Gene Therapy with Light-Stimulating Glasses for Retinitis Pigmentosa

(PIONEER Trial)

Not currently recruiting at 2 trial locations

Overseen By Magali Taiel, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GenSight Biologics

Disqualifiers: Gene therapy, Ocular surgery, Retinal detachment, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy combined with light-stimulating glasses to determine its safety and tolerability for people with Retinitis Pigmentosa, a condition that causes vision loss. The study involves different doses of an injected treatment (GS030-DP) and uses special glasses to deliver light therapy. It seeks participants diagnosed with non-syndromic Retinitis Pigmentosa who have specific vision challenges. Those who meet these vision requirements may be a good fit for the trial. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative 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 might be best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this gene therapy and light-stimulating device are safe for treating Retinitis Pigmentosa?

Research has shown that the gene therapy GS030-DP is generally safe and well-tolerated. One study found it remained safe for at least one year after injection at all tested doses, indicating participants did not experience major negative effects. Additionally, using GS030-MD (the light-stimulating glasses) with the gene therapy did not raise any safety concerns. Overall, the treatment has a good safety record, making it a promising option for people with retinitis pigmentosa. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for retinitis pigmentosa, which often focus on managing symptoms or slowing disease progression with medications or visual aids, GS030-DP offers a novel approach through gene therapy combined with light-stimulating glasses. This treatment specifically targets the genetic root of the condition by delivering a therapeutic gene to retinal cells, potentially restoring vision. Researchers are excited about this approach because it represents a shift from symptomatic treatment to addressing the underlying genetic cause, with the added use of light-stimulating glasses to enhance effectiveness. This innovative combination could lead to significant improvements in vision for individuals who have limited options with existing therapies.

What evidence suggests that this gene therapy and light-stimulating glasses could be effective for Retinitis Pigmentosa?

Research has shown that GS030-DP, a new gene therapy under study in this trial, may help treat retinitis pigmentosa, a condition affecting vision. In earlier studies, some patients experienced improvements in their vision after receiving this treatment. The therapy targets specific cells in the eye that are crucial for vision. Safety data collected over a year indicates that GS030-DP is generally safe and does not cause major side effects. While these early results are promising, further research is needed to confirm its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Magali Taiel, MD

Principal Investigator

GenSight Biologics

Are You a Good Fit for This Trial?

Adults aged 18-75 with non-syndromic Retinitis Pigmentosa (RP), confirmed by specific tests, who have not had gene therapy before or significant eye surgery within the last 3 months. Participants should have a certain range of visual acuity and refractive error, as well as an appropriate interpupillary distance.

Inclusion Criteria

Visual acuity in the dose-escalation cohorts of no better LP

Relatively preserved ganglion cell layer volume and retinal nerve fiber layer thickness as measured with SD-OCT

Interpupillary distance of ≥51 mm and ≤72 mm

Exclusion Criteria

I have never received gene therapy.

I have not had major eye surgery in the last 3 months.

I have a condition affecting my eye's central vision due to vitreo-macular adhesion or similar issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravitreal injection of GS030-DP and repeated light stimulation using GS030-MD

52 weeks

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Extension cohort at the highest well-tolerated dose with additional subjects

Varies

What Are the Treatments Tested in This Trial?

Interventions

• GS030-DP
• GS030-MD

Trial Overview

The trial is testing GS030-DP, a new gene therapy given through an injection in the eye, alongside GS030-MD, special glasses that provide light stimulation. The study aims to find out how safe these treatments are and what doses are tolerable for people with RP.

How Is the Trial Designed?

Group I: Cohort Experimental Treatment 1 Intervention

3 dose escalation cohorts (low, medium and high dose) with 3 subjects per cohort followed by an extension cohort at the highest-well tolerated dose with 3 to 9 subjects.

GS030-DP is already approved in European Union, United States for the following indications:

Approved in European Union as GS030 for:

• Orphan Drug Designation for Retinitis Pigmentosa

Approved in United States as GS030 for:

• Orphan Drug Designation for Retinitis Pigmentosa
• Fast Track Status for Retinitis Pigmentosa

Who Is Running the Clinical Trial?

GenSight Biologics

Lead Sponsor

Trials

9

Recruited

320+

Published Research Related to This Trial

There are over 100 drugs currently in development for Retinitis Pigmentosa (RP), with 50% being advanced therapy medicinal products (ATMPs), highlighting a significant push towards innovative treatments for this condition.

Gene therapies aim to restore vision by targeting non-functional photoreceptors, while cell therapies offer broader applications as they do not depend on the presence of viable photoreceptors, making them potentially more accessible for patients at various disease stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Future Treatment of Retinitis Pigmentosa. Cross, N., van Steen, C., Zegaoui, Y., et al.[2022]

The study developed Span-polyarginine (SP-PA) nanoparticles for delivering the PRPF31 gene to treat autosomal dominant retinitis pigmentosa (adRP), showing effective gene transfer in a mouse model with a specific mutation.

Treatment with SP-PA nanoparticles resulted in significant improvements in visual acuity and retinal thickness in the affected mice, indicating potential efficacy for this gene therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa. Pensado, A., Diaz-Corrales, FJ., De la Cerda, B., et al.[2018]

The study demonstrates that bReaChES, a high sensitivity opsin, can restore vision in a mouse model of severe retinal degeneration by making normally light-insensitive retinal neurons responsive to light, achieving action potentials at levels comparable to bright indoor lighting.

Intravitreal gene therapy using bReaChES not only restored visual responses in treated mice but also showed potential for application in humans, as human retinal explants successfully transduced with the treatment vector, indicating its feasibility for future clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optogenetic restoration of high sensitivity vision with bReaChES, a red-shifted channelrhodopsin. Too, LK., Shen, W., Protti, DA., et al.[2023]

Optogenetic tools, which involve gene delivery of light-activated channels to surviving retinal cells, have shown promise in restoring photosensitivity in animal models of retinitis pigmentosa, a condition affecting two million people globally.

Recent in vitro studies using post-mortem human retinas suggest that this optogenetic approach has significant translational potential for treating RP, although there are still limitations to consider in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optogenetic therapy for retinitis pigmentosa. Busskamp, V., Picaud, S., Sahel, JA., et al.[2012]

The study developed a combination gene therapy using dual adeno-associated viruses (AAVs) that both ablate the mutated Rho gene and replace it with a healthy version, showing significant improvements in photoreceptor structure and function in mouse models of retinitis pigmentosa (RP).

Results indicated that the ablate-and-replace therapy led to a 17% to 36% increase in outer nuclear layer thickness and significantly better preservation of electroretinographic responses compared to gene replacement therapy alone, suggesting its potential as a universal treatment for various Rho mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clustered Regularly Interspaced Short Palindromic Repeats-Based Genome Surgery for the Treatment of Autosomal Dominant Retinitis Pigmentosa. Tsai, YT., Wu, WH., Lee, TT., et al.[2022]

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]

Over the past 20 years, various proof-of-concept gene therapy studies have been conducted for autosomal dominant retinitis pigmentosa caused by mutations in the rhodopsin gene, showcasing different approaches and strategies.

The review compiles significant results from these studies, highlighting advancements in gene silencing and delivery methods that could lead to potential treatments for this form of retinal degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa. Sudharsan, R., Beltran, WA.[2020]

This study successfully demonstrated the expression of human rhodopsin in bipolar cells of a mouse model of retinal degeneration (rd1) using modified AAV capsids, which could enhance optogenetic therapy for vision restoration.

The research also introduced the first instance of human cone opsin expression in bipolar cells, expanding the optogenetic toolkit and paving the way for potential future trials aimed at restoring vision in human patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV Induced Expression of Human Rod and Cone Opsin in Bipolar Cells of a Mouse Model of Retinal Degeneration. McClements, ME., Staurenghi, F., Visel, M., et al.[2022]

The study demonstrated successful vision restoration in animal models of retinal degeneration using a new opsin called MCO1, delivered via a safe viral method, which significantly improved visually guided behavior.

MCO1 showed effectiveness at much lower light intensities compared to traditional opsins, suggesting it could be a promising gene therapy for various retinal diseases without compromising retinal cell viability under chronic light exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoring vision in mice with retinal degeneration using multicharacteristic opsin. Wright, W., Gajjeraman, S., Batabyal, S., et al.[2022]

The study demonstrated successful vision restoration in animal models of retinal degeneration using a new opsin called MCO1, delivered via a safe viral method, which significantly improved visually guided behavior.

MCO1 showed effectiveness at much lower light intensities compared to traditional opsins, suggesting it could be a promising gene therapy for various retinal diseases without compromising retinal cell viability under chronic light exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoring vision in mice with retinal degeneration using multicharacteristic opsin. Wright, W., Gajjeraman, S., Batabyal, S., et al.[2020]

Citations

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GenSight Biologics Announces 1 Year Safety data and ...

Encouraging signs of efficacy at 1 year were demonstrated in some patients after GS030 optogenetic treatment with a vision that improved from ...

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GenSight Biologics Announces 1 Year Safety Data and ...

GS030 is safe and well tolerated for at least 1 year after injection at all tested doses Encouraging efficacy signals observed in some ...

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cgtlive.com/view/gene-therapy-continues-to-be-well-tolerated-in-retinitis-pigmentosa

Gene Therapy Continues to be Well-Tolerated in Retinitis ...

The gene therapy GS030 (GenSight Biologics) has continued to have a favorable safety profile in patients treated for retinitis pigmentosa (RP) in the phase 1/2 ...

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GS030-DP is an optogenetic gene therapy being investigated for the treatment of retinitis pigmentosa. It targets retinal ganglion cells that ...

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GenSight Biologics Announces 1 Year Safety data and ...

Encouraging signs of efficacy at 1 year were demonstrated in some patients after GS030 optogenetic treatment with a vision that improved from ...

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Optogenetics in the Clinic: PIONEER, a Phase 1/2a Gene ...

The use of GS030-MD to stimulate ChR-tdT was initiated two months after administration of gene therapy and showed no safety concerns, before or after IVT with ...