OBJECTIVES To assess the efficacy and safety of GED-0301, an antisense oligodeoxynucleotide to Smad7, in active Crohn's disease (CD). METHODS This phase 3, blinded study randomized patients (1:1:1:1) to placebo or 1 of 3 once-daily oral GED-0301 regimens: 160 mg for 12 weeks followed by 40 mg continuously or alternating placebo with 40 or 160 mg every 4 weeks through week 52. RESULTS In all, 701 patients were randomized and received study medication before premature study termination; 78.6% (551/701) completed week 12, and 5.8% (41/701) completed week 52. The primary endpoint, clinical remission achievement (CD Activity Index score <150) at week 12, was attained in 22.8% of patients on GED-0301 vs 25% on placebo (P = 0.6210). At study termination, proportions of patients achieving clinical remission at week 52 were similar among individual GED-0301 groups and placebo. More placebo vs GED-0301 patients achieved endoscopic response (>50% decrease from baseline Simple Score for CD) at week 12 (18.1% vs 10.1%). Additional endoscopic endpoints were similar between groups at weeks 12 and 52. More placebo vs GED-0301 patients had clinical response (≥100-point decrease in the CD Activity Index score) at week 12 (44.4% vs 33.3%); at week 52, clinical response rates were similar. Adverse events were predominantly gastrointestinal and related to active CD, consistent with lack of clinical and endoscopic response to treatment. Two deaths occurred (GED-0301 total group) due to small intestinal obstruction and pneumonia; neither was suspected by the investigator to be treatment-related. DISCUSSION GED-0301 did not demonstrate efficacy vs placebo in active CD.

中文翻译：

---

Mongersen (GED-0301) 治疗活动性克罗恩病

目的 评估 GED-0301（一种 Smad7 的反义寡脱氧核苷酸）在活动性克罗恩病 (CD) 中的疗效和安全性。方法 该 3 期盲法研究将患者（1:1:1:1）随机分配至安慰剂或 3 种每日一次口服 GED-0301 方案中的一种：160 毫克，持续 12 周，然后连续 40 毫克或安慰剂与 40 或 160 mg 每 4 周至第 52 周。 结果 总共有 701 名患者被随机分组​​并在提前终止研究前接受研究药物治疗；78.6% (551/701) 完成第 12 周，5.8% (41/701) 完成第 52 周。 22.8% 的患者在第 12 周达到主要终点，临床缓解成就（CD 活动指数评分 <150） GED-0301 对比安慰剂的 25% (P = 0.6210)。在研究终止时，个体 GED-0301 组和安慰剂组在第 52 周达到临床缓解的患者比例相似。与 GED-0301 相比，更多的安慰剂患者在第 12 周（18.1% 对 10.1%）实现了内窥镜反应（从 CD 的基线简单评分下降 > 50%）。在第 12 周和第 52 周时，两组之间的其他内窥镜终点相似。在第 12 周（44.4% 对 33.3%），更多的安慰剂患者与 GED-0301 患者有临床反应（CD 活动指数评分下降≥100 分）；在第 52 周，临床反应率相似。不良事件主要是胃肠道，与活动性 CD 相关，与临床和内镜治疗缺乏反应一致。2例因小肠梗阻和肺炎死亡（GED-0301组）；调查人员怀疑两者都与治疗有关。