AAV Gene Therapy for Color Blindness

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called AGTC-401 for individuals with color blindness caused by changes in the CNGB3 gene. The goal is to determine the treatment's safety and its potential to improve vision. Participants will receive the treatment in one eye, and the study will assess both safety and effectiveness. This trial may suit those diagnosed with achromatopsia (a type of color blindness) due to CNGB3 gene mutations and who have difficulty seeing clearly (vision not better than 20/80). 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 the chance to be among the first to potentially benefit from this innovative 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.

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

Research has shown that AAV gene therapy, such as AGTC-401, has been tested in humans for other eye conditions and maintains a strong safety record. No serious side effects have been linked to the delivery method. Tests on animals, specifically mice with a condition similar to the one being studied, have also confirmed the safety and distribution of this gene therapy. Results from these studies suggest that the treatment is generally well-tolerated. Specifically, previous patients with achromatopsia (a condition affecting color vision) demonstrated that AGTC-401 is well-tolerated without major safety concerns. ^{1 2 3 4 5}

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

Researchers are excited about AGTC-401 because it offers a groundbreaking approach to treating color blindness through gene therapy. Unlike traditional methods, which often rely on corrective lenses or visual aids, AGTC-401 uses an adeno-associated virus (AAV) to deliver a healthy copy of the CNGB3 gene directly to the cells in the retina. This method targets the root cause of color blindness by potentially restoring normal color vision at the genetic level. With this innovative mechanism, AGTC-401 could significantly improve the quality of life for individuals with color blindness, offering a long-lasting solution rather than a temporary fix.

What evidence suggests that this trial's treatments could be effective for achromatopsia?

Research has shown that AAV gene therapy can help treat color blindness caused by CNGB3 gene mutations. In earlier studies, this therapy improved vision in 10 out of 11 dogs with similar genetic issues. Electroretinography (ERG) measured this improvement by assessing eye function. Other studies on mice have demonstrated that the therapy is safe and distributes well in the eye. Early evidence suggests that this treatment works best when administered to younger individuals. In this trial, various groups will receive different dosages of AGTC-401 to evaluate its effectiveness and safety. Overall, gene therapy holds strong promise for those with achromatopsia due to these genetic mutations. ^{1 2 3 6 7}

Who Is on the Research Team?

David Jacobs, MD, MBA

Principal Investigator

Applied Genetic Technologies Corporation

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02599922

NCT02599922 | Safety and Efficacy Trial of AAV Gene ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4851180/

Safety and Biodistribution Evaluation in CNGB3-Deficient ... We report here results of a study evaluating safety and biodistribution of rAAV2tYF-PR1.7-hCNGB3 in CNGB3-deficient mice.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02599922?term=Cngb3&viewType=Table&rank=4

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-401 administered to one eye by subretinal injection in individuals ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5733843/

Gene Therapy for Color Blindness - PMC - PubMed Central The evidence to date suggests that gene therapy for achromatopsia will need to be applied early in childhood to be effective.

5. withpower.com withpower.com/trial/phase-2-color-vision-defects-1-2016-fc84e

AAV Gene Therapy for Color Blindness · Info for Participants AAV-mediated gene therapy successfully restored vision in 10 out of 11 RPE65(-/-) dogs, as evidenced by improved electroretinography (ERG) results and ...

6. researchgate.net researchgate.net/publication/306183024_Safety_and_Biodistribution_Evaluation_in_CNGB3-Deficient_Mice_of_rAAV2tYF-PR17-hCNGB3_a_Recombinant_AAV_Vector_for_Treatment_of_Achromatopsia

Safety and Biodistribution Evaluation in CNGB3-Deficient Mice of ... We report here results of a study evaluating safety and biodistribution of rAAV2tYF-PR1.7-hCNGB3 in CNGB3-deficient mice. Three groups of animals (n = 35 males ...

7. 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 ...