AGTC-501 for Retinitis Pigmentosa

Enrolling by invitation at 6 trial locations

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: Beacon Therapeutics

Disqualifiers: Other mutations, Pre-existing eye conditions, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Several weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AGTC-501, a gene therapy for individuals with retinitis pigmentosa (RP), a condition affecting vision. The goal is to determine if AGTC-501 is safe for those who have previously tried a gene therapy targeting the RPGR protein. The study includes three groups: one receiving a lower dose with standard steroid treatment, another with a higher dose and standard steroids, and the last with a higher dose but a faster steroid taper. Individuals previously treated with similar gene therapy in one eye and experiencing vision challenges in the other eye may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in RP 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 team or your doctor.

Is there any evidence suggesting that AGTC-501 is likely to be safe for humans?

Research has shown that AGTC-501, a treatment for X-linked retinitis pigmentosa (XLRP), is generally safe for patients. In earlier studies, all participants experienced at least one side effect from the treatment, but most were mild. This indicates that while side effects are common, they are usually not serious.

AGTC-501 employs gene therapy, using a modified virus to deliver a healthy gene to the eye. This approach has shown promise in improving vision without causing major harm. Ongoing studies continue to monitor safety to ensure that any side effects remain manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about AGTC-501 for retinitis pigmentosa because it offers a novel approach using gene therapy to address the underlying cause of this condition. Unlike standard treatments like vitamin A supplements or retinal implants that mainly slow progression or support vision, AGTC-501 aims to correct genetic defects directly. This treatment involves a unique delivery method, injecting the therapy directly into the retina, potentially leading to more effective and lasting results. Additionally, the use of different corticosteroid regimens in the trial may optimize the treatment's safety and efficacy, providing valuable insights for future therapies.

What evidence suggests that AGTC-501 could be an effective treatment for Retinitis Pigmentosa?

Research shows that AGTC-501, a gene therapy, could help treat X-linked retinitis pigmentosa (XLRP), a condition affecting vision. In earlier studies, people who received AGTC-501 noticed improvements in their sight. Recent trial data revealed that the treatment was generally safe, with no serious side effects directly linked to it. Some participants experienced mild side effects, but these were not serious enough to outweigh the potential benefits. In this trial, researchers will divide participants into different groups to receive varying doses and corticosteroid regimens. The therapy uses a virus to deliver a healthy version of the RPGR gene, often defective in people with XLRP. This method aims to slow down or even reverse vision loss. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for males with X-linked Retinitis Pigmentosa who've had previous gene therapy. Participants must be at least 12, have certain levels of visual acuity and macular sensitivity, and one eye previously treated. They can't join if they have active eye infections, other genetic mutations affecting the study, a history of high eye pressure due to steroids, recent eye surgery or conditions that could complicate surgery.

Inclusion Criteria

Have detectable EZ line in the study eye as assessed by SD-OCT and confirmed by the CRC

Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant's reliability and fixation, per the Investigator's discretion

I am at least 12 years old.

Exclusion Criteria

I have an active eye infection or inflammation.

I do not have genetic mutations that could affect the study treatment's effectiveness.

I do not have eye conditions that would make surgery risky or affect study results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive a single subretinal injection of AGTC-501 at either a high or low dose, followed by a corticosteroid regimen

Several weeks

Baseline visit for injection

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including full-field stimulus threshold and mobility tests

12 months

Long-term follow-up

Participants continue to be monitored for long-term safety and efficacy outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• AGTC-501

Trial Overview The DAWN study tests AGTC-501 in two doses (low and high) combined with corticosteroids on men who've had prior RPGR-targeting gene therapy. It's an open-label Phase 2 trial where everyone knows which treatment they're getting; it's not randomized.

How Is the Trial Designed?

Group I: Group 3 (High Dose, Modified Corticosteroid) Experimental Treatment 1 Intervention

Following a pars plana vitrectomy, the previously untreated eye of participants (n=approximately 3-6) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. Participants in Group 3 (high dose, modified corticosteroid) will have a more rapid corticosteroid taper.

Group II: Group 2 (Low Dose, Standard Corticosteroid) Experimental Treatment 1 Intervention

Following a pars plana vitrectomy, the previously untreated eye of participants (n=6) will receive a central subretinal injection at the low dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks.

Group III: Group 1 (High Dose, Standard Corticosteroid) Experimental Treatment 1 Intervention

Following a pars plana vitrectomy, the previously untreated eye of participants (n=up to 12) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks.

Who Is Running the Clinical Trial?

Beacon Therapeutics

Lead Sponsor

Trials

13

Recruited

390+

Published Research Related to This Trial

AGTC-501, a gene therapy using a recombinant adeno-associated virus vector, was well tolerated in a study involving 16 RPGR mutant dogs, showing no systemic toxicity after subretinal injections.

The treatment demonstrated significant rescue of photoreceptor function and structure at low and mid doses, while the high dose indicated potential toxicity, establishing a safe dosage limit of 6 × 10^11 vector genomes/mL for future clinical studies in patients with X-linked retinitis pigmentosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and Efficacy Evaluation of an Adeno-Associated Virus Vector Expressing Codon-Optimized RPGR Delivered by Subretinal Injection in a Canine Model of X-linked Retinitis Pigmentosa. Dufour, VL., Cideciyan, AV., Ye, GJ., et al.[2021]

Gene augmentation therapy using adeno-associated virus vectors has shown effectiveness in treating canine models of X-linked retinitis pigmentosa, with preserved photoreceptor structure and function observed after treatment.

The therapy resulted in significant improvements in both rod and cone photoreceptor function, suggesting a promising pathway for future human clinical applications in treating hereditary retinal blindness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Beltran, WA., Cideciyan, AV., Lewin, AS., et al.[2022]

Voretigene neparvovec-rzyl (VN) gene therapy for RPE65 mutation-associated inherited retinal dystrophy showed durable improvements in navigational ability and light sensitivity, with benefits lasting up to 4 years after treatment in a study involving 40 subjects.

The safety profile of VN therapy was consistent with the procedures used, showing no harmful immune responses, indicating it is a safe option for patients with this degenerative eye disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials. Maguire, AM., Russell, S., Wellman, JA., et al.[2020]

The rAAV vector AGTC-501, designed to deliver the RPGR gene, was well tolerated in a safety study involving 60 Rd9 mice, with no systemic toxicity or significant ocular changes observed after subretinal injection.

The study demonstrated dose-dependent expression of the RPGR protein in treated mice, supporting the potential efficacy of AGTC-501 for treating retinitis pigmentosa caused by RPGR mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice. Song, C., Conlon, TJ., Deng, WT., et al.[2020]

In a study involving a canine model of X-linked retinitis pigmentosa (XLRP), the rAAV2tYF-GRK1-hRPGRco gene therapy showed promising results in correcting early disease markers without significant ocular complications, except for some retinal detachment in the highest dose group.

The therapy demonstrated a dose-dependent expression of the RPGR gene and a rescue effect on retinal structure, supporting its potential for clinical trials in humans with RPGR mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose Range Finding Studies with Two RPGR Transgenes in a Canine Model of X-Linked Retinitis Pigmentosa Treated with Subretinal Gene Therapy. Song, C., Dufour, VL., Cideciyan, AV., et al.[2021]

The first-in-human phase 1/2 clinical trial of retinal gene therapy for X-linked retinitis pigmentosa (RP) involving 18 patients showed that the treatment was generally safe, with only mild steroid-responsive inflammation noted at higher doses.

Significant visual field improvements were observed in six patients starting from one month after treatment and lasting through the 6-month follow-up, indicating potential efficacy of the gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., et al.[2023]

In a study of 18 male patients with RPGR X-linked retinitis pigmentosa, significant thinning of the foveal photoreceptor outer segments was observed compared to 30 normal subjects, indicating a potential reason for their reduced visual acuity.

The mean outer segment thickness in RPGR patients was approximately 35.5 µm, while normal subjects had a thickness of about 61.9 µm, highlighting the need to consider these measurements when evaluating the effectiveness of retinal gene therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Cone Photoreceptor Outer Segment Length Shortening in RPGR X-Linked Retinitis Pigmentosa. Menghini, M., Jolly, JK., Nanda, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39643074/

Subretinal Gene Therapy Drug AGTC-501 for XLRP Phase ... Subretinal AGTC-501 was generally well-tolerated. Despite all participants experiencing at least one TEAE, most of these events were mild in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03316560

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects ... This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis ...

3. horizonscandb.pcori.org horizonscandb.pcori.org/report/topics/996

Laruparetigene zovaparvovec (laru-zova; AGTC-501) to ... Laruparetigene zovaparvovec (laru-zova; AGTC-501) is an investigational gene therapy intended to treat patients with XLRP, a severe form of ...

4. scge.mcw.edu scge.mcw.edu/platform/data/clinicalTrials/report/NCT04850118

A Clinical Trial Evaluating the Safety and Efficacy ... Beacon Therapeutics Announces Positive 3-Month Data from Phase 2 DAWN Trial of laru-zova (AGTC-501) in Patients with X-Linked Retinitis Pigmentosa (XLRP) ...

5. beacontx.com beacontx.com/news-and-events/beacon-therapeutics-announces-positive-3-month-data-from-phase-2-dawn-trial-of-laru-zova-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa-xlrp/

Beacon Therapeutics Announces Positive 3-Month Data ... The three-month data show that laru-zova has been well-tolerated by all participants. No study agent-related treatment emergent adverse events (TEAEs) were ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07174726

NCT07174726 | A Phase 2 Open-label Study to Evaluate ... It causes night blindness and gradual worsening of your vision. The purpose of this Phase 2 Study is to see if the investigational study drug, ...

7. beacontx.com beacontx.com/news-and-events/beacon-therapeutics-announces-positive-phase-2-interim-6-month-data-from-dawn-trial-of-laru-zova-in-patients-with-x-linked-retinitis-pigmentosa-xlrp-at-arvo-2025/

Beacon Therapeutics Announces Positive Phase 2 Interim ... Laru-zova was generally well-tolerated by all DAWN participants evaluated at 6 months or beyond and initial data showed promising improvements in visual ...