Pivotal 1 Study of ABBV-RGX-314 (Also Known as RGX-314) Gene Therapy Administered Via Subretinal Delivery One Time in Participants With nAMD
- Conditions
- AMDnAMDWet Age-related Macular DegenerationNeovascular AMDwAMDWet AMDCNVNeovascular Age-related Macular DegenerationChoroidal Neovascularization
- Interventions
- Registration Number
- NCT04704921
- 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 or nAMD). 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 (anti-VEGF) therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to maintain or prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every 4 to 16 weeks in frequency, to maintain efficacy. Due to the burden of these treatments, patients often experience a decline in vision with reduced frequency of treatment over time.
- Detailed Description
This randomized, partially masked, active-controlled, Phase 2b/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 ABBV-RGX-314 relative to an active comparator. The primary endpoint of this study is the mean change from baseline in best-corrected visual acuity (BCVA) of ABBV-RGX-314 relative to ranibizumab at Week 54. Approximately 540 participants who meet the inclusion/exclusion criteria, will be enrolled into one of 3 arms.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 540
- Age ≥ 50 years and ≤ 89 years
- An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye
- Diagnosis of subfoveal 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, as determined by CRC
- 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
- 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
- Recent myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABBV-RGX-314 Dose 1 ABBV-RGX-314 ABBV-RGX-314 Dose 1 administered via subretinal delivery one time. ABBV-RGX-314 Dose 2 ABBV-RGX-314 ABBV-RGX-314 Dose 2 administered via subretinal delivery one time. Control Arm Ranibizumab (LUCENTIS®) Ranibizumab administered via intravitreal injection approximately every 28 days Control Arm Ranibizumab (LUCENTIS®) Ranibizumab administered via intravitreal injection approximately every 28 days RGX-314 Dose 1 RGX-314 RGX-314 Dose 1 administered via subretinal delivery one time. RGX-314 Dose 2 RGX-314 RGX-314 Dose 2 administered via subretinal delivery one time.
- 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 Mean change from Week 54 to Week 98 in BCVA (control arm participants who cross over to ABBV-RGX-314) Week 54 to Week 98 Mean change in BCVA based on ETDRS score
Mean change from baseline in CRT as measured by SD-OCT Week 54; (ABBV-RGX-314 randomized participants) Week 98 Mean change in CRT as measured by SD-OCT
Proportion of participants with ≤ 2 supplemental anti-VEGF injections through Week 54 (ABBV-RGX-314 randomized participants) Through Week 54 Proportion of supplemental anti-VEGF injections.
Proportion of participants with no supplemental anti-VEGF injections through Week 54 (ABBV-RGX-314 randomized participants) Through Week 54 Proportion of supplemental anti-VEGF injections.
Percent reduction in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants) Through Week 54 Supplemental anti-VEGF treatments required
Mean change from Baseline in BCVA Week 54 BCVA measured by ETDRS
Incidences of ocular and overall AEs over 54 weeks Through Week 54 AEs over 54 weeks
Incidences of ocular and overall AEs over 98 weeks Through Week 98 AEs over 98 weeks
Mean change from baseline in BCVA to Week 98 (ABBV-RGX-314 randomized participants) based on the ETDRS score Week 98 BCVA measured by ETDRS
Proportion of participants with worsened BCVA Week 54; Week 98 Proportion with worsened BCVA
Proportion of participants with improved BCVA Week 54; Week 98 Proportion with improved BCVA
Proportion of participants (1) gaining or losing > 0 letters; (2) maintaining vision (compared with baseline as per BCVA) Week 54; Week 98 Proportion gaining or losing \> 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 injections (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 98 in CRT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) from Week 54 to Week 98 Mean change in CRT as measured by SD-OCT
Mean change from baseline in CPT as measured by SD-OCT Week 54; (ABBV-RGX-314 randomized participants) Week 98 Mean change in CPT as measured by SD-OCT
Mean change from Week 54 to Week 98 in CPT as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314) from Week 54 to Week 98 Mean change in CPT as measured by SD-OCT
Proportion of participants with a reduction in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants) Through Week 54 and Week 98 Proportion of participants with a reduction of in anti-VEGF injection annualized rate compared with the prior year
Percent reduction in anti-VEGF injection annualized rate compared with the prior year (ABBV-RGX-314 randomized participants) Week 98 Supplemental anti-VEGF injection annualized rate
Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms through Week 54 and Week 98 Through Week 54 and Week 98 Supplemental anti-VEGF injection annualized rate
Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 98 relative to the year prior to the study (control arm participants who cross over to ABBV-RGX-314) After Week 58 through Week 98 Percent reduction in anti-VEGF injection annualized rate
Supplemental anti-VEGF injection annualized rate after Week 58 through Week 98 (control arm participants who cross over to ABBV-RGX-314) After Week 58 to Week 98 Supplemental anti-VEGF injection annualized rate
Time to first supplemental anti-VEGF injection after the Week 2 injection in the ABBV-RGX-314 arms Week 98 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 to Week 98 Time to first supplemental anti-VEGF injection
Mean change from baseline in NEI-VFQ-25 (composite score) at Week 54 and (for ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314) Week 98 Week 54; Week 98 Mean change in NEI VGQ-25 (composite score) at week 54 (control arm participants who cross over to ABBV-RGX-314)
Mean change from baseline in MacTSQ (composite score) at Week 54 and (for ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314) Week 98 Week 54; Week 98 Mean change from baseline in MacTSQ (composite score) at week 54 and (control arm participants who cross over to ABBV-RGX-314) at Week 98
Aqueous ABBV-RGX-314 TP concentrations (ABBV-RGX-314 randomized participants) Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98 Aqueous ABBV-RGX-314 TP concentration
Aqueous ABBV-RGX-314 TP concentrations (control arm participants who cross over to ABBV-RGX-314) Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98 Aqueous ABBV-RGX-314 TP concentration
Immunogenicity measurements (ABBV-RGX-314 randomized participants) Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98 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) Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98 Immunogenicity measurements (serum antibodies to AAV8 and serum antibodies to ABBV-RGX-314 TP)
Trial Locations
- Locations (91)
170-Barnet Dulaney Perkins Eye Center
🇺🇸Sun City, Arizona, United States
188-Colorado Retina Associates (CRA) - Red Rocks Medical Center Location
🇺🇸Lakewood, Colorado, United States
291-The Retina Institute
🇺🇸Saint Louis, Missouri, United States
118-Retinal Consultants of Arizona, Ltd.
🇺🇸Phoenix, Arizona, United States
292-Univ of Arkansas Medical Sciences Jones Eye Institute
🇺🇸Little Rock, Arkansas, United States
133-Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
142-Retinal Diagnostic Center
🇺🇸Campbell, California, United States
160-The Retina Partners - Encino
🇺🇸Encino, California, United States
150-Retina Consultants of Orange County - Fullerton Office
🇺🇸Fullerton, California, United States
284- Salehi Retina Institute
🇺🇸Huntington Beach, California, United States
193-University of California Irvine - School of Medicine - The Gavin Herbert Eye Institute
🇺🇸Irvine, California, United States
187-Doheny Eye Institute - Doheny Eye Center
🇺🇸Los Angeles, California, United States
132-Northern California Retina Vitreous Associates Medical Group, Inc. - Mountain View Office
🇺🇸Mountain View, California, United States
UCLA Doheny Eye Center
🇺🇸Pasadena, California, United States
185-California Eye Specialists Medical Group Inc. - Pasadena
🇺🇸Pasadena, California, United States
121-Retina Consultants San Diego
🇺🇸Poway, California, United States
163-Retina Consultants
🇺🇸Sacramento, California, United States
190-West Coast Retina Medical Group - San Francisco Office
🇺🇸San Francisco, California, United States
137-UCSF Medical Center - Retina and Vitreous Clinic
🇺🇸San Francisco, California, United States
182-Orange County Retina Medical Group
🇺🇸Santa Ana, California, United States
114-California Retina Consultants
🇺🇸Santa Barbara, California, United States
177-Retina Consultants of Southern Colorado PC- Colorado Springs
🇺🇸Colorado Springs, Colorado, United States
141-Southwest Retina Consultants
🇺🇸Durango, Colorado, United States
180-Retina Group of New England - New London
🇺🇸Waterford, Connecticut, United States
199-Advanced Research, LLC
🇺🇸Deerfield Beach, Florida, United States
148-Vitreo Retinal Associates PA - The Millennium Center
🇺🇸Gainesville, Florida, United States
205-Florida Retina Consultants - Lakeland
🇺🇸Lakeland, Florida, United States
181-Bascom Palmer Eye Institute - University of Miami Health System
🇺🇸Miami, Florida, United States
152-Retina Specialty Institute - Pensacola
🇺🇸Pensacola, Florida, United States
122-Southeast Retina Center
🇺🇸Augusta, Georgia, United States
165-Retina Vitreous Associates of Florida (RVA) - Saint Petersburg
🇺🇸Saint Petersburg, Florida, United States
278-Southern Vitreoretinal Associates, P.L.
🇺🇸Tallahassee, Florida, United States
145-Georgia Retina PC - Marietta
🇺🇸Marietta, Georgia, United States
295-Marietta Eye Clinic
🇺🇸Marietta, Georgia, United States
297- Thomas Eye Group
🇺🇸Sandy Springs, Georgia, United States
164 Retina Consultants of Hawaii (RCH) - Pali Momi Medical Center Location
🇺🇸'Aiea, Hawaii, United States
151-Illinois Eye and Ear Infirmary at UI Health UIC
🇺🇸Chicago, Illinois, United States
183-University Retina and Macula Associates, P.C. - Lemont Office
🇺🇸Lemont, Illinois, United States
184-University Retina and Macula Associates, PC - Oak Forest
🇺🇸Oak Forest, Illinois, United States
226-Springfield Clinic
🇺🇸Springfield, Illinois, United States
162-Midwest Eye Institute
🇺🇸Indianapolis, Indiana, United States
174-John-Kenyon American Eye Institute - New Albany
🇺🇸New Albany, Indiana, United States
186-Retina Associates, P.A. - Shawnee Mission
🇺🇸Lenexa, Kansas, United States
294-Retina Associates - New Orleans
🇺🇸Metairie, Louisiana, United States
288 Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
146-The Retina Care Center, LLC
🇺🇸Baltimore, Maryland, United States
108-The Johns Hopkins Hospital - Wilmer Eye Institute - East Baltimore
🇺🇸Baltimore, Maryland, United States
192 - The Retina Group of Washington
🇺🇸Chevy Chase, Maryland, United States
149-Cumberland Valley Retina Consultants (CVRC)
🇺🇸Hagerstown, Maryland, United States
106-Ophthalmic Consultants of Boston, Inc.
🇺🇸Boston, Massachusetts, United States
257-Retina Associates of Michigan - Grand Blanc Office
🇺🇸Grand Blanc, Michigan, United States
153-Associated Retinal Consultants P.C.
🇺🇸Royal Oak, Michigan, United States
155-VitreoRetinal Surgery, PA - Edina Location
🇺🇸Minneapolis, Minnesota, United States
166-Mayo Clinic - Minnesota
🇺🇸Rochester, Minnesota, United States
119- Sierra Eye Associates
🇺🇸Reno, Nevada, United States
125-Eye Associates of New Mexico - Albuquerque - Retina Center Location
🇺🇸Albuquerque, New Mexico, United States
124-Long Island Vitreoretinal Consultants - Great Neck
🇺🇸Great Neck, New York, United States
289- Retina Vitreous Surgeons of Central NY Syracuse
🇺🇸Liverpool, New York, United States
131-Duke Eye Center - Erwin Road - Duke University Medical Center
🇺🇸Durham, North Carolina, United States
283-Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
138-Cincinnati Eye Institute - Blue Ash
🇺🇸Cincinnati, Ohio, United States
167-Retina Associates of Cleveland, Inc
🇺🇸Cleveland, Ohio, United States
173-Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
175-Retina Vitreous Center (RVC)
🇺🇸Edmond, Oklahoma, United States
290- Verum Research, LLC
🇺🇸Eugene, Oregon, United States
143-Retina Northwest, PC
🇺🇸Portland, Oregon, United States
252-Erie Retinal Surgery, Inc
🇺🇸Erie, Pennsylvania, United States
287-Retina Vitreous Consultants - Monroeville
🇺🇸Monroeville, Pennsylvania, United States
105 Mid Atlantic Retina - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
210-Charleston Neuroscience Institute
🇺🇸Ladson, South Carolina, United States
156-Black Hills Regional Eye Institute
🇺🇸Rapid City, South Dakota, United States
109-Charles Retina Institute
🇺🇸Germantown, Tennessee, United States
144-West Texas Retina Consultants (WTRC) - Abilene Location
🇺🇸Abilene, Texas, United States
168-Austin Retina Associates
🇺🇸Austin, Texas, United States
147-Retina Consultants of Austin
🇺🇸Austin, Texas, United States
157-Austin Clinical Research, LLC
🇺🇸Austin, Texas, United States
293-Retina Consultants of Texas - Beaumont, TX
🇺🇸Beaumont, Texas, United States
286-Retina and Vitreous of TX PLLC
🇺🇸Bellaire, Texas, United States
189-Baylor Scott & White Surgicare
🇺🇸Burleson, Texas, United States
139-Texas Retina Associates
🇺🇸Dallas, Texas, United States
279 Star Vision Consultants
🇺🇸Fort Worth, Texas, United States
237-Retina Associates of South Texas, PA - San Antonio
🇺🇸San Antonio, Texas, United States
268-Retinal Consultants of San Antonio (RCSA) - Medical Center
🇺🇸San Antonio, Texas, United States
172-Retina Center of Texas - Southlake
🇺🇸Southlake, Texas, United States
117-Retina Consultants of Texas - The Woodlands
🇺🇸The Woodlands, Texas, United States
161-Retina Associates of Utah, PC
🇺🇸Salt Lake City, Utah, United States
176-John A. Moran Eye Center - University of Utah Health Care
🇺🇸Salt Lake City, Utah, United States
253-Pacific Northwest Retina
🇺🇸Bellevue, Washington, United States
262-Retina Center Northwest - Silverdale
🇺🇸Silverdale, Washington, United States
140 Wagner Macula & Retina Center - Norfolk, VA Office
🇺🇸Norfolk, Virginia, United States
154-University of Wisconsin Health - University Station Clinic
🇺🇸Madison, Wisconsin, United States