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

Achromatopsia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02599922
• Other study ID #: AGTC_CNGB3-001
• Secondary ID: R24EY022023
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 11, 2016
• Est. completion date: July 2026

Study information

• Verified date: July 2022
• Source: Applied Genetic Technologies Corp
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: July 2026
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Achromatopsia
• Color Vision Defects

Intervention

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.

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse for People Who Are Blind or Visually Imp	Chicago	Illinois
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Duke Eye Center, Duke University Medical Center	Durham	North Carolina
United States	VitreoRetinal Associates	Gainesville	Florida
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Casey Eye Institute, Oregon Health and Sciences University	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Applied Genetic Technologies Corp	National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Proportion of participants experiencing grade 3 or greater adverse events	1 year
Secondary	Visual acuity	Changes in best corrected visual acuity compared to pre-treatment	1 year
Secondary	Light aversion	Changes in light discomfort testing compared to pre-treatment	1 year
Secondary	Color vision	Changes in color vision testing compared to pre-treatment	1 year

External Links

•   Sponsor website