## Protocol Section
### Identification Module
**NCT ID:** 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")

#### Organization Study ID Info
**ID:** 1991-201-008
#### Organization
**Class:** INDUSTRY
**Full Name:** Editas Medicine, Inc.
### Status Module
#### Completion Date
**Date:** 2025-05-23

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-12-05

**Type:** ACTUAL

**Last Update Submit Date:** 2022-12-02

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2025-05-23

**Type:** ESTIMATED

#### Start Date
**Date:** 2019-09-26

**Type:** ACTUAL

**Status Verified Date:** 2022-12

#### Study First Post Date
**Date:** 2019-03-13
**Type:** ACTUAL
**Study First Submit Date:** 2018-10-12
**Study First Submit QC Date:** 2019-03-11
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Editas Medicine, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- 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

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 34

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Single dose of EDIT-101 administered by subretinal injection surgery

**Intervention Names:**

- Drug: EDIT-101

**Label:** Adults Low Dose

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Single dose of EDIT-101 administered by subretinal injection surgery

**Intervention Names:**

- Drug: EDIT-101

**Label:** Adults Middle Dose

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Single dose of EDIT-101 administered by subretinal injection surgery

**Intervention Names:**

- Drug: EDIT-101

**Label:** Adults High Dose

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Single dose of EDIT-101 administered by subretinal injection surgery

**Intervention Names:**

- Drug: EDIT-101

**Label:** Pediatric Middle Dose

**Type:** EXPERIMENTAL

#### Arm Group 5

**Description:** Single dose of EDIT-101 administered by subretinal injection surgery

**Intervention Names:**

- Drug: EDIT-101

**Label:** Pediatric High Dose

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Adults High Dose

- Adults Low Dose

- Adults Middle Dose

- Pediatric High Dose

- Pediatric Middle Dose

**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.

**Name:** EDIT-101

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Frequency of Adverse Events related to EDIT-101

**Time Frame:** 1 year

**Measure:** Number of participants experiencing procedural related adverse events

**Time Frame:** 1 year

**Measure:** Incidence of dose limiting toxicities

**Time Frame:** 1 year

#### Secondary Outcomes

**Measure:** Maximum tolerated dose as determined by occurrence of dose limiting toxicities

**Time Frame:** 1 year

**Description:** 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.

**Measure:** Change from baseline in Mobility course score

**Time Frame:** 1 year

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

**Measure:** Change from baseline in LogMAR measurement of BCVA

**Time Frame:** 1 year

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

**Measure:** Change from baseline in pupillary response

**Time Frame:** 1 year

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

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

**Time Frame:** 1 year

**Measure:** Change from baseline in macula thickness

**Time Frame:** 1 year

**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.

**Measure:** Change from baseline in contrast sensitivity

**Time Frame:** 1 year

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

**Measure:** Change from baseline in macular sensitivity as measured by microperimetry

**Time Frame:** 1 year

**Description:** 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.

**Measure:** Change from baseline in color vision score using the Farnsworth 15 score

**Time Frame:** 1 year

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

**Time Frame:** 1 year

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

**Time Frame:** 1 year

**Measure:** 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

**Measure:** 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

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

**Measure:** Change from baseline in visual field using kinetic perimetry

**Time Frame:** 1 year

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

**Measure:** Change from baseline in Patient Global Impressions of Change score

**Time Frame:** 1 year

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

**Measure:** Change from baseline in gaze tracking

**Time Frame:** 1 year

### Eligibility Module

**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

**Minimum Age:** 3 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Miami

**Country:** United States

**Facility:** Bascom Palmer Eye Institute

**State:** Florida

**Zip:** 33136

**Location 2:**

**City:** Boston

**Country:** United States

**Facility:** Massachusetts Eye and Ear Infirmary

**State:** Massachusetts

**Zip:** 02114

**Location 3:**

**City:** Ann Arbor

**Country:** United States

**Facility:** W.K. Kellogg Eye Center - University of Michigan

**State:** Michigan

**Zip:** 48105

**Location 4:**

**City:** Portland

**Country:** United States

**Facility:** Casey Eye Institute - OSHU

**State:** Oregon

**Zip:** 97239

**Location 5:**

**City:** Philadelphia

**Country:** United States

**Facility:** University of Pennsylvania

**State:** Pennsylvania

**Zip:** 19104

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**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.

**PMID:** 34629400

**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.

**PMID:** 33497524

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012678

- Term: Sensation Disorders

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000000013

- Term: Congenital Abnormalities

### Condition Browse Module - Browse Branches

- Abbrev: BC11

- Name: Eye Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M8271

- Name: Eye Diseases

- Relevance: HIGH

- As Found: Eye Disease

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M14999

- Name: Retinal Diseases

- Relevance: HIGH

- As Found: Retinal Disease

- ID: M5047

- Name: Blindness

- Relevance: HIGH

- As Found: Amaurosis

- ID: M8267

- Name: Eye Abnormalities

- Relevance: HIGH

- As Found: Eye Disorders Congenital

- ID: M17530

- Name: Vision Disorders

- Relevance: HIGH

- As Found: Vision Disorders

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: HIGH

- As Found: Diseases, Hereditary

- ID: M14997

- Name: Retinal Degeneration

- Relevance: HIGH

- As Found: Retinal Degeneration

- ID: M29107

- Name: Retinal Dystrophies

- Relevance: HIGH

- As Found: Retinal Dystrophy

- ID: M18339

- Name: Eye Diseases, Hereditary

- Relevance: HIGH

- As Found: Eye Diseases, Hereditary

- ID: M28730

- Name: Leber Congenital Amaurosis

- Relevance: HIGH

- As Found: Leber Congenital Amaurosis

- ID: M15490

- Name: Sensation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: T3335

- Name: Leber Congenital Amaurosis

- Relevance: HIGH

- As Found: Leber Congenital Amaurosis

- ID: T3337

- Name: Leber Congenital Amaurosis 10

- Relevance: HIGH

- As Found: Leber Congenital Amaurosis 10

### Condition Browse Module - Meshes

- ID: D000001766

- Term: Blindness

- ID: D000014786

- Term: Vision Disorders

- ID: D000005128

- Term: Eye Diseases

- ID: D000012164

- Term: Retinal Diseases

- ID: D000012162

- Term: Retinal Degeneration

- ID: D000058499

- Term: Retinal Dystrophies

- ID: D000057130

- Term: Leber Congenital Amaurosis

- ID: D000015785

- Term: Eye Diseases, Hereditary

- ID: D000005124

- Term: Eye Abnormalities

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Intervention Browse Module - Browse Branches

- Abbrev: AA

- Name: Amino Acids

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: T4

- Name: Cysteine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
