Clinical trial NCT02685683: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Crohn's Disease
GED-0301
Open-label
Pharmacodynamic
Mongersen
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2016-02-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
measure: Change from baseline of Smad7 (Mothers Against Decapentaplegic homolog 7) expression in the intestinal mucosa
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change from baseline in messenger ribonucleic acid (mRNA) expression of inflammatory cytokines
timeFrame: Baseline and Week 12
measure: The proportion of subjects achieving clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score < 150, at Weeks 4, 8, and 12
timeFrame: Up to week 12
measure: Change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 and 52
timeFrame: Week 12 and week 52
measure: Number of Adverse Events
timeFrame: Up to Week 56
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Rome
country: Italy
facility: Policlinico Tor Vergata
Study officials:
affiliation: Celgene
name: Keith Usiskin, MD
role: STUDY_DIRECTOR
References:
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.