A prospective multicenter study to characterize magnetic resonance enterography assays for assessment of fibrosis in patients with Crohn's disease

For patients who will have surgery for their Crohn's disease, generally scans
are performed before the operation in order to assess the disease. This study
is intended to find out whether magnetic resonance enterografie (MRE) may be
used as an imaging method to assess the status of intestinal wall fibrosis in
patients with Crohn's disease. MRE is a special type of magnetic resonance
imaging (MRI) with which images of the colon and surrounding tissues are made,
using radio waves and a strong magnetic field. This method does not use
ionizing radiation.
Detection of fibrosis is necessary for an accurate / comprehensive evaluation
of patients with CD, as the presence of fibrosis can affect the determination
of whether the patient has to undergo medical or surgical treatment. Up to now
only a few studies have been performed on the possible promising role of MRE in
detecting fibrosis and detection of narrowing complications of CD. More
information about previously conducted clinical studies on the potential of MRE
in CD is described on pages 13 and 14 of the Protocol (Protocol GA29423,
Version1).

The overall aim of this study is to assess the feasibility of implementing MRE
for use in evaluating fibrosis in patients with Crohn*s Disease (CD) in a
multicenter setting.
The primary objective for this study is to evaluate *gain of enhancement* as an
MRE-fibrosis metric using histopathology from surgically resected intestinal
segments as the reference standard.
The technical objective for this study is to evaluate the feasibility of
utilizing a standardized CD MRE-fibrosis protocol in a multicenter setting to
obtain high quality MRE-fibrosis data.
The secondary objective for this study is to evaluate magnetization transfer
(MT) contrast as an MRE fibrosis metric.
Exploratory Objectives
The exploratory objectives for this study are as follows:
*To evaluate diffusion-weighted imaging as an MRE-fibrosis metric
*To evaluate candidate serum and tissue biomarkers for bowel wall fibrosis in CD
*To explore new serum, plasma, and tissue biomarkers for bowel wall
inflammation and fibrosis in CD

This is a prospective, multicenter imaging study conducted at six study sites
in Europe. Approximately 60 patients (approximately 5 -15 patients per site)
with a known diagnosis of CD who will be undergoing elective bowel surgery for
management of their CD will be enrolled in the study. Eligible patients will
have their CD well characterized clinically with respect to disease duration,
disease phenotype (fistulizing, fibrostenosing, luminal, or mixed), disease
location, concomitant medications for CD (including current and prior biologics
use), past surgical history for CD, and smoking status. At screening, a blood
chemistry profile will be completed to estimate glomerular filtration rate
(GFR). Enrolled patients will undergo an MRE scan with IV and oral contrast
during the study. If the surgical resection involves the colon, the MRE scan
will be performed with colonic contrast as well. In addition to being able to
define the fibrotic burden, the MRE will help guide the surgical resection.
The MRE scan must be performed no more than 8 weeks (preferably within 4 weeks
or less) prior to the patient*s surgery.
Patients will be contacted by telephone within 48 hours after the MRE scan to
monitor for any additional adverse events associated with the MRE.
Serum, plasma, and PAXgene blood RNA samples for biomarker assessments will be
obtained during the MRE study visit (prior to the MRE scan) and after surgery.
Representative samples and specimen pictures, will be obtained from the
surgically resected tissue of the most stenosed region and/or lesions of
interest including fistulas, ulcers, and fissures. These samples will be
analyzed at the central histopathology center at the University Hospitals
Leuven and at Genentech. All MRE scans will be electronically submitted to
Genentech, where quality checking will be performed before the scans are
forwarded to the central MRE reading center at the Hospital Clinic de
Barcelona.There is no therapeutic intervention in this study; the planned
elective surgery for CD is being performed as standard of care for the
patient. Patients should continue on their prescribed medications at the same
doses from the time of the MRE until surgery.
Patients will be considered to have completed the study if they complete all
study assessments; study completion will occur 24-72 hours after surgery.
Patients who do not complete the MRE or undergo surgery within 8 weeks after
MRE will be discontinued from the study. Patients discontinuing early from the
study may be replaced as determined by Genentech to achieve a target of
approximately 60 patients.

This non-experimental study looks at the results of regular medical care and
research, the patient will not be exposed to additional potential risks.
In this study, patients will undergo an MRE scan before the scheduled surgery
takes place (no more than 8 weeks before surgery). Since this technique uses
strong magnets, people with pacemakers, artificial heart valve, very large
tattoos or a metal plate, pin, or other non-compatible medical implants or
other metal objects in their bodies (including bullets, shrapnel, or dental
implants) are not eligible for this procedure.
Pregnant patients are not eligible to participate in this study, if applicable,
a pregnancy test will be done per patient.
There are risks associated with the use of gadolinium-containing contrast
medium used for MRE scans. Patients with renal impairment are at higher risk.
The most serious side effect of gadolinium is nephrogenic systemic fibrosis /
nephrogenic fibrosing dermopathy (NSF / NFD), a scarring condition that can
lead to kidney failure. NSF / NFD is very rare and is mainly observed in
patients with impaired renal function. Because of this risk, blood of the
patients will be tested prior to the MRE scan in order to determine the
patients renal function. If the blood tests show that renal function is
impaired, the patient cannot participate in this study.
During the MRE scan patients may experience claustrophobia (fear of being stuck
in an enclosed space).
During this study, several small amounts of blood will be collected from a vein
of the patients for laboratory testing for safety and for research into
biomarkers (proteins). Bloodcollection can cause pain at the site where the
needle is inserted, and there is a small risk of bruising and / or infection at
the puncture site. Some people get dizzy, get an upset stomach or faint when
their blood is collected.