A PHASE II TRIAL OF RITUXAN IN MULTIPLE SCLEROSIS

Rituxan 治疗多发性硬化症的 II 期试验

• 批准号: 7377183
• 负责人: DOROTHY ANNE CROSS
• 金额: $ 2.83万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377183
• 关键词: PHASE; II; TRIAL; RITUXAN; MULTIPLE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rituxan (Genetech) is a humanized monoclonal antibody directed against the B-cell specific antigen, CD20. It has been used for several years in the therapy of non-Hodgkin's lymphoma. There is experience using this agent in several hundred human subjects, but not in MS patients. The agent will be administered intravenously in 4 doses, one week apart of 375mg/m2. This dose eliminates circulating B cells completely for up to 6 months following therapy. There is considerable data that B cells and/or antibody may be involved in the jpathogenesis of MS. However, to determine whether B cells truly play a role will require an assessment of whether their eliminiation benefits the course of MS. Therefore, as a first step we propose a 30 patient, Phase II trial of the safety and efficacy of Rituxan in 30 patients with active, relapsing MS. Patients will continue taking the standard dose of beta-interferon while in the trial. Subjects enrolled in the trial must have evidence of two gadolinium0enhacing lesions on any of three pre-treatment brain MRIs, and will have had at least one clinical relapse in the 18months prior to enrollment, despite being on beta-interferon therapy. The endpoints will be safety, in terms of toxicity of the agent and the possibility of worsening of MS, and efficacy based on the surrogate measure of MRI activity. The primary efficacy endpoint will be reduction in volume of gadolinium-enhancing lesions on the 3-once-monthly brain MRIs performed post-treatment in comparison to the three once-monthly MRIs performed pre-treatment.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Rituxan（Genetech）是一种针对B细胞特异性抗原CD 20的人源化单克隆抗体。它已被用于非霍奇金淋巴瘤的治疗多年。有在数百名人类受试者中使用这种药物的经验，但没有在MS患者中使用。该药物将分4次静脉给药，间隔一周，剂量为375 mg/m2。该剂量可在治疗后6个月内完全消除循环B细胞。有相当多的数据表明B细胞和/或抗体可能参与MS的发病机制。然而，为了确定B细胞是否真正发挥作用，将需要评估它们的消除是否有益于MS的过程。因此，作为第一步，我们提出了一项30名患者的II期试验，在30名活动性MS患者中研究Rituxan的安全性和疗效，复发性MS患者在试验期间将继续服用标准剂量的β-干扰素。入组试验的受试者必须在三次治疗前脑部MRI中的任何一次上有两处钆增强病变的证据，并且在入组前18个月内至少有一次临床复发，尽管正在接受β-干扰素治疗。终点将是安全性（就药物毒性和MS恶化的可能性而言）和基于MRI活性替代指标的疗效。主要有效性终点将是与治疗前进行的每月一次的3次MRI相比，治疗后进行的每月一次的3次脑部MRI中钆增强病变的体积减少。