What is the mechanism of action of this treatment?

The most common treatments for Age-Related Macular Degeneration (AMD) involve anti-VEGF (vascular endothelial growth factor) therapies. These treatments inhibit VEGF, a protein that stimulates the growth of abnormal blood vessels in the retina, which can leak and lead to vision loss in wet AMD. RGX-314, a gene therapy under investigation, aims to provide a sustained anti-VEGF effect through a one-time treatment, potentially reducing the need for frequent intraocular injections. This is crucial for AMD patients as it could enhance treatment adherence and maintain vision more effectively over the long term.

What side effects are associated with this type of intervention?

Anti-VEGF therapies for Age-Related Macular Degeneration (AMD) involve repeated intraocular injections and can cause side effects such as eye pain, increased intraocular pressure, inflammation, and rarely, retinal detachment or endophthalmitis. Gene therapies like RGX-314, which aim to provide sustained anti-VEGF expression through a one-time treatment, may lead to immune reactions and inflammation, with long-term effects still under investigation. Both approaches aim to prevent vision loss but carry distinct risks.

What prior FDA approvals exist?

The FDA has approved several anti-VEGF therapies for the treatment of Age-Related Macular Degeneration (AMD), which work by inhibiting vascular endothelial growth factor (VEGF) to prevent the growth of abnormal blood vessels in the retina. Notable drugs include ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin). These treatments require regular intraocular injections to maintain efficacy. RGX-314, currently under trial, represents a novel approach as a one-time gene therapy designed to provide sustained anti-VEGF expression, potentially reducing the need for frequent injections.

What other types of research exist?

Promising novel alternatives to RGX-314 for AMD patients include: 1) Faricimab, a bispecific antibody targeting both VEGF and Ang-2, which has shown efficacy in reducing injection frequency. 2) KSI-301, an anti-VEGF biopolymer conjugate designed for extended durability. 3) Port Delivery System with Ranibizumab (PDS), a refillable ocular implant that provides continuous delivery of ranibizumab. These therapies aim to reduce the treatment burden and maintain efficacy in managing AMD.

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Gene Therapy

RGX-314 Gene Therapy for Age-Related Macular Degeneration (ASCENT Trial)

Phase 3

Recruiting

Research Sponsored by AbbVie

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥ 50 years and ≤ 89 years

Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry

Must not have

Prior treatment with gene therapy

Advanced glaucoma or history of secondary glaucoma in the study eye

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 54, week 74, week 90, and week 108

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new one-time gene therapy called RGX-314 for patients with wet AMD. The goal is to reduce the need for regular treatments by helping the eye produce its own protective proteins. This could make treatment easier and more effective for patients.

Who is the study for?

This trial is for people aged 50-89 with wet age-related macular degeneration (AMD) who've had cataract surgery at least 12 weeks ago and responded to previous anti-VEGF treatments. They should have a certain level of vision as measured by the ETDRS score. Those with recent serious heart events, retinal detachment, other eye conditions or surgeries, or prior gene therapy can't join.

What is being tested?

The study tests RGX-314, a one-time gene therapy for wet AMD that could replace frequent injections currently needed for treatment. Two different doses of RGX-314 are being compared against Aflibercept (EYLEA®), an existing standard care medication.

What are the potential side effects?

While specific side effects of RGX-314 aren't listed here, gene therapies can sometimes cause immune reactions, changes in vision, discomfort at the injection site, and potential long-term risks which are still unknown.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 50 and 89 years old.

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I responded well to previous anti-VEGF treatment.

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My eye condition was treated with injections due to AMD.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously undergone gene therapy.

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I have advanced glaucoma or a history of it in one eye.

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My vision loss is not due to AMD but another cause.

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I have scarring or tissue loss in the center of my vision in one eye.

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I have not had a heart attack, stroke, or mini-stroke in the last 6 months.

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I have or had a detached retina or currently have a tear in my study eye.

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I haven't had any eye injections except for anti-VEGF in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 54, week 74, week 90, and week 108

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 54, week 74, week 90, and week 108

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 54, week 74, week 90, and week 108 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Mean change from baseline in Best Corrected Visual Acuity (BCVA)

Secondary study objectives

Aqueous ABBV-RGX-314 TP concentration (control arm participants who cross over to ABBV-RGX-314)

Aqueous ABBV-RGX-314 transgene product (TP) concentration (ABBV-RGX-314 randomized participants)

Immunogenicity measurements (ABBV-RGX-314 randomized participants)

+24 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: ABBV-RGX-314 Dose 2Experimental Treatment1 Intervention

ABBV-RGX-314 Dose 2 administered via subretinal delivery one time.

Group II: ABBV-RGX-314 Dose 1Experimental Treatment1 Intervention

ABBV-RGX-314 Dose 1 administered via subretinal delivery one time.

Group III: Control ArmActive Control1 Intervention

Aflibercept administered via intravitreal injection approximately every 8 weeks

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Age-Related Macular Degeneration (AMD) involve anti-VEGF (vascular endothelial growth factor) therapies. These treatments inhibit VEGF, a protein that stimulates the growth of abnormal blood vessels in the retina, which can leak and lead to vision loss in wet AMD. RGX-314, a gene therapy under investigation, aims to provide a sustained anti-VEGF effect through a one-time treatment, potentially reducing the need for frequent intraocular injections. This is crucial for AMD patients as it could enhance treatment adherence and maintain vision more effectively over the long term.