To demonstrate that spesolimab is effective in maintaining Symptomatic Stenosis Responseand / or inducing Radiographic Stenosis Response (defined in Table 2.3: 1) in patients withsymptomatic CD-related small bowel stenosis, who have achieved…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients with maintained Symptomatic Stenosis Response (defined
in Table 2.3: 1) at Week 48
Proportion of patients with Radiographic Stenosis Response (defined in Table
2.3: 1) at Week 48
Secondary outcome
Proportion of patients with maintained Symptomatic Stenosis Response (defined
in Table 2.3: 1) at Week 24
Proportion of patients with Radiographic Stenosis Response (defined in Table
2.3: 1) at Week 24
Background summary
Crohn*s disease (CD) is a chronic condition that manifests clinically as
recurrent gut
inflammatory episodes followed by periods of inflammatory remission and is one
of the
recognized subtypes of Inflammatory Bowel Disease (IBD).
Under normal physiologic conditions acute gut inflammation, e.g. viral or
bacterial
gastroenteritis, is followed by a complex tissue repairing or tissue
remodelling response. This
response aims to repair the damage caused by inflammation and to recover normal
structure
and function of the intestinal mucosa and rest of the layers of the gut wall.
Tissue
remodelling response includes among others activation of mesenchymal cells,
which produce
an extracellular matrix, mainly collagen and fibronectin, which leads to wound
healing.
However, in IBD patients, the chronic or recurrent activation of tissue
remodelling responses
leads to excessive accumulation of this extracellular matrix causing
destruction of the
interstitium and increased apposition of collagen or fibronectins, which leads
to fibrosis,
which manifest clinically as intestinal stenosis
Study objective
To demonstrate that spesolimab is effective in maintaining Symptomatic Stenosis
Response
and / or inducing Radiographic Stenosis Response (defined in Table 2.3: 1) in
patients with
symptomatic CD-related small bowel stenosis, who have achieved Symptomatic
Stenosis
Response after standard medical therapy
Study design
The study has a screening period of up to 14 weeks until randomization.
In this lead-in period, the patient starts treatment for corticosteroids as
described in section 4.2.1 in the protocol. As soon as the results of the
therapeutic drug monitoring are known, the optimization of anti-inflammatory
treatment with biologics will start.
After randomization, the treatment period with the study drug follows. The
patient comes to the hospital every 4 weeks for an infusion of the study drug.
During the treatment period, the patient receives an MRE 3 times, an endoscopy
3 times, during which a biopsy is taken.
Questionnaires are taken every visit, blood taken for for example safety.
Stools are also collected 5 times for biomarker and pathogen analysis.
Intervention
IMP
Spesolimab is a humanized antagonistic monoclonal IgG1 antibody that blocks
human IL36R signalling. Binding of spesolimab to IL36R is anticipated to
prevent the subsequent activation of IL36R and downstream activation of
pro-inflammatory and pro-fibrotic pathways in inflammatory skin and bowel
diseases. Spesolimab may be unique in directly suppressing not only
pro-inflammatory but also profibrotic mechanisms in these
diseases.
Lead-in period
CORTICOSTEROIDS
Methylprednisolone 40 mg/d i.v. or 40 mg/d of oral prednisolone (or the
equivalent dose of any systemic steroid formulation. Budesonide is not allowed)
Patients receiving i.v. steroids should be switched to oral prednisolone when
clinically justified, to complete 2 weeks of steroid treatment followed by a
defined tapering regime
Tapering Regime: Decrease by 5 mg/1wk until 10 mg and then decrease by 2.5
mg/1wk until 0 mg
OPTIMIZATION OF ANTI-INFLAMMATORY BIOLOGICAL TREATMENT
Anti-inflammatory biological treatment shall be individually optimized
dependent on the prior (failed) treatment of each patient by introducing
approved doses of TNF inhibitors (TNFi), vedolizumab, or ustekinumab following
the algorithm below, optimization period of 8 weeks starts with the dose
adaptation or treatment change as described in the protocol under section
4.2.1.1. This is restricted to locally approved dosing regimens of proposed
agents.
Treatment period
After achievement of Symptomatic Stenosis Response patients need to maintain
their optimized anti-inflammatory treatment initiated during the Lead-in Period
after randomization and throughout the Blinded Randomized Treatment Period.
IMP
Intravenous administration of 1200 mg every 4 weeks (q4w) until Week 8 then
1200 mg every 8 weeks (q8w) until Week 40 (last trial drug administration)
Study burden and risks
- Patient may not experience results from study drug
- The patient may experience side effects from the study drug
- Patient must undergo examinations as part of the study that may be
uncomfortable, such as an MRE or an endoscopy and a biopsy taken.
- Blood is taken regularly, which can be experienced as unpleasant.
- The patient is asked to fill in questionnaires, which may be perceived as
burdensome.
Comeniusstraat 6
Alkmaar 1817MS
NL
Comeniusstraat 6
Alkmaar 1817MS
NL
Listed location countries
Age
Inclusion criteria
-Male and female patients, 18 to 75 years when signing informed consent at
screening
-Established diagnosis of clinical CD prior to screening
-Suspicion of symptomatic small bowel stenosis
-Presence of abdominal pain after eating or limitation in amount or types of
food at screening
-1 or 2 naïve or anastomotic stenoses in the terminal ileum at screening,
confirmed by MRE at randomization
-Have achieved Symptomatic Stenosis Response before randomization (i.e. 7 day
average scores <2 for diary questions on the abdominal pain after eating AND on
the limitation in amount or types of food)
-Endoscopic activity defined by Colonic Simple Endoscopic Score in CD (SES-CD)
*12 after Lead-in Period, at the time of randomization
Exclusion criteria
- Failure of > 2 different biological drug classes prior to screening (e.g. TNF
inhibitors, Integrin Receptor antagonists and IL-12 / IL-23 antagonists)
- More than 2 small intestinal stenoses
- Systemic corticosteroid treatment of current obstructive symptoms for >1 week
prior to screening
- Endoscopic balloon dilation or surgical treatment of the same small bowel
stenosis within the last 6 months prior to screening Visit 1
- Patients who require immediate EBD or surgical intervention as per the
investigator*s discretion
- Current complications of CD at screening Visit 1 and randomization (Day 1)
that would possibly confound the evaluation of benefit from treatment with
spesolimab
- Current stenosis in the colon
- Previous strictureplasty on current stricture, ileostomy, colostomy
- Any kind of bowel resection or diversion within 6 months or any other
intra-abdominal surgery (except for abscess drainage) within 3 months prior to
screening Visit 1
- Colorectal cancer present and past (<;5 years) history
Design
Recruitment
Medical products/devices used
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 | EUCTR2020-005770-99-NL |
| CCMO | NL77271.056.21 |
| Other | volgt nog |