Pharmacodynamic and Clinical Outcome Study of Mongersen in Patients With Crohn's Disease

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase 2, Open-label Study to Explore the Pharmacodynamic and Clinical Effects of Mongersen (GED-0301) in Subjects With Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: GED-0301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GED-0301 Induction (160mg) followed by intermittent 160 mg<br>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 | Drug: GED-0301<br>* 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).<br>* Other names: Mongersen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of Smad7 (Mothers Against Decapentaplegic homolog 7) expression in the intestinal mucosa | Smad7 is a protein important in cell interactions and stands for Mothers against decapentaplegic homolog 7 protein | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in messenger ribonucleic acid (mRNA) expression of inflammatory cytokines | 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 | Baseline and Week 12 | 
| The proportion of subjects achieving clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score < 150, at Weeks 4, 8, and 12 | The CDAI is a measure of disease activity in patients with Crohn's Disease. | Up to week 12 | 
| Change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 and 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 | Week 12 and week 52 | 
| Number of Adverse Events | 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 | Up to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, GED-0301, Open-label, Pharmacodynamic, Mongersen