A Randomized, Partially Masked, Controlled, Phase 2b/3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 671
- 试验地点
- 169
- 主要终点
- Mean change from baseline in Best Corrected Visual Acuity (BCVA)
研究概览
简要总结
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.
详细描述
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 630 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.
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
The administration of ABBV-RGX-314 requires an outpatient surgical procedure performed in an operating room, while the active control, ranibizumab, 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 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, 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
- •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 (Week -2)
- •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.
研究组 & 干预措施
ABBV-RGX-314 Dose 1
ABBV-RGX-314 Dose 1 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 (Genetic)
ABBV-RGX-314 Dose 2
ABBV-RGX-314 Dose 2 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 (Genetic)
Control Arm
Ranibizumab administered via intravitreal injection approximately every 28 days
干预措施: Ranibizumab (LUCENTIS®) (Biological)
ABBV-RGX-314 Dose 1
ABBV-RGX-314 Dose 1 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 (Genetic)
ABBV-RGX-314 Dose 2
ABBV-RGX-314 Dose 2 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 (Genetic)
Control Arm
Ranibizumab administered via intravitreal injection approximately every 28 days
干预措施: Ranibizumab (LUCENTIS®) (Biological)
ABBV-RGX-314 Dose 1
ABBV-RGX-314 Dose 1 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 (Genetic)
ABBV-RGX-314 Dose 2
ABBV-RGX-314 Dose 2 administered via subretinal delivery one time.
干预措施: ABBV-RGX-314 (Genetic)
Control Arm
Ranibizumab administered via intravitreal injection approximately every 28 days
干预措施: Ranibizumab (LUCENTIS®) (Biological)
结局指标
主要结局
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
Incidence of ocular AEs and any SAEs
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
Incidence of ocular AEs and any SAEs
次要结局
- Incidences of ocular and overall AEs over 54 weeks(Through Week 54)
- Mean change from baseline in BCVA to Week 98 (ABBV-RGX-314 randomized participants) based on the ETDRS score(Week 98)
- Proportion of participants with worsened BCVA(Week 54; Week 98)
- Proportion of participants with improved BCVA(Week 54; Week 98)
- Proportion of participants (1) gaining > 0 letters; (2) losing > 0 letters; maintaining vision (not losing ≥ 15 letters) compared with baseline as per BCVA(Week 54; Week 98)
- 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 from baseline in CRT as measured by SD-OCT(Week 54; (ABBV-RGX-314 randomized participants) Week 98)
- 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 from baseline in CPT as measured by SD-OCT(Week 54; (ABBV-RGX-314 randomized participants) Week 98)
- 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)
- Percent reduction in anti-VEGF injection annualized rate compared with the prior year (ABBV-RGX-314 randomized participants)(Through Week 54 and Week 98)
- 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)
- 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)
- 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 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)
- 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 concentrations (control arm participants who cross over to ABBV-RGX-314)(Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98)
- Immunogenicity measurements (ABBV-RGX-314 randomized participants)(Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98)
- Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)(Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98)
- 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 timepoints(Through Week 50)
- Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed timepoints(Through Week 50)
- Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate(Through Week 50)
- Bilateral Treatement Substudy: Mean number of supplemental anti-VEGF injections(Through Week 50)
- Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations(Wk 26, Wk 34, Wk 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(Wk 18, Wk 34, Wk 50)
- Proportion of participants with no supplemental anti-VEGF injections through Week 54 (ABBV-RGX-314 randomized participants)(Through Week 54)
- Incidences of ocular and overall AEs over 54 weeks(Through Week 54)
- Incidences of ocular and overall AEs over 98 weeks(Through Week 98)
- Mean change from baseline in BCVA to Week 98 (ABBV-RGX-314 randomized participants) based on the ETDRS score(Week 98)
- Proportion of participants with worsened BCVA(Week 54; Week 98)
- Proportion of participants with improved BCVA(Week 54; Week 98)
- Proportion of participants (1) gaining > 0 letters; (2) losing > 0 letters; maintaining vision (not losing ≥ 15 letters) compared with baseline as per BCVA(Week 54; Week 98)
- 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 from baseline in CRT as measured by SD-OCT(Week 54; (ABBV-RGX-314 randomized participants) Week 98)
- 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 from baseline in CPT as measured by SD-OCT(Week 54; (ABBV-RGX-314 randomized participants) Week 98)
- 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)
- 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)
- Percent reduction in anti-VEGF injection annualized rate compared with the prior year (ABBV-RGX-314 randomized participants)(Through Week 54 and Week 98)
- Supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 arms through Week 54 and Week 98(Through Week 54 and Week 98)
- 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)
- 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)
- 22. 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 after the Week 58 injection in the control arm participants who cross over to ABBV-RGX-314(After Week 58 to Week 98)
- 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 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)
- 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 concentrations (control arm participants who cross over to ABBV-RGX-314)(Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98)
- Immunogenicity measurements (ABBV-RGX-314 randomized participants)(Wk -2, Wk 14, Wk 26, Wk 38, Wk 54, and Wk 98)
- Immunogenicity measurements (control arm participants who cross over to ABBV-RGX-314)(Wk 54, Wk 66, Wk 78, Wk 90, and Wk 98)
- 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 timepoints(Through Week 50)
- Bilateral Treatment Substudy: Mean change from Baseline in CRT at assessed timepoints(Through Week 50)
- Bilateral Treatment Substudy: Supplemental anti-VEGF injection annualized rate(Through Week 50)
- Bilateral Treatement 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 particpants with ≤2 supplemental anti-VEGF injections(Through Week 50)
- Bilateral Treatment Substudy: Aqueous humor and serum ABBV-RGX-314 TP concentrations(Wk 26, Wk 34, Wk 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(Wk 18, Wk 34, Wk 50)
- Mean change from baseline in BCVA for participants who received 0 or more supplemental anti-VEGF injections (ABBV-RGX-314 randomized participants)(Week 54; Week 98)
- Mean number of supplemental anti-VEGF injections from Baseline through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (ABBV-RGX-314 randomized participants and control arm participants who cross over to ABBV-RGX-314)(Through Week 98)
- Proportion of participants with 0, 1, 2, and 3 supplemental injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314)(Through Week 98)
- Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314)(Through Week 98)
- Proportion of participants that received 1 or 2 injections through Week 54 and Week 98 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 98 (control arm participants who cross over to ABBV-RGX-314)(Through Week 98)
- Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants)(Through Week 98)
- Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate through Week 54 and Week 98 compared with the prior year (ABBV-RGX-314 randomized participants)(Through Week 98)
- Supplemental anti-VEGF injection annualized rate through Week 54 and Week 98 (ABBV-RGX-314 randomized participants)(Through Week 54 and Week 98)
- Time to first supplemental anti-VEGF injection after the Week 2 injection (ABBV-RGX-314 randomized participants)(Week 98)
- Time to first supplemental anti-VEGF injection after the Week 58 injection (control arm participants who cross over to ABBV-RGX-314)(After Week 58 to Week 98)
- Bilateral Treatment Substudy: Proportion of participants with 0, ≤ 1, ≤ 2, and ≤ 3 supplemental anti-VEGF injections(Through Week 50)