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

(ATMOSPHERE Trial)

Recruiting at 226 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: REGENXBIO, Inc.

Must be taking: Anti-VEGF

Must not be taking: Intravitreal steroids

Disqualifiers: Retinal detachment, Advanced glaucoma, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

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.

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

Research on gene therapy for wet age-related macular degeneration suggests that using adeno-associated virus (AAV) vectors to deliver anti-VEGF proteins can reduce the need for frequent eye injections and improve vision outcomes. Studies have shown that similar gene therapies, like rAAV.sFLT-1, have been tested for safety and potential effectiveness in treating this condition. ^{1 2 3 4 5}

Is RGX-314 gene therapy safe for humans?

Research on gene therapy for wet age-related macular degeneration, including RGX-314, has shown it to be generally safe in humans, with no serious adverse events related to the treatment reported in clinical trials. ^{1 2 4 5 6}

How is the RGX-314 treatment different from other treatments for wet age-related macular degeneration?

RGX-314 is a gene therapy that aims to provide long-term treatment for wet age-related macular degeneration with a single administration, potentially reducing the need for frequent eye injections that are common with current treatments. It works by using a viral vector to deliver a gene that helps the eye produce its own anti-VEGF protein, which can help prevent vision loss. ^{1 2 3 4 5}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• RGX-314 (Gene Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. 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]

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

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

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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]