A Phase IIIb, Multicenter, Randomized, Controlled Study of the Safety, Tolerability and Efficacy of IVT 0.5mg Ranibizumab Monthly Compared to a Treat & Extend Protocol in Patients With Wet Age-related Macular Degeneration (T-REX)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Mean Change in BCVA by ETDRS Letter Score From Baseline
研究概览
简要总结
TREX is a phase IIIb, multicenter, randomized, controlled clinical study. Subjects will be randomized 1:2 to "monthly" (control arm) or "treat and extend" protocol (comparator arm) respectively. TREX assess the safety, tolerability and efficacy of intravitreal injections (IVT) of 0.5mg ranibizumab given monthly for up to 100 weeks followed by pro re nata (PRN) treatment for 56 weeks compared to a Treat and Extend protocol for 156 weeks in patients with wet age-related macular degeneration (AMD). Subjects treated in a treat and extend protocol receive 3 consecutive IVT 0.5 mg ranibizumab (visits 2, 4 and 5). Starting at week 8, if a subject has achieved a "dry" macula; signs of active exudation have resolved will begin a Treat and Extend protocol (visits lengthened by 2 week intervals every visit a dry macular is maintained). At the beginning of the 104-week endpoint subjects initially randomized to the TREX cohort will transition to PRN re-treatment when there is no exudative disease activity at the 12-week interval.
详细描述
This trial will compare the results of 2 cohorts, with different treatment intervals, to assess the safety, tolerability and efficacy of IVT of ranibizumab for the treatment of wet AMD. Specifically, this trial will evaluate the ability to reduce the amount of visits and IVT ranibizumab treatments needed all while maintaining an exudation-free macula. Subjects in both cohorts will be followed for a total of 156 weeks.
Cohort A (control arm, monthly, n=20) Subjects will receive monthly treatment of IVT 0.5 mg ranibizumab from Day 0 to week 100. Monthly treatment is defined as every 28 days (±7 days). Dosing should not occur earlier than 21 days after the previous treatment.
Week 104 - Week 156 Starting at week 104 subjects will be seen monthly and treated with IVT ranibizumab pro re nata (PRN) based on pre-defined re-treatment criteria.
Retreatment criteria for PRN phase
Re-treatment will be initiated if any of the following criteria are meet:
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
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide written informed consent and comply with study assessments for the full duration of the study
- •Age > 50 years
- •Ability and willingness to return for all scheduled visits and assessments
- •Any CNVM lesion (Occult, Minimally Classic or Classic) (i.e., leakage on fluorescein angiography or subretinal, intraretinal activity on SDOCT) secondary to age-related macular degeneration.
- •Best corrected visual acuity in the study eye, using ETDRS testing, between 20/32 and 20/400 (Snellen equivalent), inclusive.
- •The total area of subretinal hemorrhage and fibrosis must comprise less than 50% of the total lesion. Clear ocular media and adequate pupillary dilation to permit good quality fundus imaging.
排除标准
- •Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either > 50% of the total area of the lesion or > 1 disc area (2.54 mm2) in size
- •Subfoveal fibrosis or atrophy in the study eye
- •CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
研究组 & 干预措施
Monthly IVT ranibizumab
Monthly intravitreal injections (IVT) ranibizumab for 24 months, not less than 21 days apart to not more than 35 days apart
干预措施: 0.5 mg ranibizumab (Drug)
Treat and Extend IVT ranibizumab
0.5 mg intravitreal injections (IVT) ranibizumab for 3 consecutive months followed by a treat and extend protocol in which follow-up intervals are increased when there is no clinical and SD-OCT evidence of disease activity by 2-week intervals and patients are treated at every visit. (Comparator arm)
干预措施: 0.5 mg ranibizumab (Drug)
结局指标
主要结局
Mean Change in BCVA by ETDRS Letter Score From Baseline
时间窗: 6, 12, 18, 24, 30, and 36 months
Mean change in Best-Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline through weeks 24-28, baseline through weeks 48-56, baseline through weeks 72-82, baseline to week 104, baseline through weeks 128-132 and baseline to week 156. The ETDRS protocol is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning. The scale ranges from 0 to 100 letters
次要结局
- CNVM Lesion Size(6, 12, 18, 24, 30, and 36 months)
- Mean Change in Central Foveal Thickness(12, 24, and 36 months)
- Incidence and Severity of Adverse Events (Ocular and Non-ocular)(36 months)
- Total Number of Office Visits and Imaging Studies Performed During Study Period(6, 12, 18, 24, 30, and 36 months)
- Percentage of Patients With Persistent Leakage on Fluorescein Angiography(6, 12, 18, 24, 30, and 36 months)
- Total Number of Intravitreal Injections Required(12, 24, and 36 months)
- Percentage of Subjects With Persistent Active Exudation on SD-OCT(12, 24, and 36 months)
研究者
Charles C Wykoff, PhD, MD
Deputy Director of Research
Greater Houston Retina Research