A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 735
- 试验地点
- 542
- 主要终点
- Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs
研究概览
简要总结
ABBV-RGX-314 (also known as RGX-314 and surabgene lomparvovec (sura-vec)) 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.
详细描述
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 714 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), while 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
ABBV-RGX-314 administration is performed as an outpatient surgical procedure in an operating room, while the active control, aflibercept, is administered via intravitreal injection in an office setting. This study will be partially masked which will include masking of key study assessors and study drug dose.
入排标准
- 年龄范围
- 50 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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 medicinal product, other than an intravitreal therapy for AMD, in the 6 months prior to Week -6
- •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
- •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 the study eye, such as intravitreal steroid injection or investigational medicinal product, other than an intravitreal therapy for AMD, in the 6 months prior to Week -
- •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
研究组 & 干预措施
Control Arm
Aflibercept administered via intravitreal injection approximately every 8 weeks
干预措施: Aflibercept (EYLEA®) (Biological)
ABBV-RGX-314 Dose 1
ABBV-RGX-314 Dose 1 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 Dose 1 (Genetic)
ABBV-RGX-314 Dose 2
ABBV-RGX-314 Dose 2 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 Dose 2 (Genetic)
结局指标
主要结局
Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs
时间窗: Week 50
AEs and SAEs through Week 50
Mean change from baseline in Best Corrected Visual Acuity (BCVA)
时间窗: At Week 54
To evaluate the noninferiority of ABBV-RGX-314 relative to aflibercept in mean change from Baseline BCVA at Week 54
Mean change from baseline in Best Corrected Visual Acuity (BCVA)
时间窗: At Week 54
BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
Bilateral Treatment Substudy: Incidence of ocular AEs and any SAEs
时间窗: Week 50
AEs and SAEs through Week 50
次要结局
- Immunogenicity measurements (ABBV-RGX-314 randomized participants)(Week -2, Week 14, Week 38, and Week 54)
- 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)
- Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)(Week 54, Week 74, Week 90, and Week 108)
- Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed time points(Through Week 50)
- Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate(Through Week 50)
- Bilateral Treatment Substudy: Mean number of supplemental anti-VEGF injections(Through Week 50)
- Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations(Week 26, Week 34, Week 50)
- Proportion of participants with worsened BCVA(Week 54)
- Proportion of participants with improved BCVA(Week 54)
- Proportion of participants (1) gaining or losing greater than 0 letters; (2) maintaining vision compared with baseline as per BCVA(Week 54)
- Incidences of ocular and overall AEs(Through Week 54)
- 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 central retinal thickness (CRT) as measured by SD-OCT(Through Week 108)
- Mean change in central point thickness (CPT) as measured by SD-OCT(Through Week 108)
- Mean number of supplemental anti-VEGF injections from Baseline through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- Proportion of participants with 0, 1, 2, and 3 supplemental injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- Proportion of participants that received 1 or 2 injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)(Through Week 54)
- Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)(Through Week 54)
- 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 injection annualized rate through Week 54 (ABBV-RGX-314 randomized participants)(Through Week 54)
- Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 108 relative to the year prior to study (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- Supplemental anti-VEGF injection annualized rate after Week 58 through Week 108 (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- 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 after the Week 58 injection (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- Mean change from Baseline in NEI VFQ-25 (composite score) at Week 54 and (control arm participants who cross over to ABBV-RGX-314) Week 108(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) Week 108(Week 54 and Week 108)
- Aqueous humor ABBV-RGX-314 TP concentrations at Week -2, Week 14, Week 38, and Week 54 (ABBV-RGX-314 randomized participants)(Through Week 54)
- Aqueous humor ABBV-RGX-314 TP concentrations at Week 54, Week 74, Week 90, and Week 108 (control arm participants who cross over to ABBV-RGX-314)(Through Week 108)
- Serum ABBV-RGX-314 TP concentrations (at select sites)(Through Week 54)
- Bilateral Treatment Substudy: Incidence of nonocular AEs and any AESIs(Week 50)
- Bilateral Treatment Substudy: Mean change from Baseline in BCVA at assessed time points(Week 50)
- Bilateral Treatment Substudy: Proportion of participants with 0, ≤ 1, ≤ 2, and ≤ 3 supplemental anti-VEGF injections(Through Week 50)
- Bilateral Treatment Substudy: Immunogenicity measurements (serum anti-ABBV-RGX-314 TP antibodies, serum anti-AAV8 antibodies) and enzyme-linked immunospot at assessed time points(Week 50)
- Proportion of participants with ≤ 2 supplemental anti-VEGF injections(Through Week 54 (ABBV-RGX-314 randomized participants only))
- Proportion of participants with no supplemental anti-VEGF injections(Through Week 54 (ABBV-RGX-314 randomized participants only))
- Incidences of ocular and overall SAEs over 54 weeks(Through Week 54)
- Proportion of participants with worsened BCVA(Week 54)
- Proportion of participants with improved BCVA(Week 54)
- Proportion of participants (1) gaining or losing greater than 0 letters; (2) maintaining vision compared with baseline as per BCVA(Week 54)
- 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 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 from baseline in central retinal thickness (CRT) as measured by SD-OCT(Week 54)
- 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 from baseline in center point thickness (CPT) as measured by SD-OCT(Week 54)
- 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)
- Proportion of participants with a reduction in anti-VEGF injection annualized rate(Through Week 54)
- Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms(Through Week 54)
- 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)
- 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)
- 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 after the Week 58 injection in the control arm participants who cross over to ABBV-RGX-314(After Week 58 through Week 108)
- Mean change from baseline in NEI VFQ-25 (composite score)(Week 54 and Week 108)
- Mean change from baseline in MacTSQ (composite score)(Week 54 and 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 (control arm participants who cross over to ABBV-RGX-314)(Week 54, Week 74, Week 90, and Week 108)
- Serum ABBV-RGX-314 TP concentrations (at select sites)(Week -2, Week 14, Week 38, and Week 54)
- Immunogenicity measurements (ABBV-RGX-314 randomized participants)(Week -2, Week 14, Week 38, and Week 54)
- Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)(Week 54, Week 74, Week 90, and Week 108)
- Bilateral Treatment Substudy: Incidence of nonocular AEs and any AEs of special interest(Week 50)
- Bilateral Treatment Substudy: Mean change from Baseline in BCVA at assessed time points(Through Week 50)
- Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed time points(Through Week 50)
- Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate(Through Week 50)
- Bilateral Treatment Substudy: Mean number of supplemental anti-VEGF injections(Through Week 50)
- Bilateral Treatment Substudy: Proportion of participants with no supplemental anti-VEGF injections(Through Week 50)
- Bilateral Treatment Substudy: Proportion of participants with ≤ 2 supplemental anti-VEGF injections(Through Week 50)
- Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations(Week 26, Week 34, Week 50)
- 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)