AGTC-501 for Retinitis Pigmentosa

Not currently recruiting at 5 trial locations

Age: < 65

Sex: Male

Trial Phase: Phase 2

Sponsor: Beacon Therapeutics

Must not be taking: Anticoagulants, Corticosteroids, Immunosuppressives, Antivirals

Disqualifiers: Herpes, Immunosuppression, Systemic infection, 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: Single occasion

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for X-linked retinitis pigmentosa (XLRP), a genetic condition affecting vision. Researchers aim to determine if the drug AGTC-501 (also known as Laruparetigene zosaparvovec, BIIB-088, or rAAV2tYF-GRK1-RPGR) is safe and effective in improving vision for those with the RPGR gene mutation. Participants will receive either a low or high dose of the treatment. Males with a confirmed RPGR mutation and a diagnosis of XLRP may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening or if you intend to use them during screening.

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

A previous study found that AGTC-501 was generally well-tolerated by participants. Although all participants experienced at least one treatment-related side effect, most were mild and not serious. The study involved individuals with X-linked retinitis pigmentosa, a genetic eye condition affecting vision. So far, early studies suggest the treatment is safe for humans, but ongoing research will provide a clearer understanding of its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for retinitis pigmentosa?

Researchers are excited about AGTC-501 for retinitis pigmentosa because it uses a cutting-edge gene therapy approach. Unlike current treatments, which primarily focus on managing symptoms or slowing disease progression, AGTC-501 targets the root cause by delivering a functional copy of the RPGR gene directly to retinal cells. This method could potentially restore vision or significantly halt the progression of vision loss, offering hope for more effective long-term outcomes. Additionally, the use of an adeno-associated virus (AAV) vector for gene delivery is designed to ensure precise targeting and minimal side effects, making it a promising alternative to existing therapies.

What evidence suggests that AGTC-501 might be an effective treatment for retinitis pigmentosa?

Research has shown that AGTC-501, a gene therapy, could help treat X-linked retinitis pigmentosa (XLRP). In this trial, participants will receive either a low or high dose of AGTC-501. Studies have found that people treated with AGTC-501 experience better night vision and clearer vision test results. The therapy uses a harmless virus to deliver a helpful gene to eye cells affected by the RPGR mutation. Early results suggest that AGTC-501 is generally safe, with most side effects being mild. These findings offer hope for improving vision in people with XLRP. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for male subjects with a specific eye condition called X-linked Retinitis Pigmentosa, which must be caused by mutations in the RPGR gene. The eligibility criteria are not fully listed here, so additional requirements may apply.

Inclusion Criteria

Have a BCVA no better than 75 letters and no worse than 35 letters based on an ETDRS chart at each screening visit.

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

Have detectable baseline mean macular sensitivity measured by (MAIA) microperimetry, as determined by the investigator and confirmed by the Central Reading Center (CRC).

Exclusion Criteria

For subjects with herpes simplex virus (HSV):

Have a history of ocular herpes.

Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of AGTC-501 in one eye, randomized to either a low or high dose group

Single occasion

Follow-up

Participants are monitored for safety and efficacy after receiving the treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• AGTC-501

Trial Overview

The study is testing the safety and effectiveness of a gene therapy named rAAV2tYF-GRK1-RPGR on patients with X-linked Retinitis Pigmentosa due to RPGR mutations. It will compare two different doses of this treatment.

How Is the Trial Designed?

Group I: Low Dose Group Experimental Treatment 1 Intervention

Male subjects at least 8 y/o treated with a lower dose (Dose 2 in RPGR-001 Horizon Phase 1/2 study) of rAAV2tYF-GRK1-RPGR study drug.

Group II: High Dose Group Experimental Treatment 1 Intervention

Male subjects at least 8 y/o treated with a higher dose (Dose 5 in RPGR-001 Horizon Phase 1/2 study) of rAAV2tYF-GRK1-RPGR study drug.

Who Is Running the Clinical Trial?

Beacon Therapeutics

Lead Sponsor

Trials

13

Recruited

390+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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/NCT06333249

NCT06333249 | A Study Comparing Two Doses of AGTC- ...

The purpose of the Phase 2 study is to evaluate the efficacy, safety, and tolerability of two doses of AGTC-501 in male subjects between 8 - 50 years of age ( ...

3.

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 ...

4.

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 ...

Data showed improvements across several key measures of visual function, including low luminance visual acuity and microperimetry.

5.

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) ...

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, ...