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

Primary Purpose

Crohn's Disease

Status

Terminated

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

GED-0301

About this trial

This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's Disease, GED-0301, Open-label, Pharmacodynamic, Mongersen

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Fondazione IRCCS Policlinico San Matteo
Policlinico Tor Vergata

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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.

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

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

Full Information

NCT ID

NCT02685683

First Posted

February 15, 2016

Last Updated

August 10, 2018

Sponsor

Celgene

1. Study Identification

Unique Protocol Identification Number

NCT02685683

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Terminated

Why Stopped

Study terminated by Sponsor following a recommendation from external DMC to terminate the ongoing Phase 3 CD studies; there were no new emergent safety findings

Study Start Date

April 4, 2016 (Actual)

Primary Completion Date

September 25, 2017 (Actual)

Study Completion Date

November 9, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celgene

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn's Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

GED-0301

Other Intervention Name(s)

Mongersen

Intervention Description

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).

Primary Outcome Measure Information:

Title

Change from baseline of Smad7 (Mothers Against Decapentaplegic homolog 7) expression in the intestinal mucosa

Description

Smad7 is a protein important in cell interactions and stands for "Mothers against decapentaplegic homolog 7" protein

Time Frame

Baseline and Week 12

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and Week 12

Title

The proportion of subjects achieving clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score < 150, at Weeks 4, 8, and 12

Description

The CDAI is a measure of disease activity in patients with Crohn's Disease.

Time Frame

Up to week 12

Title

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

Description

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

Time Frame

Week 12 and week 52

Title

Number of Adverse Events

Description

Time Frame

Up to Week 56

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Keith Usiskin, MD

Organizational Affiliation

Celgene

Official's Role

Study Director

Facility Information:

Facility Name

Fondazione IRCCS Policlinico San Matteo

City

Pavia

ZIP/Postal Code

27100

Country

Italy

Facility Name

Policlinico Tor Vergata

City

Rome

ZIP/Postal Code

0133

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

33871807

Citation

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.

Results Reference

derived

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

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