Pharmacodynamic and Clinical Outcome Study of Mongersen in Patients With Crohn's Disease
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 2, Open-label Study to Explore the Pharmacodynamic and Clinical Effects of Mongersen (GED-0301) in Subjects With Active Crohn's Disease|
- Change from baseline of Smad7 (Mothers Against Decapentaplegic homolog 7) expression in the intestinal mucosa [ Time Frame: Baseline and Week 12 ]Smad7 is a protein important in cell interactions and stands for "Mothers against decapentaplegic homolog 7" protein
- Change from baseline in messenger ribonucleic acid (mRNA) expression of inflammatory cytokines [ Time Frame: Baseline and Week 12 ]Change from baseline in the mRNA expression of inflammatory cytokines such as, but not limited to, interleukin (IL)-10, IL-25, chemokine (C-C motif) ligand 20 (CCL20) and tumor necrosis factor alpha (TNF-α) in the intestinal mucosa at Week 12, from biopsy samples during ileocolonoscopy
- The proportion of subjects achieving clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score < 150, at Weeks 4, 8, and 12 [ Time Frame: Up to week 12 ]The CDAI is a measure of disease activity in patients with Crohn's Disease.
- Change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 and 52 [ Time Frame: Week 12 and week 52 ]The SES-CD is a measure that indicates mucosal inflammation in the end part of the ileum (or small intestine) and colon (or large intestine) in patients with Crohn's Disease
- Number of Adverse Events [ Time Frame: Up to Week 56 ]The evaluation of safety and tolerability of GED-0301, assessed by the type, frequency and severity of adverse events, and its relationship to investigational product (IP), discontinuation due to adverse events, and clinically significant changes in electrocardiograms (ECGs), vital signs, and/or laboratory findings
|Actual Study Start Date:||April 4, 2016|
|Estimated Study Completion Date:||October 28, 2019|
|Estimated Primary Completion Date:||January 26, 2018 (Final data collection date for primary outcome measure)|
Experimental: GED-0301 Induction (160mg) followed by intermittent 160 mg
GED-0301 160 mg "by mouth" (PO) daily (QD) for 12 weeks, followed by alternating GED 0301 160 mg QD for 4 weeks and no IP for 4 week, up to Week 100
During Induction period patient will receive mongersen 160 mg daily for 12 weeks. This study also offers subjects the option to continue with maintenance treatment at the discretion of the Investigator, beginning after the Week 12 Visit with alternating no IP for 4 weeks, followed by mongersen (GED-0301) 160 mg QD for 4 weeks, up through the Week 52 Visit during the Maintenance Period. At Week 52, subjects who have achieved an endoscopic improvement of >50% from baseline based on the SES-CD, as assessed by the central reader, and clinical improvement (HBI <7), will have the option to continue receiving treatment for an additional year, up through Year 2 (ie, the Week 100 Visit).
Other Name: Mongersen
Subjects will be screened to provide 20 enrolled subjects who complete 12 weeks of mongersen (GED-0301) 160 mg QD treatment as open-label therapy.
The study will consist of 4 periods:
- Screening Period - up to 4 weeks
- Induction Period - 12 weeks (Week 0 Visit through Week 12 Visit)
- Maintenance Period - 88 weeks (after Week 12 Visit through Week 100 Visit)
- Follow-up Period - 4 weeks (ie, no IP taken)
Subjects who prematurely discontinue treatment from this study prior to Week 100 will have an Early Termination Visit and also enter the 4-week Follow-up Period.
At the Screening Visit, all subjects who meet the entrance criteria will be eligible to enter the study. The number of subjects with previous exposure to Tumor Necrosis Factor-Alpha (TNF-α) blockers is targeted to be approximately 40% (ie, approximately 8 subjects).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02685683
|Contact: Associate Director Clinical Trial Disclosureemail@example.com|
|Fondazione IRCCS Policlinico San Matteo||Recruiting|
|Pavia, Italy, 27100|
|Policlinico Tor Vergata||Recruiting|
|Rome, Italy, 0133|
|Study Director:||Keith Usiskin, MD||Celgene|