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.
A bilateral treatment substudy conducted at US sites is an open-label, partially randomized, parallel arm study to evaluate the safety and efficacy of subretinal ABBV-RGX-314 administered bilaterally in participants who have bilateral nAMD. Previously treated crossover participants from the control arm of the main study who crossed over and received ABBV-RGX-314 in the study eye will receive the same ABBV-RGX-314 dose in the contralateral eye (ie, same dose as in the study eye), and newcomers (participants who have not been randomized in an ABBV-RGX-314 study) and untreated crossover participants (ongoing control participants in the main study who have completed Week 54 but have not crossed over to receive ABBV-RGX-314 in the main study) will be randomized in a 2:1 ratio to receive ABBV-RGX-314 Dose 1 or ABBV-RGX-314 Dose 2 in both eyes. Up to 15 participants who qualify for the substudy will be enrolled and followed for a minimum of 50 weeks.
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
Inclusion Criteria (Bilateral Treatment Substudy)*:
- An ETDRS BCVA letter score between ≤ 83 and ≥ 40 in both eyes
- Diagnosis of subfoveal choroidal neovascularization (CNV) secondary to AMD in both eyes
- Must be pseudophakic (at least 12 weeks postcataract surgery) in both eyes
- Willing and able to provide written, signed informed consent for this study
- Newcomers must have active disease in the study eye; crossover participants must have active disease in the eye not treated in the main study
- 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
Exclusion Criteria (Bilateral Treatment Substudy)*:
- CNV or macular edema in either eye secondary to any causes other than AMD
- Subfoveal fibrosis or atrophy in either eye
- Any condition in the investigator's opinion that could limit VA improvement in either eye
- Active or history of retinal detachment, or current retinal tear that cannot be treated in either eye
- Advanced glaucoma or history of secondary glaucoma in either eye
- Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
- History of intraocular surgery in either eye within 12 weeks prior to randomization
- History of intravitreal therapy in either eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening
- Prior treatment with gene therapy (*) For previously treated crossover participants, criteria apply to the eye not treated in the main study only.
Note: Other inclusion/exclusion criteria apply
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)
Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs Week 50 AEs and SAEs through Week 50
- Secondary Outcome Measures
Name Time Method 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
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
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)
Bilateral Treatment Substudy: Incidence of nonocular AEs and any AEs of special interest Week 50 Nonocular AEs and AEs of Special Interest
Bilateral Treatment Substudy: Mean change from Baseline in BCVA at assessed time points Through Week 50 BCVA measured by ETDRS
Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed time points Through Week 50 Mean change in CRT as measured by SD-OCT
Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate Through Week 50 Supplemental anti-VEGF injection annualized rate
Bilateral Treatment Substudy: Mean number of supplemental anti-VEGF injections Through Week 50 Mean supplemental anti-VEGF injections
Bilateral Treatment Substudy: Proportion of participants with no supplemental anti-VEGF injections Through Week 50 Proportion of participants with no supplemental anti-VEGF injections
Bilateral Treatment Substudy: Proportion of participants with ≤ 2 supplemental anti-VEGF injections Through Week 50 Proportion of participants with ≤ 2 supplemental anti-VEGF injections
Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations Week 26, Week 34, Week 50 Aqueous humor and serum ABBV-RGX-314 TP concentrations
Bilateral Treatment Substudy: Immunogenicity measurements (serum anti-ABBV-RGX-314 TP antibodies, serum antiAAV8 antibodies) and enzyme-linked immunospot at assessed time points Week 18, Week 34, Week 50 Immunogenicity measurements
Trial Locations
- Locations (181)
Barnet Dulaney Eye Center-Phoenix /ID# 256340
🇺🇸Phoenix, Arizona, United States
Retinal Research Institute /ID# 256238
🇺🇸Phoenix, Arizona, United States
Retina Macula Institute of Arizona /ID# 271026
🇺🇸Scottsdale, Arizona, United States
California Retina Consultants - Bakersfield /ID# 256240
🇺🇸Bakersfield, California, United States
Retina Vitreous Assoc Med Grp /ID# 256246
🇺🇸Beverly Hills, California, United States
Retinal Diagnostic Center /ID# 256262
🇺🇸Campbell, California, United States
The Retina Partners - Encino /ID# 259660
🇺🇸Encino, California, United States
Retina Consultants of Orange County /ID# 256267
🇺🇸Fullerton, California, United States
Hamilton Glaucoma Center Shiley Eye Center UCSD /ID# 256320
🇺🇸La Jolla, California, United States
California Retina Consultants - Oxnard - North Ventura Road /ID# 262883
🇺🇸Oxnard, California, United States
Scroll for more (171 remaining)Barnet Dulaney Eye Center-Phoenix /ID# 256340🇺🇸Phoenix, Arizona, United States