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Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia

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ClinicalTrials.gov Identifier: NCT02599922
Recruitment Status : Recruiting
First Posted : November 9, 2015
Last Update Posted : April 6, 2021
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
Applied Genetic Technologies Corp

Study Description
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Brief Summary:
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.

Condition or disease Intervention/treatment Phase
Achromatopsia Biological: rAAV2tYF-PR1.7-hCNGB3 Phase 1 Phase 2

Detailed Description:

This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.

Subjects will be enrolled sequentially in seven dosing groups. Subjects in Groups 1, 2, 3, 4, 5, and 6 will be at least 18 years of age and will receive varying dose levels of study agent. Subjects in Group 4a will be 6 to 17 years of age and will receive the same dose as Group 4. Subjects in Groups 5a and 7 will be between 4 and 8 years of age. Subjects in Group 5a will receive the same dose as Group 5, and subjects in Group 7 will receive the maximum tolerated dose identified in Groups 1, 2, 3, 4, 4a, 5, 5a, and 6.

Safety will be monitored by evaluation of ocular and non-ocular adverse events and hematology and clinical chemistry parameters. Efficacy parameters will include visual acuity, light discomfort testing, color vision, static visual field, ERG, adaptive optics retinal imaging, functional MRI (fMRI), color brightness test and OCT.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing CNGB3 in Patients With Congenital Achromatopsia Caused by Mutations in the CNGB3 Gene
Study Start Date : February 2016
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Group 1: 2.0 x 10^11 vg/mL of AGTC-401
Subjects at least 18 y/o treated with 2.0 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 2: 4.0 x 10^10 vg/mL of AGTC-401
Subjects at least 18 y/o treated with 4.0 x 10^10 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 3: 1.2 x 10^11 vg/mL of AGTC-401
Subjects at least 18 y/o treated with 1.2 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 4: 3.6 x 10^11 vg/mL of AGTC-401
Subjects at least 18 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 4a: 3.6 x 10^11 vg/mL of AGTC-401
Subjects 6 to 17 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 5: 1.1 x 10^12 vg/mL of AGTC-401
Subjects at least 18 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 5a: 1.1 x 10^12 vg/mL of AGTC-401
Subjects 4 to 8 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 6: 3.2 x 10^12 vg/mL of AGTC-401
Subjects at least 18 y/o treated with 3.2 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401
Experimental: Group 7: MTD of AGTC-401
Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGB3 study drug determined by Groups 1-6.
 Biological: rAAV2tYF-PR1.7-hCNGB3
rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.
Other Name: AGTC-401


Outcome Measures
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Primary Outcome Measures :
  1. Adverse events [ Time Frame: 1 year ]
    Proportion of participants experiencing grade 3 or greater adverse events


Secondary Outcome Measures :
  1. Visual acuity [ Time Frame: 1 year ]
    Changes in best corrected visual acuity compared to pre-treatment

  2. Light aversion [ Time Frame: 1 year ]
    Changes in light discomfort testing compared to pre-treatment

  3. Color vision [ Time Frame: 1 year ]
    Changes in color vision testing compared to pre-treatment


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria include:

  1. Male or female subjects with documented mutations in both alleles of the CNGB3 gene;
  2. Retinal disease consistent with a clinical diagnosis of achromatopsia;
  3. At least 18 years of age for Groups 1, 2, 3, 4, 5 and 6. At least 6 years of age for Group 4a, and 4-8 years of age for Groups 5a and 7;
  4. Able to perform tests of visual and retinal function;
  5. Visual acuity in the study eye not better than 55 ETDRS letters (Snellen equivalent 20/80) based on the average of two examinations at the baseline visit;
  6. Acceptable laboratory parameters;
  7. For females of childbearing potential: A negative pregnancy test within 2 days before administration of study agent.

Exclusion Criteria include:

  1. Best-corrected visual acuity difference between the two eyes of > 15 ETDRS letters (3 lines);
  2. Evidence of degenerative myopia in the study eye;
  3. Pre-existing eye conditions that would contribute to vision loss in either eye or increase the risk of subretinal injection in the study eye.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02599922


Contacts
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Contact: Jill Dolgin, PharmD 833-770-2862 advocacy@agtc.com

Locations
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United States, California
University of California, San Francisco Not yet recruiting
San Francisco, California, United States, 94158
United States, Florida
VitreoRetinal Associates Recruiting
Gainesville, Florida, United States, 32607
Bascom Palmer Eye Institute Recruiting
Miami, Florida, United States, 33136
United States, Illinois
Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse for People Who Are Blind or Visually Imp Completed
Chicago, Illinois, United States, 60608
United States, Massachusetts
Massachusetts Eye and Ear Infirmary Recruiting
Boston, Massachusetts, United States, 02114
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
United States, New York
Columbia College of Physicians and Surgeons Completed
New York, New York, United States, 10032
United States, North Carolina
Duke Eye Center, Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Eye Institute Recruiting
Cincinnati, Ohio, United States, 45242
Cleveland Clinic, Cole Eye Institute Not yet recruiting
Cleveland, Ohio, United States, 44195
United States, Oregon
Casey Eye Institute, Oregon Health and Sciences University Recruiting
Portland, Oregon, United States, 97239
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin, McPherson Eye Research Institute Not yet recruiting
Madison, Wisconsin, United States, 53705
Israel
Hadassah-Hebrew University Medical Center Not yet recruiting
Jerusalem, Israel, 91120
Sponsors and Collaborators
Applied Genetic Technologies Corp
National Eye Institute (NEI)
Investigators
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Study Director: Matt Feinsod, MD Applied Genetics Technologies Corporation
More Information
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Applied Genetic Technologies Corp
ClinicalTrials.gov Identifier: NCT02599922    
Other Study ID Numbers: AGTC_CNGB3-001
R24EY022023 ( U.S. NIH Grant/Contract )
First Posted: November 9, 2015    Key Record Dates
Last Update Posted: April 6, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Color Vision Defects
Vision Disorders
Sensation Disorders
Neurologic Manifestations
 Nervous System Diseases
Cone Dystrophy
Eye Diseases, Hereditary
Eye Diseases