AAV Gene Therapy for Color Blindness

Recruiting at 12 trial locations

Overseen By Jill Dolgin, PharmD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Applied Genetic Technologies Corp

Disqualifiers: Degenerative myopia, Pre-existing eye conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Varies by group

32 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment AGTC-401 for color blindness?

Research on similar gene therapies, like AGTC-402 for achromatopsia, shows improved vision in animal models, suggesting potential effectiveness for AGTC-401. These studies indicate that gene therapy can restore some visual functions, which may be promising for treating color blindness. ^{1 2 3 4 5}

Is AAV gene therapy for color blindness safe for humans?

AAV gene therapy has been tested in humans for other eye conditions and has shown a strong safety record, with no serious adverse events related to the vector. In animal studies, mild to moderate eye irritation was observed but generally resolved quickly, and there were some cases of retinal changes that need careful monitoring. ^{2 6 7 8 9}

How does the treatment AGTC-401 for color blindness differ from other treatments?

AGTC-401 is a gene therapy using an adeno-associated virus (AAV) vector to deliver a corrective gene directly to the retina, which is unique because it targets the genetic root of color blindness rather than just managing symptoms. This approach is novel as there are no standard treatments for color blindness that address the underlying genetic cause. ^{2 3 5 10 11}

Research Team

David Jacobs, MD, MBA

Principal Investigator

Applied Genetic Technologies Corporation

Eligibility Criteria

This trial is for individuals at least 18 years old (or as young as 6 for certain groups) with achromatopsia due to CNGB3 gene mutations. They should have visual acuity not better than 20/80 in the study eye and be able to perform vision tests. Women must test negative for pregnancy. Those with significant vision differences between eyes or other eye conditions that could affect results are excluded.

Inclusion Criteria

I am between 4 and 8 years old.

I can undergo tests for my eyesight and retina.

Your vision in the study eye is not better than 20/80 on the eye chart.

Exclusion Criteria

The difference in vision between your two eyes is more than three lines on a standard eye chart.

My eye condition is due to severe nearsightedness.

I have eye conditions that could worsen with certain treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia

Varies by group

Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular visits for safety and efficacy assessments

Treatment Details

Interventions

• AGTC-401

Trial Overview The trial is testing a new gene therapy called rAAV2tYF-PR1.7-hCNGB3, given through an injection into one eye of patients with color blindness caused by CNGB3 mutations. It's an open-label, non-randomized Phase 1/2 study focusing on safety first and then how well it works.

Participant Groups

Group I: Group 7: MTD of AGTC-401 Experimental Treatment 1 Intervention

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

Group II: Group 6: 3.2 x 10^12 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Group III: Group 5a: 1.1 x 10^12 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Group IV: Group 5: 1.1 x 10^12 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Group V: Group 4a: 3.6 x 10^11 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Group VI: Group 4: 3.6 x 10^11 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Group VII: Group 3: 1.2 x 10^11 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Group VIII: Group 2: 4.0 x 10^10 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Group IX: Group 1: 2.0 x 10^11 vg/mL of AGTC-401 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Applied Genetic Technologies Corp

Lead Sponsor

Trials

11

Recruited

350+

Beacon Therapeutics

Lead Sponsor

Trials

13

Recruited

390+

Applied Genetic Technologies Corp

Lead Sponsor

Trials

11

Recruited

350+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Findings from Research

AAV-mediated gene therapy successfully restored vision in 10 out of 11 RPE65(-/-) dogs, as evidenced by improved electroretinography (ERG) results and subjective observations of reduced nystagmus, indicating significant efficacy of the treatment.

While the therapy showed promising results in restoring vision, 75% of the treated eyes developed uveitis, suggesting a potential side effect related to an immune response to the RPE65 protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Narfström, K., Katz, ML., Bragadottir, R., et al.[2021]

Gene therapy (GT) has the potential to treat and even cure various medical conditions by genetically modifying living cells, primarily using adeno-associated virus (AAV) vectors, which dominate the market.

Despite its promise, AAV-based gene therapy raises unique safety concerns, including the risk of unintended gene expression and long-term effects, highlighting the need for thorough preclinical safety evaluations before human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considerations for Preclinical Safety Assessment of Adeno-Associated Virus Gene Therapy Products. Assaf, BT., Whiteley, LO.[2019]

Human gene therapy using the rAAV2 vector for treating RPE65-related Leber congenital amaurosis was found to be safe, with no serious adverse events reported in young adult subjects up to 12 months after treatment.

Patients showed sustained improvements in visual sensitivity from 3 months to 12 months post-treatment, indicating the long-term efficacy of the gene therapy in enhancing vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Cideciyan, AV., Hauswirth, WW., Aleman, TS., et al.[2022]

Gene therapy using AAV vectors to deliver the RPE65 gene has been shown to be safe and effective for treating Leber's congenital amaurosis (LCA), with positive effects on retinal and visual function lasting at least 1.5 years in patients.

The treatment did not trigger significant immune responses against the RPE65 protein, indicating that AAV-mediated gene transfer can maintain its therapeutic effects without causing harm to the retinal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Simonelli, F., Maguire, AM., Testa, F., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy Evaluation of rAAV2tYF-PR1.7-hCNGA3 Vector Delivered by Subretinal Injection in CNGA3 Mutant Achromatopsia Sheep. [2018]

3. Australia pubmed.ncbi.nlm.nih.gov

Gene therapy and the adeno-associated virus in the treatment of genetic and acquired ophthalmic diseases in humans: Trials, future directions and safety considerations. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Vision restoration: Little red booster. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Gene Therapy Trial of AAV8-hCARp.hCNGB3 in Adults and Children With CNGB3-associated Achromatopsia. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Considerations for Preclinical Safety Assessment of Adeno-Associated Virus Gene Therapy Products. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

rAAV human trial experience. [2011]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Manufacturing and regulatory strategies for clinical AAV2-hRPE65. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Adeno-Associated Virus as Gene Delivery Vehicle into the Retina. [2020]