AGTC-501 for Retinitis Pigmentosa

Recruiting at 20 trial locations

Overseen By Serva Health

Age: < 65

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Beacon Therapeutics

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Herpes, Corticosteroid allergy, Gene therapy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501/laruparetigene zovaparvovec )) to an untreated control group in male participants with X-linked retinitis pigmentosa caused by RPGR mutations.

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.

What data supports the effectiveness of the treatment AGTC-501 for Retinitis Pigmentosa?

In early human trials, some patients showed improvements in their visual field after receiving the AGTC-501 treatment, and animal studies demonstrated that the treatment helped restore some function and structure of the eye's light-sensitive cells without significant safety concerns at certain doses. ^{1 2 3 4 5}

Is AGTC-501 safe for humans?

AGTC-501, also known as Laruparetigene zosaparvovec, has been tested in animals and humans for retinitis pigmentosa. In animal studies, it was generally well tolerated with no significant systemic toxicity, although high doses showed some eye-related issues. In a human trial, the treatment was mostly safe, with some inflammation at higher doses that responded to steroids. ^{1 2 3 5 6}

What makes the treatment AGTC-501 unique for retinitis pigmentosa?

AGTC-501 is a gene therapy that uses a specially designed virus to deliver a corrected version of the RPGR gene directly to the retina, which is different from traditional treatments that may only manage symptoms. This approach targets the root cause of the disease by restoring the function of photoreceptors, the cells in the eye that detect light, potentially offering a more effective and long-lasting solution. ^{1 2 3 5 7}

Research Team

Carrie Reichley

Principal Investigator

Beacon Therapeutics

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• AGTC-501 (Virus Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice. [2020]

2. United States 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. [2023]

3. United States 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Early Cone Photoreceptor Outer Segment Length Shortening in RPGR X-Linked Retinitis Pigmentosa. [2023]

5. United States 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. [2022]

7. United States 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. [2020]