Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD
- Conditions
- nAMDwAMDWet Age-related Macular DegenerationCNVWetAMDAMD
- Interventions
- Registration Number
- NCT05407636
- Lead Sponsor
- AbbVie
- Brief Summary
ABBV-RGX-314 (also known as RGX-314) is being developed as a novel one-time gene therapy 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-vascular endothelial growth factor (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 12 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. ABBV-RGX-314 is being developed as a potential one-time treatment for wet AMD.
- Detailed Description
This randomized, partially masked, controlled, Phase 3 clinical study will evaluate the efficacy and safety of ABBV-RGX-314 gene therapy in participants with nAMD. The study will evaluate 2 dose levels of RGX-314 gene therapy relative to an active comparator. The primary endpoint of this study is mean change in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to aflibercept. Approximately 660 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 660
- Age ≥ 50 years and ≤ 89 years
- An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye
- Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in the study eye previously treated with anti-VEGF
- Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye
- Willing and able to provide written, signed informed consent for this study
- Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry
- CNV or macular edema in the study eye secondary to any causes other than AMD
- Subfoveal fibrosis or atrophy in the study eye
- Any condition in the investigator's opinion that could limit VA improvement in the study eye
- Active or history of retinal detachment, or current retinal tear that cannot be treated, in the study eye
- Advanced glaucoma or history of secondary glaucoma in the study eye
- Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.
- History of intraocular surgery in the study eye within 12 weeks prior to randomization
- History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening Visit 1.
- Prior treatment with gene therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABBV-RGX-314 Dose 1 ABBV-RGX-314 Dose 1 ABBV-RGX-314 Dose 1 administered via subretinal delivery one time. ABBV-RGX-314 Dose 2 ABBV-RGX-314 Dose 2 ABBV-RGX-314 Dose 2 administered via subretinal delivery one time. Control Arm Aflibercept (EYLEA®) Aflibercept administered via intravitreal injection approximately every 8 weeks
- Primary Outcome Measures
Name Time Method Mean change from baseline in Best Corrected Visual Acuity (BCVA) At Week 54 BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
- Secondary Outcome Measures
Name Time Method Time to first supplemental anti-VEGF injection after the Week 2 injection (ABBV-RGX-314 randomized participants) Through Week 54 Time to first supplemental anti-VEGF injection
Time to first supplemental anti-VEGF injection after the Week 58 injection in the control arm participants who cross over to ABBV-RGX-314 After Week 58 through Week 108 Time to first supplemental anti-VEGF injection
Mean change from baseline in NEI VFQ-25 (composite score) Week 54 and Week 108 Mean change in NEI VFQ-25 (composite score) at Week 54 and (control arm participants who cross over to ABBV-RGX-314) Week 108
Mean change from baseline in MacTSQ (composite score) Week 54 and Week 108 Mean change from baseline in MacTSQ (composite score) at week 54 and (control arm participants who cross over to ABBV-RGX-314) at Week 108
Aqueous ABBV-RGX-314 transgene product (TP) concentration (ABBV-RGX-314 randomized participants) Week -2, Week 14, Week 38, and Week 54 Aqueous ABBV-RGX-314 TP concentration
Aqueous ABBV-RGX-314 TP concentration (control arm participants who cross over to ABBV-RGX-314) Week 54, Week 74, Week 90, and Week 108 Aqueous ABBV-RGX-314 TP concentration
Serum ABBV-RGX-314 TP concentrations (at select sites) Week -2, Week 14, Week 38, and Week 54 Serum ABBV-RGX-314 TP concentration
Immunogenicity measurements (ABBV-RGX-314 randomized participants) Week -2, Week 14, Week 38, and Week 54 Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX-314 TP)
Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314) Week 54, Week 74, Week 90, and Week 108 Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX-314 TP)
Proportion of participants with ≤ 2 supplemental anti-VEGF injections Through Week 54 (ABBV-RGX-314 randomized participants only) Proportion of supplemental anti-VEGF injections
Proportion of participants with no supplemental anti-VEGF injections Through Week 54 (ABBV-RGX-314 randomized participants only) Proportion of supplemental anti-VEGF injections
Percent reduction in anti-VEGF injection annualized rate compared with the prior year Through Week 54 (ABBV-RGX-314 randomized participants only) Supplemental anti-VEGF treatments required
Mean change from Baseline in BCVA Week 54 BCVA measured by ETDRS
Incidences of ocular and overall SAEs over 54 weeks Through Week 54 AEs over 54 weeks
Proportion of participants with worsened BCVA Week 54 Proportion with worsened BCVA
Proportion of participants with improved BCVA Week 54 Proportion with improved BCVA
Proportion of participants (1) gaining or losing greater than 0 letters; (2) maintaining vision compared with baseline as per BCVA Week 54 Proportion gaining or losing greater than 0 letters based on ETDRS score; proportion maintaining vision
Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injection (ABBV-RGX-314 randomized participants) Week 54 Mean change in BCVA based on ETDRS score for participants who received 0 or more supplemental anti-VEGF injection
Mean change from Week 54 to Week 108 in BCVA (control arm participants who cross over to ABBV-RGX-314) Week 54 to Week 108 Mean change in BCVA based on ETDRS score
Mean change from baseline in central retinal thickness (CRT) as measured by SD-OCT Week 54 Mean change in CRT as measured by SD-OCT
Mean change from Week 54 to Week 108 in CRT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) Week 54 to Week 108 Mean change in CRT as measured by SD-OCT
Mean change from baseline in center point thickness (CPT) as measured by SD-OCT Week 54 Mean change in CPT as measured by SD-OCT
Mean change from Week 54 to Week 108 in CPT, as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) Week 54 to Week 108 Mean change in CPT as measured by SD-OCT
Proportion of participants with a reduction in anti-VEGF injection annualized rate Through Week 54 Proportion of participants with a reduction in anti-VEGF injection annualized rate compared with the prior year
Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms Through Week 54 Supplemental anti-VEGF injection annualized rate
Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 108 relative to the year prior to the study (control arm participants who cross over to ABBV-RGX 314) After Week 58 to Week 108 Percent reduction in anti-VEGF injection annualized rate
Supplemental anti-VEGF injection annualized rate after Week 58 through Week 108 (control arm participants who cross over to ABBV-RGX-314) After Week 58 through Week 108 Supplemental anti-VEGF injection annualized rate
Trial Locations
- Locations (126)
Retina Macula Institute of Arizona
🇺🇸Scottsdale, Arizona, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Hamilton Glaucoma Center Shiley Eye Center UCSD
🇺🇸La Jolla, California, United States
Byers Eye Institute Stanford
🇺🇸Palo Alto, California, United States
Kaiser Permanente
🇺🇸Riverside, California, United States
Macula Retina Vitreous Center - Torrance
🇺🇸Torrance, California, United States
Bay Area Retina Associates
🇺🇸Walnut Creek, California, United States
Vitreoretinal Associates, P.A.
🇺🇸Gainesville, Florida, United States
Fort Lauderdale Eye Institute
🇺🇸Plantation, Florida, United States
Northwestern Medicine Fertility and Reproductive Medicine
🇺🇸Chicago, Illinois, United States
Retina Partners Midwest, PC
🇺🇸Carmel, Indiana, United States
Retina Associates, LLC
🇺🇸Lenexa, Kansas, United States
Greater Baltimore Medical Ctr
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Mid Atlantic Retina Specialists
🇺🇸Hagerstown, Maryland, United States
VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Mississippi Retina Associates
🇺🇸Jackson, Mississippi, United States
Midwest Vision Research Foundation
🇺🇸Chesterfield, Missouri, United States
University of Missouri - Mason Eye Institute
🇺🇸Columbia, Missouri, United States
Washington University Ophthalmology
🇺🇸Saint Louis, Missouri, United States
Graystone Eye
🇺🇸Hickory, North Carolina, United States
Retina Associates of Cleveland
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Vision Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Charleston Neuroscience Institute - Beaufort
🇺🇸Beaufort, South Carolina, United States
Charleston Neurosciences Institute
🇺🇸Ladson, South Carolina, United States
Black Hills Regional Eye Institute
🇺🇸Rapid City, South Dakota, United States
Austin Research Center for Retina
🇺🇸Austin, Texas, United States
RCTX - San Antonio Retina Center
🇺🇸San Antonio, Texas, United States
Stone Oak Surgery Center
🇺🇸San Antonio, Texas, United States
Retina Associates of Utah
🇺🇸Salt Lake City, Utah, United States
Vistar Eye Center
🇺🇸Salem, Virginia, United States
Retina Center NW, PLLC
🇺🇸Silverdale, Washington, United States
Alberta Retina Consultants
🇨🇦Edmonton, Alberta, Canada
University of British Columbia - Eye Care Centre, Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Toronto Retina Institute
🇨🇦North York, Ontario, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
CHU Nantes - Hopital Hotel Dieu Nantes
🇫🇷Nantes, Loire-Atlantique, France
Clinique Honoré Cave
🇫🇷Montauban, Midi-Pyrenees, France
Hopital de la Crois Rousse
🇫🇷Lyon, Rhone, France
Centre Hospitalier Intercommunal de Creteil
🇫🇷Créteil, Val-de-Marne, France
AP-HP - Groupe Hospitalier 10e - Hopital Lariboisiere
🇫🇷Paris, France
Hopitaux Universitaires Paris Centre-Hopital Cochin
🇫🇷Paris, France
University Medical Center Freiburg
🇩🇪Freiburg Im Breisgau, Baden-Wurttemberg, Germany
Universitatsklinikum Bonn
🇩🇪Bonn, Nordhein-Westfalen, Germany
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hajdu-Bihar, Hungary
Budapest Retina Intezet
🇭🇺Budapest, Hungary
Azienda Ospedaliero-Universitaria di Ferrara
🇮🇹Cona, Ferrara, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Rom, Italy
IRCCS Fondazione G.B. Bietti
🇮🇹Roma, Italy
Kobe City Eye Hospital
🇯🇵Kobe, Hyogo, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
University of Miyazaki Hospital
🇯🇵Miyazaki, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Hospital Arruzafa
🇪🇸Córdoba, Cordoba, Spain
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, Oxfordshire, United Kingdom
Liverpool University Hospitals NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Moorfields Eye Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
The Retina Clinic London
🇬🇧London, United Kingdom
Barnet Dulaney Perkins Eye Center
🇺🇸Mesa, Arizona, United States
Retinal Research Institute
🇺🇸Phoenix, Arizona, United States
California Retina Consultants
🇺🇸Bakersfield, California, United States
Retina Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Retinal Diagnostic Center
🇺🇸Campbell, California, United States
The Retina Partners
🇺🇸Encino, California, United States
Retina Consultants of San Diego
🇺🇸Poway, California, United States
Retinal Consultants Medical Group, Inc
🇺🇸Sacramento, California, United States
UC Davis
🇺🇸Sacramento, California, United States
Orange County Retina Medical Group
🇺🇸Santa Ana, California, United States
Retina Consultants of Southern Colorado P.C.
🇺🇸Colorado Springs, Colorado, United States
Southwest Retina Consultants
🇺🇸Durango, Colorado, United States
Colorado Retina Associates
🇺🇸Lakewood, Colorado, United States
Eye Care Center of Northern Colorado
🇺🇸Longmont, Colorado, United States
Rand Eye Institute
🇺🇸Deerfield Beach, Florida, United States
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
Vitreo Retinal Associates PA
🇺🇸Gainesville, Florida, United States
Florida Retina Consultants
🇺🇸Lakeland, Florida, United States
Florida Retina Institute
🇺🇸Orlando, Florida, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
Center for Retina and Macular Disease
🇺🇸Winter Haven, Florida, United States
Georgia Retina PC
🇺🇸Marietta, Georgia, United States
Retina Consultants of Hawaii
🇺🇸'Aiea, Hawaii, United States
University Retina and Macula Associates, P.C.
🇺🇸Lemont, Illinois, United States
Illinois Retina Associates
🇺🇸Oak Park, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
John-Kenyon American Eye Institute
🇺🇸New Albany, Indiana, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Maine Eye Center
🇺🇸Portland, Maine, United States
Massachusetts Eye and Ear Infirmary
🇺🇸Boston, Massachusetts, United States
Ophthalmic Consultants of Boston, Inc
🇺🇸Boston, Massachusetts, United States
Retina Associates of Michigan
🇺🇸Grand Blanc, Michigan, United States
Associated Retinal Consultants
🇺🇸Royal Oak, Michigan, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Envision Ocular, LLC
🇺🇸Bloomfield, New Jersey, United States
Columbia University Irving Medical Center - Harness Eye Institute
🇺🇸New York, New York, United States
Retina Associates of Western New York
🇺🇸Rochester, New York, United States
Western Carolina Retina Associates P.A.
🇺🇸Asheville, North Carolina, United States
Duke Eye Center
🇺🇸Durham, North Carolina, United States
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The Ohio State University Eye & Ear Institute
🇺🇸Columbus, Ohio, United States
Retina Vitreous Center Research
🇺🇸Edmond, Oklahoma, United States
Mid Atlantic Retina
🇺🇸Philadelphia, Pennsylvania, United States
Southeastern Retina Associates
🇺🇸Johnson City, Tennessee, United States
Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
Tennessee Retina Center Murfreesboro
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Austin Clinical Research, LLC
🇺🇸Austin, Texas, United States
Retina Consultants of Texas
🇺🇸Bellaire, Texas, United States
Star Retina
🇺🇸Burleson, Texas, United States
Ophthalmology Surgery Center of Dallas
🇺🇸Dallas, Texas, United States
Texas Retina Associates
🇺🇸Fort Worth, Texas, United States
Austin Retina Associates
🇺🇸Round Rock, Texas, United States
Retina Center of Texas - Southlake
🇺🇸Southlake, Texas, United States
Rocky Mountain Retina Consultants
🇺🇸Salt Lake City, Utah, United States
Piedmont Eye Center
🇺🇸Lynchburg, Virginia, United States
Wagner Macula & Retina Center
🇺🇸Norfolk, Virginia, United States
Pacific Northwest Retina
🇺🇸Bellevue, Washington, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States
Calgary Retina Consultants
🇨🇦Calgary, Alberta, Canada
Retina Centre of Ottawa
🇨🇦Ottawa, Ontario, Canada
CHU de Quebec-Universite Laval
🇨🇦Québec, Canada
Emanuelli Research and Development Center
🇵🇷Arecibo, Puerto Rico