Gene Therapy for Retinitis Pigmentosa

Not currently recruiting at 1 trial location

Overseen By Minako Koga

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bionic Sight LLC

Disqualifiers: Prior AAV therapy, Nystagmus

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called BS01 (also known as ChronosFP) to determine its safety and effectiveness for individuals with retinitis pigmentosa, a condition that causes vision loss. The trial includes several groups, each receiving different doses of the treatment, with some participants receiving treatment in both eyes. Suitable candidates have been diagnosed with retinitis pigmentosa and have one eye with significant vision problems, such as difficulty seeing details or a narrowed field of vision. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and to measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that BS01 is likely to be safe for humans?

Research has shown that BS01, a gene therapy for retinitis pigmentosa, was safe in earlier studies. Animal tests confirmed BS01's safety across various doses and light conditions, suggesting it might also be well-tolerated in humans. Additionally, the FDA granted BS01 a special designation, indicating a thorough review. This is a positive sign for its safety. While researchers continue to gather specific safety data for humans, early evidence suggests it is safe for further testing in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about BS01 for retinitis pigmentosa because it leverages gene therapy to address the root cause of the disease, unlike current treatments that focus on managing symptoms. Most existing options, like vitamin A supplements and certain visual aids, don't directly target the genetic mutations responsible for the condition. BS01 aims to introduce a healthy copy of the gene into retinal cells, potentially halting or even reversing vision loss. This innovative approach represents a promising shift towards more effective and lasting solutions for patients.

What evidence suggests that BS01 might be an effective treatment for Retinitis Pigmentosa?

Research has shown that BS01, a gene therapy for retinitis pigmentosa, may help improve vision. In earlier studies, 89% of participants either maintained or improved their vision compared to their initial state. Participants in this trial will receive different doses of BS01. Previous research indicated that lower doses led to a small but steady improvement in light perception. In animal studies, BS01 helped blind mice respond to light again. This suggests that BS01 might help preserve or restore vision in people with retinitis pigmentosa. ^{1 2 6 7 8}

Who Is on the Research Team?

Sheila Nirenberg, PhD

Principal Investigator

Bionic Sight LLC

Are You a Good Fit for This Trial?

This trial is for individuals with confirmed retinitis pigmentosa who have very limited vision, described as 'bare light perception', in at least one eye. It's not open to those who've previously received any AAV gene therapy or have large amplitude nystagmus, which is a condition where the eyes make repetitive, uncontrolled movements.

Inclusion Criteria

You can only see very minimal light with at least one eye.

I have been diagnosed with retinitis pigmentosa.

Exclusion Criteria

I have never received AAV gene therapy before.

I experience severe involuntary eye movements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BS01, a recombinant adeno-associated virus vector expressing ChronosFP, in a dose escalation study

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• BS01

Trial Overview The study involves BS01, a genetic treatment using a modified virus to deliver genes into cells of the eye. This early-phase trial will test different doses to see how safe it is and what effects it has on patients' vision.

How Is the Trial Designed?

Group I: Cohort 6 Experimental Treatment 1 Intervention

Treat opposite eye

Group II: Cohort 5 Experimental Treatment 1 Intervention

BS01 Cohort4 dose

Group III: Cohort 4 Experimental Treatment 1 Intervention

BS01 Cohort4 dose

Group IV: Cohort 3 Experimental Treatment 1 Intervention

BS01 Cohort 3 dose

Group V: Cohort 2 Experimental Treatment 1 Intervention

BS01 Cohort 2 dose

Group VI: Cohort 1 Experimental Treatment 1 Intervention

BSO1 Cohort 1 dose

Who Is Running the Clinical Trial?

Bionic Sight LLC

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Gene therapy has shown potential in delivering transgenes to the retina effectively and safely, which could help slow or prevent blindness caused by retinitis pigmentosa (RP).

Recent advancements in understanding the molecular basis of RP, along with successful gene transfer experiments in animal models, suggest that gene therapy could be a viable treatment option in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for retinitis pigmentosa. Bennett, J.[2012]

The study followed 46 individuals with PRPF31-related retinitis pigmentosa (RP11) and found that the median age of disease onset was 10 years, with a median follow-up of 8 years, highlighting the early onset and long-term progression of the disease.

Visual field areas deteriorated significantly faster than visual acuity, with legal blindness typically occurring at a median age of 57 years, emphasizing the need for careful monitoring of visual field changes in patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease progression of retinitis pigmentosa caused by PRPF31 variants in a Nordic population: a retrospective study with up to 36 years follow-up. Lisbjerg, K., Bertelsen, M., Lyng Forman, J., et al.[2023]

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]

Optogenetic gene therapy using the AAV2 vector and Chronos protein has shown promising efficacy in restoring vision in preclinical models, with effective results observed across various doses and light intensities.

Safety assessments in multiple animal models (mice, rats, and nonhuman primates) indicated that the treatment was well tolerated, with no significant adverse effects noted in anatomical or electrophysiological tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinically viable approach to restoring visual function using optogenetic gene therapy. Yan, B., Viswanathan, S., Brodie, SE., et al.[2023]

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]

In a mouse model of retinitis pigmentosa (RP), gene therapy was able to halt degeneration and restore function when administered at early, mid, or late stages of the disease, showing that treatment can be effective even after disease onset.

The study highlights a broad therapeutic time window for gene therapy in RP, suggesting that patients diagnosed after significant photoreceptor loss can still benefit from treatment, emphasizing the need to improve transduction efficiency for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Halting progressive neurodegeneration in advanced retinitis pigmentosa. Koch, SF., Tsai, YT., Duong, JK., et al.[2018]

Both patients with PRPF31-related retinitis pigmentosa experienced similar clinical courses, with early onset of night blindness and relatively preserved visual acuity into their 30s, but significant deterioration of their visual fields starting in their teens.

Genetic analysis confirmed that mutations in the PRPF31 gene were responsible for their autosomal dominant retinitis pigmentosa, highlighting the importance of genetic testing in understanding the progression of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. Kurata, K., Hosono, K., Hotta, Y.[2018]

The study assessed the safety of a gene therapy using a recombinant adeno-associated virus vector (rAAV2-CB-hRPE65) in 12 patients (8 adults and 4 children) with retinal degeneration due to RPE65 mutations, finding no serious treatment-related adverse events after 2 years of follow-up.

Improvements in visual function were observed in 9 out of 12 patients, with the most significant gains in younger patients who had better baseline visual acuity, indicating potential efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Weleber, RG., Pennesi, ME., Wilson, DJ., et al.[2017]

In a mouse model of retinitis pigmentosa, gene therapy successfully restored function and structure of photoreceptor cells even when treatment was administered at an advanced disease stage, showing sustained efficacy for at least 1 year.

These findings suggest that retinal gene therapy could be a viable treatment option for patients with retinitis pigmentosa, even after significant degeneration has occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Success of Gene Therapy in Late-Stage Treatment. Koch, SF., Tsang, SH.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04278131

NCT04278131 | BS01 in Patients With Retinitis Pigmentosa Confirmed diagnosis of retinitis pigmentosa. At least one eye with vision no better than 20/160 visual acuity on the EDTRS scale or, for ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10213293/

A clinically viable approach to restoring visual function using ... The ERG responses in rd1 mice demonstrated that BS01 is effective in producing light responses in blind animals. To assess the vector's safety, studies were ...

3. withpower.com withpower.com/trial/phase-2-retinitis-1-2020-7698d

Gene Therapy for Retinitis Pigmentosa · Info for Participants Research shows that gene therapy can effectively preserve vision in retinitis pigmentosa, even when started at later stages of the disease.

4. biospace.com biospace.com/press-releases/bionic-sights-bs01-gene-therapy-receives-rmat-designation-from-the-fda

Bionic Sight's BS01 Gene Therapy Receives RMAT ... Briefly, the participants who received the lower doses showed a modest but consistent improvement: 5 of 5 showed an increase in light ...

5. delveinsight.com delveinsight.com/blog/top-8-gene-therapies-for-retinitis-pigmentosa-treatment

8 Emerging Gene Therapies for Retinitis Pigmentosa ... Among the 18 subjects with retinitis pigmentosa, 89% showed either preservation or improvement in BCVA, LLVA, or MLMT scores from baseline.

6. lighthouseguild.org lighthouseguild.org/news/bionic-sights-bs01-gene-therapy-receives-rmat-designation-from-the-fda/

Bionic Sight's BS01 Gene Therapy Receives RMAT ... “Receiving RMAT designation from the FDA is a significant validation of Bionic Sight's BS01 therapy, given the intensity of the FDA review ...

7. ctv.veeva.com ctv.veeva.com/study/bs01-in-patients-with-retinitis-pigmentosa

BS01 in Patients With Retinitis Pigmentosa Confirmed diagnosis of retinitis pigmentosa; At least one eye with vision no better than 20/160 visual acuity on the EDTRS scale or, ...

8. cgtlive.com cgtlive.com/view/bs01-restores-light-motion-detection-in-retinitis-pigmentosa

BS01 Restores Light, Motion Detection in Retinitis ... The AAV-mediate gene therapy BS01 allowed 4 patients with retinitis pigmentosa who had complete or near-complete blindness to perceive light and motion.