Ibudilast Phase II trial in progressive MS

异丁司特治疗进展性多发性硬化症的 II 期试验

• 批准号: 8701420
• 负责人: Robert J. Fox
• 金额: $ 337.65万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8701420
• 关键词: Affect; American; Animals; Asthma; Atrophic; Biological; Biological Markers; Brain; Cerebrospinal Fluid; Cerebrovascular Disorders; Clinical; Clinical Research; Clinical Trials; Data; Diffusion Magnetic Resonance Imaging; Disease; Frequencies; Future; Image; In Vitro; Inflammatory Response; Japan; Lesion; Light; Magnetic Resonance Imaging; Measurement; Measures; Metric; Migration Inhibitory Factor; Multiple Sclerosis; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neuroprotective Agents; Optical Coherence Tomography; Outcome; Outcome Measure; Patient Self-Report; Patients; Performance; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Placebo Control; Placebos; Plasma; Property; Pyramidal Tracts; Randomized; Relapse; Research Infrastructure; Safety; Sample Size; Signal Transduction; Staging; Techniques; Testing; Therapeutic; Time; arm; base; brain tissue; cerebral atrophy; clinically relevant; cost; design; disability; dosage; efficacy testing; imaging modality; inhibitor/antagonist; injured; neurofilament; neuroprotection; phenylpyruvate tautomerase; phosphoric diester hydrolase; placebo controlled study; prevent; primary outcome; public health relevance; repaired; response; young adult

DESCRIPTION (provided by applicant): Current therapies for multiple sclerosis (MS) inhibit the inflammatory response, but neither sufficiently inhibits ongoing degeneration within the brain nor provide potential repair to injured brain tissue. Consequently, there are no therapies with demonstrated efficacy in slowing, stopping, or reversing the progressive stage of MS, therefore representing an extreme unmet need in neurologic disease. Complicating matters, there are no biological or imaging markers with demonstrated utility for use in Phase 2 trials to screen putative therapies for progressive MS. This study proposes to both test the activity of a potential neuroprotection therapy - ibudilast - in progressive MS and test several candidate imaging measures for their utility in future studies of neuroprotection in progressive MS. We plan to conduct a 2-year; placebo-controlled trial of ibudilast in progressive MS. Multiple advanced imaging modalities will be used to evaluate the activity of ibudilast. At the conclusion of the tril, we will have a clear understanding of the effect of ibudilast on advanced imaging metrics and its safety and potential clinical benefit in progressive MS. Through additional analyses, we will determine which imaging metric provides the most robust and practical outcome for implementation in future clinical trials in progressive MS. Hopefully, this study will show efficac of ibudilast that leads to the first primary neuroprotective drug. Even if ibudilast is not found beneficial, the study will be crucial to the MS field by comparing imaging metrics to support practical Phase II trials for a group of MS patients for whom there is no treatment option.

描述（由申请人提供）：目前多发性硬化症（MS）的疗法可抑制炎症反应，但既不能充分抑制大脑内正在进行的退化，也不能为受损的脑组织提供潜在的修复。因此，没有任何疗法能够有效减缓、停止或逆转多发性硬化症的进展阶段，因此神经系统疾病的需求极度未得到满足。让事情变得更复杂的是，没有任何生物或成像标记物被证明可以在二期试验中用于筛选进展性多发性硬化症的推定疗法。这项研究建议测试潜在的活性 神经保护疗法——异丁司特——在进行性多发性硬化症中的应用，并测试了几种候选影像学方法在未来进行性多发性硬化症神经保护研究中的实用性。我们计划进行为期2年的；异丁司特治疗进展性多发性硬化症的安慰剂对照试验。将使用多种先进的成像方式来评估异丁司特的活性。在试验结束时，我们将清楚地了解异丁司特对先进成像指标的影响及其安全性和进行性多发性硬化症的潜在临床益处。通过额外的分析，我们将确定哪种成像指标能够为未来进展性多发性硬化症临床试验提供最可靠、最实用的结果。希望这项研究能够证明异丁司特的功效，从而成为第一种主要的神经保护药物。即使异丁司特没有被发现有益，这项研究对于多发性硬化症领域也至关重要，通过比较成像指标来支持针对一组没有治疗选择的多发性硬化症患者的实际 II 期试验。