Pharmacodynamic and Clinical Outcome Study of Mongersen in Patients With Crohn's Disease
- Registration Number
- NCT02685683
- Lead Sponsor
- Celgene
- Brief Summary
This study is designed to explore mechanism of action of mongersen (GED-0301) 160 mg once daily in patients with active Crohn's Disease
- Detailed Description
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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 18
- Male or female ≥ 18 years of age.
- Active Crohn's disease (CD) disease as determined by the Crohn's Disease Activity Index (CDAI) score and the Simple Endoscopic Score for Crohn's Disease (SES-CD)
- Subject must have failed or experienced intolerance to at least one of the following: budesonide; systemic corticosteroids; immunosuppressants (eg, azathiopurine, 6-mercaptopurine, or methotrexate); or biologics for the treatment of CD.
- Subject must use protocol approved contraception
- Diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis
- Crohn's Disease (CD) manifestations such as abscesses, short bowel syndrome; or intestinal strictures with prestenotic dilatation, requiring procedural intervention or not passable with an adult colonoscope.
- Intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit
- Ileostomy or a colostomy
- Prior treatment with more than 2 TNF-α blockers (eg, infliximab or adalimumab).
- Prior treatment with any integrin antagonists (eg, natalizumab or vedolizumab).
- Subject is pregnant or breastfeeding.
- Subject has received prior treatment with mongersen (GED-0301), or participation in a clinical study involving mongersen (GED-0301).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description GED-0301 Induction (160mg) followed by intermittent 160 mg GED-0301 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
- Primary Outcome Measures
Name Time Method Change from baseline of Smad7 (Mothers Against Decapentaplegic homolog 7) expression in the intestinal mucosa Baseline and Week 12 Smad7 is a protein important in cell interactions and stands for "Mothers against decapentaplegic homolog 7" protein
- Secondary Outcome Measures
Name Time Method The proportion of subjects achieving clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score < 150, at Weeks 4, 8, and 12 Up to week 12 The CDAI is a measure of disease activity in patients with Crohn's Disease.
Change from baseline in messenger ribonucleic acid (mRNA) expression of inflammatory cytokines 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
Change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 and 52 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 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
Trial Locations
- Locations (2)
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Policlinico Tor Vergata
🇮🇹Rome, Italy