PHASE II STUDY OF HU23F2G IN ACUTE EXCERBATIONS OF MULTIPLE SCLEROSIS

多中心研究计划共纳入188例患者。 后 入组后，患者将被随机分配至四种治疗之一 组：安慰剂，甲基强的松龙1克，每天静脉注射3天，Hu23F2G lmg/kg IV或Hu23F2G 2mg/kg IV。 受试者将在治疗后随访一年，以便 评估与急性加重相关的早期变化（第0天至 90)以及随后的疗程（第91天至第365天）。 临床 将通过神经学检查表测量对治疗的反应 这三个数字得分是：斯克里普斯得分，总和 功能系统（FS）和修改的扩展残疾状态 量表（EDSS）。 主要终点为Scripps评分的变化 从第0天到第90天。 斯克里普斯评分被选为 主要结果指标，因为我们假设它会更 对急性加重环境变化的敏感性高于 另外两个分数。 第0天至第90天FS和EDSS总和的变化将 是次要终点。 将在以下时间之前获得脑部MRI： 治疗和第5天。 异常程度的变化 从第0天至第5天在MRI上检测到的将是次要终点。 由于皮质类固醇补救治疗将适用于被认为 分配的治疗失败，皮质类固醇抢救的时间 将是次要终点。 一年来的临床过程 将通过确定至 下一次急性加重和第365天的EDSS;这些参数还将 是次要终点。 体外生物活性和体内 Hu23F2G在实验性变态反应性非人灵长类动物模型中的功效 脑脊髓炎（EAE）支持在治疗中的潜在应用 MS的急性加重部分将在 这个协议。 基本原理是，EAE模型与 神经功能缺损急性发作和中枢神经系统新发病变 神经系统（CNS），类似于急性MS的事件 加重 在急性加重环境中，通常提供的治疗是三种 五天的皮质类固醇 该治疗持续时间相当 在一次给药后观察到的最大药效学效应的持续时间 在1期研究中，使用1至2mg/kg的单次IV剂量的Hu23F2G。 由于皮质类固醇治疗目前用于许多患者， 急性加重，在这项研究中，Hu23F2G治疗的效果将 与标准皮质类固醇方案沿着安慰剂进行比较。 皮质类固醇治疗也将适用于被认为 未能接受指定的治疗。

A total of 188 patients are planned for the multi-center study. Upon enrollment, patients will be randomly assigned to one of four treatment group: placebo, methylprednisolone 1 gram IV daily for 3 days, Hu23F2G 1 mg/kg IV, or Hu23F2G 2 mg/kg IV. The subjects will be followed for one year after treatment in order to assess the early changes related to the acute exacerbation (Day 0 to Day 90) as well as the subsequent course (Day 91 to Day 365). The clinical response to treatment will be measured by a neurologic examination form which three numerical scores are derived: the Scripps score, the sum of the Functional System (FS), and modified Expanded Disability Status Scale (EDSS). The primary endpoint will be the change in Scripps score form Day 0 through Day 90. The Scripps score was selected as the primary outcome measure because we hypothesize that it will be more sensitive to change in the setting of an acute exacerbation than the other two scores. The change in the sum of the FS and EDSS form Day 0 through Day 90 will be secondary endpoints. MRI of the brain will be obtained prior to treatment and on Day 5. The change in the extent of abnormalities detected on the MRI form Day 0 to Day 5 will be a secondary endpoint. Since corticosteroid rescue will be available for patients deemed to have failed the assigned treatment, the time to corticosteroid rescue will be a secondary endpoint. The clinical course over the year following treatment will be assessed by determining the time to the next exacerbation and the EDSS on Day 365; these parameters will also be secondary endpoints. The in vitro biologic activity and in vivo efficacy of Hu23F2G in a nonhuman primate model of experimental allergic encephalomyelitis (EAE) support a potential application in the treatment of MS. The acute exacerbation component of MS will be studied under this protocol. The rationale is that the EAE model is associated with acute onset of neurologic deficits and new lesions in the central nervous system (CNS), events that are analogous to the acute MS exacerbation. In the acute exacerbation setting, a treatment commonly offered is three to five days of corticosteroids. This treatment duration is comparable to the duration of maximal pharmacodynamic effects observed after a single IV dose of 1 to 2 mg/kg of Hu23F2G in Phase 1 studies. Since corticosteroids therapy is currently used for many patients with acute exacerbations, in this study the effects of Hu23F2G treatment will be compared to a standard corticosteroid regimen along with placebo. Corticosteroid therapy will also be available for patients deemed to have failed the assigned treatment.