Gene Therapy for Retinitis Pigmentosa

Recruiting at 2 trial locations

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

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy (AAV5-hRKp.RPGR) for individuals with X-linked retinitis pigmentosa, a genetic eye condition that causes vision loss. The researchers aim to determine if the therapy, delivered directly under the retina, is safe and tolerable. Participants will be divided into groups to receive different doses or to be observed if surgery is not possible. This trial is open to those who have previously received this gene therapy in an earlier study and are willing to adhere to the study's guidelines. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the AAV5-hRKp.RPGR gene therapy is generally safe and well-tolerated. Most side effects have been minor and temporary, often related to the surgery required for delivery. Importantly, no serious issues have emerged that would limit the dose participants can receive. Participants have not experienced severe side effects that would prevent them from receiving higher doses if needed. Overall, previous research indicates that the treatment appears safe. ^{1 2 3 4 5}

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

Unlike the standard treatments for retinitis pigmentosa, which often focus on managing symptoms or slowing progression, the AAV5-hRKp.RPGR gene therapy aims to address the genetic root of the disease. Researchers are excited about this treatment because it uses an adeno-associated virus (AAV5) to deliver a healthy copy of the RPGR gene directly under the retina, potentially restoring function in damaged retinal cells. This innovative approach could provide a more lasting solution by targeting the underlying genetic cause, rather than just treating symptoms.

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

Studies have shown promising results for the AAV5-hRKp.RPGR gene therapy in treating X-linked retinitis pigmentosa. Research indicates that this therapy is generally safe and well-tolerated, with most side effects being temporary and related to the surgery. Early trials demonstrated that this treatment has an acceptable safety profile and may improve vision in affected individuals. In this trial, participants in Cohort 1 will receive a low or intermediate dose of AAV5-hRKp.RPGR under the retina. Once safety is confirmed in Cohort 1, Cohort 2 will receive the treatment dose in the second eye. The therapy delivers a healthy copy of the RPGR gene directly into the retina, which helps slow down or possibly reverse vision loss. While more data are needed, initial findings suggest that this gene therapy could be a helpful treatment option for those with this genetic form of vision impairment. ^{1 2 3 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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 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]

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 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]

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]

Citations

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

Safety and Efficacy in RPGR-Associated X-Linked Retinitis ... AAV5-hRKp.RPGR was safe and well tolerated, with no reported dose-limiting events. Most adverse events (AEs) were transient and related to the surgical ...

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

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene ... Purpose. To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis ...

3. 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 ... Treatment with botaretigene sparoparvovec was found to have an acceptable safety profile, and efficacy assessments in this proof-of-concept ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03252847

NCT03252847 | Gene Therapy for X-linked Retinitis ... This is an open-label phase 1/2 dose-escalation and cohort expansion trial to determine the safety and efficacy of subretinal administration of AAV5-hRKp.RPGR ...

5. jnjmedicalconnect.com jnjmedicalconnect.com/products/botaretigene-sparoparvovec/medical-content/phase-12-clinical-trials

Phase 1/2 Clinical Trials Botaretigene sparoparvovec (AAV5-RPGR) is an investigational AAV5 gene therapy being studied for the treatment of XLRP caused by variants in the RPGR gene.

6. fiercebiotech.com fiercebiotech.com/biotech/jj-gene-therapy-fails-improve-visual-navigation-late-stage-rare-eye-disease-trial

J&J gene therapy fails ph. 3 rare eye disease trial The treatment failed to improve the vision-guided mobility of patients with the eye disease X-linked retinitis pigmentosa (XLRP) in a phase 3 trial.

7. semanticscholar.org semanticscholar.org/paper/Phase-1-2-AAV5-hRKp.RPGR-(Botaretigene-Gene-Safety-Michaelides-Besirli/e0129281092ca9d01bfd2a37cb6f0ec6869dba46

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) ... Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-associated X-linked Retinitis Pigmentosa. · 13 Citations · 29 ...