Back to results

Single Ascending Dose Study in Participants With LCA10

Primary Purpose

Leber Congenital Amaurosis 10, Inherited Retinal Dystrophies, Eye Diseases, Hereditary

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

EDIT-101

About this trial

This is an interventional treatment trial for Leber Congenital Amaurosis 10 focused on measuring CEP290, LCA10, Retinal degenerative diseases (RDD), Leber congenital amaurosis (LCA), Congenital Retinal Blindness, p.Cys998X, c.2991+1655A>G, CRISPR Treatment, Cas9 Protein, Eye Diseases Signs and Symptoms, Genetic Diseases, Inborn, Congenital Abnormalities, Eye Abnormalities, CRISPR-Cas9, CRISPR Associated Protein 9, Cas9 Enzyme

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Bascom Palmer Eye Institute
Massachusetts Eye and Ear Infirmary
W.K. Kellogg Eye Center - University of Michigan
Casey Eye Institute - OSHU
University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Adults Low Dose

Adults Middle Dose

Adults High Dose

Pediatric Middle Dose

Pediatric High Dose

Arm Description

Single dose of EDIT-101 administered by subretinal injection surgery

Outcomes

Primary Outcome Measures

Frequency of Adverse Events related to EDIT-101

Number of participants experiencing procedural related adverse events

Incidence of dose limiting toxicities

Secondary Outcome Measures

Maximum tolerated dose as determined by occurrence of dose limiting toxicities

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.

Change from baseline in LogMAR measurement of BCVA

The test will evaluate visual acuity in ranges from light perception to normal vision.

Change from baseline in pupillary response

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)

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

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.

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.

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.

Change from baseline in QOL score for Age <8 years using the Children's Visual Function Questionnaire

Change from baseline in QOL score for Age 8 to <18 years using the Impact of Vision Impairment for Children

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

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

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

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.

Change from baseline in gaze tracking

Video clips of the eyes are used to measure eye position and stability over time.

Full Information

NCT ID

NCT03872479

First Posted

October 12, 2018

Last Updated

December 2, 2022

Sponsor

Editas Medicine, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03872479

Brief Title

Single Ascending Dose Study in Participants With LCA10

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")

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 26, 2019 (Actual)

Primary Completion Date

May 23, 2025 (Anticipated)

Study Completion Date

May 23, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Editas Medicine, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

CEP290, LCA10, Retinal degenerative diseases (RDD), Leber congenital amaurosis (LCA), Congenital Retinal Blindness, p.Cys998X, c.2991+1655A>G, CRISPR Treatment, Cas9 Protein, Eye Diseases Signs and Symptoms, Genetic Diseases, Inborn, Congenital Abnormalities, Eye Abnormalities, CRISPR-Cas9, CRISPR Associated Protein 9, Cas9 Enzyme

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Adults Low Dose

Arm Type

Experimental

Arm Description

Single dose of EDIT-101 administered by subretinal injection surgery

Arm Title

Adults Middle Dose

Arm Type

Experimental

Arm Description

Single dose of EDIT-101 administered by subretinal injection surgery

Arm Title

Adults High Dose

Arm Type

Experimental

Arm Description

Single dose of EDIT-101 administered by subretinal injection surgery

Arm Title

Pediatric Middle Dose

Arm Type

Experimental

Arm Description

Single dose of EDIT-101 administered by subretinal injection surgery

Arm Title

Pediatric High Dose

Arm Type

Experimental

Arm Description

Single dose of EDIT-101 administered by subretinal injection surgery

Intervention Type

Drug

Intervention Name(s)

EDIT-101

Intervention Description

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.

Primary Outcome Measure Information:

Title

Frequency of Adverse Events related to EDIT-101

Time Frame

1 year

Title

Number of participants experiencing procedural related adverse events

Time Frame

1 year

Title

Incidence of dose limiting toxicities

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Maximum tolerated dose as determined by occurrence of dose limiting toxicities

Time Frame

1 year

Title

Change from baseline in Mobility course score

Description

Time Frame

1 year

Title

Change from baseline in LogMAR measurement of BCVA

Description

The test will evaluate visual acuity in ranges from light perception to normal vision.

Time Frame

1 year

Title

Change from baseline in pupillary response

Description

Measuring the change in pupil diameter in response to a light stimulus.

Time Frame

1 year

Title

Change from baseline in dark adapted visual sensitivity using Full field light sensitivity threshold (FST)

Description

Flashes of light of varying luminance are presented to the eye and the subject reports is the flash was seen.

Time Frame

1 year

Title

Change from baseline in macula thickness

Time Frame

1 year

Title

Change from baseline in contrast sensitivity

Description

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.

Time Frame

1 year

Title

Change from baseline in macular sensitivity as measured by microperimetry

Description

Visual field test measuring the amount of light perceived in specific parts of the macula.

Time Frame

1 year

Title

Change from baseline in color vision score using the Farnsworth 15 score

Description

Time Frame

1 year

Title

Change from baseline in QOL score for Age <8 years using the Children's Visual Function Questionnaire

Time Frame

1 year

Title

Change from baseline in QOL score for Age 8 to <18 years using the Impact of Vision Impairment for Children

Time Frame

1 year

Title

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

Title

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

Title

Change from baseline in visual field using kinetic perimetry

Description

Kinetic perimetry looks as the visual field to identify regions of normal and abnormal sensitivity to light

Time Frame

1 year

Title

Change from baseline in Patient Global Impressions of Change score

Description

This QOL has 5 non-numeric choices for the subject to select how they believe their condition has changed.

Time Frame

1 year

Title

Change from baseline in gaze tracking

Description

Video clips of the eyes are used to measure eye position and stability over time.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Bascom Palmer Eye Institute

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Massachusetts Eye and Ear Infirmary

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

W.K. Kellogg Eye Center - University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48105

Country

United States

Facility Name

Casey Eye Institute - OSHU

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34629400

Citation

Harvey JP, Sladen PE, Yu-Wai-Man P, Cheetham ME. Induced Pluripotent Stem Cells for Inherited Optic Neuropathies-Disease Modeling and Therapeutic Development. J Neuroophthalmol. 2022 Mar 1;42(1):35-44. doi: 10.1097/WNO.0000000000001375. Epub 2021 Sep 30.

Results Reference

derived

PubMed Identifier

33497524

Citation

Zhang X, Zhang D, Thompson JA, Chen SC, Huang Z, Jennings L, McLaren TL, Lamey TM, De Roach JN, Chen FK, McLenachan S. Gene correction of the CLN3 c.175G>A variant in patient-derived induced pluripotent stem cells prevents pathological changes in retinal organoids. Mol Genet Genomic Med. 2021 Mar;9(3):e1601. doi: 10.1002/mgg3.1601. Epub 2021 Jan 26.

Results Reference

derived

Links:

URL

https://studylca.com/us/en/about

Description

Clinical Trial Informational Website

Learn more about this trial

Single Ascending Dose Study in Participants With LCA10

We'll reach out to this number within 24 hrs