Gene Therapy for Retinitis Pigmentosa

Recruiting at 55 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

97 Participants Needed

Trial Summary

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.

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, with some studies reporting visual field improvements and preserved photoreceptor function in animal models. Additionally, early human trials have shown safety and some visual improvements, suggesting potential effectiveness. ^{1 2 3 4 5}

Is gene therapy for retinitis pigmentosa safe for humans?

In a clinical trial for retinitis pigmentosa, the gene therapy was generally safe, with some patients experiencing inflammation that responded to steroids, especially at higher doses. Animal studies also showed no significant safety concerns, supporting its use in humans. ^{1 3 4 5 6}

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 eye's photoreceptor cells, which is different from other treatments that may not target the genetic cause of the disease. This approach is unique because it aims to correct the underlying genetic defect, potentially preserving or improving vision in patients with retinitis pigmentosa caused by RPGR mutations. ^{3 4 6 7 8}

What is the purpose of this trial?

This trial tests a gene therapy for people with X-linked retinitis pigmentosa. It uses a harmless virus to deliver a healthy gene to eye cells, aiming to improve their function and slow down vision loss. Gene therapy targeting the RPE65 gene has shown promise in treating inherited retinal dystrophies, including retinitis pigmentosa.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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 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]

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 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]

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]

References

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

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

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

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

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

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Strategies for RPGR Gene Therapy. [2023]

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

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