Crohn's DiseasePhase 2NCT02685683
Pharmacodynamic and Clinical Outcome Study of Mongersen in Patients With Crohn's Disease
A Phase 2 study testing GED-0301 in people with Crohn's Disease, run by Celgene at 2 sites in Italy.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- GED-0301
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesItaly
- Study dates
- 4 Apr 2016to 9 Nov 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Policlinico Tor Vergata
Rome, 0133
About this study
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
This study is designed to explore mechanism of action of mongersen (GED-0301) 160 mg once daily in patients with active Crohn's Disease
Read the 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).
- Conditions
- Crohn's Disease
- Being tested
- GED-0301
- Keywords
- Crohn's Disease, GED-0301, Open-label, Pharmacodynamic, Mongersen
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GED-0301Drug
Also called Mongersen
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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: GED-0301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and Week 12
Secondary outcomes (4)
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
Measured: 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.
Measured: 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
Measured: 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
Measured: Up to Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study start4 Apr 2016
- Primary completion25 Sep 2017
- Study completion9 Nov 2017
Why it 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Keith Usiskin, MD, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02685683
- Sponsor's protocol ID
- GED-0301-CD-005
- Status last verified
- Aug 2018
- First submitted
- 15 Feb 2016
- Last updated
- 14 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 33871807
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02685683
- Acronym / sponsor ID
- GED-0301-CD-005
- Conditions
- Crohn's Disease
- Keywords
- Crohn's Disease, GED-0301, Open-label, Pharmacodynamic, Mongersen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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
- Enrolment
- 18 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2016 (actual)
- Primary completion
- 25 Sep 2017 (actual)
- Study completion
- 9 Nov 2017 (actual)
- First posted
- 19 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GED-0301 Induction (160mg) followed by intermittent 160 mg | Experimental | Drug: GED-0301GED-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GED-0301Also: MongersenDuring 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). | Drug | GED-0301 Induction (160mg) followed by intermittent 160 mg |
Primary outcome
Change from baseline of Smad7 (Mothers Against Decapentaplegic homolog 7) expression in the intestinal mucosa
Time frame: Baseline and Week 12
Smad7 is a protein important in cell interactions and stands for "Mothers against decapentaplegic homolog 7" protein
4 secondary outcomes
Change from baseline in messenger ribonucleic acid (mRNA) expression of inflammatory cytokines
Time frame: 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
Time frame: Up to week 12
Change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 and 52
Time frame: Week 12 and week 52
Number of Adverse Events
Time frame: Up to Week 56
Results and safety
The study was stopped early (reason given: 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). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2018.
- Derived from this study: PubMed 33871807Marafini 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith Usiskin, MD study director
Celgene
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GED-0301 in people with Crohn's Disease, run by Celgene at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: 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). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of Smad7 (Mothers Against Decapentaplegic homolog 7) expression in the intestinal mucosa (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02685683, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2018.