Single Ascending Dose Study in Participants With LCA10

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ClinicalTrials.gov Identifier: NCT03872479

Recruitment Status : Recruiting

First Posted : March 13, 2019

Last Update Posted : December 22, 2020

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Editas Medicine, Inc.

Tracking Information

First Submitted Date ^ICMJE

October 12, 2018

First Posted Date ^ICMJE

March 13, 2019

Last Update Posted Date

December 22, 2020

Actual Study Start Date ^ICMJE

September 26, 2019

Estimated Primary Completion Date

March 22, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Frequency of Adverse Events related to EDIT-101 [ Time Frame: 1 year ]
Number of participants experiencing procedural related adverse events [ Time Frame: 1 year ]
Incidence of dose limiting toxicities [ Time Frame: 1 year ]

Original Primary Outcome Measures ^ICMJE

Frequency of Adverse Events related to AGN-151587 [ Time Frame: 1 year ]
Number of participants experiencing procedural related adverse events [ Time Frame: 1 year ]
Incidence of dose limiting toxicities [ Time Frame: 1 year ]

Change History

Current Secondary Outcome Measures ^ICMJE

Maximum tolerated dose as determined by occurrence of dose limiting toxicities [ Time Frame: 1 year ]
Change from baseline in Mobility course score [ Time Frame: 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 LogMAR measurement of BCVA [ Time Frame: 1 year ]
The test will evaluate visual acuity in ranges from light perception to normal vision.
Change from baseline in pupillary response [ Time Frame: 1 year ]
Measuring the change in pupil diameter in response to a light stimulus.
Change from baseline in dark adapted visual sensitivity using Full field light sensitivity threshold (FST) [ Time Frame: 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 macula thickness [ Time Frame: 1 year ]
Change from baseline in contrast sensitivity [ Time Frame: 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 macular sensitivity as measured by microperimetry [ Time Frame: 1 year ]
Visual field test measuring the amount of light perceived in specific parts of the macula.
Change from baseline in color vision score using the Farnsworth 15 score [ Time Frame: 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 [ Time Frame: 1 year ]
Change from baseline in QOL score for Age 8 to <18 years using the Impact of Vision Impairment for Children [ Time Frame: 1 year ]
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 [ Time Frame: 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 [ Time Frame: 1 year ]
Change from baseline in visual field using kinetic perimetry [ Time Frame: 1 year ]
Kinetic perimetry looks as the visual field to identify regions of normal and abnormal sensitivity to light
Change from baseline in Patient Global Impressions of Change score [ Time Frame: 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 gaze tracking [ Time Frame: 1 year ]
Video clips of the eyes are used to measure eye position and stability over time.

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Single Ascending Dose Study in Participants With LCA10

Official Title ^ICMJE

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")

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. Approximately 18 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 Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Blindness
Leber Congenital Amaurosis 10
Vision Disorders
Eye Diseases
Eye Diseases, Hereditary
Eye Disorders Congenital
Retinal Disease
Retinal Degeneration

Intervention ^ICMJE

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.

Study Arms ^ICMJE

Experimental: Adults Low Dose
Single dose of EDIT-101 administered by subretinal injection surgery

Intervention: Drug: EDIT-101
Experimental: Adults Middle Dose
Single dose of EDIT-101 administered by subretinal injection surgery

Intervention: Drug: EDIT-101
Experimental: Adults High Dose
Single dose of EDIT-101 administered by subretinal injection surgery

Intervention: Drug: EDIT-101
Experimental: Pediatric Middle Dose
Single dose of EDIT-101 administered by subretinal injection surgery

Intervention: Drug: EDIT-101
Experimental: Pediatric High Dose
Single dose of EDIT-101 administered by subretinal injection surgery

Intervention: Drug: EDIT-101

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

March 22, 2024

Estimated Primary Completion Date

March 22, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.
Best corrected visual acuity of light perception to 0.4 logMAR (20/50 Snellen equivalent).

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

3 Years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Editas Medicine's Clinical Trial Team

617-401-9007

patients@editasmed.com

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03872479

Other Study ID Numbers ^ICMJE

1991-201-008

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement ^ICMJE

Plan to Share IPD:

Responsible Party

Editas Medicine, Inc.

Study Sponsor ^ICMJE

Editas Medicine, Inc.

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Not Provided

PRS Account

Editas Medicine, Inc.

Verification Date

December 2020

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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