Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial)

Phase 1

Active, not recruiting

• Conditions: Achromatopsia
• Interventions: Biological: AGTC-402

• Registration Number: NCT02935517
• 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-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.

Study Timeline

• Study First Submitted: 2016-10-13
• Study First Submitted QC: 2016-10-13
• Study First Posted: 2016-10-17
• Study Start: 2017-08-03
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-20
• Last Update Posted: 2022-07-22
• Primary Completion: 2022-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 24

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 1: 4.0 x 10^10 vg/mL of AGTC-402	AGTC-402	Subjects at least 18 y/o treated with 4.0 x 10\^10 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
Group 5: 3.2 x 10^12 vg/mL of AGTC-402	AGTC-402	Subjects at least 18 y/o treated with 3.2 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
Group 3: 3.6 x 10^11 vg/mL of AGTC-402	AGTC-402	Subjects at least 18 y/o treated with 3.6 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
Group 4: 1.1 x 10^12 vg/mL of AGTC-402	AGTC-402	Subjects at least 18 y/o treated with 1.1 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
Group 2: 1.2 x 10^11 vg/mL of AGTC-402	AGTC-402	Subjects at least 18 y/o treated with 1.2 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
Group 3a: 3.6 x 10^11 vg/mL of AGTC-402	AGTC-402	Subjects 6 to 17 y/o treated with 3.6 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
Group 4a: 1.1 x 10^12 vg/mL of AGTC-402	AGTC-402	Subjects 4 to 8 y/o treated with 1.1 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.
Group 6: MTD of AGTC-402	AGTC-402	Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGA3 study drug determined by Groups 1-5.

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
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

Trial Locations

Locations (6)

Massachusetts Eye and Ear Infirmary; 🇺🇸 Boston, Massachusetts, United States

VitreoRetinal Associates; 🇺🇸 Gainesville, Florida, United States

Bascom Palmer Eye Institute; 🇺🇸 Miami, Florida, United States

Cincinnati Eye Institute; 🇺🇸 Cincinnati, Ohio, United States

Hadassah-Hebrew University Medical Center; 🇮🇱 Jerusalem, Israel

Casey Eye Institute, Oregon Health and Sciences University; 🇺🇸 Portland, Oregon, United States