Chair Grant for the Comparison of AMD Treatment Trials

描述（由申请人提供）：年龄相关性黄斑变性（AMD）是65岁以上美国人失明的主要原因，大多数视力丧失可归因于新生血管性黄斑变性。目前的治疗方法一般有效，但没有一种能可靠地改善视力。最近的研究表明，雷尼珠单抗（Lucentis）每4周注射一次，持续1年，可以稳定95%的患者的视力，并显著改善34%的患者的视力。广泛实施这一给药方案具有明显的局限性，而且这些重复注射的费用预计会很高。替代给药方案尚未在大型比较临床试验中进行评估。Bevacizumab （Avastin(r)）是Lucentis（tm）衍生的单克隆抗体。迄今为止的轶事证据表明，玻璃体内阿瓦斯汀(r)也可能对治疗新生血管性AMD有效。尽管没有任何随机临床试验数据支持其眼内使用，但它可用于标签外使用，并已被许多视网膜专家采用为新生血管性AMD的一线治疗。此外，一些药物与阿瓦斯汀（Avastin）或Lucentis（Lucentis）联合使用时，有可能改善视力，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治疗试验的比较（CATT）。第一项试验（单药治疗试验）的具体目的是确定1230例新血管性AMD患者以下治疗方法的相对安全性和有效性：1)Lucentis（tm）固定给药方案，2)Lucentis（tm）适应证（根据临床治疗反应驱动的可变给药方案），或3)Avastin(r)适应证。主要的结果测量将是视力的变化。次要结果将包括治疗次数、OCT和荧光素血管造影的解剖变化、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治疗试验。第二项研究的具体目的是确定从第一次试验中确定的最佳单药治疗（6MT）与以下几种联合治疗的相对安全性和有效性：1)BMT单独治疗，2)BMT联合光动力治疗与维托酚芬，或3)BMT联合醋酸盐治疗。治疗将使用与单药治疗试验相同的标准进行评估。这些研究的结果有望改善新血管性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，并为医疗保险每年减少46.2亿美元的潜在成本。联合治疗可以进一步改善视力，减少所需的治疗次数，并增加成本节约。

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.