A Phase 2, Randomized, Dose-escalation, Ranibizumab-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 Gene Therapy Delivered Via One or Two Suprachoroidal Space (SCS) Injections in Participants With Neovascular Age-Related Macular Degeneration (nAMD) (AAVIATE)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 140
- 试验地点
- 18
- 主要终点
- Mean change from baseline in BCVA to Week 40 based on the Early Treatment Diabetic Retinopathy Study (ETDRS) score
研究概览
简要总结
This interventional study is being conducted with an investigational gene therapy treatment called ABBV-RGX-314 (also known as RGX-314) and is being developed as a potential one-time gene therapy treatment for neovascular (wet) age-related macular degeneration (wet AMD or nAMD). The typical treatment for nAMD is frequent injections of anti-VEGF therapy. Researchers are testing ABBV-RGX-314 to see if it has similar effects as the current approved standard of care, such as Lucentis® or Eylea® injections.
The duration of this study will be up to 52 weeks or for ranibizumab control participants who cross over to ABBV-RGX-314 after week 52, up to 80 weeks post-randomization.
The primary outcome measure for this investigational study is to evaluate the mean change in best-corrected visual acuity (BCVA) for ABBV-RGX-314 compared with ranibizumab monthly at the Week 40 visit.
详细描述
This phase 2, randomized, dose-escalation study is designed to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 gene therapy in subjects with nAMD.
ABBV-RGX-314 will be injected into the SCS part of the eye. Approximately 140 participants who meet the inclusion/exclusion criteria will be enrolled into one of 7 cohorts. Participants will be randomized in Cohorts 1 and 2 to receive ABBV-RGX-314 or the intravitreal ranibizumab control. Participants enrolled in Cohorts 3 through 5 will receive ABBV-RGX-314. Participants enrolled in Cohort 6 will receive ABBV-RGX-314 and will be randomized to one of two different post-procedural steroid regimens. Participants randomized in Cohort 7 will receive ABBV-RGX-314 with a protocol mandated steroid regimen or the intravitreal ranibizumab control. Cohort 1 will evaluate ABBV-RGX-314 Dose 1, Cohorts 2 and 3 will evaluate ABBV-RGX-314 Dose 2, Cohorts 4, 5, and 6 will evaluate ABBV-RGX-314 Dose 3, and Cohort 7 will evaluate ABBV-RGX-314 Dose 4.
The duration of the study will be up to 52 weeks or for ranibizumab control participants who cross over to ABBV-RGX-314, up to 80 weeks post-randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The vision examiners and central reading center (CRC) graders will be masked, meaning they will be unaware of the participants' treatment assignment. All other individuals affiliated with the study (investigators, all study center personnel apart from the vision examiners, the participants, all staff of Sponsor and its research collaborator, all staff affiliated with the contract research organization, and all CRC staff apart from the CRC graders) will have knowledge of the treatment assignment.
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 and </= 89
- •Diagnosis of CNV secondary to age-related macular degeneration in the study eye.
- •Participants must have demonstrated a meaningful response to anti-VEGF therapy.
- •Willing and able to provide written, signed informed consent for this 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 study eye.
- •Participants who have had a prior vitrectomy.
- •Active or history of retinal detachment in the study eye.
- •History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product (IP), other than anti-VEGF therapy, in the 6 months prior to study entry.
- •Received any gene therapy.
- •Any condition preventing visualization of the fundus or VA improvement in the study eye, eg, cataract.
- •History of intraocular surgery in the study eye within 12 weeks of study entry.
- •Receipt of any IP within 30 days of study entry or 5 half-lives of the IP.
- •Myocardial infarction, cerebrovascular accident, or transient ischemic attacks within 6 months of study entry.
- •Cohorts 1 - 5 only: Uncontrolled glaucoma in the study eye.
- •COHORT 6 AND 7 ONLY:
- •Active or history of glaucoma or ocular hypertension (steroid-induced ocular hypertension (Cohort 7 only)) in the study eye.
- •Certain OCT characteristics including: Large Pigment Epithelial Detachments (PED), clinically significant Epiretinal Membrane (ERM) in the study eye at Visit
- •Note: Other inclusion/exclusion criteria apply.
研究组 & 干预措施
ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid
ABBV-RGX-314 Dose 3 and Topical Steroid
干预措施: ABBV-RGX-314 Dose 3 (Genetic)
ABBV-RGX-314 Treatment Arm (Dose 3) and Topical Steroid
ABBV-RGX-314 Dose 3 and Topical Steroid
干预措施: Topical Steroid (Drug)
ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid
ABBV-RGX-314 Dose 4 and Topical Steroid
干预措施: Topical Steroid (Drug)
Ranibizumab control
Control treatment arm
干预措施: Ranibizumab (Biological)
ABBV-RGX-314 Treatment Arm (Dose 1)
ABBV-RGX-314 Dose 1
干预措施: ABBV-RGX-314 Dose 1 (Genetic)
ABBV-RGX-314 Treatment Arm (Dose 2)
ABBV-RGX-314 Dose 2
干预措施: ABBV-RGX-314 Dose 2 (Genetic)
ABBV-RGX-314 Treatment Arm (Dose 3)
ABBV-RGX-314 Dose 3
干预措施: ABBV-RGX-314 Dose 3 (Genetic)
ABBV-RGX-314 Treatment Arm (Dose 3) and Local Steroid
ABBV-RGX-314 Dose 3 and Local Steroid
干预措施: ABBV-RGX-314 Dose 3 (Genetic)
ABBV-RGX-314 Treatment Arm (Dose 3) and Local Steroid
ABBV-RGX-314 Dose 3 and Local Steroid
干预措施: Local Steroid (Drug)
ABBV-RGX-314 Treatment Arm (Dose 4) and Topical Steroid
ABBV-RGX-314 Dose 4 and Topical Steroid
干预措施: ABBV-RGX-314 Dose 4 (Genetic)
结局指标
主要结局
Mean change from baseline in BCVA to Week 40 based on the Early Treatment Diabetic Retinopathy Study (ETDRS) score
时间窗: 40 weeks
The scale used is the early treatment diabetic retinopathy study (ETDRS) letter score from 0-100 and higher score being better vision.
次要结局
- Incidence of overall and ocular adverse events (AEs) and serious adverse events (SAEs)(52 weeks)
- Vector shedding analysis in serum, urine, and tears(52 Weeks)
- Proportion of participants who experience ocular inflammation following SCS ABBV-RGX-314 administration(52 weeks)
- Mean change from baseline in choroidal neovascularization (CNV) lesion size and leakage area based on fluorescein angiography (FA)(Up to Week 80)
- Mean change from baseline in BCVA based on ETDRS score(Up to Week 80)
- Proportion of participants (1) gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 letters; (2) losing ≥ 15, ≥ 10, ≥ 5, or > 0 letters (3) maintaining vision (not losing ≥ 15 letters) compared with baseline as per BCVA(Up to Week 52)
- Mean change from baseline in CRT as measured by SD-OCT(Up to Week 80)
- Mean supplemental anti-VEGF injection annualized rate in the ABBV-RGX-314 treatment arms(Up to Week 80)
- Mean percent reduction in supplemental anti-VEGF injection annualized rate(Up to Week 80)
- Proportion of participants who have a reduction of ≥ 50% and ≥ 75% in supplemental anti-VEGF- injection annualized rate(52 Weeks)
- Proportion of participants with 0, ≤ 1, and ≤ 2 supplemental injections(Up to Week 80)
- Time from ABBV-RGX-314 administration to first supplemental anti-VEGF injection(80 Weeks)
- Aqueous humor ABBV-RGX- 314 TP concentration over time(52 Weeks)
- Mean change from baseline in serum ABBV-RGX-314 TP concentration over time(80 Weeks)