Gene Therapy for Retinitis Pigmentosa

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

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

97 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a gene therapy that uses a harmless virus to deliver a healthy gene to eye cells. It targets people with X-linked retinitis pigmentosa, aiming to help their eye cells work better and slow down vision loss. Gene therapy targeting the RPE65 gene has shown promise in treating retinal diseases, with the first FDA-approved therapy in 2017.

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 gene therapy for retinitis pigmentosa safe?

In a clinical trial for retinitis pigmentosa, the gene therapy using AAV8-coRPGR was generally safe, with only some patients experiencing inflammation that responded to steroids. High doses in animal studies showed retinal toxicity, so careful dose management is important. ^{1 2 3 4 5}

How is the AAV5-RPGR treatment different from other treatments for retinitis pigmentosa?

AAV5-RPGR is a gene therapy that uses a modified virus to deliver a healthy copy of the RPGR gene directly to the retina, which is unique because it targets the genetic cause of retinitis pigmentosa rather than just managing symptoms. This approach is novel as it aims to restore the function of photoreceptors, potentially slowing or stopping vision loss. ^{1 2 5 6 7}

What data supports the effectiveness of the treatment AAV5-RPGR for retinitis pigmentosa?

Gene therapy using similar treatments has shown promise in improving vision in patients with retinitis pigmentosa, as seen in a trial where six patients experienced visual field improvements. Additionally, studies in dogs and mice with similar genetic conditions demonstrated preserved retinal structure and function after treatment, suggesting potential benefits for humans. ^{1 2 3 4 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 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

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]

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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Early Cone Photoreceptor Outer Segment Length Shortening in RPGR X-Linked Retinitis Pigmentosa. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. [2022]

3. United States 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A long-term efficacy study of gene replacement therapy for RPGR-associated retinal degeneration. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Strategies for RPGR Gene Therapy. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice. [2020]

8. England pubmed.ncbi.nlm.nih.gov

RPGR gene therapy presents challenges in cloning the coding sequence. [2023]