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

NCT02685683 | Terminated Phase 2 DMC

• 1 other identifier: GED-0301-CD-005
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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

Conditions

Crohn's Disease

Keywords

Crohn's Disease; GED-0301; Open-label; Pharmacodynamic; Mongersen

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change from baseline in messenger ribonucleic acid (mRNA) expression of inflammatory cytokines

  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

  Up to week 12

• Change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 and 52

  Week 12 and week 52

• Number of Adverse Events

  Up to Week 56

Study Arms (1)

GED-0301 Induction (160mg) followed by intermittent 160 mg

EXPERIMENTAL

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

Interventions

GED-0301 DRUG

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).

Also known as: Mongersen

GED-0301 Induction (160mg) followed by intermittent 160 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Celgene: lead

Study Sites (2)

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Policlinico Tor Vergata

Rome, 0133, Italy

Location

Related Publications (1)

• 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.

  PMID: 33871807 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

GED0301

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Keith Usiskin, MD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: February 19, 2016
• Study Start: April 4, 2016
• Primary Completion: September 25, 2017
• Study Completion: November 9, 2017
• Last Updated: August 14, 2018

Record last verified: 2018-08

Locations

IT (2)