Single Ascending Dose Study in Participants With LCA10

Overview

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").

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 23, 2025

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.

Interventions

  • 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.

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Editas Medicine, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor

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