RGX-314 Gene Therapy for Wet Age-Related Macular Degeneration
(ATMOSPHERE Trial)
Recruiting in Palo Alto (17 mi)
+226 other locations
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.
12345Is 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.
12456How 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.
12345Eligibility 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
+3 more
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.
+6 more
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
Participant Groups
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.
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
Ranibizumab administered via intravitreal injection approximately every 28 days
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Portland LocationPortland, OR
Rapid City LocationRapid City, SD
Dallas LocationDallas, TX
Baltimore LocationBaltimore, MD
More Trial Locations
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Who Is Running the Clinical Trial?
REGENXBIO, Inc.Lead Sponsor
Regenxbio Inc.Lead Sponsor
AbbVieLead Sponsor
REGENXBIO Inc.Industry Sponsor
References
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]Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related macular degeneration with a single subretinal injection.
Gene therapy for age-related macular degeneration. [2018]In neovascular age related macular degeneration (nAMD), gene therapy to chronically express anti-vascular endothelial growth factor (VEGF) proteins could ameliorate the treatment burden of chronic intravitreal therapy and improve limited visual outcomes associated with 'real world' undertreatment. Areas covered: In this review, the authors assess the evolution of gene therapy for AMD. Adeno-associated virus (AAV) vectors can transduce retinal pigment epithelium; one such early application was a phase I trial of AAV2-delivered pigment epithelium derived factor gene in advanced nAMD. Subsequently, gene therapy for AMD shifted to the investigation of soluble fms-like tyrosine kinase-1 (sFLT-1), an endogenously expressed VEGF inhibitor, binding and neutralizing VEGF-A. After some disappointing results, research has centered on novel vectors, including optimized AAV2, AAV8 and lentivirus, as well as genes encoding other anti-angiogenic proteins, including ranibizumab, aflibercept, angiostatin and endostatin. Also, gene therapy targeting the complement system is being investigated for geographic atrophy due to non-neovascular AMD. Expert opinion: The success of gene therapy for AMD will depend on the selection of the most appropriate therapeutic protein and its level of chronic expression. Future investigations will center on optimizing vector, promoter and delivery methods, and evaluating the risks of the chronic expression of anti-angiogenic or anti-complement proteins.
Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. [2022]Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal blood vessels growing into the subretinal space, leading to retinal pigment epithelial (RPE) cell degeneration and vision loss. Vessel growth results from an imbalance of pro-angiogenic (e.g., vascular endothelial growth factor [VEGF]) and anti-angiogenic factors (e.g., pigment epithelium-derived factor [PEDF]). Current treatment using intravitreal injections of anti-VEGF antibodies improves vision in about 30% of patients but may be accompanied by side effects and non-compliance. To avoid the difficulties posed by frequent intravitreal injections, we have proposed the transplantation of pigment epithelial cells modified to overexpress human PEDF. Stable transgene integration and expression is ensured by the hyperactive Sleeping Beauty transposon system delivered by pFAR4 miniplasmids, which have a backbone free of antibiotic resistance markers. We demonstrated efficient expression of the PEDF gene and an optimized PEDF cDNA sequence in as few as 5 × 103 primary cells. At 3 weeks post-transfection, PEDF secretion was significantly elevated and long-term follow-up indicated a more stable secretion by cells transfected with the optimized PEDF transgene. Analysis of transgene insertion sites in human RPE cells showed an almost random genomic distribution. The results represent an important contribution toward a clinical trial aiming at a non-viral gene therapy of nvAMD.
Review of gene therapies for age-related macular degeneration. [2023]Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.
Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. [2022]We present the results of a Phase 2a randomized controlled trial investigating the safety, and secondary endpoints of subretinal rAAV.sFLT-1 gene therapy in patients with active wet age-related macular degeneration (wAMD).
Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. [2022]Human gene therapy with rAAV2-vector was performed for the RPE65 form of childhood blindness called Leber congenital amaurosis. In three contemporaneous studies by independent groups, the procedure was deemed safe and there was evidence of visual gain in the short term. At 12 months after treatment, our young adult subjects remained healthy and without vector-related serious adverse events. Results of immunological assays to identify reaction to AAV serotype 2 capsid were unchanged from baseline measurements. Results of clinical eye examinations of study and control eyes, including visual acuities and central retinal structure by in vivo microscopy, were not different from those at the 3-month time point. The remarkable improvements in visual sensitivity we reported by 3 months were unchanged at 12 months. The retinal extent and magnitude of rod and cone components of the visual sensitivity between 3 and 12 months were also the same. The safety and efficacy of human retinal gene transfer with rAAV2-RPE65 vector extends to at least 1 year posttreatment.