MEthotrexate Response in Treatment of UC - MERIT-UC

描述（由申请人提供）：我们提出了一项前瞻性安慰剂对照研究，以调查活动性UC患者每周一次皮下注射25mg MIX的安全性和有效性，这些患者要么是类固醇依赖，要么是对硫唑嘌呤/6-巯基嘌呤治疗不耐受或无反应，或者在研究纳入之前对英夫利昔单抗无反应/无反应。在实施计划（U34）拨款的背景下，我们最终确定了该试验的研究方案和相关的正式要求。我们获得了领先的IRB批准，目前正在获得参与站点的IRB批准。我们向FDA注册了IND号（108,560），并利用美国克罗恩病和结肠炎基金会（CCFA）临床研究联盟（CRA）的中心框架，为这项前瞻性安慰剂对照多中心研究建立了研究基础设施。该试验的具体目的是：1)评估25 mg MTX的安全性和耐受性，每周一次，持续48周。2)评估MTX维持治疗与安慰剂在32周内的无复发生存期。3)评估MTX在16周内诱导无类固醇缓解的疗效。4)建立DNA、血浆和血清文库，评估临床和药物基因组学模型，预测UC患者对MTX治疗的反应。

DESCRIPTION (provided by applicant): We propose a prospective placebo controlled study to investigate the safety and efficacy of 25 mg MIX applied subcutaneously once weekly in patients with active UC, who are either steroid dependent or are intolerant or not responding to azathioprine/6-mercaptopurine therapy or have no response/ lost response to infliximab prior to the study inclusion. In the setting of an implementation-planning (U34) grant we finalized the study protocol and associated formal requirements for this trial. We obtained a lead IRB approval and are currently obtaining IRB approvals of the participating sites. We registered an IND number (108,560) with the FDA and established the study infrastructure for this prospective placebo-controlled multi-center study using the center framework of the Crohn's and Colitis Foundation of America (CCFA) Clinical Research Alliance (CRA). The Specific Aims of the trial are: 1) To evaluate the safety and tolerability of 25 mg MTX applied sq once weekly over a time period of 48 weeks. 2) To evaluate the relapse-free survival of MTX maintenance therapy compared to placebo over a time period of 32 weeks. 3) To evaluate the efficacy of MTX over a time period of 16 weeks to induce steroid free remission. 4) To establish a DNA, plasma and serum library to enable the evaluation of clinical and pharmacogenomic models to predict the response to MTX therapy in patients with UC.