Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial)

July 20, 2022 updated by: Applied Genetic Technologies Corp

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32607
        • VitreoRetinal Associates
      • Miami, Florida, United States, 33136
        • Bascom Palmer Eye Institute
    • Illinois
      • Chicago, Illinois, United States, 60608
        • Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse for People Who Are Blind or Visually Imp
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear Infirmary
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Eye Center, Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Cincinnati Eye Institute
    • Oregon
      • Portland, Oregon, United States, 97239
        • Casey Eye Institute, Oregon Health and Sciences University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • AGTC-401

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: 1 year
Proportion of participants experiencing grade 3 or greater adverse events
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual acuity
Time Frame: 1 year
Changes in best corrected visual acuity compared to pre-treatment
1 year
Light aversion
Time Frame: 1 year
Changes in light discomfort testing compared to pre-treatment
1 year
Color vision
Time Frame: 1 year
Changes in color vision testing compared to pre-treatment
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Applied Genetic Technologies Corp

Collaborators

National Eye Institute (NEI)

Investigators

  • Study Director: David Jacobs, MD, MBA, Applied Genetic Technologies Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 11, 2016

Primary Completion (Anticipated)

July 1, 2022

Study Completion (Anticipated)

July 1, 2026

Study Registration Dates

First Submitted

November 5, 2015

First Submitted That Met QC Criteria

November 5, 2015

First Posted (Estimate)

November 9, 2015

Study Record Updates

Last Update Posted (Actual)

July 22, 2022

Last Update Submitted That Met QC Criteria

July 20, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AGTC_CNGB3-001
  • R24EY022023 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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