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

这是MSC在SLE （MiSLE）试验的4型临床试验扩展，以确定MSC是否为狼疮治疗提供了一种安全有效的替代方案。拟议的延长将能够完成数据清理、统计分析和机制研究。患者就诊和MSC准备的资金支持由美国狼疮基金会提供，这是一种相对独特的合作安排，使这项试验成为可能。NIAID的五年支持将于2023年3月31日结束。批准了一项无成本延期，允许结转资金继续进行试验及其组成部分，同时等待标题4的批准。需要延长这一期限，以抵消因COVID大流行而导致的试验入组延迟。随着大流行开始，由于患者担心到医疗中心就诊，注册人数有所放缓。根据当地IRB的决定，该试验已停止入组。即使在重新开放后，由于持续的患者担忧，登记也放慢了速度。在过去的3-4个月里，入学率已恢复到covid前的水平。此时，在双盲登记和随机分组中，56/81例患者以2/1的比例输注MSCs与安慰剂的研究产品。我们建议在延期的前12-18个月完成入组，在延期的36个月结束前完成数据分析和机制研究。试验的所有方面，包括招募、同意、输液、随访、数据输入和生物样本处理，都达到了试验前的目标。我们增加了两个新的网站（范斯坦和俄克拉何马医学研究基金会）来增加注册人数。我们目前的入组率是每月2例患者。这项研究最初的两个目的没有改变。目的一是完成MSCs在标准治疗难治性狼疮患者中的多中心双盲安慰剂对照试验。目的二是对患者治疗前后进行深入的免疫表型分析，确定充注MSC对B细胞、T细胞和单核细胞表型和功能的影响。该试验将深入了解MSC输注治疗狼疮的安全性和有效性，或证实中国非盲法试验的阳性结果。机制研究将为MSCs的免疫机制提供信息。

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.