Table 2.

Overview of clinical studies with mongersen.

Study drug	Study	Phase	Study population	Study design	Cohort size	Drug dosage and frequency of doses	Primary endpoint	Results
GED0301	Phase I clinical trial of Smad7 knockdown using antisense oligonucleotide in patients with active Crohn's disease (Monteleone et al., 2012)	Phase 1	CD patients with moderate to severe active disease (CDAI>220)	open-label study	15 CD patients	The patients were randomized to three treatment groups: GED0301 at a dosage of 40, 80, or 160 mg. The drug was administered orally once daily for 7 days	Safety and tolerability of the drug	The study evidenced good tolerability and safety of the drug
GED0301	A phase 1 open-label trial shows that smad7 antisense oligonucleotide (GED0301) does not increase the risk of small bowel strictures in Crohn's disease (Zorzi et al., 2012)	Phase 1	CD patients with an inflammatory phenotype and dependence and/or resistance to steroids	open-label study	15 CD patients	The patients were randomized to three treatment groups: GED0301 at a dosage of 40, 80, or 160 mg. The drug was administered orally once daily for 7 days	To evaluate whether GED0301 is associated with the formation of small bowel strictures	The treatment with GED0301 is not associated with the development of small bowel stricture as assessed by intestinal sonography
Mongersen (GED0301)	Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease (Monteleone et al., 2015)	Phase 2	CD patients with ileitis and/or right-sided colonic disease and moderate to severe active disease (CDAI 220–400)	Double-blind, placebo-controlled study	166 CD patients	The patients were randomized to four treatment arms: mongersen at a dosage of 10 mg per day, 40 mg per day, 160 mg per day or placebo. The drug was administered orally once daily for 2 weeks	Clinical remission (CDAI < 150) at day 15 and maintenance of remission for at least 2 weeks	Clinical remission at day 15 and maintenance for 2 weeks was evidenced in 55% of the patients treated with 40 mg of the drug, 65% of those treated with 160 mg and in 10% of placebo patients. This difference was statistically significant. Clinical remission at days 28 and 84 was significantly higher in the patients treated with 40 or 160 mg of the drug than in the group treated with 10 mg of the drug or with placebo
Mongersen (GED0301)	Effects of mongersen (GED-0301) on endoscopic and clinical outcomes in patients with active Crohn's disease (Feagan et al., 2018)	Phase 1	CD patients with active disease (CDAI≥220 to ≤ 450)	Double-blind study	63 CD patients	The patients were randomized to three treatment groups: GED0301 at a dosage of 160 mg per day for 4 weeks, 160 mg per day for 8 weeks and 160 mg per day for 12 weeks. The drug was administered orally	To evaluate endoscopic outcomes at week 12	The study evidenced endoscopic improvement (25% reduction SES-CD) in 37% of the patients with evaluable endoscopy at week 12. No significant difference was evidenced between treatment groups

CDAI, Crohn's disease Activity Index; Smad7, Mothers against decapentaplegic homolog 7; CD, Crohn's disease.