AGTC-501 for Retinitis Pigmentosa

Not currently recruiting at 24 trial locations

Overseen By Serva Health

Age: < 65

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Beacon Therapeutics

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Herpes, Corticosteroid allergy, Gene therapy, 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: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial explores a new treatment called AGTC-501 (also known as Laruparetigene zosaparvovec, an experimental gene therapy) for individuals with X-linked retinitis pigmentosa, a genetic eye condition affecting vision. The goal is to assess the safety and effectiveness of two different doses compared to no treatment. Only male participants with a confirmed RPGR gene mutation and a diagnosis of X-linked retinitis pigmentosa are eligible. This trial may suit those experiencing vision difficulties due to this condition. As a Phase 2, Phase 3 trial, the research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering a chance to advance treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as anti-coagulant agents like warfarin or heparin, at least 7 days before the study treatment. Also, you should not have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening.

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

Research has shown that AGTC-501, a gene therapy for X-linked retinitis pigmentosa, is generally well-tolerated. In earlier studies, all participants experienced at least one side effect after treatment, but most were mild. Importantly, safety results were positive across different dose groups, with no major differences between them. This suggests the treatment might be safe for most people, though individual experiences can vary. ^{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 gene therapy to target the root cause of the condition. Unlike current treatments that focus mainly on managing symptoms, AGTC-501 is designed to correct the genetic defects responsible for the disease. This approach holds the promise of not just slowing down vision loss but potentially restoring some vision by addressing the problem at its source. Additionally, the subretinal injection method delivers the therapy directly to the affected area, which could enhance its effectiveness.

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

Research has shown that AGTC-501 may help treat X-linked retinitis pigmentosa (XLRP), a genetic condition affecting vision. In one study, participants who received AGTC-501 experienced improvements in their vision. The treatment was generally well-tolerated, with most side effects being mild. Positive results from another 12-month study also support that AGTC-501 can improve vision for patients with XLRP. This trial includes different groups, with some participants receiving varying doses of AGTC-501, while others are in an untreated control group. This gene therapy works by delivering a healthy copy of the RPGR gene directly to the eye to address the genetic issue causing the condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Carrie Reichley

Principal Investigator

Beacon Therapeutics

Are You a Good Fit for This Trial?

This trial is for males aged 8-50 with X-linked retinitis pigmentosa (XLRP) due to RPGR gene mutations. Participants must have vision that falls within a specific range, not too good and not too poor, as measured by an eye chart test.

Inclusion Criteria

Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200) in the study eye.

Have a LLVA ≤64 letters (approximately Snellen 20/50) in the study eye.

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

Exclusion Criteria

For participants 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 subretinal injection of AGTC-501 Dose 1 or Dose 2

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular visits (in-person and virtual)

Open-label extension (optional)

Participants in the control group may opt to receive the study drug in the fellow eye after Month 12, if eligible

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AGTC-501

Trial Overview The study tests two doses of AGTC-501, a gene therapy delivered via injection into the eye, against no treatment in patients with XLRP. It aims to assess the safety and effectiveness of this potential new treatment.

How Is the Trial Designed?

Group I: Group 3: Control Experimental Treatment 2 Interventions

Male participants 12-50 years of age in the untreated control group. Participants in the control group will be followed for a minimum of 24 months. After all participants have reached Month 12, participants in the control group will be given the option to receive the study drug in the fellow eye, if eligible.

Group II: Group 1: Dose Active Control 1 Intervention

Male participants 12-50 years of age treated by subretinal injection with the of AGTC-501

Group III: Group 2: Dose Active Control 1 Intervention

Male participants 12-50 years of age treated by subretinal injection with the dose of AGTC-501

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 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]

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]

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]

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]

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]

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

Gene Therapy Trial Report A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP ; Indication, 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 ... Beacon Therapeutics Announces Positive 12-Month Data from Phase 2 SKYLINE Trial of laru-zova (AGTC-501) in Patients with X-Linked Retinitis Pigmentosa. 08 ...

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

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

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/wp-content/uploads/2024/10/2023-12-03-FLORetina-FINAL-SKYLINE-M3-unmasked-safety-efficacy-Andreas-Lauer-V3.1_website-002.pdf

Subretinal Gene Therapy Drug AGTC-501 for X-Linked ... AGTC-501 for X-Linked Retinitis Pigmentosa Phase. 2 Randomized, Controlled ... • Favorable safety data in both dose groups. • No difference between ...