Chair Grant for the Comparison of AMD Treatment Trials

AMD 治疗试验比较主席 Grant

• 批准号: 7174018
• 负责人: DANIEL F MARTIN
• 金额: $ 19.57万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7174018
• 关键词: aging; clinical research; clinical trials; combination therapy; lead; macular degeneration; monoclonal antibody; motivation; visual perception

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of blindness among Americans over the age of 65 with the majority of visual loss attributable to the neovascular form of AMD. Current treatments are modestly effective but none have reliably improved visual outcomes. Recent studies have shown that ranibizumab (Lucentis(tm)), when injected every 4 weeks into the eye for 1 year, can stabilize visual acuity in 95% of patients and substantially improve vision in 34% of patients. Widespread implementation of this dosing schedule has obvious limitations and the cost of these repeated injections is expected to be high. Alternative dosing schedules have not been evaluated in large comparative clinical trials. Bevacizumab (Avastin(r)) is the monoclonal antibody from which Lucentis(tm) was derived. Anecdotal evidence to date suggests that intravitreal Avastin(r) may also be effective for the treatment of neovascular AMD. It is available for off-label use and has been adopted as a first line therapy for neovascular AMD by many retina specialists, despite the absence of any randomized clinical trial data to support its intraocular use. In addition, a number of drugs when combined with Avastin(r) or Lucentis(tm), have the potential to improve visual outcomes but have not been evaluated in large clinical trials. In this application, we propose two consecutive multi-center, randomized clinical trials to be known as the Comparison of AMD Treatment Trials (CATT). The specific aim of the first trial (Monotherapy Trial) will be to determine the relative safety and efficacy of the following treatments for neovascular AMD in 1230 patients: 1) Lucentis(tm) on a fixed dosing schedule, 2) Lucentis(tm) on indication (variable dosing schedule driven by clinical response to treatment), or 3) Avastin(r) on indication. The primary outcome measure will be change in visual acuity. Secondary outcomes will include number of treatments, anatomical changes on OCT and fluorescein angiography, adverse events, and cost. Once the optimal monotherapy has been determined, we will proceed with the Combination Therapy Trial. The specific aim of this second study will be to determine the relative safety and efficacy of treatment with the best monotherapy (6MT) determined from the first trial versus several combination therapies as follows: 1) BMT alone, 2) BMT combined with photodynamic therapy with verteporfin, or 3) BMT combined with treatment with anecortave acetate. Treatments will be evaluated using the same criteria as the Monotherapy Trial. The results of these studies will hopefully improve the treatment of neovascular AMD. Reducing the number and type of treatments without compromising efficacy would reduce the treatment burden for patients as well as produce a potential cost reduction to Medicare of $4.62 billion per year. Combination therapies could further improve visual outcomes, reduce the number of treatments required, and increase cost savings.

描述(由申请人提供)：老年性黄斑变性(AMD)是65岁以上美国人失明的主要原因，大部分视力丧失可归因于AMD的新生血管形式。目前的治疗方法是适度有效的，但没有一种方法能可靠地改善视力结果。最近的研究表明，雷尼比珠单抗(Lucentis(Tm))每4周向眼睛内注射一年，可以稳定95%的患者的视力，并显著提高34%的患者的视力。这种给药计划的广泛实施具有明显的局限性，而且这些重复注射的成本预计将很高。替代给药方案尚未在大型对比临床试验中进行评估。贝伐单抗(阿瓦斯丁(R))是Lucentis(Tm)的衍生单抗。到目前为止，坊间证据表明，玻璃体内注射阿瓦斯丁(R)也可能对治疗新生血管性AMD有效。它可用于标签外使用，并已被许多视网膜专家作为新生血管性AMD的一线治疗方法，尽管缺乏任何随机临床试验数据来支持其眼内使用。此外，一些药物与阿瓦斯丁(R)或Lucentis(Tm)联合使用时，有可能改善视力结果，但尚未在大型临床试验中进行评估。在本申请中，我们提出了两个连续的多中心随机临床试验，称为AMD治疗试验比较(CATT)。第一个试验(单一疗法试验)的具体目的将是在1230名患者中确定以下治疗新生血管性AMD的相对安全性和有效性：1)按固定剂量计划使用Lucentis(Tm)，2)按适应症(临床治疗反应驱动可变剂量计划)使用Lucentis(Tm)，或3)按适应症使用阿瓦斯丁(R)。主要的结果衡量标准是视力的变化。次要结果将包括治疗次数、OCT和荧光血管造影术的解剖变化、不良事件和费用。一旦确定了最佳的单一疗法，我们将继续进行联合疗法试验。第二项研究的具体目的将是确定从第一次试验中确定的最佳单一疗法(6MT)与以下几种组合疗法的相对安全性和有效性：1)单用骨髓移植，2)骨髓移植联合维替普芬光动力疗法，或3)骨髓移植联合醋酸可可他明治疗。治疗将使用与单一疗法试验相同的标准进行评估。这些研究的结果有望改善新生血管性AMD的治疗。在不影响疗效的情况下减少治疗的数量和类型将减轻患者的治疗负担，并为医疗保险带来每年46.2亿美元的潜在成本削减。联合疗法可以进一步改善视觉效果，减少所需的治疗次数，并增加成本节约。