AAV Gene Therapy for Color Blindness

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gene therapy treatment called AGTC-402 for individuals with color blindness caused by specific gene mutations. The main goal is to determine the safety and effectiveness of this treatment when injected into one eye. Participants will receive varying doses to identify the optimal one. Individuals with color blindness due to CNGA3 gene mutations, who experience difficulties with vision tests and have specific visual acuity limitations, might be suitable for this study. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in gene therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AGTC-402 appears safe based on studies. Tests with sheep having a similar condition demonstrated that the treatment was well-tolerated, with no serious side effects observed. Another study found that AGTC-402 was also well-tolerated in people with achromatopsia, a type of color blindness. This suggests the treatment might be safe for humans, but further research is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for color blindness?

Researchers are excited about AGTC-402 because it represents a groundbreaking approach to treating color blindness using gene therapy. Unlike traditional treatments like color-filtering glasses or contact lenses, which only help manage the symptoms, AGTC-402 aims to address the root cause by delivering a functional copy of the CNGA3 gene directly into the eye. This innovative use of adeno-associated virus (AAV) vectors could potentially correct the genetic defect responsible for color blindness, offering a long-term solution rather than a temporary aid. This approach could fundamentally change how we think about treating genetic vision disorders.

What evidence suggests that AGTC-402 might be an effective treatment for color blindness?

Research has shown that AGTC-402 may help treat color blindness caused by CNGA3 gene mutations. In studies with sheep that have similar eye issues, AGTC-402 improved their ability to see colors and function better in bright light. These results suggest the treatment might also help people with achromatopsia. Early research supports its potential effectiveness, but more studies in humans are needed to confirm these findings. Participants in this trial will receive different dosages of AGTC-402 to determine its safety and effectiveness in correcting the faulty gene, believed to be a main cause of the condition. ^{1 2 3 6 7}

Who Is on the Research Team?

David Jacobs, MD, MBA

Principal Investigator

Applied Genetics Technologies Corporation

Are You a Good Fit for This Trial?

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 have mutations in both copies of my CNGA3 gene.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28478700/

Safety and Efficacy Evaluation of rAAV2tYF-PR1.7- ... The results are herein reported of a study evaluating safety and efficacy of AGTC-402 in CNGA3-deficient sheep. Thirteen day-blind sheep divided into three ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02935517

Safety and Efficacy Trial of AAV Gene Therapy in Patients ... 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 ...

3. liebertpub.com liebertpub.com/doi/abs/10.1089/humc.2017.028?journalCode=humc

Safety and Efficacy Evaluation of rAAV2tYF-PR1.7 ... Two animals treated with the higher dose of AGTC-402 and three of the efficacy control group animals had microscopic findings of outer retinal atrophy with or ...

4. researchgate.net researchgate.net/publication/316842655_Safety_and_Efficacy_Evaluation_of_rAAV2tYF-PR17-hCNGA3_Vector_Delivered_by_Subretinal_Injection_in_CNGA3_Mutant_Achromatopsia_Sheep

Safety and Efficacy Evaluation of rAAV2tYF-PR1.7- ... We report here results of a study evaluating safety and efficacy of AGTC-402 in CNGA3-deficient sheep. Thirteen day-blind sheep divided into ...

5. withpower.com withpower.com/trial/phase-2-color-vision-defects-4-2017-f92b8

AAV Gene Therapy for Color Blindness · Info for Participants 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 ...

6. cgtlive.com cgtlive.com/view/agtc-402-and-agtc-402-gene-therapies-well-tolerated-in-achromatopsia

AGTC-401, AGTC-402 Gene Therapies Well-Tolerated in ... AGTC-401 and AGTC-402 (Applied Genetic Technologies Corporation), subretinal gene therapies for achromatopsia, were seen to be well-tolerated in ...

7. vethospital.huji.ac.il vethospital.huji.ac.il/sites/default/files/vethospital/files/published_-safetyefficacy_of_raav2tyf-pr1.7-hcnga3_in_cnga3_mutant_sheep.pdf

Safety and Efficacy Evaluation of rAAV2tYF-PR1.7- ... There was an increase in cone-mediated ERG responses and resolution of day blindness in the treated eyes at both dose levels. Results of this ...