To evaluate the efficacy of GED-0301 at Week 12, administered as either a single 160 mg tablet or as four 40 mg tablets, compared with placebo on clinical activity in subjects with active CD
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The proportion of subjects achieving clinical remission, defined as a CDAI
score < 150, at Week 12
Secondary outcome
The proportion of subjects who have a clinical response, defined as a decrease
from baseline in CDAI score >= 100 points, at Week 12
The proportion of subjects with endoscopic response-25 (ER-25), defined as a
reduction of at least 25% from baseline in 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
The proportion of subjects achieving clinical remission, defined as a CDAI
score < 150, at Week 4
The proportion of subjects with endoscopic response-50 (ER-50), defined as a
reduction of at least 50% in SES-CD compared with baseline, at Week 12
The proportion of subjects achieving clinical remission, defined as a PCDAI
score <= 10 at Week 12 (adolescent subjects only)
The plasma concentration of GED-0301 at Week 4 and Week 8
Type, frequency, severity, seriousness, and relationship of AEs to IP
Number of subjects who discontinue IP due to any AE
Clinically significant changes in vital signs, ECG, and/or laboratory findings
Type, frequency, severity, seriousness, and relationship of AEs to IP
Number of subjects who discontinue IP due to any AE through Week 12
Clinically significant changes in vital signs, ECG, and/or laboratory findings
through Week 12 and 4-week Follow-up
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 at Week 12, administered as either a
single 160 mg tablet or as four 40 mg tablets, compared with placebo on
clinical activity in subjects with active CD
Study design
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter
study to evaluate the efficacy and safety of oral GED-0301, administered as
either a single 160 mg tablet or as four 40 mg tablets, versus placebo in
subjects with active CD.
Intervention
Subjects will receive double-blind treatment with oral GED-0301 160 mg or
placebo QD for 12 weeks as follows:
• GED-0301 (1 x 160 mg gastro-resistant, delayed release, pH-dependent tablet)
and 4 placebo tablets (identical in appearance to GED-0301 40 mg tablet);
• GED-0301 (4 x 40 mg gastro-resistant, delayed release, pH-dependent tablets)
and 1 placebo tablet (identical in appearance to GED-0301 160 mg tablet);
• Placebo (4 placebo tablets identical in appearance to GED-0301 40 mg tablet
and 1 placebo tablet identical in appearance to GED-0301 160 mg tablet).
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
• Presence of ileitis, ileocolitis, or colitis, as determined by ileocolonoscopy at screening
• Active disease, defined as a CDAI score >= 220 and <= 450 at screening
• Must have a 7-day average daily liquid or soft stool frequency >= 3.5 or abdominal pain >= 1.5 at screening
• 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, AZA, 6-MP, or MTX); or biologics for the treatment of CD (ie, infliximab, adalimumab, certolizumab, or vedolizumab)
Exclusion criteria
1. diagnosis of UC, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis, diverticular disease-associated colitis, or colitis due to immunodeficiency.
2. local manifestations of CD such as abscesses, short bowel syndrome, or other disease complications for which surgery might be indicated or which could confound the evaluation of efficacy.
3. strictures with prestenotic dilatation, requiring procedural intervention, or with obstructive symptoms. In addition, subjects with colonic strictures that are not passable with an age-appropriate colonoscope, or strictures in the ileum or ileocecal valve that are fibrotic in nature, will be excluded.
4. intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit.
5. ileostomy or a colostomy.
6. prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®) within 8 weeks prior to the Screening Visit.
7. intravenous (IV) corticosteroids within 2 weeks prior to the Screening Visit.
8. changed or discontinued the dose of oral aminosalicylates within 2 weeks prior to the Screening Visit.
9. changed or discontinued the dose of oral corticosteroids (prednisone <= 20 mg/day or equivalent, budesonide <= 9 mg/day) within 3 weeks prior to the Screening Visit.
10. Adolescents with delayed growth or pubertal development who are on corticosteroids at baseline and who should not continue treatment with the same dose of corticosteroids until Week 12 visit.
11. immunosuppressants (eg, AZA, 6-MP, or MTX) within 12 weeks prior to the Screening Visit and has changed or discontinued the dose of immunosuppressants within 8 weeks prior to the Screening Visit.
12. topical GI treatments, such as, 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks prior to the Screening Visit.
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 | EUCTR2015-001924-40-NL |
| CCMO | NL60150.000.17 |