Clinical trial NCT02935517: Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial)
Official title: A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of AGTC 402, a Recombinant Adeno-associated Virus Vector Expressing CNGA3, in Patients With Congenital Achromatopsia Caused by Mutations in the CNGA3 Gene
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Achromatopsia
Keywords: Color vision deficiency
Color vision defects
Vision disorders
Sensation disorders
Neurologic manifestations
Nervous system diseases
Eye diseases
Signs and symptoms
Lead sponsor: Beacon Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-10-17
Enrollment: 24
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Visual acuity
timeFrame: 1 year
measure: Light aversion
timeFrame: 1 year
measure: Color vision
timeFrame: 1 year
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: VitreoRetinal Associates
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Portland
country: United States
facility: Casey Eye Institute, Oregon Health and Sciences University
state: Oregon
city: Jerusalem
country: Israel
facility: Hadassah-Hebrew University Medical Center
Study officials:
affiliation: Applied Genetics Technologies Corporation
name: David Jacobs, MD, MBA
role: STUDY_DIRECTOR
References:
citation: Banin E, Gootwine E, Obolensky A, Ezra-Elia R, Ejzenberg A, Zelinger L, Honig H, Rosov A, Yamin E, Sharon D, Averbukh E, Hauswirth WW, Ofri R. Gene Augmentation Therapy Restores Retinal Function and Visual Behavior in a Sheep Model of CNGA3 Achromatopsia. Mol Ther. 2015 Sep;23(9):1423-33. doi: 10.1038/mt.2015.114. Epub 2015 Jun 19.