RGX-314 Gene Therapy for Age-Related Macular Degeneration

(AAVIATE Trial)

Recruiting at 29 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

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy treatment for wet age-related macular degeneration (AMD), a condition that can cause vision loss due to leaky blood vessels in the retina. The goal is to determine if a one-time treatment with RGX-314 (also known as ABBV-RGX-314) can provide a long-term solution compared to current treatments that require frequent eye injections. The trial includes several groups testing different doses of RGX-314, with and without steroids, to identify the most effective approach. Individuals diagnosed with wet AMD who have responded well to anti-VEGF therapies might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to groundbreaking advancements in AMD therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RGX-314 has promising safety results from earlier studies. One study found that patients using RGX-314 needed 97% fewer other treatments over nine months, suggesting safety, as fewer treatments often mean fewer side effects.

Past studies have also tested RGX-314 for safety and patient tolerance. These studies showed that RGX-314 was generally well-tolerated by patients with wet age-related macular degeneration (AMD). There were no major safety issues, and any side effects were usually mild.

In summary, the safety data so far indicate that RGX-314 is well-tolerated, with few side effects. This makes it a promising option for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RGX-314 because it offers a novel approach to treating age-related macular degeneration (AMD). Unlike standard treatments, which often involve regular injections of anti-VEGF drugs like ranibizumab directly into the eye, RGX-314 utilizes gene therapy to potentially provide a more long-lasting solution. This innovative treatment delivers a gene that enables the eye to produce its own anti-VEGF protein, potentially reducing the frequency of treatments. Additionally, some variations of RGX-314 are being tested with the addition of local or topical steroids, which could enhance the therapy’s effectiveness and reduce inflammation, offering further benefits over current options.

What evidence suggests that this trial's treatments could be effective for wet AMD?

Studies have shown that RGX-314 gene therapy can significantly reduce the need for frequent eye injections in people with wet age-related macular degeneration (AMD). Research indicates a 97% decrease in the number of treatments needed nine months after receiving the therapy, meaning patients require fewer injections. The therapy blocks a protein called VEGF-A, which causes leaky blood vessels in the eye. Early results suggest that RGX-314 can help maintain vision and effectively control fluid buildup in the eye. Researchers are exploring this gene therapy as a potential one-time treatment option for managing wet AMD. Participants in this trial may receive different doses of RGX-314 or a combination with steroids, while others will receive Ranibizumab as a control treatment. ^{1 3 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid Experimental Treatment 2 Interventions

ABBV-RGX-314 Dose 4 and Topical Steroid

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

ABBV-RGX-314 Dose 3 and Topical Steroid

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

ABBV-RGX-314 Dose 3 and Local Steroid

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

ABBV-RGX-314 Dose 3

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

ABBV-RGX-314 Dose 2

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

ABBV-RGX-314 Dose 1

Group VII: 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+

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

REGENXBIO Inc.

Industry Sponsor

Trials

25

Recruited

3,100+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

Citations

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ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-data-phase-ii-study-subretinal-abbv

Release Details

97% reduction in treatment burden at nine months after treatment with ABBV-RGX-314; Data consistent with that from multiple previous studies ...

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thelancet.com/journals/lancet/article/PIIS0140-6736(24)00310-6/abstract

Gene therapy for neovascular age-related macular ...

We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD.

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pubmed.ncbi.nlm.nih.gov/38554726/

Gene therapy for neovascular age-related macular ...

RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, ...

4.

news.abbvie.com

news.abbvie.com/2025-01-13-AbbVie-and-REGENXBIO-Announce-Updates-on-the-ABBV-RGX-314-Clinical-Program

AbbVie and REGENXBIO Announce Updates on the ABBV ...

ABBV-RGX-314 is being investigated as a potential one-time treatment for wet AMD, diabetic retinopathy and potentially other chronic retinal conditions.

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clinicaltrials.gov/study/NCT04704921

NCT04704921 | Pivotal 1 Study of ABBV-RGX-314 (Also ...

This randomized, partially masked, active-controlled, Phase 2b/3 clinical study will evaluate the efficacy and safety of ABBV-RGX-314 gene therapy in ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT03066258

NCT03066258 | Safety and Tolerability of RGX-314 ...

This Phase I/IIa, open-label, multiple-cohort, dose-escalation study was designed to evaluate the safety and tolerability of RGX-314 gene therapy in subjects ...

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abbvieclinicaltrials.com/study/?id=RGX-314-2102

RGX-314 Gene Therapy Administered in the ...

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 ...