RGX-314 Gene Therapy for Wet Age-Related Macular Degeneration

(ATMOSPHERE Trial)

Recruiting at 309 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: REGENXBIO, Inc.

Must be taking: Anti-VEGF

Must not be taking: Intravitreal steroids

Disqualifiers: Retinal detachment, Advanced 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: 54 weeks

630 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an innovative gene therapy called RGX-314 for treating wet age-related macular degeneration (AMD), a condition that causes vision loss due to leaky blood vessels in the eye. The goal is to determine if a one-time treatment can improve vision and reduce the need for frequent injections required by current therapies. Participants will receive either one of two doses of RGX-314 or a standard treatment for comparison. Those treated with anti-VEGF injections for wet AMD and who have undergone at least one cataract surgery may be suitable for this trial. As a Phase 2/3 trial, this study evaluates RGX-314's effectiveness in a larger group and represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have been previously treated with anti-VEGF therapy, so you may need to continue with that treatment.

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

Research has shown that RGX-314, a gene therapy for wet age-related macular degeneration (AMD), was well-tolerated in earlier studies. In these studies, patients received a one-time injection under the retina. The results suggest that this treatment significantly reduces the need for frequent eye injections. Fewer injections mean fewer chances for complications, indicating a good safety profile.

The studies also consistently show that the treatment does not cause unexpected or severe side effects. While some patients might experience mild side effects typical of eye procedures, the overall safety results are promising. This suggests that RGX-314 could be a safer option compared to ongoing injections for managing wet AMD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for wet AMD?

Unlike the standard of care for wet age-related macular degeneration, which often involves regular intravitreal injections of anti-VEGF drugs like ranibizumab, RGX-314 is a gene therapy delivered just once via subretinal injection. This innovative approach uses a viral vector to deliver a gene that helps the eye produce its own anti-VEGF protein, potentially reducing or eliminating the need for frequent injections. Researchers are excited about RGX-314 because it represents a shift towards a longer-lasting treatment that could improve patients' quality of life by minimizing the burden of repeated medical visits.

What evidence suggests that RGX-314 might be an effective treatment for wet AMD?

Research has shown that RGX-314 is a promising one-time gene therapy for wet age-related macular degeneration (wet AMD). In this trial, participants will receive either RGX-314 at different doses or a control treatment. Specifically, studies found that patients who received RGX-314 needed 97% fewer eye injections after nine months. This therapy reduces a protein called VEGF-A, which causes harmful blood vessels to grow in the eye. By controlling this protein, RGX-314 can help maintain stable vision and reduce fluid buildup in the retina. Early results suggest that RGX-314 could significantly lessen the need for frequent treatments while preserving vision in people with wet AMD. ^{1 2 3 5 6}

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 50-89 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.

Inclusion Criteria

Willing and able to provide written, signed informed consent for this study

I am between 50 and 89 years old.

An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye

Exclusion Criteria

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

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

I have not had any eye injections except for anti-VEGF in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time subretinal delivery of ABBV-RGX-314 gene therapy or control treatment with ranibizumab administered approximately every 28 days

54 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

44 weeks

Extension

Participants may continue to be monitored for long-term safety and efficacy outcomes

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• RGX-314

Trial Overview 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.

How Is the Trial Designed?

Group I: ABBV-RGX-314 Dose 2 Experimental Treatment 1 Intervention

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

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

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

Group III: Control Arm Active Control 1 Intervention

Ranibizumab administered via intravitreal injection approximately every 28 days

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]

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]

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]

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]

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]

Citations

1. 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.

2. thelancet.com 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05407636

NCT05407636 | Pivotal 2 Study of RGX-314 Gene Therapy ... This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of ABBV-RGX-314 gene therapy in participants with ...

4. ir.regenxbio.com 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 ...

5. pubmed.ncbi.nlm.nih.gov 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, ...

6. clinicaltrials.gov 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 ...