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克拉屈滨片剂：评估多发性硬化症对中枢神经系统生物标志物影响的合作研究 (CLOCK-MS)

2026年7月26日 更新者：Gregory Wu
本研究的目的是通过探索对中枢神经系统 (CNS) 和与复发型多发性硬化症 (RMS；包括复发缓解型 MS) 相关的血液生物标志物的影响，更好地了解克拉屈滨片剂的作用机制 (MoA) [RRMS] 或活跃的二次进展性 MS）。

研究概览

地位

完全的

条件

干预/治疗

详细说明

这是一项开放标签、随机、多中心合作研究的第 4 期生物标志物研究，旨在生成假设以更好地了解克拉屈滨片剂在 RMS（包括 RRMS 或活动性继发进展型 MS）中的 MoA。 该研究旨在通过评估患有 RMS 的研究参与者之前和期间的淋巴细胞亚群、其他免疫细胞、神经元损伤标志物和可溶性免疫标志物的脑脊髓 (CSF) 水平，来生成关于克拉屈滨片剂活性对 CNS 的影响和相关性的假设用克拉屈滨片剂治疗，以及这些 CSF 标志物与相应血液标志物和临床结果的关联。

研究类型

介入性

注册 (实际的)

47

阶段

  • 第四阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • Missouri
      • St Louis、Missouri、美国、63110
        • Washington University School of Medicine
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73104
        • Oklahoma Medical Research Foundation
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19104
        • University of Pennsylvania
    • Texas
      • Dallas、Texas、美国、75390
        • University of Texas Southwestern Medical Center
    • Wisconsin
      • Milwaukee、Wisconsin、美国、53226
        • Medical College of Wisconsin

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 65年 (成人、年长者)

接受健康志愿者

不

描述

纳入标准：

  1. 患有复发型多发性硬化症（RMS；包括 RRMS 或活动性继发性进行性 MS）
  2. 愿意并能够接受至少 2 次腰椎穿刺
  3. 筛选期间的 EDSS 为 0 至 ≤ 5.5
  4. 在过去 12 个月内至少有 1 次复发或 1 次钆增强或 1 次新的或扩大的 T2 病灶
  5. 绝对淋巴细胞计数 (ALC) 在当地实验室的正常范围内或在 3 周筛选期内由研究者评估为正常，并且满足克拉屈滨片剂治疗的所有其他资格标准
  6. 能够签署知情同意书

排除标准：

  1. 有腰椎穿刺禁忌症
  2. 目前有恶性肿瘤
  3. 感染了人类免疫缺陷病毒（HIV）
  4. 有活动性慢性感染（例如 肝炎或肺结核）
  5. 在 MRI 中有提示进行性多灶性脑白质病 (PML) 的体征或症状
  6. 对克拉屈滨或克拉屈滨片剂美国处方信息中列出的任何赋形剂有过敏史
  7. 对钆过敏或超敏反应和/或任何其他进行 MRI 的禁忌症
  8. 有任何其他妨碍参与的合并症
  9. 以前接受过克拉屈滨治疗
  10. 以前曾接受过 ocrelizumab、alemtuzumab、rituximab 或 daclizumab 治疗
  11. 在过去 6 个月内接受过那他珠单抗治疗
  12. 目前正在接受免疫抑制或骨髓抑制治疗，例如甲氨蝶呤、环磷酰胺、环孢菌素或硫唑嘌呤，或全身性皮质类固醇的长期治疗
  13. 在过去 6 个月内接受过免疫抑制或骨髓抑制治疗
  14. 在过去 4 周内接受过长期全身性皮质类固醇治疗
  15. 有中度或重度肝功能损害（Child-Pugh 评分 >6）
  16. 有中度或重度肾功能损害（肌酐清除率
  17. 怀孕或在克拉屈滨药片给药期间和每个疗程最后一次给药后 6 个月内不愿意或不能使用有效的避孕措施
  18. 打算在克拉屈滨药片治疗当天和/或最后一次服用克拉屈滨药片后的 10 天内进行母乳喂养。

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：基础科学
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
其他：第 1 组：基线和第 5 周的 LP
第 1 组：基线和第 5 周结束时的 LP。第 5 周是评估 CSF 中克拉屈滨浓度的最佳时间点
药品：克拉屈滨
根据美国处方信息 (USPI)（每个疗程 1.75 mg/kg；第 1 年和第 2 年治疗），所有参与者将接受 10 mg 克拉屈滨片剂，累积剂量为 3.5 mg/kg，分为 2 个疗程。 患者将以 1:2:2:1 的比例随机分配，在治疗周期的特定时间点接受总共 2 次腰椎穿刺。
其他：第 3 组：基线和第 1 年末的 LP
第 3 组：基线和第 1 年末的 LP。 评估克拉屈滨对脑脊液标志物的影响是否在第一个治疗周期结束时得以维持
药品：克拉屈滨
根据美国处方信息 (USPI)（每个疗程 1.75 mg/kg；第 1 年和第 2 年治疗），所有参与者将接受 10 mg 克拉屈滨片剂，累积剂量为 3.5 mg/kg，分为 2 个疗程。 患者将以 1:2:2:1 的比例随机分配，在治疗周期的特定时间点接受总共 2 次腰椎穿刺。
其他：第 4 组：基线和第 2 年末的 LP
第 4 组：基线和第 2 年末的 LP。评估克拉屈滨对 CSF 标志物的影响是否在最后一个治疗周期结束时得以维持
药品：克拉屈滨
根据美国处方信息 (USPI)（每个疗程 1.75 mg/kg；第 1 年和第 2 年治疗），所有参与者将接受 10 mg 克拉屈滨片剂，累积剂量为 3.5 mg/kg，分为 2 个疗程。 患者将以 1:2:2:1 的比例随机分配，在治疗周期的特定时间点接受总共 2 次腰椎穿刺。
其他：Group 2: LP at Baseline and Week 10
Group 2: LP at Baseline and end of Week 10. Week 10 is the hypothesized "nadir" time for lymphocyte and monocyte levels in CSF
药品：克拉屈滨
根据美国处方信息 (USPI)（每个疗程 1.75 mg/kg；第 1 年和第 2 年治疗），所有参与者将接受 10 mg 克拉屈滨片剂，累积剂量为 3.5 mg/kg，分为 2 个疗程。 患者将以 1:2:2:1 的比例随机分配，在治疗周期的特定时间点接受总共 2 次腰椎穿刺。

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change in CD3+ T Cells % From Baseline to Week 5
大体时间：Baseline to Week 5 (5 weeks after first cladribine dose)
Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.
Baseline to Week 5 (5 weeks after first cladribine dose)
Change in CD3+ T Cells % From Baseline to Week 10
大体时间：Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.
Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CD3+ T Cells % From Baseline to Year 1
大体时间：Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.
Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CD3+ T Cells % From Baseline to Year 2
大体时间：Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.
Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 5
大体时间：Baseline to Week 5
Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.
Baseline to Week 5
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 10
大体时间：Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.
Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 1
大体时间：Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.
Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 2
大体时间：Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.
Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CD19+ B Cells % From Baseline to Week 5
大体时间：Baseline to Week 5 (5 weeks after first cladribine dose)
Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.
Baseline to Week 5 (5 weeks after first cladribine dose)
Change in CD19+ B Cells % From Baseline to Week 10
大体时间：Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.
Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CD19+ B Cells % From Baseline to Year 1
大体时间：Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.
Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CD19+ B Cells % From Baseline to Year 2
大体时间：Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.
Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 5
大体时间：Baseline to Week 5 (5 weeks after first cladribine dose)
Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.
Baseline to Week 5 (5 weeks after first cladribine dose)
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 10
大体时间：Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.
Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 1
大体时间：Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.
Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 2
大体时间：Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.
Baseline to Year 2 (45 weeks after last cladribine dose)
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 5
大体时间：Baseline to Week 5 (5 weeks after first cladribine dose)
Change in CSF level NfL (measured in pg/mL) from baseline to week 5 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.
Baseline to Week 5 (5 weeks after first cladribine dose)
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 10
大体时间：Baseline to Week 10 (10 weeks after first cladribine dose)
Change in CSF level NfL (measured in pg/mL) from baseline to Week 10 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.
Baseline to Week 10 (10 weeks after first cladribine dose)
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 1
大体时间：Baseline to Year 1 (45 weeks after first cladribine dose)
Change in CSF level NfL (measured in pg/mL) from baseline to Year 1 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.
Baseline to Year 1 (45 weeks after first cladribine dose)
Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 2
大体时间：Baseline to Year 2 (45 weeks after last cladribine dose)
Change in CSF level NfL (measured in pg/mL) from baseline to year 2 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.
Baseline to Year 2 (45 weeks after last cladribine dose)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Gregory Wu

合作者

EMD Serono

调查人员

  • 首席研究员：Gregory Wu, MD, PhD、Washington University School of Medicine

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2019年10月28日

初级完成 (实际的)

2025年5月27日

研究完成 (实际的)

2025年5月27日

研究注册日期

首次提交

2019年5月23日

首先提交符合 QC 标准的

2019年5月23日

首次发布 (实际的)

2019年5月24日

研究记录更新

最后更新发布 (实际的)

2026年7月28日

上次提交的符合 QC 标准的更新

2026年7月26日

最后验证

2026年7月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • MS700568_0049-201906092

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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