What is the mechanism of action of this treatment?

The most common treatments for Age-Related Macular Degeneration (AMD) include anti-VEGF (vascular endothelial growth factor) therapies, which work by inhibiting the growth of abnormal blood vessels in the retina that cause vision loss. These treatments, such as ranibizumab and aflibercept, require frequent intraocular injections to maintain their efficacy. RGX-314, a gene therapy under investigation, aims to provide a one-time treatment that enables sustained anti-VEGF expression, potentially reducing the treatment burden and improving long-term outcomes for patients. This is significant for AMD patients as it could lead to more consistent management of the disease and better preservation of vision with fewer interventions.

What side effects are associated with this type of intervention?

The most common treatments for Age-Related Macular Degeneration (AMD) involve anti-VEGF therapies such as ranibizumab, aflibercept, and bevacizumab, which are administered via intraocular injections. Common side effects include eye pain, vitreous floaters, increased intraocular pressure, and inflammation. Rare but serious side effects can include retinal detachment, endophthalmitis, and intraocular hemorrhage. Gene therapy like RGX-314 aims to provide a one-time treatment to reduce the frequency of these injections, potentially minimizing the associated risks.

What prior FDA approvals exist?

FDA-approved treatments for Age-Related Macular Degeneration (AMD) primarily include anti-VEGF therapies such as ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin, used off-label). These drugs inhibit vascular endothelial growth factor (VEGF) to prevent the formation of new, leaky blood vessels in the retina, requiring frequent intraocular injections. RGX-314 is a novel gene therapy under investigation that aims to provide sustained anti-VEGF expression with a one-time treatment, potentially reducing the need for repeated injections.

What other types of research exist?

Promising alternatives to RGX-314 for AMD treatment include: 1) Bevacizumab combined with other agents like capecitabine, which has shown efficacy in clinical trials. 2) Patisiran, an RNAi therapeutic, which has demonstrated benefits in reducing protein deposits in tissues. 3) Vutrisiran, another siRNA treatment, which targets mutant and wild-type TTR mRNA, reducing serum TTR protein levels. These therapies offer potential sustained benefits and reduced treatment frequency.

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Gene Therapy

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

Phase 2 & 3

Recruiting

Research Sponsored by REGENXBIO, Inc.

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

Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.

History of intraocular surgery in the study eye within 12 weeks prior to Screening Visit 1

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at week 98 (rgx-314 randomized participants only)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new one-time gene therapy called RGX-314 for patients with wet AMD. It aims to help the eye make its own medicine to stop harmful blood vessels from causing vision loss. This could reduce the need for regular injections. RGX-314 modifies the retina's cells to create a treatment that may only be needed once.

Who is the study for?

This trial is for people aged 50-89 with wet age-related macular degeneration (AMD) who've had a positive response to anti-VEGF therapy. They must have certain vision scores, be pseudophakic post-cataract surgery, and able to consent. Excluded are those with other eye conditions or treatments, gene therapy history, or recent severe cardiovascular events.

What is being tested?

The study tests RGX-314, a potential one-time gene therapy for wet AMD against Ranibizumab (LUCENTIS®), the current standard requiring frequent injections. The goal is to see if RGX-314 can maintain vision without regular treatments.

What are the potential side effects?

While specific side effects of RGX-314 aren't listed here, gene therapies may cause immune reactions, changes in vision, discomfort at injection site or inflammation inside the eye.

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 have shown improvement with anti-VEGF therapy.

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

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I have not had eye surgery in the past 3 months.

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I have or had a detached retina in my eye being studied.

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My glaucoma in one eye is not under control.

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

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

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I have previously undergone gene therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at week 98 (rgx-314 randomized participants only)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at week 98 (rgx-314 randomized participants only)

This trial's timeline: 3 weeks for screening, Varies for treatment, and at week 98 (rgx-314 randomized participants only) 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

Incidences of ocular and overall adverse events (AEs)

Mean change from baseline in BCVA

Side effects data

From 2021 Phase 1 & 2 trial • 42 Patients • NCT03066258

67%

Retinal Haemorrhage

67%

Intraocular Inflammation

50%

Visual Acuity Reduced/Impairment

33%

Conjunctival Haemorrhage

33%

Photopsia

17%

Pneumonia

17%

Eye Pain

17%

Hypervolaemia

17%

Arthritis

17%

Respiratory Failure

17%

Intraocular Pressure Increased

17%

Vision Blurred

17%

Dry Age-Related Macular Degeneration

17%

Photophobia

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1

Cohort 4

Cohort 2

Cohort 3

Cohort 5

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: RGX-314 Dose 2Experimental Treatment1 Intervention

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

Group II: RGX-314 Dose 1Experimental Treatment1 Intervention

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

Group III: Control ArmActive Control1 Intervention

Ranibizumab administered via intravitreal injection approximately every 28 days

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

RGX-314

2021

Completed Phase 2

~110

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) include anti-VEGF (vascular endothelial growth factor) therapies, which work by inhibiting the growth of abnormal blood vessels in the retina that cause vision loss. These treatments, such as ranibizumab and aflibercept, require frequent intraocular injections to maintain their efficacy. RGX-314, a gene therapy under investigation, aims to provide a one-time treatment that enables sustained anti-VEGF expression, potentially reducing the treatment burden and improving long-term outcomes for patients. This is significant for AMD patients as it could lead to more consistent management of the disease and better preservation of vision with fewer interventions.