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Single Ascending Dose Study in Participants With LCA10

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03872479
Recruitment Status : Active, not recruiting
First Posted : March 13, 2019
Last Update Posted : December 5, 2022
Sponsor:
Information provided by (Responsible Party):
Editas Medicine, Inc.

Study Description
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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").

Condition or disease Intervention/treatment Phase
Leber Congenital Amaurosis 10 Inherited Retinal Dystrophies Eye Diseases, Hereditary Retinal Disease Retinal Degeneration Vision Disorders Eye Disorders Congenital Drug: EDIT-101 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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")
Actual Study Start Date : September 26, 2019
Estimated Primary Completion Date : May 23, 2025
Estimated Study Completion Date : May 23, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Adults Low Dose
Single dose of EDIT-101 administered by subretinal injection surgery
 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.
Experimental: Adults Middle Dose
Single dose of EDIT-101 administered by subretinal injection surgery
 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.
Experimental: Adults High Dose
Single dose of EDIT-101 administered by subretinal injection surgery
 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.
Experimental: Pediatric Middle Dose
Single dose of EDIT-101 administered by subretinal injection surgery
 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.
Experimental: Pediatric High Dose
Single dose of EDIT-101 administered by subretinal injection surgery
 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.


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

Secondary Outcome Measures :
  1. Maximum tolerated dose as determined by occurrence of dose limiting toxicities [ Time Frame: 1 year ]
  2. 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.

  3. 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.

  4. Change from baseline in pupillary response [ Time Frame: 1 year ]
    Measuring the change in pupil diameter in response to a light stimulus.

  5. 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.

  6. Change from baseline in macula thickness [ Time Frame: 1 year ]
  7. 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.

  8. 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.

  9. 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.

  10. Change from baseline in QOL score for Age <8 years using the Children's Visual Function Questionnaire [ Time Frame: 1 year ]
  11. Change from baseline in QOL score for Age 8 to <18 years using the Impact of Vision Impairment for Children [ Time Frame: 1 year ]
  12. 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 ]
  13. 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 ]
  14. 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

  15. 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.

  16. 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.


Eligibility Criteria
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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03872479


Locations
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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 - University of Michigan
Ann Arbor, Michigan, United States, 48105
United States, Oregon
Casey Eye Institute - OSHU
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Editas Medicine, Inc.
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Editas Medicine, Inc.
ClinicalTrials.gov Identifier: NCT03872479    
Other Study ID Numbers: 1991-201-008
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: December 5, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Editas Medicine, Inc.:
CRISPR Treatment
CRISPR-Cas9
CRISPR Associated Protein 9
CEP290
LCA10
Retinal degenerative diseases (RDD)
Leber congenital amaurosis (LCA)
Congenital Retinal Blindness
 p.Cys998X
c.2991+1655A>G
Cas9 Protein
Eye Diseases Signs and Symptoms
Genetic Diseases, Inborn
Congenital Abnormalities
Eye Abnormalities
Cas9 Enzyme
Additional relevant MeSH terms:
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Blindness
Vision Disorders
Eye Diseases
Retinal Diseases
Retinal Degeneration
Retinal Dystrophies
Leber Congenital Amaurosis
Eye Diseases, Hereditary
 Eye Abnormalities
Genetic Diseases, Inborn
Disease
Pathologic Processes
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Congenital Abnormalities