Clinical trial NCT02599922: Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Achromatopsia
Lead sponsor: Beacon Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: National Eye Institute (NEI)
First posted: 2015-11-09
Enrollment: 32
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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: Chicago
country: United States
facility: Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse for People Who Are Blind or Visually Imp
state: Illinois
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke Eye Center, Duke University Medical Center
state: North Carolina
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
Study officials:
affiliation: Applied Genetic Technologies Corporation
name: David Jacobs, MD, MBA
role: STUDY_DIRECTOR
References:
citation: Komaromy 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.
citation: Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.