RGX-314 Gene Therapy for Age-Related Macular Degeneration
(AAVIATE Trial)
Recruiting in Palo Alto (17 mi)
+14 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: REGENXBIO, Inc.
Must be taking: Anti-VEGF
Must not be taking: Intravitreal steroids, Gene therapy
Disqualifiers: Retinal detachment, Glaucoma, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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 AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to twelve weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are on any investigational products or have had certain eye treatments recently, you may need to wait before joining the study.
What data supports the effectiveness of the treatment RGX-314 for age-related macular degeneration?
Gene therapies like RGX-314 aim to provide long-term treatment for age-related macular degeneration by delivering therapeutic genes to the eye, potentially reducing the need for frequent injections. Research on similar gene therapies has shown promise in targeting retinal diseases, suggesting that RGX-314 could offer a significant improvement in managing this condition.
12345Is RGX-314 gene therapy safe for humans?
Research on RGX-314 and similar gene therapies for age-related macular degeneration suggests they are generally safe, with no serious adverse events reported in clinical trials. These therapies use adeno-associated virus (AAV) vectors, which have been tested in other eye conditions and shown to be safe for at least one year post-treatment.
12367What makes the RGX-314 treatment unique for age-related macular degeneration?
RGX-314 is a gene therapy that offers a potentially long-lasting solution for age-related macular degeneration by delivering a therapeutic gene to the eye, reducing the need for frequent injections. Unlike traditional treatments that require regular administration, RGX-314 aims to provide sustained anti-VEGF (a protein that promotes blood vessel growth) therapy from a single treatment.
12389Eligibility Criteria
This trial is for people aged 50 to 89 with neovascular age-related macular degeneration (wet AMD) in one eye. They must have had a positive response to previous anti-VEGF therapy and be willing to consent to the study.Inclusion Criteria
You are between 50 and 89 years old.
You have a vision condition called "age-related macular degeneration" that has led to abnormal blood vessels in your study eye.
You are able to read and sign a document that explains the details of the study and agree to participate.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive RGX-314 gene therapy or ranibizumab control, with dose escalation across cohorts
52 weeks
Regular visits for treatment and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial tests RGX-314, a potential one-time gene therapy for wet AMD. It's compared against standard treatments like Ranibizumab. Participants will receive different doses of RGX-314 or local/topical steroids.
6Treatment groups
Experimental Treatment
Active Control
Group I: RGX-314 Treatment Arm (Dose 3) and Topical SteroidExperimental Treatment2 Interventions
RGX-314 Dose 3 and Topical Steroid
Group II: RGX-314 Treatment Arm (Dose 3) and Local SteroidExperimental Treatment2 Interventions
RGX-314 Dose 3 and Local Steroid
Group III: RGX-314 Treatment Arm (Dose 3)Experimental Treatment1 Intervention
RGX-314 Dose 3
Group IV: RGX-314 Treatment Arm (Dose 2)Experimental Treatment1 Intervention
RGX-314 Dose 2
Group V: RGX-314 Treatment Arm (Dose 1)Experimental Treatment1 Intervention
RGX-314 Dose 1
Group VI: Ranibizumab controlActive Control1 Intervention
Control treatment arm
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mountain View LocationMountain View, CA
Poway LocationPoway, CA
Phoenix LocationPhoenix, AZ
Albuquerque LocationAlbuquerque, NM
More Trial Locations
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Who Is Running the Clinical Trial?
REGENXBIO, Inc.Lead Sponsor
Regenxbio Inc.Lead Sponsor
REGENXBIO Inc.Lead Sponsor
AbbVieLead Sponsor
References
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.
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.
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).
Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives. [2012]Retinal degenerative diseases such as retinal macular degeneration and retinitis pigmentosa constitute a broad group of diseases that all share one critical feature, the progressive apoptotic loss of cells in the retina. There is currently no effective treatment available by which the course of these disorders can be modified, and visual dysfunction often progresses to total blindness. Gene therapy represents an attractive approach to treating retinal degeneration because the eye is easily accessible and allows local application of therapeutic vectors with reduced risk of systemic effects. Furthermore, transgene expression within the retina and effects of treatments may be monitored by a variety of noninvasive examinations. An increasing number of strategies for molecular treatment of retinal disease rely on recombinant adeno-associated virus (rAAV) as a therapeutic gene delivery vector. Before rAAV-mediated gene therapy for retinal degeneration becomes a reality, there are a number of important requirements that include: (1) evaluation of different rAAV serotypes, (2) screening of vectors in large animals in order to ensure that they mediate safe and long-term gene expression, (3) appropriate regulation of therapeutic gene expression, (4) evaluation of vectors carrying a therapeutic gene in relevant animal models, (5) identification of suitable patients, and finally (6) manufacture of clinical grade vector. All these steps towards gene therapy are still being explored. Outcomes of these studies will be discussed in the order in which they occur, from vector studies to preclinical assessment of the therapeutic potential of rAAV in animal models of retinal degeneration.
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.
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. [2022]To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human choroideremia (CHM)-encoding cDNA in CHM.
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.
Adeno-associated virus-vectored gene therapy for retinal disease. [2012]Recombinant adeno-associated viral (AAV) vectors have become powerful gene delivery tools for the treatment of retinal degeneration in a variety of animal models that mimic corresponding human diseases. AAV vectors possess a number of features that render them ideally suited for retinal gene therapy, including a lack of pathogenicity, minimal immunogenicity, and the ability to transduce postmitotic cells in a stable and efficient manner. In the sheltered environment of the retina, AAV vectors are able to maintain high levels of transgene expression in the retinal pigmented epithelium (RPE), photoreceptors, or ganglion cells for long periods of time after a single treatment. Each cell type can be specifically targeted by choosing the appropriate combination of AAV serotype, promoter, and intraocular injection site. The focus of this review is on examples of AAV-mediated gene therapy in those animal models of inherited retinal degeneration caused by mutations directly affecting the interacting unit formed by photoreceptors and the RPE. In each case discussed, expression of the therapeutic gene resulted in significant recovery of retinal structure and/or visual function. Because of the key role of the vasculature in maintaining a healthy retina, a summary of AAV gene therapy applications in animal models of retinal neovascular diseases is also included.