MEthotrexate Response in Treatment of UC - MERIT-UC

描述（由申请人提供）：我们提出一项前瞻性安慰剂对照研究，以调查每周一次皮下注射 25 mg MIX 治疗活动性 UC 患者的安全性和有效性，这些患者要么是类固醇依赖性的，要么是对硫唑嘌呤/6-巯基嘌呤治疗不耐受或无反应，或者是在研究纳入之前对英夫利昔单抗没有反应/失去反应。在实施计划 (U34) 拨款的设定中，我们最终确定了本次试验的研究方案和相关正式要求。我们获得了主要 IRB 的批准，目前正在获得参与站点的 IRB 批准。我们向 FDA 注册了 IND 编号 (108,560)，并使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。该试验的具体目标是： 1) 评估在 48 周内每周一次使用 25 mg MTX 的安全性和耐受性。 2) 评估 MTX 维持治疗与安慰剂相比 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功效。 4) 建立DNA、血浆和血清库，以评估临床和药物基因组模型，以预测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.