To evaluate the efficacy of GED-0301 compared with placebo on clinical activity at Week 12, as measured by the Crohn's Disease Activity Index (CDAI) in subjects with active Crohn's disease (CD).
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy as clinical remision: the proportion of subjects achieving clinical
remission defined as a Crohn's Disease Activity Index (CDAI) score < 150 at
Week 12.
Secondary outcome
* The proportion of subjects with endoscopic remission, defined as Simple
Endoscopic Score for Crohn's Disease (SES-CD) * 2 at Week 52.
* The proportion of subjects achieving clinical remission, defined as a CDAI
score < 150 at Week 52 .
* The proportion of subjects who have a clinical response, defined as a
decrease from baseline in CDAI * 100 points at Week 12.
* The proportion of subjects with endoscopic response -50 (ER-50), defined as a
reduction of at least 50% in the SES-CD compared with baseline, at Week 52.
* The proportion of subjects achieving sustained clinical remission, defined as
a CDAI score < 150, at both Week 12 and Week 52.
* The proportion of subjects who achieve corticosteroid-free clinical remission
(CADI <150) at Week 52 among subjects receiving oral
corticosteroids at baseline.
* The proportion of subjects with endoscopic response -25 (ER-25), defined as a
reduction of at least 25% from baseline in the SES-CD, at Week 12.
* The proportion of subjects who have a clinical response, defined as a
decrease from baseline in CDAI * 100 points at Week 4.
Background summary
Mongersen (GED-0301) is being studied for the treatment of subjects with active
Crohn*s disease (CD). Although the etiology of CD has not been completely
elucidated, there has been significant advancement in the understanding of the
disease pathogenesis. There is evidence that the chronic intestinal
inflammation is caused by an excessive immune response to mucosal antigens that
is not appropriately controlled by the normal counter-regulatory mechanisms.
GED-0301 is an antisense oligodeoxynucleotide that is complementary to the
sequence of the messenger ribonucleic acid (mRNA) transcript of Smad7, and
consequently inhibits Smad7 mRNA. GED-0301 is formulated as a gastro-resistant
delayed release pH-dependent tablet designed to deliver the active substance in
the distal gastrointestinal (GI) tract. This formulation is not intended to
achieve systemic absorption, but rather to obtain a local release and
therapeutic benefit directly on the intestinal inflammatory lesions. This
information supports the potential efficacy of GED-0301 in the treatment of CD.
Study objective
To evaluate the efficacy of GED-0301 compared with placebo on clinical activity
at Week 12, as measured by the Crohn's Disease Activity Index (CDAI) in
subjects with active Crohn's disease (CD).
Study design
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter
study to evaluate the efficacy and safety of 3 treatment regimens of oral
GED-0301 versus placebo in subjects with active CD.
Subjects will participate for a maximum of 60 weeks in this study: up to 4
weeks in the
Screening Period; 52 weeks in the Double-blind Treatment Period; and 4 weeks in
the Follow-up Period.
Intervention
Subjects will receive double-blind, oral GED-0301 or identically appearing
placebo (QD) as follows:
* GED-0301 160 mg QD for 12 weeks; followed by placebo QD for 4 weeks; followed
by alternating GED-0301 160 mg QD for 4 weeks and placebo QD for 4 weeks, until
the the Week 52 Visit;
* GED-0301 160 mg QD for 12 weeks; followed by placebo QD for 4 weeks; followed
by alternating GED-0301 40 mg QD for 4 weeks and placebo QD for 4 weeks, until
the Week 52 Visit;
* GED-0301 160 mg QD for 12 weeks; followed by continuous GED-0301 40 mg QD,
until the Week 52 Visit;
* Placebo QD until the Week 52 Visit.
Study burden and risks
Treatment of patients with CD represents a difficult challenge. The natural
history of CD is characterized by a remitting and relapsing course that
progresses to complications and surgery in the majority of patients. A stepwise
approach according to disease location and severity at presentation has been
advocated, with the primary aim of inducing and maintaining clinical remission,
improving quality of life (QoL), and minimizing short- and long-term toxicity
and complications. Treatment of CD currently involves pharmacological treatment
and surgery, the latter of which is indicated for medically refractory disease,
strictures, abscesses and neoplastic lesions.
Based on current data available, potential therapeutic benefit, and the safety
monitoring specified in the protocol, it is appropriate to proceed with the
proposed study in the patient population at the dose regimen specified in the
protocol.
Morris Avenue 86
Summit, New Jersey 07901
US
Morris Avenue 86
Summit, New Jersey 07901
US
Listed location countries
Age
Inclusion criteria
Diagnosis of CD with a duration of at least 3 months prior to the
Screening Visit
Diagnosis of ileitis, ileocolitis or colitis, as determined by ileocolonoscopy at screening
Active disease, defined as a CDAI score * 220 and * 450 at screening
Subject must have a 7-day average stool frequency * 3.5 or abdominal
pain * 1.5 at screening
Subject must have a total SES-CD * 6 at screening, or the ileum
segmental SES-CD * 4 at screening
Must have failed or experienced intolerance to at least one of the
following: budesonide; systemic corticosteroids; immunosuppressants
(ie, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate
[MTX]); or biologics for the treatment of CD (ie, infliximab,
adalimimumab, certolizumab, vedolizumab)
Exclusion criteria
Diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic
colitis, microscopic colitis, radiation colitis or diverticular disease-
associated colitis
Subject has local manifestations of CD such as strictures, abscesses,
short bowel syndrome; or other disease complications for which surgery
might be indicated or could confound the evaluation of efficacy
Strictures with prestenotic dilatation, requiring procedural intervention,
or with obstructive symptoms. In addition, colonic strictures that are not
passable with an adult colonoscope, or strictures in the ileum or
ileocecal valve that are fibrotic in nature, will be excluded.
Subject had any intestinal resection within 6 months or any intraabdominal
surgery within 3 months prior to the Screening Visit.
Subject had prior treatment with mycophenolic acid, tacrolimus,
sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®)
within 8 weeks prior to the Screening Visit.
Use of intravenous (IV) corticosteroids within 2 weeks prior to the
Screening Visit.
Use of topical GI treatment such as 5-aminosalicylic acid (5-ASA) or
corticosteroid enemas or suppositories within 2 weeks prior to the
Screening Visit.
Use of bile acid sequestrants, (eg, cholestyramine) within 3 weeks prior
to the Screening Visit.
Prior treatment with biologics for the treatment of CD (approved or
investigational), other than infliximab, adalimimumab, certolizumab or
vedolizumab.
Prior treatment with more than 3 biologics for the treatment of CD (ie,
infliximab, adalimimumab, certolizumab, vedolizumab).
Treatment with a biologic within 8 weeks prior to the Screening Visit, or
5 elimination half lives, whichever is longer.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001925-18-NL |
| ClinicalTrials.gov | NCT02596893 |
| CCMO | NL55490.000.16 |