Clinical Trials

Date: 2016-10-18

Type of information: Presentation of results at a congress

phase: 1

Announcement: presentation of results at the United European Gastroenterology Week (UEGW)

Company: Celgene (USA - NJ)

Product: GED-0301 (mongersen)

Action mechanism:

• antisense drug/oligonucleotide/antisense oligonucleotide. Mongersen (GED-0301) is an antisense oligonucleotide that targets the messenger RNA (mRNA) for Smad7, thereby reducing Smad7 protein levels. In patients with Crohn's disease, abnormally high levels of Smad7 interfere with TGF-?1 anti-inflammatory pathways in the gut, leading to increased inflammation. The distinct formulation of the tablet is designed to release GED-0301 into the far end of the small intestine (the terminal ileum) and near the end of the colon (right colon), where it is thought to act locally to reduce Smad7 levels.

Disease: Crohn disease

Therapeutic area: Autoimmune diseases - Inflammatory diseases - Digestive diseases

Country: Australia, Canada, Hungary, Slovakia, USA

Trial details:

• CD-001 is a phase 1b randomized, double-blind, multicenter, exploratory study evaluating the effects of oral GED-0301 on endoscopic and clinical outcomes in patients with active Crohn's disease. A total of 63 patients were randomized in a 1:1:1 ratio to receive one of three treatment regimens in a 12-week treatment phase: GED-0301 160 mg once daily for 12 weeks; GED-0301 160 mg once daily for eight weeks followed by four weeks of placebo; or GED-0301 160 mg once daily for four weeks followed by eight weeks of placebo. This treatment phase was followed by an off-treatment observation phase for up to 52 weeks. Eligible patients can also enter an extension phase (on treatment) for an additional 24 weeks. (NCT02367183)

Latest news:

• • On October 18, 2016, Celgene presented data from a randomized, double-blind, multicenter, exploratory phase Ib study evaluating the effects of oral GED-0301 (mongersen) on both endoscopic and clinical outcomes in patients with active Crohn's disease  at the United European Gastroenterology Week. Patients with active Crohn's disease [Crohn's disease activity index (CDAI) score 220-450], a total simple endoscopic score for Crohn's disease (SES-CD) ?7, or an ileal disease SES-CD ?4, were randomized to three different active treatment regimens of four, eight or 12 weeks of GED-0301 160 mg daily, followed by an observation period off treatment. Endoscopic and clinical assessments were reported through week 12. A total of 63 patients were enrolled in the study. The study was designed to further enhance the understanding of GED-0301 activity in a difficult-to-treat, moderate to severe patient population. This population was more diverse than prior GED-0301 studies and included patients with endoscopically confirmed mucosal damage at entry and those who had previous surgeries. The study also included both biologic-exposed and biologic-naïve patients, as well as patients with a diagnosis of Ileitis, Ileocolitis or colitis. Clinical improvement was seen by week 2, and clinical response (CDAI decrease ?100) and remission (CDAI < 150) rates were highest in the 12-week treatment group at 67 and 48 percent respectively, at week 12. The mean CDAI reduction from baseline at week 12 in the 12-week treatment group was 133 points. Of the patients with evaluable endoscopies at week 12 (n=52), 37 percent had an endoscopic response (?25 percent reduction in SES-CD score from baseline), with no meaningful difference across treatment groups. In addition, of those patients with greater endoscopic disease activity at baseline (SES-CD score of > 12; n=16), 63 percent exhibited a reduction ?25 percent in SES-CD score and 31 percent had a reduction of ?50 percent. The rates of adverse events and serious adverse events were low and similar across treatment groups. There were no new safety signals for oral GED-0301 160 mg daily reported in this study.
• * On September 12, 2016, Celgene announced interim topline data from a randomized, double-blind, multicenter, exploratory phase 1b study evaluating the effects of oral GED-0301 (mongersen) on both endoscopic and clinical outcomes in patients with active Crohn's disease. The trial, CD-001, is an ongoing study evaluating three different treatment regimens of GED-0301 in a 12-week treatment phase, followed by an observation phase up to 52 weeks (off treatment). The primary objective of the study is to explore the effect of GED-0301 on endoscopic outcomes. The trial enrolled a total of 63 patients across multiple countries. The study was designed to further enhance the understanding of GED-0301 activity in a difficult-to-treat, moderate-to-severe patient population. This population was more diverse than prior GED-0301 studies and included patients with endoscopically confirmed mucosal damage at entry and those who had previous surgeries. The study also included both biologic exposed and biologic naïve patients as well as patients with a diagnosis of Ileitis, Ileocolitis or colitis. Topline data from CD-001 show that in a proportion of patients treated with oral GED-0301 there was endoscopic improvement (defined as a 25 percent improvement from baseline) and clinical response and remission across all treatment groups at week 12. Findings to date reveal no new safety signals and tolerability is consistent with earlier studies. "At this early 12-week timepoint, we're looking at the proportion of patients who had a 25 percent or greater endoscopic improvement, suggesting mucosal healing is underway in these patients," said Dr. William Sandborn , M.D., Professor of Medicine and Chief, Division of Gastroenterology and Director, University of California San Diego Inflammatory Bowel Disease Center . "These data support the notion that GED-0301, a potential first-in-class oral antisense therapy, may target an underlying cause of Crohn's disease, rather than simply improving symptoms." Full data from the 12-week timepoint have been submitted for presentation at an upcoming scientific meeting later this year. The CD-001 study is ongoing until all patients complete the observation phase. Data from the observation portion of the trial are expected in 2017. The Phase III registration program is ongoing.

Is general: Yes