Achromatopsia
Conditions
Keywords
Color vision deficiency, Color vision defects, Vision disorders, Sensation disorders, Neurologic manifestations, Nervous system diseases, Eye diseases, Signs and symptoms
Brief summary
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-402, administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGA3 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-402 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGA3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy. Subjects will be enrolled sequentially in six groups. Subjects in Groups 1, 2, 3, 4, and 5 will be at least 18 years of age and will receive varying dose levels of study agent. Subjects in Group 3a will be 6 to 17 years of age and will receive the same dose as Group 3. Subjects in Group 4a and 6 will be between 4 and 8 years of age. Subjects in Group 4a will receive the same dose as Group 4, and subjects in Group 6 will receive the maximum tolerated dose identified in Groups 1, 2, 3, 3a, 4, 4a, and 5. 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.
Interventions
BIOLOGICALAGTC-402
AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.
Sponsors
Beacon Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects with documented mutations in both alleles of the CNGA3 gene; 2. Retinal disease consistent with a clinical diagnosis of achromatopsia; 3. At least 18 years of age for Groups 1, 2, 3, 4, and 5. At least 6 years of age for Group 3a, and and 4-8 years of age for Groups 4a and 6; 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 1 year | Proportion of participants experiencing grade 3 or greater adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Color vision | 1 year | Changes in color vision testing compared to pre-treatment |
| Light aversion | 1 year | Changes in light discomfort testing compared to pre-treatment |
| Visual acuity | 1 year | Changes in best corrected visual acuity compared to pre-treatment |
Countries
Israel, United States
Outcome results
None listed