Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial)
- Conditions
- Achromatopsia
- Interventions
- Biological: rAAV2tYF-PR1.7-hCNGB3
- Registration Number
- NCT02599922
- Lead Sponsor
- Applied Genetic Technologies Corp
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2: 4.0 x 10^10 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects at least 18 y/o treated with 4.0 x 10\^10 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Group 5: 1.1 x 10^12 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects at least 18 y/o treated with 1.1 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Group 6: 3.2 x 10^12 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects at least 18 y/o treated with 3.2 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Group 3: 1.2 x 10^11 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects at least 18 y/o treated with 1.2 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Group 7: MTD of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGB3 study drug determined by Groups 1-6. Group 1: 2.0 x 10^11 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects at least 18 y/o treated with 2.0 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Group 5a: 1.1 x 10^12 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects 4 to 8 y/o treated with 1.1 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Group 4: 3.6 x 10^11 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects at least 18 y/o treated with 3.6 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug. Group 4a: 3.6 x 10^11 vg/mL of AGTC-401 rAAV2tYF-PR1.7-hCNGB3 Subjects 6 to 17 y/o treated with 3.6 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.
- Primary Outcome Measures
Name Time Method Adverse events 1 year Proportion of participants experiencing grade 3 or greater adverse events
- Secondary Outcome Measures
Name Time Method Visual acuity 1 year Changes in best corrected visual acuity compared to pre-treatment
Light aversion 1 year Changes in light discomfort testing compared to pre-treatment
Color vision 1 year Changes in color vision testing compared to pre-treatment
Trial Locations
- Locations (8)
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
Casey Eye Institute, Oregon Health and Sciences University
🇺🇸Portland, Oregon, United States
VitreoRetinal Associates
🇺🇸Gainesville, Florida, United States
Bascom Palmer Eye Institute
🇺🇸Miami, Florida, United States
Massachusetts Eye and Ear Infirmary
🇺🇸Boston, Massachusetts, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States