Robarts Clinical Trials and Western University, London, Ontario, Canada.
Icahn School of Medicine at Mount Sinai, New York, New York.
Gastroenterology. 2018 Jan;154(1):61-64.e6. doi: 10.1053/j.gastro.2017.08.035. Epub 2017 Aug 25.
GED-0301 is an antisense oligodeoxynucleotide with a sequence complementary to the Smad7 mRNA transcript. Smad7 is a negative regulator of transforming growth factor-β, which is increased in the intestinal mucosa of patients with active Crohn's disease (CD). We randomly assigned 63 CD patients to 4-, 8-, or 12-week treatment groups receiving oral GED-0301 (160 mg/day). The primary objective was to determine GED-0301's effect on endoscopic CD measures; secondary objectives included effects on clinical activity. Endoscopic improvement was observed in 37% of participants with evaluable endoscopy results at week 12. At week 12, 32% (4 weeks), 35% (8 weeks), and 48% (12 weeks) of patients receiving GED-0301 were in remission (CD activity index score <150); corresponding reductions from baseline in mean CD activity index scores were -124, -112, and -133 points. No new safety signals were observed. These findings support a GED-0301 benefit in active CD. ClinicalTrials.gov no: NCT02367183.
GED-0301 是一种与 Smad7 mRNA 转录本互补的反义寡脱氧核苷酸。Smad7 是转化生长因子-β的负调节剂，在活动性克罗恩病（CD）患者的肠道黏膜中增加。我们将 63 名 CD 患者随机分配到 4、8 或 12 周治疗组，接受口服 GED-0301（每天 160mg）治疗。主要目标是确定 GED-0301 对内镜 CD 测量的影响；次要目标包括对临床活动的影响。在第 12 周具有可评估内镜结果的参与者中，观察到 37%的内镜改善。在第 12 周，32%（4 周）、35%（8 周）和 48%（12 周）接受 GED-0301 治疗的患者处于缓解状态（CD 活动指数评分<150）；与基线相比，平均 CD 活动指数评分分别降低了-124、-112 和-133 分。未观察到新的安全信号。这些发现支持 GED-0301 在活动性 CD 中的获益。ClinicalTrials.gov 编号：NCT02367183。
