RGX-314 Gene Therapy for Age-Related Macular Degeneration

(AAVIATE Trial)

Recruiting at 14 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: REGENXBIO, Inc.

Must be taking: Anti-VEGF

Must not be taking: Intravitreal steroids, Gene therapy

Disqualifiers: Retinal detachment, Glaucoma, others

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: Unknown

Duration: 52 weeks

115 Participants Needed

Trial Summary

What is the purpose of this trial?

RGX-314 is being developed as a potential novel one-time gene therapy treatment for the treatment of neovascular (wet) age related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to twelve weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on any investigational products or have had certain eye treatments recently, you may need to wait before joining the study.

What data supports the effectiveness of the treatment RGX-314 for age-related macular degeneration?

Gene therapies like RGX-314 aim to provide long-term treatment for age-related macular degeneration by delivering therapeutic genes to the eye, potentially reducing the need for frequent injections. Research on similar gene therapies has shown promise in targeting retinal diseases, suggesting that RGX-314 could offer a significant improvement in managing this condition. ^{1 2 3 4 5}

Is RGX-314 gene therapy safe for humans?

Research on RGX-314 and similar gene therapies for age-related macular degeneration suggests they are generally safe, with no serious adverse events reported in clinical trials. These therapies use adeno-associated virus (AAV) vectors, which have been tested in other eye conditions and shown to be safe for at least one year post-treatment. ^{1 2 3 6 7}

What makes the RGX-314 treatment unique for age-related macular degeneration?

RGX-314 is a gene therapy that offers a potentially long-lasting solution for age-related macular degeneration by delivering a therapeutic gene to the eye, reducing the need for frequent injections. Unlike traditional treatments that require regular administration, RGX-314 aims to provide sustained anti-VEGF (a protein that promotes blood vessel growth) therapy from a single treatment. ^{1 2 3 8 9}

Eligibility Criteria

This trial is for people aged 50 to 89 with neovascular age-related macular degeneration (wet AMD) in one eye. They must have had a positive response to previous anti-VEGF therapy and be willing to consent to the study.

Inclusion Criteria

You are between 50 and 89 years old.

You have a vision condition called "age-related macular degeneration" that has led to abnormal blood vessels in your study eye.

You are able to read and sign a document that explains the details of the study and agree to participate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RGX-314 gene therapy or ranibizumab control, with dose escalation across cohorts

52 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• RGX-314

Trial Overview The trial tests RGX-314, a potential one-time gene therapy for wet AMD. It's compared against standard treatments like Ranibizumab. Participants will receive different doses of RGX-314 or local/topical steroids.

Participant Groups

Group I: RGX-314 Treatment Arm (Dose 3) and Topical Steroid Experimental Treatment 2 Interventions

RGX-314 Dose 3 and Topical Steroid

Group II: RGX-314 Treatment Arm (Dose 3) and Local Steroid Experimental Treatment 2 Interventions

RGX-314 Dose 3 and Local Steroid

Group III: RGX-314 Treatment Arm (Dose 3) Experimental Treatment 1 Intervention

RGX-314 Dose 3

Group IV: RGX-314 Treatment Arm (Dose 2) Experimental Treatment 1 Intervention

RGX-314 Dose 2

Group V: RGX-314 Treatment Arm (Dose 1) Experimental Treatment 1 Intervention

RGX-314 Dose 1

Group VI: Ranibizumab control Active Control 1 Intervention

Control treatment arm

Who Is Running the Clinical Trial?

REGENXBIO, Inc.

Lead Sponsor

Trials

20

Recruited

2,800+

Regenxbio Inc.

Lead Sponsor

Trials

20

Recruited

2,800+

REGENXBIO Inc.

Lead Sponsor

Trials

25

Recruited

3,100+

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

Retinal gene therapies, particularly for age-related macular degeneration (AMD), are showing promise in clinical trials, with five therapies (Luxturna, ADVM-022, RGX-314, GT-005, and HMR59) being evaluated for their effectiveness against this common condition.

These therapies could potentially provide long-lasting treatment with a single administration, significantly changing the treatment landscape for chronic retinal diseases and reducing the ongoing burden of care for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of gene therapies for age-related macular degeneration. Khanani, AM., Thomas, MJ., Aziz, AA., et al.[2023]

The gene therapy rAAV.sFLT-1 was found to be safe and well tolerated in a phase 1 trial involving nine patients with wet age-related macular degeneration, with no drug-related adverse events reported.

A significant portion of the treatment group (67%) did not require any rescue injections after the therapy, suggesting that a single subretinal injection could provide long-term benefits compared to the frequent injections currently needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. Rakoczy, EP., Lai, CM., Magno, AL., et al.[2022]

Gene therapy for neovascular age-related macular degeneration (nAMD) aims to provide a long-term solution by using adeno-associated virus (AAV) vectors to deliver anti-VEGF proteins, potentially reducing the need for frequent injections and improving visual outcomes.

Current research is focusing on optimizing gene delivery methods and exploring various therapeutic proteins, such as soluble fms-like tyrosine kinase-1 (sFLT-1) and other anti-angiogenic agents, to enhance the efficacy and safety of treatments for AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for age-related macular degeneration. Moore, NA., Bracha, P., Hussain, RM., et al.[2018]

In a Phase 2a trial with 32 patients suffering from wet age-related macular degeneration, the gene therapy rAAV.sFLT-1 was found to be safe, with mainly self-resolving ocular adverse events and no serious safety concerns linked to the treatment.

Patients receiving rAAV.sFLT-1 showed a median improvement in visual acuity compared to the control group, with 57% maintaining or improving vision, and they required fewer ranibizumab retreatments, suggesting that this gene therapy could be a promising option for managing wAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. Constable, IJ., Pierce, CM., Lai, CM., et al.[2022]

Gene therapy using recombinant adeno-associated virus (rAAV) is a promising approach for treating retinal degenerative diseases, as it allows for localized treatment with minimal systemic side effects and enables monitoring of treatment effects noninvasively.

Before rAAV-mediated gene therapy can be implemented for retinal degeneration, several critical steps must be completed, including evaluating different rAAV serotypes and conducting safety and efficacy tests in large animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives. Rolling, F.[2012]

Human gene therapy using the rAAV2 vector for treating RPE65-related Leber congenital amaurosis was found to be safe, with no serious adverse events reported in young adult subjects up to 12 months after treatment.

Patients showed sustained improvements in visual sensitivity from 3 months to 12 months post-treatment, indicating the long-term efficacy of the gene therapy in enhancing vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Cideciyan, AV., Hauswirth, WW., Aleman, TS., et al.[2022]

In a phase I/II clinical trial involving 15 patients with choroideremia, subretinal delivery of the AAV2-hCHM vector was found to be safe, with no vector-related or systemic toxicities reported over a 2-year follow-up period.

Visual acuity remained stable within 15 letters of baseline in 13 out of 15 patients, although two patients experienced complications, indicating a potential risk associated with the injection procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial. Aleman, TS., Huckfeldt, RM., Serrano, LW., et al.[2022]

Transplanting pigment epithelial cells that overexpress the anti-angiogenic factor PEDF could provide a new treatment for neovascular age-related macular degeneration (nvAMD), potentially reducing the need for frequent and invasive anti-VEGF injections.

The study demonstrated successful and stable expression of the PEDF gene in primary retinal pigment epithelial cells, suggesting a promising approach for long-term therapy in nvAMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. Thumann, G., Harmening, N., Prat-Souteyrand, C., et al.[2022]

Recombinant adeno-associated viral (AAV) vectors are effective tools for gene therapy in retinal degeneration, showing long-term transgene expression and minimal side effects in various animal models.

AAV-mediated gene therapy has demonstrated significant recovery of retinal structure and visual function in models of inherited retinal degeneration, highlighting its potential for treating similar human conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-associated virus-vectored gene therapy for retinal disease. Dinculescu, A., Glushakova, L., Min, SH., et al.[2012]

References

1. England pubmed.ncbi.nlm.nih.gov

Review of gene therapies for age-related macular degeneration. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Gene therapy for age-related macular degeneration. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. [2022]

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

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives. [2012]

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

Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. [2022]

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

Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial. [2022]

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

Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. [2022]

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

Adeno-associated virus-vectored gene therapy for retinal disease. [2012]