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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 : March 20, 2019
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 March 20, 2019
Study Start Date  ICMJE February 2016
Estimated Primary Completion Date June 2020   (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 Complete list of historical versions of study NCT02599922 on ClinicalTrials.gov Archive Site
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 (rAAV2tYF-PR1.7-hCNGB3) 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 rAAV2tYF-PR1.7-hCNGB3 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 rAAV2tYF-PR1.7-hCNGB3 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 four groups. Subjects in Groups 1, 2 and 3 will be at least 18 years of age and will receive a lower, middle or higher dose of study agent. Subjects in Group 4 will be at least 6 years of age and will receive the maximum tolerated dose identified in Groups 1, 2 and 3.

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 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.
Study Arms  ICMJE
  • Experimental: Lower dose
    rAAV2tYF-PR1/7-hCNGB3 will be administered at the lowest of three planned dose levels.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • Experimental: Middle dose
    rAAV2tYF-PR1/7-hCNGB3 will be administered at the middle of three planned dose levels.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • Experimental: Higher dose
    rAAV2tYF-PR1/7-hCNGB3 will be administered at the highest of three planned dose levels.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
  • Experimental: Maximum tolerated dose
    rAAV2tYF-PR1/7-hCNGB3 will be administered at the maximum tolerated dose identified from Groups 1, 2 and 3.
    Intervention: Biological: rAAV2tYF-PR1.7-hCNGB3
Publications * Komáromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA, Kaya A, Tanaka JC, Acland GM, Hauswirth WW, Aguirre GD. Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet. 2010 Jul 1;19(13):2581-93. doi: 10.1093/hmg/ddq136. Epub 2010 Apr 8. Erratum in: Hum Mol Genet. 2011 Dec 15;20(24):5024.

*   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: November 5, 2015)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria include:

  1. Retinal disease consistent with a diagnosis of achromatopsia and documented mutations in both alleles of the CNGB3 gene;
  2. At least 18 years of age for Groups 1, 2 and 3 and at least 6 years of age for Group 4;
  3. Able to perform tests of visual and retinal function;
  4. 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;
  5. Acceptable laboratory parameters;
  6. For females of childbearing potential: A negative pregnancy test within 2 days before administration of study agent.

Exclusion Criteria include:

  1. Refractive error of ≥ -8.00 diopters (spherical equivalent) of myopia in the study eye;
  2. Evidence of degenerative myopia regardless of the refractive error 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 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jill Dolgin, PharmD advocacy@agtc.com
Listed Location Countries  ICMJE 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 March 2019

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