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

这是MSC在系统性红斑狼疮(MISLE)试验中的4型临床试验扩展，以确定MSCs是否为目前的狼疮治疗提供了一种安全有效的替代方案。拟议的延期将使数据清理、统计分析和机制研究得以完成。美国狼疮基金会以一种相对独特的合作安排为患者就诊和MSC准备提供资金支持，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。批准了无费用延期，允许结转资金继续审判及其组成部分，同时等待第4章所希望的批准。这一延期是为了抵消由于新冠状病毒大流行而导致的试验登记延迟。由于患者对来医疗中心的担忧，随着大流行的开始，注册人数放缓。这项试验不对遵守当地IRB决定的注册人员开放。即使在重新开放注册人数因持续的患者担忧而放缓之后。在过去的3-4个月中，注册人数已恢复到COVID之前的水平。此时，在双盲登记和随机试验中，56/81名患者接受了研究产品的输注，比例为MSCs和安慰剂的2/1。我们建议在延期的头12-18个月内完成登记，并在延期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。我们目前的投保率是每月2名患者。这项研究的两个最初目的保持不变。目的一是完成标准治疗难治性狼疮患者间充质干细胞的多中心双盲安慰剂对照试验。目的二是对患者治疗前后的免疫表型进行深入研究，以确定骨髓间充质干细胞输注对B细胞、T细胞和单核细胞表型及功能的影响。这项试验将为骨髓间充质干细胞输注治疗狼疮的安全性和有效性提供深入的见解，或者证实中国的非盲法试验的积极结果。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.