Clinical trial NCT05407636: Pivotal 2 Study of RGX-314 Gene Therapy in Participants With nAMD
Official title: A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: AMD
nAMD
Wet Age-related Macular Degeneration
wAMD
WetAMD
CNV
Keywords: Age-Related Macular Degeneration
Neovascular Age-Related Macular Degeneration
Macular Degeneration
Wet Macular Degeneration
Choroidal Neovascularization
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
Aflibercept
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Gene Therapy
Anti-vascular endothelial grown factory therapy
Anti-VEGF therapy
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: REGENXBIO Inc.
First posted: 2022-06-07
Enrollment: 660
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 ABBV-RGX-314 treatment arms, 1 control arm (aflibercept)
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 50 years and ≤ 89 years
2. An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye
3. Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in the study eye previously treated with anti-VEGF
4. Must be pseudophakic (at least 12 weeks postcataract surgery) in the study eye
5. Willing and able to provide written, signed informed consent for this study
6. Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry

Exclusion Criteria:

1. CNV or macular edema in the study eye secondary to any causes other than AMD
2. Subfoveal fibrosis or atrophy in the study eye
3. Any condition in the investigator's opinion that could limit VA improvement in the study eye
4. Active or history of retinal detachment, or current retinal tear that cannot be treated, in the study eye
5. Advanced glaucoma or history of secondary glaucoma in the study eye
6. Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months.
7. History of intraocular surgery in the study eye within 12 weeks prior to randomization
8. 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.
9. Prior treatment with gene therapy.

Primary outcomes:
measure: Mean change from baseline in Best Corrected Visual Acuity (BCVA)
timeFrame: At Week 54
Secondary outcomes:
measure: Proportion of participants with ≤ 2 supplemental anti-VEGF injections
timeFrame: Through Week 54 (ABBV-RGX-314 randomized participants only)
measure: Proportion of participants with no supplemental anti-VEGF injections
timeFrame: Through Week 54 (ABBV-RGX-314 randomized participants only)
measure: Percent reduction in anti-VEGF injection annualized rate compared with the prior year
timeFrame: Through Week 54 (ABBV-RGX-314 randomized participants only)
measure: Mean change from Baseline in BCVA
timeFrame: Week 54
measure: Incidences of ocular and overall SAEs over 54 weeks
timeFrame: Through Week 54
measure: Proportion of participants with worsened BCVA
timeFrame: Week 54
measure: Proportion of participants with improved BCVA
timeFrame: Week 54
measure: Proportion of participants (1) gaining or losing greater than 0 letters; (2) maintaining vision compared with baseline as per BCVA
timeFrame: Week 54
measure: Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injection (ABBV-RGX-314 randomized participants)
timeFrame: Week 54
measure: Mean change from Week 54 to Week 108 in BCVA (control arm participants who cross over to ABBV-RGX-314)
timeFrame: Week 54 to Week 108
measure: Mean change from baseline in central retinal thickness (CRT) as measured by SD-OCT
timeFrame: Week 54
measure: 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)
timeFrame: Week 54 to Week 108
measure: Mean change from baseline in center point thickness (CPT) as measured by SD-OCT
timeFrame: Week 54
measure: 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)
timeFrame: Week 54 to Week 108
measure: Proportion of participants with a reduction in anti-VEGF injection annualized rate
timeFrame: Through Week 54
measure: Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms
timeFrame: Through Week 54
measure: 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)
timeFrame: After Week 58 to Week 108
measure: Supplemental anti-VEGF injection annualized rate after Week 58 through Week 108 (control arm participants who cross over to ABBV-RGX-314)
timeFrame: After Week 58 through Week 108
measure: Time to first supplemental anti-VEGF injection after the Week 2 injection (ABBV-RGX-314 randomized participants)
timeFrame: Through Week 54
measure: Time to first supplemental anti-VEGF injection after the Week 58 injection in the control arm participants who cross over to ABBV-RGX-314
timeFrame: After Week 58 through Week 108
measure: Mean change from baseline in NEI VFQ-25 (composite score)
timeFrame: Week 54 and Week 108
measure: Mean change from baseline in MacTSQ (composite score)
timeFrame: Week 54 and Week 108
measure: Aqueous ABBV-RGX-314 transgene product (TP) concentration (ABBV-RGX-314 randomized participants)
timeFrame: Week -2, Week 14, Week 38, and Week 54
measure: Aqueous ABBV-RGX-314 TP concentration (control arm participants who cross over to ABBV-RGX-314)
timeFrame: Week 54, Week 74, Week 90, and Week 108
measure: Serum ABBV-RGX-314 TP concentrations (at select sites)
timeFrame: Week -2, Week 14, Week 38, and Week 54
measure: Immunogenicity measurements (ABBV-RGX-314 randomized participants)
timeFrame: Week -2, Week 14, Week 38, and Week 54
measure: Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)
timeFrame: Week 54, Week 74, Week 90, and Week 108
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Retinal Research Institute
state: Arizona
city: Scottsdale
country: United States
facility: Retina Macula Institute of Arizona
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates Medical Group
state: California
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: La Jolla
country: United States
facility: Hamilton Glaucoma Center Shiley Eye Center UCSD
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute Stanford
state: California
city: Poway
country: United States
facility: Retina Consultants of San Diego
state: California
city: Riverside
country: United States
facility: Kaiser Permanente
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group, Inc
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Medical Group
state: California
city: Torrance
country: United States
facility: Macula Retina Vitreous Center - Torrance
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado P.C.
state: Colorado
city: Durango
country: United States
facility: Southwest Retina Consultants
state: Colorado
city: Lakewood
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Longmont
country: United States
facility: Eye Care Center of Northern Colorado
state: Colorado
city: Deerfield Beach
country: United States
facility: Rand Eye Institute
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Gainesville
country: United States
facility: Vitreo Retinal Associates PA
state: Florida
city: Gainesville
country: United States
facility: Vitreoretinal Associates, P.A.
state: Florida
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Marietta
country: United States
facility: Georgia Retina PC
state: Georgia
city: 'Aiea
country: United States
facility: Retina Consultants of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Medicine Fertility and Reproductive Medicine
state: Illinois
city: Lemont
country: United States
facility: University Retina and Macula Associates, P.C.
state: Illinois
city: Oak Park
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Carmel
country: United States
facility: Retina Partners Midwest, PC
state: Indiana
city: New Albany
country: United States
facility: John-Kenyon American Eye Institute
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Lenexa
country: United States
facility: Retina Associates, LLC
state: Kansas
city: Portland
country: United States
facility: Maine Eye Center
state: Maine
city: Baltimore
country: United States
facility: Greater Baltimore Medical Ctr
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Hagerstown
country: United States
facility: Mid Atlantic Retina Specialists
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston, Inc
state: Massachusetts
city: Grand Blanc
country: United States
facility: Retina Associates of Michigan
state: Michigan
city: Royal Oak
country: United States
facility: Associated Retinal Consultants
state: Michigan
city: Minneapolis
country: United States
facility: VitreoRetinal Surgery PLLC DBA Retina Consultants of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: Mississippi Retina Associates
state: Mississippi
city: Chesterfield
country: United States
facility: Midwest Vision Research Foundation
state: Missouri
city: Columbia
country: United States
facility: University of Missouri - Mason Eye Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Ophthalmology
state: Missouri
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Envision Ocular, LLC
state: New Jersey
city: New York
country: United States
facility: Columbia University Irving Medical Center - Harness Eye Institute
state: New York
city: Rochester
country: United States
facility: Retina Associates of Western New York
state: New York
city: Asheville
country: United States
facility: Western Carolina Retina Associates P.A.
state: North Carolina
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Hickory
country: United States
facility: Graystone Eye
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Cleveland
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Eye & Ear Institute
state: Ohio
city: Edmond
country: United States
facility: Retina Vitreous Center Research
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Vision Institute
state: Pennsylvania
city: Beaufort
country: United States
facility: Charleston Neuroscience Institute - Beaufort
state: South Carolina
city: Charleston
country: United States
facility: Charleston Neurosciences Institute
state: South Carolina
city: Ladson
country: United States
facility: Charleston Neurosciences Institute
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Chattanooga
country: United States
facility: Southeastern Retina Associates
state: Tennessee
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Johnson City
country: United States
facility: Southeastern Retina Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Retina Center Murfreesboro
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Research Center for Retina
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research, LLC
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Burleson
country: United States
facility: Star Retina
state: Texas
city: Dallas
country: United States
facility: Ophthalmology Surgery Center of Dallas
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Round Rock
country: United States
facility: Austin Retina Associates
state: Texas
city: San Antonio
country: United States
facility: RCTX - San Antonio Retina Center
state: Texas
city: San Antonio
country: United States
facility: Stone Oak Surgery Center
state: Texas
city: Southlake
country: United States
facility: Retina Center of Texas - Southlake
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates of Utah
state: Utah
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Norfolk
country: United States
facility: Wagner Macula & Retina Center
state: Virginia
city: Salem
country: United States
facility: Vistar Eye Center
state: Virginia
city: Bellevue
country: United States
facility: Pacific Northwest Retina
state: Washington
city: Silverdale
country: United States
facility: Retina Center NW, PLLC
state: Washington
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Calgary
country: Canada
facility: Calgary Retina Consultants
state: Alberta
city: Edmonton
country: Canada
facility: Alberta Retina Consultants
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia - Eye Care Centre, Vancouver General Hospital
state: British Columbia
city: North York
country: Canada
facility: Toronto Retina Institute
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Ottawa
country: Canada
facility: Retina Centre of Ottawa
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Québec
country: Canada
facility: CHU de Quebec-Universite Laval
state: Quebec
city: Nantes
country: France
facility: CHU Nantes - Hopital Hotel Dieu Nantes
state: Loire-Atlantique
city: Montauban
country: France
facility: Clinique Honoré Cave
state: Midi-Pyrenees
city: Lyon
country: France
facility: Hopital de la Crois Rousse
state: Rhone
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Creteil
state: Val-de-Marne
city: Paris
country: France
facility: AP-HP - Groupe Hospitalier 10e - Hopital Lariboisiere
city: Paris
country: France
facility: Hopitaux Universitaires Paris Centre-Hopital Cochin
city: Freiburg Im Breisgau
country: Germany
facility: University Medical Center Freiburg
state: Baden-Wurttemberg
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
state: Nordhein-Westfalen
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
state: Hajdu-Bihar
city: Budapest
country: Hungary
facility: Budapest Retina Intezet
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara
state: Ferrara
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Rom
city: Roma
country: Italy
facility: IRCCS Fondazione G.B. Bietti
city: Kobe
country: Japan
facility: Kobe City Eye Hospital
state: Hyogo
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Miyazaki
country: Japan
facility: University of Miyazaki Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center
city: Córdoba
country: Spain
facility: Hospital Arruzafa
state: Cordoba
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: Oxfordshire
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: The Retina Clinic London
Study officials:
References: