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）：虽然类风湿关节炎（RA）的治疗已经取得了相当大的进展，但只有少数接受缓解疾病抗风湿药物最佳方案治疗的患者达到了临床缓解。实现临床缓解是治疗的理想目标，因为它与关节破坏的放射学进展最小或没有相关。为此，我们提出一项针对早期 RA 的随机、双盲、安慰剂对照试验，比较甲氨蝶呤 (MTX) 加阿巴西普与 MTX 和抗肿瘤坏死因子 (TNF) 抑制剂治疗后获得的缓解率。拟议的研究设计包括一个新的停药阶段，在此期间，达到最低疾病活动水平的患者将停止指定的治疗，即阿巴西普或 TNF 抑制剂，并再随访 9 个月，以评估持续的临床缓解情况。我们建议将一些机制研究整合到试验中，旨在确定治疗反应的预后生物标志物。为了实现这一综合研究战略的宏伟目标，需要为期 12 个月的密集规划阶段，这也是拟议项目的重点。该项目将由 E. William St.Clair 博士领导，他是一位经验丰富的临床研究人员，在 RA 治疗方面拥有专业知识。规划阶段的目标如下： 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制定最佳的临床试验设计并指导方案开发的其他重要阶段； 2) 制定研究策略，使用各种单重和多重检测平台来识别治疗反应的生物标志物； 3) 与免疫耐受网络建立有效的合作，以获得其多重检测平台，包括 RNA 表达阵列和高通量流式细胞术，以及实现特定目标 2 目标的分析工具。对此规划阶段的支持将使我们能够产生临床方案开发的关键成果、一套高度集成的创新生物标志物研究以及用于试验实施的强大基础设施，总体目标是提交 向 NIAMS 提交了一项未决申请，为拟议的临床试验提供资金。类风湿性关节炎 (RA) 治疗的下一个主要步骤是针对人们独特的基因组成和其他因素量身定制的治疗方法，以实现缓解。研究已经表明，此类疗法可以有益于公共健康。拟议的临床试验将比较两种新型治疗早期 RA 的缓解诱导能力，并寻找预测治疗反应的生物标志物。