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

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

This study is designed to explore mechanism of action of mongersen (GED-0301) 160 mg once daily in patients with active Crohn's Disease

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: GED-0301

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).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Rome, Italy, 0133
    • Policlinico Tor Vergata

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: GED-0301; 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 Names: Mongersen

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Keith Usiskin, MD, Celgene

Publications and helpful links

General Publications

• Marafini I, Stolfi C, Troncone E, Lolli E, Onali S, Paoluzi OA, Fantini MC, Biancone L, Calabrese E, Di Grazia A, Monteleone I, Lenti MV, Di Sabatino A, Monteleone G. A Pharmacological Batch of Mongersen that Downregulates Smad7 is Effective as Induction Therapy in Active Crohn's Disease: A Phase II, Open-Label Study. BioDrugs. 2021 May;35(3):325-336. doi: 10.1007/s40259-021-00482-x. Epub 2021 Apr 19.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2016
• Primary Completion (Actual): September 25, 2017
• Study Completion (Actual): November 9, 2017

Study Registration Dates

• First Submitted: February 15, 2016
• First Submitted That Met QC Criteria: February 15, 2016
• First Posted (Estimate): February 19, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Open-label; Crohn's Disease; Pharmacodynamic; GED-0301; Mongersen
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: GED-0301-CD-005