A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus

同种异体间充质干细胞治疗难治性狼疮的 II 期对照试验

• 批准号: 10827646
• 负责人: Gary S Gilkeson
• 金额: $ 46.44万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-19 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10827646
• 关键词: Phase; II; Controlled; Trial; Allogeneic; Phase; II; Controlled; Trial; Allogeneic

This a Type 4 clinical trial extension for the MSC in SLE (MiSLE) trial to determine if MSCs provide a safe and effective alternative to current therapies in lupus. The proposed extension will enable completion of the data cleaning, statistical analysis and mechanistic studies. The monetary support for patient visits and MSC preparation is provided by the Lupus Foundation of America in a relatively unique collaborative arrangement making this trial possible. The five years of NIAID support end on 03/31/2023. A No Cost Extension was granted allowing carryover of funds to continue the trial and its components while awaiting the hoped for Title 4 approval. This extension is needed to offset the delays in enrollment in the trial due to the COVID pandemic. Enrollment slowed as the pandemic began due to patient concerns for coming to a medical center. The trial was closed to enrollment in abiding by local IRB determinations. Even after re-opening enrollment was slowed by ongoing patient concerns. Over the last 3-4 months enrollment has returned to pre-COVID rates. At this time, 56/81 patients are infused with investigational product in a 2/1 ratio of MSCs versus placebo in a double blind enrollment and randomization. We propose to complete enrollment in the first 12-18 months of the extension, with completion of the data analysis and mechanistic studies by the 36 month end of the extension. All aspects of the trial including recruitment, consent, infusion, followup, data entry and biologic sample handling have met pretrial goals. We added two new sites (Feinstein and Oklahoma Medical Research Foundation) to enhance enrollment. Our current enrollment rate is 2 patients per month. The two original aims of the study remain unchanged. Aim one is to complete the multicenter double blind placebo controlled trial of MSCs in standard of care refractory lupus patients. Aim two is to perform in depth immune phenotype of the patients pre and post treatment to determine the impacts of MSC infusions on B cell, T cell and mononuclear cell phenotypes and function. This trial will provide insight into the safety and efficacy of MSC infusion in lupus either confirming the positive results in unblinded trials from China. Mechanistic studies will inform immune mechanisms of MSCs.

这是SLE（MISLE）试验中MSC的4型临床试验扩展，以确定MSC是否为狼疮目前疗法提供了安全有效的替代方法。 拟议的扩展将使数据清洁，统计分析和机理研究完成。美国狼疮基金会在相对独特的协作安排中提供了对患者就诊和MSC准备的货币支持，这使这项试验成为可能。 NIAID支持五年将于2010年3月31日结束。允许延期延长成本，允许承担资金继续进行审判及其组件，同时等待希望获得第4章的批准。需要此扩展以抵消由于共同大流行而导致的审判延迟。由于患者担心来医疗中心的担忧，入学率放缓。该试验因当地IRB确定而持续下来，以纳入该试验。 即使在重新开放后，持续的患者担忧也减慢了入学率。 在过去的3-4个月中，入学率已经恢复到前循环率。 目前，在双盲入学和随机分组中，将56/81例患者注入了2/1的MSC与安慰剂的比例。我们建议在扩展的最初12-18个月内完成入学，并在扩展的36个月结束之前完成数据分析和机械研究。试验的所有方面，包括招聘，同意，输液，随访，数据输入和生物样品处理，都达到了审前目标。我们添加了两个新站点（Feinstein和Oklahoma医学研究基金会），以增强入学率。 我们目前的入学率为每月2名患者。 研究的两个原始目标保持不变。 目的是完成MSC的多中心双盲安慰剂对照试验在护理标准的难治性狼疮患者中。 目标二是在治疗前和治疗后的患者深度进行免疫表型，以确定MSC输注对B细胞，T细胞和单核细胞表型和功能的影响。 该试验将洞悉狼疮中MSC输注的安全性和功效，要么证实中国无盲试验的积极成果。机械研究将为MSC的免疫机制提供信息。