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History of Changes for Study: NCT03872479
Single Ascending Dose Study in Participants With LCA10
Latest version (submitted July 13, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 11, 2019 None (earliest Version on record)
2 July 17, 2019 Study Status and Contacts/Locations
3 July 22, 2019 Recruitment Status, Study Status and Contacts/Locations
4 August 19, 2019 Study Status, Conditions and References
5 October 25, 2019 Study Status and Contacts/Locations
6 November 20, 2019 Study Status and Contacts/Locations
7 March 4, 2020 Study Status
8 March 17, 2020 Contacts/Locations and Study Status
9 April 17, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Description
10 May 4, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Description
11 May 26, 2020 Contacts/Locations and Study Status
12 June 16, 2020 Study Status and Contacts/Locations
13 September 17, 2020 Study Status and Contacts/Locations
14 December 18, 2020 IPDSharing, Contacts/Locations, Arms and Interventions, Sponsor/Collaborators, Study Identification, Study Description, Study Status, References and Outcome Measures
15 October 13, 2021 Study Status and References
16 March 30, 2022 Study Status and Contacts/Locations
17 April 13, 2022 Study Status, Study Design and Study Description
18 May 17, 2022 Study Status and Eligibility
19 July 12, 2022 Study Status and Eligibility
20 July 13, 2022 Conditions and Study Status
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Study NCT03872479
Submitted Date:  March 11, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 1991-201-008
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 AGN-151587 (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")
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2019
Overall Status: Not yet recruiting
Study Start: June 3, 2019
Primary Completion: March 22, 2024 [Anticipated]
Study Completion: March 22, 2024 [Anticipated]
First Submitted: October 12, 2018
First Submitted that
Met QC Criteria:
March 11, 2019
First Posted: March 13, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
March 11, 2019
Last Update Posted: March 13, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Allergan
Responsible Party: Sponsor
Collaborators: Editas Medicine, Inc.
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of AGN-151587 (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 AGN-151587 (EDIT-101) in adult and pediatric (ie, ages 3 to 17) participants with LCA10-IVS26. Approximately 18 participants will be enrolled in up to 5 cohorts to evaluate up to 3 dose levels of AGN-151587 in this study. AGN-151587 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.
Open or close this module Conditions
Conditions: Leber Congenital Amaurosis 10
Keywords: CEP290
LCA10
Retinal degenerative diseases (RDD)
Leber congenital amaurosis (LCA)
CRISPR Treatment
LCA10-IVS26
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
Number of Arms: 5
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 18 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Adults Low Dose
Single dose of AGN-151587 administered by subretinal injection surgery
Drug: AGN-151587
Participants will receive a single dose of AGN-151587 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 AGN-151587 administered by subretinal injection surgery
Drug: AGN-151587
Participants will receive a single dose of AGN-151587 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 AGN-151587 administered by subretinal injection surgery
Drug: AGN-151587
Participants will receive a single dose of AGN-151587 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 AGN-151587 administered by subretinal injection surgery
Drug: AGN-151587
Participants will receive a single dose of AGN-151587 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 AGN-151587 administered by subretinal injection surgery
Drug: AGN-151587
Participants will receive a single dose of AGN-151587 administered via subretinal injection in the study eye. Up to 5 cohorts across 3 doses will be enrolled in this study.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Frequency of Adverse Events related to AGN-151587
[ 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.
Open or close this module Eligibility
Minimum Age: 3 Years
Maximum Age:
Sex: All
Gender Based:
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.
  • Best corrected visual acuity of light perception to 0.4 logMAR (20/50 Snellen equivalent).

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
Open or close this module Contacts/Locations
Central Contact Person: Clinical Trials Registry Team
Telephone: 1-877-277-8566
Email: IR-CTRegistration@allergan.com
Study Officials: Francisco Lopez, MD, PhD
Study Director
Allergan
Locations: United States, Massachusetts
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, United States, 02114
Open or close this module IPDSharing
Plan to Share IPD: Yes
Allergan will share de-identified patient-level data and study-level data including protocols and clinical study reports for phase 2 - 4 trials completed after 2008 that are registered to ClinicalTrials.gov or EudraCT, have received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published. To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes. More information can be found on http://www.allerganclinicaltrials.com/.
Supporting Information:
Study Protocol
Clinical Study Report (CSR)
Time Frame:
After having received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published.
Access Criteria:
To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes.
URL: http://www.allerganclinicaltrials.com
Open or close this module References
Links:
Available IPD/Information:

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