Gene Therapy for Retinitis Pigmentosa

Not currently recruiting at 58 trial locations

Overseen By MeiraGTx Clinical Project Manager

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: MeiraGTx UK II Ltd

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: Up to 60 months

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial explores a new gene therapy called AAV5-RPGR for individuals with X-linked retinitis pigmentosa (XLRP), a genetic eye condition that can lead to vision loss. The research aims to determine how well this treatment can improve or stabilize vision in affected individuals. Participants are divided into groups based on their previous treatment doses or whether they've already received the therapy. This trial may suit individuals diagnosed with XLRP by a retinal specialist and who have a specific genetic change confirmed in their RPGR gene. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering a promising opportunity for those seeking advanced therapeutic options.

Do I need to stop my current medications for the trial?

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

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

Research has shown that the gene therapy AAV5-RPGR is safe and well-tolerated in earlier studies. No serious problems related to the dosage occurred. Most side effects were temporary and linked to the surgery required for the treatment. Thus, any discomfort was short-lived and due to the procedure itself, not the gene therapy. Overall, the treatment was considered safe, as it did not cause serious issues in patients who received it. ^{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 groundbreaking approach using gene therapy. Unlike traditional treatments that mainly aim to manage symptoms, AAV5-RPGR directly targets the underlying genetic cause of the disease by delivering a correct copy of the RPGR gene to retinal cells. This method has the potential to halt or even reverse vision loss, which is a significant advancement over current options like vitamin A supplements and retinal implants. By directly addressing the genetic defect, AAV5-RPGR could potentially offer longer-lasting and more effective results.

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

Research has shown that AAV5-RPGR gene therapy may help treat X-linked retinitis pigmentosa (XLRP). In earlier studies, patients who received this therapy saw better in dim light, indicating improved retinal sensitivity. They also moved around more easily, reflecting gains in functional vision. These improvements remained noticeable nine months after treatment, suggesting lasting effects. In this trial, participants will join different treatment arms, including those already treated and those receiving deferred treatment at low or intermediate doses. Overall, the gene therapy appears to improve vision for those with XLRP. ^{1 2 6 7 8}

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 change in the RPGR gene verified by an accredited lab.

Inclusion Criteria

I am 3 or older with XLRP confirmed by a specialist and a genetic test.

Exclusion Criteria

N/A

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

Up to 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

What Are the Treatments Tested in This Trial?

Interventions

• AAV5-RPGR

Trial Overview The study tests two doses of AAV5-RPGR, a gene therapy vector, to treat XLRP. Patients will receive one of the two doses to see how well it works and what side effects occur.

How Is the Trial Designed?

Group I: Deferred Treatment From MGT-RPGR-021 of Intermediate Dose Experimental Treatment 1 Intervention

Deferred treatment

Group II: Deferred Treatment From MGT-RPGR-021 Low Dose Experimental Treatment 1 Intervention

Deferred treatment

Group III: Already Treated in MGT-RPGR-021 Experimental Treatment 2 Interventions

Already treated

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 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]

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]

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]

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]

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]

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]

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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05926583

NCT05926583 | A Study of AAV5-hRKp.RPGR for the ... The purpose of the study is to assess the safety and tolerability of bilateral subretinal delivery of adeno-associated virus vector with a serotype 5 capsid ...