AAV Gene Therapy for Color Blindness

Recruiting at 9 trial locations

Overseen By Jill Dolgin, PharmD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Beacon Therapeutics

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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests AGTC-402, an eye injection treatment, in people with a specific genetic vision problem. The treatment is injected under the retina to target the genetic issue directly.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment AGTC-402 for color blindness?

In a study with sheep that had a similar eye condition, the treatment AGTC-402 improved their ability to see colors and navigate better in bright light. This suggests it might help people with color blindness, but more research is needed to confirm its safety and effectiveness in humans. ^{1 2 3 4 5}

Is AAV gene therapy, including AGTC-402, generally safe for humans?

AAV gene therapy, including AGTC-402, has shown a strong safety record in various studies, with no serious adverse events related to the vector reported in humans. In animal studies, mild to moderate eye-related side effects were observed but generally resolved quickly, and careful monitoring for inflammatory effects is recommended. ^{4 6 7 8 9}

How does the treatment AGTC-402 differ from other treatments for color blindness?

AGTC-402 is unique because it uses a gene therapy approach with an adeno-associated virus (AAV) vector to deliver a functional CNGA3 gene directly to the retina, aiming to restore cone function and improve color vision, which is not addressed by standard treatments. ^{4 5 10 11 12}

Research Team

David Jacobs, MD, MBA

Principal Investigator

Applied Genetics Technologies Corporation

Eligibility Criteria

This trial is for males and females with a specific type of color blindness called CNGA3 achromatopsia. Participants must have mutations in both alleles of the CNGA3 gene, be at least 18 years old (or as young as 6 for certain groups), and have visual acuity not better than 20/80. Women who can bear children must test negative for pregnancy.

Inclusion Criteria

I am a woman who can have children and have a recent negative pregnancy test.

I can undergo tests for my eyesight and retina.

I am at least 18 years old, or I am 6-8 years old if in specific groups.

Exclusion Criteria

The vision in one eye is much worse than the other by more than 3 lines on an 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-402 administered to one eye by subretinal injection in individuals with achromatopsia

Varies by group

Multiple visits for dose administration 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-402

Trial Overview The trial tests AGTC-402, a new gene therapy given through an injection into one eye to treat achromatopsia caused by CNGA3 mutations. It's an open-label study, meaning everyone knows they're getting the treatment, focusing on safety first and then how well it works.

Participant Groups

Group I: Group 6: MTD of AGTC-402 Experimental Treatment 1 Intervention

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

Group II: Group 5: 3.2 x 10^12 vg/mL of AGTC-402 Experimental Treatment 1 Intervention

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

Group III: Group 4a: 1.1 x 10^12 vg/mL of AGTC-402 Experimental Treatment 1 Intervention

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

Group IV: Group 4: 1.1 x 10^12 vg/mL of AGTC-402 Experimental Treatment 1 Intervention

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

Group V: Group 3a: 3.6 x 10^11 vg/mL of AGTC-402 Experimental Treatment 1 Intervention

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

Group VI: Group 3: 3.6 x 10^11 vg/mL of AGTC-402 Experimental Treatment 1 Intervention

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

Group VII: Group 2: 1.2 x 10^11 vg/mL of AGTC-402 Experimental Treatment 1 Intervention

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

Group VIII: Group 1: 4.0 x 10^10 vg/mL of AGTC-402 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Beacon Therapeutics

Lead Sponsor

Trials

13

Recruited

390+

Applied Genetic Technologies Corp

Lead Sponsor

Trials

11

Recruited

350+

Applied Genetic Technologies Corp

Lead Sponsor

Trials

11

Recruited

350+

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]

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 (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]

Coadministration of low doses of chemotherapeutic agents, such as doxorubicin, significantly enhances the transduction efficiency of rAAV2 vectors in retinal cells without causing toxicity, making it a promising strategy for gene therapy.

In a rat model of inherited retinal degeneration, combining rAAV2-CNTF with doxorubicin resulted in a two-fold increase in photoreceptor layer thickness, indicating improved therapeutic efficacy and protection of retinal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of rAAV2-mediated transgene expression in retina cells in vitro and in vivo by coadministration of low-dose chemotherapeutic drugs. Zhang, S., Wu, J., Wu, X., et al.[2013]

Recombinant adeno-associated viral (AAV) vectors are effective tools for gene therapy in retinal degeneration, showing long-term transgene expression and minimal side effects in various animal models.

AAV-mediated gene therapy has demonstrated significant recovery of retinal structure and visual function in models of inherited retinal degeneration, highlighting its potential for treating similar human conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-associated virus-vectored gene therapy for retinal disease. Dinculescu, A., Glushakova, L., Min, SH., et al.[2012]

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

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

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. 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]

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

Restoration of cone vision in a mouse model of achromatopsia. [2021]

6. 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]

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

rAAV human trial experience. [2011]

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

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

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

Present and future of adeno associated virus based gene therapy approaches. [2019]

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

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

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

Enhancement of rAAV2-mediated transgene expression in retina cells in vitro and in vivo by coadministration of low-dose chemotherapeutic drugs. [2013]

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

Adeno-associated virus-vectored gene therapy for retinal disease. [2012]