NCT03872479

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").

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
34

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2019

Longer than P75 for phase_1

Geographic Reach
1 country

5 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 12, 2018

Completed
5 months until next milestone

First Posted

Study publicly available on registry

March 13, 2019

Completed
7 months until next milestone

Study Start

First participant enrolled

September 26, 2019

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 23, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 23, 2025

Completed
Last Updated

December 5, 2022

Status Verified

December 1, 2022

Enrollment Period

5.7 years

First QC Date

October 12, 2018

Last Update Submit

December 2, 2022

Conditions

Keywords

CEP290LCA10Retinal degenerative diseases (RDD)Leber congenital amaurosis (LCA)Congenital Retinal Blindnessp.Cys998Xc.2991+1655A>GCRISPR TreatmentCas9 ProteinEye Diseases Signs and SymptomsGenetic Diseases, InbornCongenital AbnormalitiesEye AbnormalitiesCRISPR-Cas9CRISPR Associated Protein 9Cas9 Enzyme

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (16)

  • Maximum tolerated dose as determined by occurrence of dose limiting toxicities

    1 year

  • Change from baseline in Mobility course score

    1 year

  • Change from baseline in LogMAR measurement of BCVA

    1 year

  • Change from baseline in pupillary response

    1 year

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

    1 year

  • +11 more secondary outcomes

Study Arms (5)

Adults Low Dose

EXPERIMENTAL

Single dose of EDIT-101 administered by subretinal injection surgery

Drug: EDIT-101

Adults Middle Dose

EXPERIMENTAL

Single dose of EDIT-101 administered by subretinal injection surgery

Drug: EDIT-101

Adults High Dose

EXPERIMENTAL

Single dose of EDIT-101 administered by subretinal injection surgery

Drug: EDIT-101

Pediatric Middle Dose

EXPERIMENTAL

Single dose of EDIT-101 administered by subretinal injection surgery

Drug: EDIT-101

Pediatric High Dose

EXPERIMENTAL

Single dose of EDIT-101 administered by subretinal injection surgery

Drug: EDIT-101

Interventions

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.

Adults High DoseAdults Low DoseAdults Middle DosePediatric High DosePediatric Middle Dose

Eligibility Criteria

Age3 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

W.K. Kellogg Eye Center - University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Casey Eye Institute - OSHU

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

  • Pierce EA, Aleman TS, Jayasundera KT, Ashimatey BS, Kim K, Rashid A, Jaskolka MC, Myers RL, Lam BL, Bailey ST, Comander JI, Lauer AK, Maguire AM, Pennesi ME. Gene Editing for CEP290-Associated Retinal Degeneration. N Engl J Med. 2024 Jun 6;390(21):1972-1984. doi: 10.1056/NEJMoa2309915. Epub 2024 May 6.

  • 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.

  • 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.

MeSH Terms

Conditions

Leber Congenital Amaurosis 10Eye Diseases, HereditaryRetinal DiseasesRetinal DegenerationVision DisordersEye AbnormalitiesMeckel Syndrome, Type 4Leber Congenital AmaurosisGenetic Diseases, InbornCongenital Abnormalities

Condition Hierarchy (Ancestors)

Eye DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSensation DisordersNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 12, 2018

First Posted

March 13, 2019

Study Start

September 26, 2019

Primary Completion

May 23, 2025

Study Completion

May 23, 2025

Last Updated

December 5, 2022

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will not share

Locations