Gene Therapy for Retinitis Pigmentosa

No longer recruiting at 62 trial locations

Overseen By MeiraGTx Clinical Project Manager

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: MeiraGTx UK II Ltd

Disqualifiers: Ocular surgery, Retinal surgery, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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 for individuals with X-linked retinitis pigmentosa (XLRP), a genetic eye condition that can lead to vision loss. The study examines the effectiveness and safety of the AAV5-RPGR gene therapy. Participants will receive either immediate or deferred treatment with varying doses to determine the most effective approach. Suitable candidates have XLRP confirmed by a specialist and a specific genetic change identified by a lab. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on any investigational or other ocular treatments, you may need to stop them as they could affect the study results.

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

Research has shown that the AAV5-RPGR gene therapy is generally safe and well-tolerated. Several studies found no harmful effects at any dose. Most side effects were temporary and related to the surgery required to deliver the gene therapy. These findings suggest the treatment is safe for people with X-linked retinitis pigmentosa (XLRP). ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for retinitis pigmentosa?

Researchers are excited about AAV5-RPGR for retinitis pigmentosa because it offers a novel approach through gene therapy. Unlike current treatments, which primarily focus on managing symptoms or slowing progression, AAV5-RPGR directly targets the root cause by delivering a correct copy of the RPGR gene using an adeno-associated virus (AAV) vector. This method has the potential to restore function to damaged retinal cells, which is a groundbreaking advancement compared to traditional options like vitamin A supplements or the use of optical aids. Additionally, the potential for long-term benefits from a single treatment makes this therapy particularly promising for patients.

What evidence suggests that AAV5-RPGR might be an effective treatment for retinitis pigmentosa?

Research has shown that AAV5-RPGR gene therapy could be beneficial for treating X-linked retinitis pigmentosa (XLRP). In earlier studies, patients who received this therapy experienced better retinal sensitivity and improved vision after six months. Another study with 49 men confirmed the treatment's safety and effectiveness, noting improvements in vision-related activities and other eye functions. In this trial, participants will receive either immediate treatment with AAV5-RPGR at different doses or deferred treatment. These findings suggest that AAV5-RPGR may help slow or improve the symptoms of XLRP. ^{1 2 5 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for males and females aged 3 or older with X-linked retinitis pigmentosa (XLRP) confirmed by a specialist. Participants must have a specific genetic variant in the RPGR gene verified by an accredited lab.

Inclusion Criteria

I am either male or female.

I am at least 3 years old.

I have X-linked retinitis pigmentosa confirmed by a specialist and genetic testing.

Exclusion Criteria

I haven't had any experimental eye treatments that could affect study results.

I haven't had eye surgery in the last 3 months and don't plan to have any in the next 6 months.

I have had eye surgery or treatments that involved the central part of my retina.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the AAV5-RPGR vector treatment for X-linked retinitis pigmentosa

52 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AAV5-RPGR

Trial Overview The trial is testing AAV5-RPGR, a form of gene therapy designed to treat XLRP. This intervention involves using a harmless virus to deliver corrected genes into the body.

How Is the Trial Designed?

Group I: Experimental Immediate Treatment Experimental Treatment 1 Intervention

Low dose.

Group II: Experimental - Immediate Treatment Experimental Treatment 1 Intervention

Intermediate dose.

Group III: Deferred Treatment Experimental Treatment 1 Intervention

Deferred Treatment

Who Is Running the Clinical Trial?

MeiraGTx UK II Ltd

Lead Sponsor

Trials

15

Recruited

710+

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

Mutations in the RPGR gene are a leading cause of severe retinitis pigmentosa, which leads to early blindness, and currently, there is no cure for this condition.

Recent advances in research have led to the development of AAV-mediated gene replacement therapies, which are now in phase I/II clinical trials, showing promise for treating RPGR-related retinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Strategies for RPGR Gene Therapy. Cehajic Kapetanovic, J., McClements, ME., Martinez-Fernandez de la Camara, C., et al.[2023]

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]

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]

Three Phase I/II clinical trials are currently testing different adeno-associated viral (AAV) vectors for gene therapy in patients with X-linked retinitis pigmentosa, focusing on delivering the RPGR gene to photoreceptors.

The development of these gene therapy vectors is challenging due to the instability of the RPGR gene sequence and the need for functional assays to ensure the correct protein is produced, highlighting the importance of understanding the gene's function and post-translational modifications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RPGR gene therapy presents challenges in cloning the coding sequence. Martinez-Fernandez De La Camara, C., Cehajic-Kapetanovic, J., MacLaren, RE.[2023]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0002939424002447

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene ... This study of 49 males with RPGR-XLRP assessed the safety and efficacy of subretinal AAV5-hRKp.RPGR gene therapy. Subretinal delivery of AAV5-hRKp.RPGR was ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38871269/

Safety and Efficacy in RPGR-Associated X-Linked Retinitis ... The primary outcome was safety. Secondary efficacy outcomes included static perimetry, microperimetry, vision-guided mobility, best corrected ...

3. meiragtx.com meiragtx.com/wp-content/uploads/2020/11/EURETINA-2020_RPGR-9-month.pdf

9-month Results From a Phase 1/2 Clinical Trial AAV5-RPGR Gene Therapy for. RPGR-Associated X-Linked Retinitis. Pigmentosa: 9-month Results From a Phase 1/2 Clinical Trial. Michel Michaelides,1,2* Cagri ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04671433

NCT04671433 | Gene Therapy Trial for the Treatment of X- ... Phase 3 Randomized, Controlled Study of AAV5-hRKp.RPGR for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene.

5. aao.org aao.org/eyenet/academy-live/detail/retinitis-pigmentosa-responds-to-gene-therapy

Retinitis Pigmentosa Responds to Gene Therapy At six months, eyes treated with AAV5-RPGR had improved in retinal sensitivity and functional vision in comparison with randomized controls.

6. investors.meiragtx.com investors.meiragtx.com/news-releases/news-release-details/late-breaking-phase-12-data-demonstrates-safety-profile

Late-Breaking Phase 1/2 Data Demonstrates Safety Profile of ... Treatment with botaretigene sparoparvovec was found to have an acceptable safety profile and efficacy assessments in this proof-of-concept study demonstrated ...

7. jnj.com jnj.com/media-center/press-releases/janssen-announces-late-breaking-data-from-two-gene-therapy-programs-at-the-american-academy-of-ophthalmology-2022-annual-meeting

Janssen Announces Late-Breaking Data from Two Gene ... Results from Phase 1/2 MGT009 study demonstrate safety profile of investigational gene therapy botaretigene sparoparvovec (AAV-RPGR) and suggest sustained ...