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
- Genetic: ABBV-RGX-314
- 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
- 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 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 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
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)
118-Retinal Consultants of Arizona, Ltd.
🇺🇸Phoenix, Arizona, United States
170-Barnet Dulaney Perkins Eye Center
🇺🇸Sun City, 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
Scroll for more (81 remaining)118-Retinal Consultants of Arizona, Ltd.🇺🇸Phoenix, Arizona, United States