose of EDIT-101 administered by subretinal injection surgery
Adults High Dose	EDIT-101	Single dose of EDIT-101 administered by subretinal injection surgery
Pediatric High Dose	EDIT-101	Single dose of EDIT-101 administered by subretinal injection surgery

Primary Outcome Measures

Name	Time	Method
Frequency of Adverse Events related to EDIT-101	1 year
Number of participants experiencing procedural related adverse events	1 year
Incidence of dose limiting toxicities	1 year

Secondary Outcome Measures

Name	Time	Method
Change from baseline in pupillary response	1 year	Measuring the change in pupil diameter in response to a light stimulus.
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
Change from baseline in Patient Global Impressions of Change score	1 year	This QOL has 5 non-numeric choices for the subject to select how they believe their condition has changed.
Change from baseline in contrast sensitivity	1 year	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.
Change from baseline in color vision score using the Farnsworth 15 score	1 year	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.
Change from baseline in QOL score for Age <8 years using the Children's Visual Function Questionnaire	1 year
Change from baseline in visual field using kinetic perimetry	1 year	Kinetic perimetry looks as the visual field to identify regions of normal and abnormal sensitivity to light
Change from baseline in LogMAR measurement of BCVA	1 year	The test will evaluate visual acuity in ranges from light perception to normal vision.
Change from baseline in macular sensitivity as measured by microperimetry	1 year	Visual field test measuring the amount of light perceived in specific parts of the macula.
Change from baseline in QOL score for Age 8 to <18 years using the Impact of Vision Impairment for Children	1 year
Maximum tolerated dose as determined by occurrence of dose limiting toxicities	1 year
Change from baseline in macula thickness	1 year
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
Change from baseline in Mobility course score	1 year	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.
Change from baseline in dark adapted visual sensitivity using Full field light sensitivity threshold (FST)	1 year	Flashes of light of varying luminance are presented to the eye and the subject reports is the flash was seen.
Change from baseline in gaze tracking	1 year	Video clips of the eyes are used to measure eye position and stability over time.

Trial Locations

Locations (5)

Bascom Palmer Eye Institute; 🇺🇸 Miami, Florida, United States

Massachusetts Eye and Ear Infirmary; 🇺🇸 Boston, Massachusetts, United States

W.K. Kellogg Eye Center - University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Casey Eye Institute - OSHU; 🇺🇸 Portland, Oregon, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States