NCT02599922

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
1mo left

Started Apr 2016

Longer than P75 for phase_1

Geographic Reach
1 country

8 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress99%
Apr 2016Jul 2026

First Submitted

Initial submission to the registry

November 5, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 9, 2015

Completed
5 months until next milestone

Study Start

First participant enrolled

April 11, 2016

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2022

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2026

Expected
Last Updated

July 22, 2022

Status Verified

July 1, 2022

Enrollment Period

6.2 years

First QC Date

November 5, 2015

Last Update Submit

July 20, 2022

Conditions

Achromatopsia

Outcome Measures

Primary Outcomes (1)

  • Adverse events

    Proportion of participants experiencing grade 3 or greater adverse events

    1 year

Secondary Outcomes (3)

  • Visual acuity

    1 year

  • Light aversion

    1 year

  • Color vision

    1 year

Study Arms (9)

Group 1: 2.0 x 10^11 vg/mL of AGTC-401

EXPERIMENTAL

Subjects at least 18 y/o treated with 2.0 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 2: 4.0 x 10^10 vg/mL of AGTC-401

EXPERIMENTAL

Subjects at least 18 y/o treated with 4.0 x 10\^10 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 3: 1.2 x 10^11 vg/mL of AGTC-401

EXPERIMENTAL

Subjects at least 18 y/o treated with 1.2 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 4: 3.6 x 10^11 vg/mL of AGTC-401

EXPERIMENTAL

Subjects at least 18 y/o treated with 3.6 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 4a: 3.6 x 10^11 vg/mL of AGTC-401

EXPERIMENTAL

Subjects 6 to 17 y/o treated with 3.6 x 10\^11 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 5: 1.1 x 10^12 vg/mL of AGTC-401

EXPERIMENTAL

Subjects at least 18 y/o treated with 1.1 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 5a: 1.1 x 10^12 vg/mL of AGTC-401

EXPERIMENTAL

Subjects 4 to 8 y/o treated with 1.1 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 6: 3.2 x 10^12 vg/mL of AGTC-401

EXPERIMENTAL

Subjects at least 18 y/o treated with 3.2 x 10\^12 vg/mL of rAAV2tYF-PR1/7-hCNGB3 study drug.

Biological: rAAV2tYF-PR1.7-hCNGB3

Group 7: MTD of AGTC-401

EXPERIMENTAL

Subjects 4 to 8 y/o treated with a maximum tolerated dose of rAAV2tYF-PR1/7-hCNGB3 study drug determined by Groups 1-6.

Biological: rAAV2tYF-PR1.7-hCNGB3

Interventions

rAAV2tYF-PR1.7-hCNGB3BIOLOGICAL

rAAV2tYF-PR1.7-hCNGB3 is a non-replicating, rep/cap-deleted, recombinant adeno-associated virus vector that expresses the CNGB3 gene.

Also known as: AGTC-401
Group 1: 2.0 x 10^11 vg/mL of AGTC-401Group 2: 4.0 x 10^10 vg/mL of AGTC-401Group 3: 1.2 x 10^11 vg/mL of AGTC-401Group 4: 3.6 x 10^11 vg/mL of AGTC-401Group 4a: 3.6 x 10^11 vg/mL of AGTC-401Group 5: 1.1 x 10^12 vg/mL of AGTC-401Group 5a: 1.1 x 10^12 vg/mL of AGTC-401Group 6: 3.2 x 10^12 vg/mL of AGTC-401Group 7: MTD of AGTC-401

Eligibility Criteria

Age4 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female subjects with documented mutations in both alleles of the CNGB3 gene;
  • Retinal disease consistent with a clinical diagnosis of achromatopsia;
  • 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;
  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

VitreoRetinal Associates

Gainesville, Florida, 32607, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Pangere Center for Inherited Retinal Diseases, The Chicago Lighthouse for People Who Are Blind or Visually Imp

Chicago, Illinois, 60608, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Duke Eye Center, Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

Casey Eye Institute, Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Related Publications (2)

  • 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.

    PMID: 20378608BACKGROUND

  • 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.

    PMID: 30194931DERIVED

Related Links

MeSH Terms

Conditions

Color Vision Defects

Condition Hierarchy (Ancestors)

Vision DisordersSensation DisordersNeurologic ManifestationsNervous System DiseasesCone DystrophyEye Diseases, HereditaryEye DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • David Jacobs, MD, MBA

    Applied Genetic Technologies Corporation

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2015

First Posted

November 9, 2015

Study Start

April 11, 2016

Primary Completion

July 1, 2022

Study Completion (Estimated)

July 1, 2026

Last Updated

July 22, 2022

Record last verified: 2022-07

Locations

US(8)