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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE November 5, 2015
First Posted Date  ICMJE November 9, 2015
Last Update Posted Date April 6, 2021
Study Start Date  ICMJE February 2016
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
Adverse events [ Time Frame: 1 year ]
Proportion of participants experiencing grade 3 or greater adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
  • Visual acuity [ Time Frame: 1 year ]
    Changes in best corrected visual acuity compared to pre-treatment
  • Light aversion [ Time Frame: 1 year ]
    Changes in light discomfort testing compared to pre-treatment
  • Color vision [ Time Frame: 1 year ]
    Changes in color vision testing compared to pre-treatment
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 Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Achromatopsia
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • 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.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
Publications *

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 6, 2020)
28
Original Estimated Enrollment  ICMJE
 (submitted: November 5, 2015)
24
Estimated Study Completion Date  ICMJE September 2025
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jill Dolgin, PharmD 833-770-2862 advocacy@agtc.com
Listed Location Countries  ICMJE Israel,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02599922
Other Study ID Numbers  ICMJE AGTC_CNGB3-001
R24EY022023 ( U.S. NIH Grant/Contract )
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 Not Provided
Responsible Party Applied Genetic Technologies Corp
Study Sponsor  ICMJE Applied Genetic Technologies Corp
Collaborators  ICMJE National Eye Institute (NEI)
Investigators  ICMJE
Study Director: Matt Feinsod, MD Applied Genetics Technologies Corporation
PRS Account Applied Genetic Technologies Corp
Verification Date April 2021

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