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Single Ascending Dose Study in Participants With LCA10

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ClinicalTrials.gov Identifier: NCT03872479
Recruitment Status : Not yet recruiting
First Posted : March 13, 2019
Last Update Posted : March 13, 2019
Sponsor:
Collaborator:
Editas Medicine, Inc.
Information provided by (Responsible Party):
Allergan

Tracking Information
First Submitted Date  ICMJE October 12, 2018
First Posted Date  ICMJE March 13, 2019
Last Update Posted Date March 13, 2019
Estimated Study Start Date  ICMJE June 3, 2019
Estimated Primary Completion Date March 22, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2019)
  • Frequency of Adverse Events related to AGN-151587 [ 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2019)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Single Ascending Dose Study in Participants With LCA10
Official Title  ICMJE 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")
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leber Congenital Amaurosis 10
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Experimental: Adults Low Dose
    Single dose of AGN-151587 administered by subretinal injection surgery
    Intervention: Drug: AGN-151587
  • Experimental: Adults Middle Dose
    Single dose of AGN-151587 administered by subretinal injection surgery
    Intervention: Drug: AGN-151587
  • Experimental: Adults High Dose
    Single dose of AGN-151587 administered by subretinal injection surgery
    Intervention: Drug: AGN-151587
  • Experimental: Pediatric Middle Dose
    Single dose of AGN-151587 administered by subretinal injection surgery
    Intervention: Drug: AGN-151587
  • Experimental: Pediatric High Dose
    Single dose of AGN-151587 administered by subretinal injection surgery
    Intervention: Drug: AGN-151587
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 11, 2019)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 22, 2024
Estimated Primary Completion Date March 22, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Registry Team 1-877-277-8566 IR-CTRegistration@allergan.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03872479
Other Study ID Numbers  ICMJE 1991-201-008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Supporting Materials: 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
Responsible Party Allergan
Study Sponsor  ICMJE Allergan
Collaborators  ICMJE Editas Medicine, Inc.
Investigators  ICMJE
Study Director: Francisco Lopez, MD, PhD Allergan
PRS Account Allergan
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP