Chair Grant for the Comparison of AMD Treatment Trials

AMD 治疗试验比较主席 Grant

• 批准号: 7824961
• 负责人: DANIEL F MARTIN
• 金额: $ 13.3万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 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/7824961
• 关键词: Adopted; Adverse event; Age related macular degeneration; American; Atrophic; Avastin; Blindness; Caring; Clinical; Clinical Trials; Colorectal Cancer; Combined Modality Therapy; Cost Savings; Country; Data; Dose; Elderly; Epithelial; Exudative age-related macular degeneration; Eye; Fluorescein Angiography; Grant; Half-Life; Injection of therapeutic agent; Intravenous; Label; Lasers; Lucentis; Medicare; Molecular; Monoclonal Antibodies; Multi-Institutional Clinical Trial; Numbers; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Photochemotherapy; Pigments; Randomized Clinical Trials; Rate; Relative (related person); Reporting; Request for Applications; Research Personnel; Retina; Safety; Schedule; Specialist; Standards of Weights and Measures; Therapeutic Effect; Treatment Efficacy; Treatment Protocols; United States; United States Food and Drug Administration; Vascular Endothelial Growth Factors; Verteporfin; Vision; Visual; Visual Acuity; Week; anecortave acetate; bevacizumab; comparative; cost; design; experience; improved; interest; neovascular; pegaptanib; ranibizumab; response; treatment trial; trial comparing

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）：与年龄相关的黄斑变性（AMD）是65岁以上美国人失明的主要原因，大多数视觉损失归因于AMD的新血管形式。当前的治疗方法适度有效，但没有一个可靠地改善视觉结果。最近的研究表明，当兰尼比珠单抗（Lucentis（TM））每4周注射1年，可以稳定95％的患者的视力，并大大改善34％的患者的视力。该给药时间表的广泛实施具有明显的限制，这些重复注射的成本预计将很高。 在大型比较临床试验中尚未评估替代剂量时间表。贝伐单抗（avastin（r））是从中得出Lucentis（TM）的单克隆抗体。迄今为止，轶事证据表明，玻璃体内阿瓦斯汀（R）也可能有效治疗新生血管AMD。它可用于标签外使用，尽管没有任何随机临床试验数据来支持其眼内使用，但许多视网膜专家已被许多视网膜专家作为新生血管AMD的第一线治疗。 此外，许多药物与阿瓦斯汀（R）或Lucentis（TM）结合使用，具有改善视觉结果的潜力，但在大型临床试验中尚未进行评估。 在此应用中，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（CATT）的比较。第一次试验（单一疗法试验）的具体目的是确定1230名患者的新血管AMD治疗方法的相对安全性和功效：1）lucentis（TM）（tm）在固定的给药时间表中，2）lucentis（TM）lucentis（tm）在适应症（TM）上（可变剂量时间表对治疗的临床反应驱动），或3）avastin（3）Avastin（3）Avastin（R）（R）（R）（R）。主要结果度量将是视力的变化。次要结果将包括治疗数量，OCT的解剖学变化和荧光素血管造影，不良事件和成本。一旦确定了最佳单一疗法，我们将继续进行联合治疗试验。这项第二项研究的具体目的是确定从第一次试验确定的最佳单一疗法（6MT）与几种组合疗法确定的治疗的相对安全性和功效，如下所示：1）单独使用BMT，2）BMT与光动力疗法结合使用Verteporfin，或3）BMT与Anecortave actate actate乙酸盐结合。将使用与单一疗法试验相同的标准评估治疗方法。 这些研究的结果将有望改善新生血管AMD的治疗。减少治疗的数量和类型而不损害疗效，将减轻患者的治疗负担，并使每年46.2亿美元的Medicare潜在成本降低。组合疗法可以进一步改善视觉结果，减少所需的治疗次数并增加成本节省。