Back to results

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

Primary Purpose

Achromatopsia

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AGTC-402

About this trial

This is an interventional treatment trial for Achromatopsia focused on measuring Color vision deficiency, Color vision defects, Vision disorders, Sensation disorders, Neurologic manifestations, Nervous system diseases, Eye diseases, Signs and symptoms

Eligibility Criteria

4 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female subjects with documented mutations in both alleles of the CNGA3 gene;
Retinal disease consistent with a clinical diagnosis of achromatopsia;
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;
Able to perform tests of visual and retinal function;
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;
Acceptable laboratory parameters;
For females of childbearing potential: A negative pregnancy test within 2 days before administration of study agent.

Exclusion Criteria include:

Best-corrected visual acuity difference between the two eyes of > 15 ETDRS letters (3 lines);
Evidence of degenerative myopia in the study eye;
Pre-existing eye conditions that would contribute to vision loss in either eye or increase the risk of subretinal injection in the study eye.

Sites / Locations

VitreoRetinal Associates
Bascom Palmer Eye Institute
Massachusetts Eye and Ear Infirmary
Cincinnati Eye Institute
Casey Eye Institute, Oregon Health and Sciences University
Hadassah-Hebrew University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Group 1: 4.0 x 10^10 vg/mL of AGTC-402

Group 2: 1.2 x 10^11 vg/mL of AGTC-402

Group 3: 3.6 x 10^11 vg/mL of AGTC-402

Group 3a: 3.6 x 10^11 vg/mL of AGTC-402

Group 4: 1.1 x 10^12 vg/mL of AGTC-402

Group 4a: 1.1 x 10^12 vg/mL of AGTC-402

Group 5: 3.2 x 10^12 vg/mL of AGTC-402

Group 6: MTD of AGTC-402

Arm Description

Subjects at least 18 y/o treated with 4.0 x 10^10 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Subjects at least 18 y/o treated with 1.2 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Subjects at least 18 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Subjects 6 to 17 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Subjects at least 18 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Subjects 4 to 8 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Subjects at least 18 y/o treated with 3.2 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGA3 study drug determined by Groups 1-5.

Outcomes

Primary Outcome Measures

Adverse events

Proportion of participants experiencing grade 3 or greater adverse events

Secondary Outcome Measures

Visual acuity

Changes in best corrected visual acuity compared to pre-treatment

Light aversion

Changes in light discomfort testing compared to pre-treatment

Color vision

Changes in color vision testing compared to pre-treatment

Full Information

NCT ID

NCT02935517

First Posted

October 13, 2016

Last Updated

July 20, 2022

Sponsor

Applied Genetic Technologies Corp

1. Study Identification

Unique Protocol Identification Number

NCT02935517

Brief Title

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

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 3, 2017 (Actual)

Primary Completion Date

August 2022 (Anticipated)

Study Completion Date

August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Applied Genetic Technologies Corp

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Achromatopsia

Keywords

Color vision deficiency, Color vision defects, Vision disorders, Sensation disorders, Neurologic manifestations, Nervous system diseases, Eye diseases, Signs and symptoms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: 4.0 x 10^10 vg/mL of AGTC-402

Arm Type

Experimental

Arm Description

Subjects at least 18 y/o treated with 4.0 x 10^10 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Arm Title

Group 2: 1.2 x 10^11 vg/mL of AGTC-402

Arm Type

Experimental

Arm Description

Subjects at least 18 y/o treated with 1.2 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Arm Title

Group 3: 3.6 x 10^11 vg/mL of AGTC-402

Arm Type

Experimental

Arm Description

Subjects at least 18 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Arm Title

Group 3a: 3.6 x 10^11 vg/mL of AGTC-402

Arm Type

Experimental

Arm Description

Subjects 6 to 17 y/o treated with 3.6 x 10^11 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Arm Title

Group 4: 1.1 x 10^12 vg/mL of AGTC-402

Arm Type

Experimental

Arm Description

Subjects at least 18 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Arm Title

Group 4a: 1.1 x 10^12 vg/mL of AGTC-402

Arm Type

Experimental

Arm Description

Subjects 4 to 8 y/o treated with 1.1 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Arm Title

Group 5: 3.2 x 10^12 vg/mL of AGTC-402

Arm Type

Experimental

Arm Description

Subjects at least 18 y/o treated with 3.2 x 10^12 vg/mL of rAAV2tYF-PR1/7-hCNGA3 study drug.

Arm Title

Group 6: MTD of AGTC-402

Arm Type

Experimental

Arm Description

Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGA3 study drug determined by Groups 1-5.

Intervention Type

Biological

Intervention Name(s)

AGTC-402

Other Intervention Name(s)

rAAV2tYF-PR1.7-hCNGA3

Intervention Description

AGTC-402 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGA3 gene.

Primary Outcome Measure Information:

Title

Adverse events

Description

Proportion of participants experiencing grade 3 or greater adverse events

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Visual acuity

Description

Changes in best corrected visual acuity compared to pre-treatment

Time Frame

1 year

Title

Light aversion

Description

Changes in light discomfort testing compared to pre-treatment

Time Frame

1 year

Title

Color vision

Description

Changes in color vision testing compared to pre-treatment

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female subjects with documented mutations in both alleles of the CNGA3 gene; Retinal disease consistent with a clinical diagnosis of achromatopsia; 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; Able to perform tests of visual and retinal function; 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; Acceptable laboratory parameters; For females of childbearing potential: A negative pregnancy test within 2 days before administration of study agent. Exclusion Criteria include: Best-corrected visual acuity difference between the two eyes of > 15 ETDRS letters (3 lines); Evidence of degenerative myopia in the study eye; Pre-existing eye conditions that would contribute to vision loss in either eye or increase the risk of subretinal injection in the study eye.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Jacobs, MD, MBA

Organizational Affiliation

Applied Genetics Technologies Corporation

Official's Role

Study Director

Facility Information:

Facility Name

VitreoRetinal Associates

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32607

Country

United States

Facility Name

Bascom Palmer Eye Institute

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Massachusetts Eye and Ear Infirmary

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Cincinnati Eye Institute

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45242

Country

United States

Facility Name

Casey Eye Institute, Oregon Health and Sciences University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Hadassah-Hebrew University Medical Center

City

Jerusalem

ZIP/Postal Code

91120

Country

Israel

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26087757

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.

Results Reference

background

Links:

URL

http://www.agtc.com

Description

AGTC website

Learn more about this trial

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

We'll reach out to this number within 24 hrs