RGX-314 Gene Therapy for Age-Related Macular Degeneration

(ASCENT Trial)

Recruiting at 355 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: One-time treatment for ABBV-RGX-314; every 8 weeks for aflibercept

660 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new one-time gene therapy called RGX-314 for individuals with wet age-related macular degeneration (AMD), a condition that can cause vision loss due to leaky blood vessels in the eye. The goal is to determine if this treatment can help maintain vision without the frequent eye injections required by current treatments. Participants will receive either the new gene therapy or the standard treatment of regular eye injections. Those living with wet AMD and receiving regular anti-VEGF treatments might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have been previously treated with anti-VEGF therapy, suggesting that continuing this treatment might be necessary.

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

Research has shown that RGX-314, a gene therapy, could be promising for treating wet age-related macular degeneration (AMD). In earlier studies, this treatment reduced the need for frequent eye injections by 97% over nine months, suggesting it might serve as a convenient one-time option.

Regarding safety, the data is reassuring. Most participants did not experience serious problems. Among many patients, only one encountered a serious eye-related issue potentially linked to the treatment—a change in eye color that did not cause vision loss.

Overall, the treatment appears well-tolerated. However, as with any new therapy, potential risks must be considered. Ongoing research aims to confirm these safety findings and ensure the treatment's long-term safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RGX-314 for age-related macular degeneration because it introduces a novel gene therapy approach, potentially offering longer-lasting effects with a single treatment. Unlike standard treatments like aflibercept, which require regular eye injections every 8 weeks, RGX-314 is delivered just once directly to the retina, which could significantly reduce the treatment burden for patients. This therapy works by modifying the cells in the retina to produce a therapeutic protein themselves, potentially providing sustained benefits and improved vision over time.

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

Research shows that RGX-314 gene therapy could be a promising treatment for wet age-related macular degeneration (AMD). In this trial, participants may receive one of two doses of RGX-314. Earlier studies showed a 97% reduction in the need for eye injections after nine months. This therapy controls the growth of abnormal blood vessels in the retina, a major issue in wet AMD, by delivering a gene that reduces VEGF-A, a protein promoting blood vessel growth. Early results suggest that RGX-314 can help maintain vision and manage eye fluid effectively over time. ^{1 2 3 4 6}

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 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.

Inclusion Criteria

I had cataract surgery in my study eye more than 12 weeks ago.

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

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

Exclusion Criteria

Any condition in the investigator's opinion that could limit VA improvement in the study eye

I have previously undergone gene therapy.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABBV-RGX-314 gene therapy via subretinal delivery or aflibercept via intravitreal injection

One-time treatment for ABBV-RGX-314; every 8 weeks for aflibercept

1 visit for ABBV-RGX-314, multiple visits for aflibercept

Follow-up

Participants are monitored for safety and effectiveness after treatment

54 weeks

Regular visits for monitoring

Extension

Control arm participants may cross over to receive ABBV-RGX-314 and are monitored

54 weeks

Regular visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• RGX-314

Trial Overview 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.

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

Aflibercept administered via intravitreal injection approximately every 8 weeks

Who Is Running the Clinical Trial?

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.

Lead Sponsor

Trials

20

Recruited

2,800+

Regenxbio Inc.

Lead Sponsor

Trials

20

Recruited

2,800+

REGENXBIO Inc.

Industry Sponsor

Trials

25

Recruited

3,100+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. 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 ...

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. 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, ...

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.

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04514653

Study Details | NCT04514653 | RGX-314 Gene Therapy ... 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 ...