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Leber Congenital Amaurosis 10Phase 1/2NCT03872479

Single Ascending Dose Study in Participants With LCA10

A Phase 1/2 study testing EDIT-101 in people with Leber Congenital Amaurosis 10 and Inherited Retinal Dystrophies, run by Editas Medicine, Inc. at 5 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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"). Read more about this study

Who is it for?
Ages 3 years and older
What is being tested?
EDIT-101
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
5 sitesUnited States
Study dates
26 Sep 2019to 23 May 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • W.K. Kellogg Eye Center - University of Michigan

    Ann Arbor, Michigan, 48105

  • Massachusetts Eye and Ear Infirmary

    Boston, Massachusetts, 02114

  • Bascom Palmer Eye Institute

    Miami, Florida, 33136

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Casey Eye Institute - OSHU

    Portland, Oregon, 97239

Other trials in United States

About this study

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")

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").

Read the 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.

Being tested
EDIT-101
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
Medical subject headings
Leber Congenital Amaurosis 10, Eye Diseases, Hereditary, Retinal Diseases, Retinal Degeneration, Vision Disorders, Eye Abnormalities, Meckel Syndrome, Type 4, Leber Congenital Amaurosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EDIT-101Drug

    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 groups in NCT03872479
Study groupRoleWhat they receive
Adults Low DoseExperimentalSingle dose of EDIT-101 administered by subretinal injection surgery
Receives: Drug: EDIT-101
Adults Middle DoseExperimentalSingle dose of EDIT-101 administered by subretinal injection surgery
Receives: Drug: EDIT-101
Adults High DoseExperimentalSingle dose of EDIT-101 administered by subretinal injection surgery
Receives: Drug: EDIT-101
Pediatric Middle DoseExperimentalSingle dose of EDIT-101 administered by subretinal injection surgery
Receives: Drug: EDIT-101
Pediatric High DoseExperimentalSingle dose of EDIT-101 administered by subretinal injection surgery
Receives: Drug: EDIT-101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of Adverse Events related to EDIT-101

    Measured: 1 year

  2. Number of participants experiencing procedural related adverse events

    Measured: 1 year

  3. Incidence of dose limiting toxicities

    Measured: 1 year

Secondary outcomes (16)

  1. Maximum tolerated dose as determined by occurrence of dose limiting toxicities

    Measured: 1 year

  2. 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.

    Measured: 1 year

  3. Change from baseline in LogMAR measurement of BCVA

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

    Measured: 1 year

  4. Change from baseline in pupillary response

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

    Measured: 1 year

  5. 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.

    Measured: 1 year

  6. Change from baseline in macula thickness

    Measured: 1 year

  7. 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.

    Measured: 1 year

  8. 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.

    Measured: 1 year

  9. 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.

    Measured: 1 year

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

    Measured: 1 year

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

    Measured: 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

    Measured: 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

    Measured: 1 year

  14. 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

    Measured: 1 year

  15. 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.

    Measured: 1 year

  16. Change from baseline in gaze tracking

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

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2019
  2. Study start26 Sep 2019
  3. Primary completion23 May 2025 (estimated)
  4. Study completion23 May 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03872479
Sponsor's protocol ID
1991-201-008
Status last verified
Dec 2022
First submitted
12 Oct 2018
Last updated
5 Dec 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38709228

  • 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.

    PubMed 34629400

  • 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.

    PubMed 33497524

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EDIT-101 in people with Leber Congenital Amaurosis 10 and Inherited Retinal Dystrophies, run by Editas Medicine, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of Adverse Events related to EDIT-101 (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03872479, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2022.

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