Aug. 04, 2023
Neovascular age-related macular degeneration, also called wet age-related macular degeneration (wet AMD), is the most common cause of severe vision loss across the globe. The disease impacts close to 2 million people in the United States, Europe and Japan alone. In patients with wet AMD, newly formed leaky blood vessels in their retinas diminish vision over time.
Although anti-vascular endothelial growth factor (VEGF) therapies are the current standard of care to help prevent the progression of vision loss, these therapies require intravitreal injections that need to be repeated every 4 to 12 weeks for the rest of the patient's life — a rigorous treatment schedule that often can't be maintained for the long haul. As a result, as the treatment schedule lessens over time, so does the patient's ability to see.
Sophie J. Bakri, M.D., an ophthalmologist at Mayo Clinic in Rochester, Minnesota, performed the first subretinal gene therapy at Mayo Clinic as part of a clinical study of RGX-314 as a potential one-time gene therapy for the treatment of wet AMD.
"This gene therapy is delivered surgically, by performing a pars plana vitrectomy and then injecting, under the retina, an AAV8 vector containing a gene encoding for a monoclonal antibody fragment," says Dr. Bakri. "The expressed protein is designed to neutralize vascular endothelial growth factor (VEGF) activity. Anti-VEGF therapy is an established treatment for wet macular degeneration, but currently is delivered by repeated injections. Mayo Clinic is participating in this pivotal clinical trial, and we are pleased to offer this novel therapeutic to patients enrolled."
This randomized, partially masked Mayo Clinic clinical study will evaluate the safety and effectiveness of two dose levels of RGX-314 relative to monthly intravitreal ranibizumab injections. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of RGX-314 relative to ranibizumab. Approximately 300 participants who meet the criteria will be enrolled into one of three arms.
"This trial is important because it uses gene therapy to address an unmet need for the treatment of macular degeneration — reducing the burden of intravitreal injections on the patient and caregiver," says Dr. Bakri. "There is hope that gene therapy could provide a one-time treatment for wet macular degeneration, and this trial will give us important information as to efficacy and safety."
Participation eligibility
Participant eligibility includes age, gender, type and stage of disease, as well as previous treatments or health concerns. Guidelines differ from study to study, but all participants must be able to comply with all study procedures and be available for the duration of the study.
Objectives and criteria
The primary objective of this study is to evaluate mean change in BCVA of RGX-314 relative to ranibizumab at week 38, as well as the safety and patient tolerability of RGX-314 through week 102. Overall, this clinical study will evaluate:
- The effectiveness of RGX-314 relative to ranibizumab on BCVA.
- The effectiveness of RGX-314 relative to ranibizumab on central retinal thickness (CRT) as measured by spectral domain-ocular coherence tomography (SD-OCT).
- The effectiveness of RGX-314 relative to ranibizumab on center point thickness (CPT) as measured by SD-OCT.
- The need for supplemental anti-VEGF therapy in the RGX-314 treatment arms.
- Aqueous protein concentrations of RGX-314.
- The immunogenicity of RGX-314.
During phases 1 and 2 of this clinical study, researchers will assess the safety, side effects and optimal dosages, as well as the risks and benefits of this novel treatment. In phase 3, they will determine whether the treatment works better than the current standard therapy.
Mayo Clinic receives research funding for the Regenxbio clinical trial. Dr. Bakri has served as a scientific advisor for AbbVie, Adverum, EyePoint, Novartis, Outlook Therapeutics, Ocular Therapeutix, Regeneron and Roche.
For more information
A Study to Evaluate Gene Therapy to Treat Neovascular Age-related Macular Degeneration. Mayo Clinic.
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