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Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02935517
Recruitment Status : Active, not recruiting
First Posted : October 17, 2016
Last Update Posted : July 22, 2022
Sponsor:
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-402, administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGA3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.

Condition or disease Intervention/treatment Phase
Achromatopsia Biological: AGTC-402 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-402 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGA3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.

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

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)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of AGTC 402, a Recombinant Adeno-associated Virus Vector Expressing CNGA3, in Patients With Congenital Achromatopsia Caused by Mutations in the CNGA3 Gene
Actual Study Start Date : August 3, 2017
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Group 1: 4.0 x 10^10 vg/mL of AGTC-402
Subjects at least 18 y/o treated with 4.0 x 10^10 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3
Experimental: Group 2: 1.2 x 10^11 vg/mL of AGTC-402
Subjects at least 18 y/o treated with 1.2 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3
Experimental: Group 3: 3.6 x 10^11 vg/mL of AGTC-402
Subjects at least 18 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3
Experimental: Group 3a: 3.6 x 10^11 vg/mL of AGTC-402
Subjects 6 to 17 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3
Experimental: Group 4: 1.1 x 10^12 vg/mL of AGTC-402
Subjects at least 18 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3
Experimental: Group 4a: 1.1 x 10^12 vg/mL of AGTC-402
Subjects 4 to 8 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3
Experimental: Group 5: 3.2 x 10^12 vg/mL of AGTC-402
Subjects at least 18 y/o treated with 3.2 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3
Experimental: Group 6: MTD of AGTC-402
Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGA3 study drug determined by Groups 1-5.
 Biological: AGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Other Name: rAAV2tYF-PR1.7-hCNGA3


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

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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:

  1. Male or female subjects with documented mutations in both alleles of the CNGA3 gene;
  2. Retinal disease consistent with a clinical diagnosis of achromatopsia;
  3. At least 18 years of age for Groups 1, 2, 3, 4, and 5. At least 6 years of age for Group 3a, and and 4-8 years of age for Groups 4a and 6;
  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): NCT02935517


Locations
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United States, Florida
VitreoRetinal Associates
Gainesville, Florida, United States, 32607
Bascom Palmer Eye Institute
Miami, Florida, United States, 33136
United States, Massachusetts
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, United States, 02114
United States, Ohio
Cincinnati Eye Institute
Cincinnati, Ohio, United States, 45242
United States, Oregon
Casey Eye Institute, Oregon Health and Sciences University
Portland, Oregon, United States, 97239
Israel
Hadassah-Hebrew University Medical Center
Jerusalem, Israel, 91120
Sponsors and Collaborators
Applied Genetic Technologies Corp
Investigators
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Study Director: David Jacobs, MD, MBA Applied Genetics Technologies Corporation
More Information
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Additional Information:

Publications:

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Responsible Party: Applied Genetic Technologies Corp
ClinicalTrials.gov Identifier: NCT02935517    
Other Study ID Numbers: AGTC-CNGA3-002
First Posted: October 17, 2016    Key Record Dates
Last Update Posted: July 22, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Applied Genetic Technologies Corp:
Color vision deficiency
Color vision defects
Vision disorders
Sensation disorders
 Neurologic manifestations
Nervous system diseases
Eye diseases
Signs and symptoms
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