What side effects are associated with this type of intervention?

Gene therapy for Retinitis Pigmentosa, particularly using recombinant adeno-associated virus (rAAV) vectors like rAAV2tYF-GRK1-RPGR, has shown promise in clinical trials. However, potential side effects include adverse reactions at the injection site, immune responses to the viral vector, and possible retinal damage. Electroretinography (ERG) has revealed adverse effects following subretinal (SR) delivery in some cases. Other treatments, such as vitamin A supplementation, may carry risks of toxicity and are controversial in their efficacy. Overall, while gene therapy offers hope, careful consideration of potential side effects is crucial.

What prior FDA approvals exist?

As of now, there are limited FDA-approved treatments for Retinitis Pigmentosa, particularly those involving gene therapy. One notable approval is Luxturna (voretigene neparvovec-rzyl), which is a gene therapy using an adeno-associated virus vector to treat patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. This treatment is similar in approach to the investigational rAAV2tYF-GRK1-RPGR, which targets RPGR mutations in X-linked Retinitis Pigmentosa. Both therapies utilize viral vectors to deliver functional copies of genes to retinal cells.

What other types of research exist?

Promising alternatives to rAAV2tYF-GRK1-RPGR for Retinitis Pigmentosa patients include: 1) CRISPR-Cas9 based gene editing, which offers precise correction of genetic mutations; 2) Stem cell therapy, particularly the use of induced pluripotent stem cells (iPSCs) to replace damaged retinal cells; 3) Pharmacologic treatments such as neuroprotective agents and small molecules targeting specific pathways involved in RP; and 4) Optogenetics, which involves using light-sensitive proteins to restore vision in degenerated photoreceptors.

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Virus Therapy

Gene Therapy for Retinitis Pigmentosa (HORIZON Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Beacon Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Male subjects with a documented RPGR mutation

Clinical diagnosis of X-linked retinitis pigmentosa (XLRP)

Must not have

Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or increase the risk of surgical complications (for example, glaucoma, corneal or lenticular opacities, diabetic retinopathy, retinal vasculitis)

Previous receipt of any AAV gene therapy product

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 0 - month 36

Awards & highlights

Summary

This trial is testing a new treatment for people with a genetic eye disease that causes vision loss. The treatment uses a harmless virus to deliver a healthy gene directly into the eye. This could help improve or stabilize their vision. The study will monitor safety and effectiveness over time. This marks a significant advance in treating genetic eye diseases.

Who is the study for?

This trial is for males aged 6-50 with X-linked retinitis pigmentosa (XLRP) due to RPGR gene mutations. Participants must have a certain level of visual acuity, not better than 20/32 and no worse than 20/200. They should not have other retinal diseases or previous AAV gene therapy treatments.

What is being tested?

The study tests the safety and effectiveness of rAAV2tYF-GRK1-RPGR, a genetic treatment delivered via a virus vector, in patients with XLRP caused by specific RPGR mutations.

What are the potential side effects?

While the side effects are not specified here, similar gene therapies can cause immune reactions, eye irritation or discomfort, changes in vision, headache or mild pain.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a male with a confirmed RPGR mutation.

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I have been diagnosed with X-linked retinitis pigmentosa.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have eye conditions like glaucoma or diabetic retinopathy that could complicate surgery.

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I have never received AAV gene therapy before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 0 - month 36

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 0 - month 36

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 0 - month 36 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number and proportion of Adverse Events

Other study objectives

Phase 1/2 Dose Escalation: Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters

Phase 1/2 Dose Escalation: Number and proportion of treatment-emergent adverse events

Phase 2 Dose Expansion: Overall safety evaluation

Trial Design

6Treatment groups

Experimental Treatment

Group I: Group 6 Phase 1/2 Dose EscalationExperimental Treatment1 Intervention

Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.

Group II: Group 5 Phase 1/2 Dose EscalationExperimental Treatment1 Intervention

Male subjects at least 18 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug.

Group III: Group 4 Phase 1/2 Dose EscalationExperimental Treatment1 Intervention

Group 4 male subjects at least 6 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Group IV: Group 3 Phase 1/2 Dose EscalationExperimental Treatment1 Intervention

Group 3 male subjects at least 18 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Group V: Group 2: Phase 1/2 Dose EscalationExperimental Treatment1 Intervention

Male subjects at least 18 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug.

Group VI: Group 1: Phase 1/2 Dose EscalationExperimental Treatment1 Intervention

Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Gene therapy for Retinitis Pigmentosa, such as the rAAV2tYF-GRK1-RPGR trial, involves using recombinant adeno-associated virus (rAAV) vectors to deliver functional copies of genes directly into retinal cells. This approach targets the underlying genetic mutations causing RP by restoring the normal function of defective genes, such as RPGR. By doing so, it aims to halt or slow the degeneration of photoreceptors, thereby preserving vision. This is crucial for RP patients as it addresses the root cause of the disease, offering the potential for long-term therapeutic benefits and improved quality of life.

Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium.