Abatacept Vs TNF Blockade in Early Rheumatoid Arthritis

阿巴西普与 TNF 阻断治疗早期类风湿关节炎

• 批准号: 7296349
• 负责人: Eugene William St. Clair
• 金额: $ 15.6万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-07 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7296349
• 关键词: Accounting; Antirheumatic Agents; Applications Grants; Arthritis; Biological Assay; Biological Markers; Budgets; Clinical; Clinical Investigator; Clinical Protocols; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Development; Disease; Disease remission; Environmental Risk Factor; Flow Cytometry; Funding; Genetic; Genetic Transcription; Goals; Immune Tolerance; Individual; Industry; Institutes; Joints; Lead; Methotrexate; Minority; Musculoskeletal Diseases; Numbers; Pathogenesis; Patients; Pharmacogenetics; Phase; Play; Process; Public Health; Randomized; Rate; Research; Research Design; Research Infrastructure; Research Institute; Rheumatoid Arthritis; Role; Secure; Site; Synovitis; T-Lymphocyte; Treatment Protocols; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Variant; Withdrawal; analytical tool; base; clinical research site; design; desire; disease characteristic; double-blind placebo controlled trial; experience; human TNF protein; implementation trial; inhibitor/antagonist; innovation; novel; prognostic; protocol development; response; therapy design

DESCRIPTION (provided by applicant): While considerable progress has been made in the treatment of rheumatoid arthritis (RA), only a minority of patients treated with optimal regimens of disease-modifying anti-rheumatic drugs achieve a clinical remission. Achieving a clinical remission is a desired goal of therapy because it is associated with minimal or no radiographic progression of joint destruction. To this end, we are proposing a randomized, double-blind, placebo-controlled trial in early RA comparing remission rates obtained following treatment with methotrexate (MTX) plus abatacept versus MTX and an anti-tumor necrosis factor (TNF) inhibitor. The proposed study design includes a novel withdrawal phase during which patients achieving a minimal level of disease activity will discontinue their assigned treatment, namely abatacept or a TNF inhibitor, and be followed for an additional 9 months to evaluate for sustained clinical remission. We propose to integrate a number of mechanistic studies into the trial aimed at identifying prognostic biomarkers of treatment response. To achieve the ambitious aims of such a comprehensive research strategy will require an intensive 12-month planning phase, which is the focus of the proposed project. The project will be led by Dr. E. William St.Clair, an experienced clinical investigator with expertise in the treatment of RA. The aims of the planning phase are as follows: 1) To effectively utilize a Steering Committee of disease experts and the assets of the Duke Clinical Research Institute to develop an optimal clinical trial design and guide other important phases of protocol development; 2) To develop a research strategy for identifying biomarkers of treatment response using a variety of uniplex and multiplex assay platforms; and 3) To develop an effective collaboration with the Immune Tolerance Network to obtain access to their multiplex assay platforms, including RNA expression arrays and high throughput flow cytometry, as well as analytical tools to implement the goals of specific aim 2. The support for this planning phase will enable us to produce the key deliverables of clinical protocol development, a highly integrated set of innovative biomarker studies, and a robust infrastructure for trial implementation, with the overall goal of submitting an outstanding application to NIAMS for funding of the proposed clinical trial. Therapies designed to achieve remission and tailored for people's distinct genetic make-up and other factors are the next major steps in the management of rheumatoid arthritis (RA). Research has already shown that such therapies can benefit public health. The proposed clinical trial will compare the remission-inducing capabilities of two novel therapies for early RA, and search for biomarkers that predict treatment response.

描述（由申请人提供）：虽然在治疗类风湿关节炎（RA）方面已经取得了很大进展，但只有少数接受了最佳疾病改良治疗的抗惊毒药物治疗的患者，才能实现临床缓解。实现临床缓解是治疗的理想目标，因为它与关节破坏的最小或没有影像学进展有关。为此，我们提出了一项随机的，双盲的，安慰剂对照试验的早期RA，比较了用甲氨蝶呤（MTX）加上Abatacept对MTX的治疗后获得的缓解率，并进行了抗肿瘤坏死因子（TNF）抑制剂。拟议的研究设计包括一个新的戒断阶段，在此期间，达到最低水平的疾病活性的患者将停止他们指定的治疗方法，即Abatacept或TNF抑制剂，并遵循9个月的次数，以评估持续的临床缓解。我们建议将许多机械研究整合到旨在识别治疗反应预后生物标志物的试验中。为了实现这种全面研究策略的雄心勃勃的目标，将需要一个密集的12个月计划阶段，这是拟议项目的重点。该项目将由经验丰富的临床研究人员E. William St.Clair博士领导，其治疗RA。计划阶段的目的如下：1）有效利用疾病专家指导委员会和杜克临床研究所的资产来开发最佳的临床试验设计，并指导协议开发的其他重要阶段； 2）制定一种研究策略，以使用各种独立和多重分析平台来识别治疗反应的生物标志物； 3）与免疫耐受性网络建立有效的合作，以获取对其多重测定平台的访问，包括RNA表达阵列和高吞吐量流式细胞仪，以及分析工具以实现特定目标的目标2。规划阶段将使我们能够生产临床协议开发的关键可交付成果，高度集成的创新生物标志物研究集，以及用于试验实施的强大基础架构，总体目标是向NIAM提交NIAMS以资助拟议的临床试验资金。旨在实现缓解并针对人们独特的遗传构成和其他因素量身定制的疗法是类风湿关节炎治疗（RA）的下一个主要步骤。研究已经表明，这种疗法可以使公共卫生受益。拟议的临床试验将比较两种新型RA的新疗法的缓解能力，并寻找预测治疗反应的生物标志物。