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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 : October 13, 2017
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
Applied Genetic Technologies Corp

November 5, 2015
November 9, 2015
October 13, 2017
February 2016
December 2018   (Final data collection date for primary outcome measure)
Adverse events [ Time Frame: 1 year ]
Proportion of participants experiencing grade 3 or greater adverse events
Same as current
Complete list of historical versions of study NCT02599922 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia
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
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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Achromatopsia
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.
  • 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
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.
 
Recruiting
24
Same as current
December 2022
December 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
6 Years and older   (Child, Adult, Older Adult)
No
Contact: Jill Dolgin, PharmD advocacy@agtc.com
United States
 
 
NCT02599922
AGTC_CNGB3-001
R24EY022023 ( U.S. NIH Grant/Contract )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Applied Genetic Technologies Corp
Applied Genetic Technologies Corp
National Eye Institute (NEI)
Study Director: Matt Feinsod, MD Applied Genetics Technologies Corporation
Applied Genetic Technologies Corp
October 2017

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