Gene Therapy for Retinitis Pigmentosa

Recruiting at 1 trial location

Overseen By Study Contact

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

39 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and tolerability of subretinal delivery of Adeno-associated Virus Vector (AAV5 hRKp.RPGR) gene therapy in adults and children with X-linked retinitis pigmentosa.

Will I have to stop taking my current medications?

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

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

Initial results from a clinical trial showed that the gene therapy improved visual fields in some patients with X-linked retinitis pigmentosa, and studies in dogs demonstrated preserved photoreceptor function and structure after treatment, suggesting potential effectiveness for humans. ^{1 2 3 4 5}

Is gene therapy for Retinitis Pigmentosa generally safe in humans?

In early human trials, the gene therapy for Retinitis Pigmentosa showed no major safety concerns, although some patients experienced inflammation in the eye that responded to steroids. Animal studies also indicated that the treatment was well tolerated with no significant side effects. ^{1 2 3 4 6}

How is the gene therapy treatment AAV5-hRKp.RPGR different from other treatments for retinitis pigmentosa?

The gene therapy treatment AAV5-hRKp.RPGR is unique because it uses a viral vector to deliver a healthy copy of the RPGR gene directly to the photoreceptor cells in the retina, aiming to correct the genetic defect causing retinitis pigmentosa. This approach is novel as it targets the root cause of the disease at the genetic level, unlike other treatments that may only address symptoms. ^{1 2 3 4 6}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults and children who have already been treated with AAV5-hRKp.RPGR gene therapy in a previous study (MGT009) and are either currently enrolled or have completed another study (MGT010). Participants must understand the study's purpose, procedures, and agree to follow the protocol.

Inclusion Criteria

Have been treated with AAV5-hRKp.RPGR in study MGT009 and have completed or is currently enrolled in Study MGT010

Must sign an informed consent form indicating that they understand the purpose and procedures of the study and are willing to participate

Willing to adhere to the protocol and long-term follow-up

Exclusion Criteria

There are no specific exclusion criteria to enroll in this study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subretinal delivery of AAV5 hRKp.RPGR gene therapy in the second eye

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5.5 years

Yearly visits

Long-term monitoring

Participants are assessed yearly for changes in retinal sensitivity and visual acuity

5 years

Treatment Details

Interventions

• AAV5-hRKp.RPGR

Trial Overview The trial is testing the safety of delivering a gene therapy called AAV5-hRKp.RPGR directly under the retina. It follows patients previously treated for X-linked retinitis pigmentosa to see how they do over time without additional intervention.

Participant Groups

Group I: Cohort 3 Experimental Treatment 1 Intervention

The participants who are not willing to undergo surgery or are not eligible for surgery will be assessed in this cohort. They will be assessed yearly until 5 years after their initial eye surgery in previous study MGT009.

Group II: Cohort 2 Experimental Treatment 1 Intervention

Participants will receive the treatment dose of AAV5 hRKp.RPGR under the retina (low-dose or intermediate-dose) on Day 1 in the second eye once the safety will be determined in Cohort 1.

Group III: Cohort 1 Experimental Treatment 1 Intervention

Participants will receive a dose of AAV5 hRKp.RPGR under the retina (low-dose or intermediate-dose) on Day 1 depending on the dosage administered in study MGT009 (NCT03252847) in the past. After receiving the treatment, participants will be assessed for safety.

Who Is Running the Clinical Trial?

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

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]

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]

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]

In a study involving a canine model of X-linked retinitis pigmentosa (XLRP), the rAAV2tYF-GRK1-hRPGRco gene therapy showed promising results in correcting early disease markers without significant ocular complications, except for some retinal detachment in the highest dose group.

The therapy demonstrated a dose-dependent expression of the RPGR gene and a rescue effect on retinal structure, supporting its potential for clinical trials in humans with RPGR mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose Range Finding Studies with Two RPGR Transgenes in a Canine Model of X-Linked Retinitis Pigmentosa Treated with Subretinal Gene Therapy. Song, C., Dufour, VL., Cideciyan, AV., et al.[2021]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Strategies for RPGR Gene Therapy. [2023]

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. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

Dose Range Finding Studies with Two RPGR Transgenes in a Canine Model of X-Linked Retinitis Pigmentosa Treated with Subretinal Gene Therapy. [2021]