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的安慰剂对照研究，以调查在纳入研究之前对类固醇依赖或对硫唑嘌呤/6-硫代嘌呤治疗不耐受或无反应，或对英夫利昔单抗无反应/失去反应的活动期UC患者每周皮下应用25 mg Mix的安全性和有效性。在实施规划(U34)拨款的背景下，我们最终确定了这项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，目前正在获得参与网站的IRB批准。我们在FDA注册了IND编号(108,560)，并使用美国克罗恩和结肠炎基金会(CCFA)临床研究联盟(CRA)的中心框架，为这项前瞻性的安慰剂对照的多中心研究建立了研究基础。该试验的具体目的是：1)评估25毫克甲氨蝶呤的安全性和耐受性，每周一次，持续48周。2)评估MTX维持治疗与安慰剂相比在32周内的无复发存活率。3)评价甲氨蝶呤在16周内诱导非激素缓解的疗效。4)建立DNA、血浆和血清文库，对临床模型和药物基因组模型进行评价，以预测溃疡性结肠炎患者对MTX治疗的反应。 与公共卫生相关：尽管甲氨蝶呤在市场上已经上市几十年了，但在5-ASA、硫唑嘌呤或抗肿瘤坏死因子治疗失败的患者中使用非肠道注射甲氨蝶呤的治疗方法正在开创一种潜在的新疗法。试验结果将为MTX在UC患者中的治疗价值提供必要的数据，这可能会影响目前UC的全球治疗实践。

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. PUBLIC HEALTH RELEVANCE: Despite MTX being on the market for decades, the therapeutic approach using parenteral administered MTX in patients failing established therapies such as 5-ASA, thiopurines or anti-TNF therapies is pioneering a potential novel therapy. The results of the trial will provide the necessary data for the therapeutic value of MTX in UC patients, which will likely influence the current global therapeutic practice in UC.