To determine the anatomic distribution of endoscopic and histologic improvement in patients with pancolonic ulcerative colitis (UC) after 16 to 24 weeks of treatment with a biologic or tofacitinib therapy.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• To determine the anatomic distribution of endoscopic improvement in UC
patients with pancolitis treated with biologic or tofacitinib therapies.
Improvement will be defined as any decrease of outcome scores form baseline to
post-treatment assessment.
o Measured by central reading of the Mayo Clinic Score (MCS) endoscopic
subscore, Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and visual
analog scale (VAS), before and after biologic or tofacitinib induction therapy
in at minimum 4 colonic segments (transverse colon, descending colon, sigmoid
colon, rectum)
• To determine the anatomic distribution of histologic improvement in UC
patients with pancolitis treated with biologic or tofacitinib therapies.
Improvement will be defined as any decrease of outcome scores from baseline to
post-treatment assessment.
o Measured by central reading of the Robarts Histopathology Index (RHI), Nancy
Histological Index (NHI), and Geboes Score (GS), before and after biologic or
tofacitinib induction therapy in at minimum 4 colonic segments (transverse
colon, descending colon, sigmoid colon, rectum)
Secondary outcome
• Proportion of patients achieving endoscopic remission in all colonic segments
except the distal colon, defined as: 1) endoscopic Mayo Clinic Score (MCS) = 0;
2) endoscopic MCS = 0 of 1; or 3) Ulcerative Colitis Endoscopic Index of
Severity UCEIS <= 3
• Proportion of patients achieving endoscopic response in all colonic segments
except the distal colon, defined as an improvement in endoscopic MCS >= 1-point
compared to baseline
• Proportion of patients achieving histologic remission, defined as: 1) Robarts
Histopathology Index (RHI) <= 3 with the lamina propria neutrophils and
neutrophils in epithelium scores being 0; 2) Geboes Score (GS) = 0; of 3) Nancy
Histological Index (NHI) <= 1
• Proportion of patients achieving histologic improvement, defined as: 1) 50%
reduction in baseline RHI; or 2) >= 1-point reduction in NHI
• To determine if there is a correlation between the distribution and extent of
endoscopic and histologic changes with changes in levels of fecal calprotectin
in UC patients with pancolitis.
Background summary
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon,
with an annual incidence of 0 to 19.2 cases per 100,000 persons and a
prevalence of 37.5 to 248.6 cases per 100,000 persons in North America.
Over the last decade, the treatment of moderate to severe UC has improved with
the introduction systemic Biological agents and oral small molecules
(JAK-inhibitors), and treatment targets in UC have shifted. Where the gold
standard was to achieve clinical remission currently, achieving endoscopic
remission seems to be the most reliable factor associated with improved
clinical outcomes. Histologic healing has also been determined as an important
endpoint, as even among UC Patients in endoscopic remission approximately 30%
will have persistent histologic activity.
Assessment of endoscopic and histologic healing in UC clinical trials is
typically performed by flexible sigmoidoscopy, where additional biopsies can be
taken. Currently, biopsy assessment parallels endoscopic scoring methods in UC,
but does not account for the distribution in which endoscopic and histologic
healing occurs in response to treatment. This presents a unique hurdle in drug
development: as patients with residual distal inflammation can be categorized
as non-responders even if large segments of the colon have demonstrated
endoscopic and/or histologic improvement, since the endoscopic score will
default to the worst affected part.
In addition to this, it is unclear whether a patchy distribution of healing is
observed with systemic biologic agents or oral JAK inhibitor therapies.
Understanding the pattern and directionality of histologic and endoscopic
healing in UC treated with biologicals is critical for determining where to
biopsy in UC clinical trials and for optimizing efficient drug development
strategies.
Study objective
To determine the anatomic distribution of endoscopic and histologic improvement
in patients with pancolonic ulcerative colitis (UC) after 16 to 24 weeks of
treatment with a biologic or tofacitinib therapy.
Study design
A prospective observational cohort study enrolling a convenience sample of 50
patients with UC starting on standard of care (SOC) biologic or oral JAK
inhibitor therapies with proven efficacy in UC (infliximab, adalimumab,
golimumab, vedolizumab, or tofacitinib). Eligible patients with pancolonic UC
extending to at least the ascending colon will undergo video-recorded
colonoscopy prior to starting therapy, with biopsies taken from at minimum 4
colonic segments (transverse colon, descending colon, sigmoid colon, rectum).
After 16 to 24 weeks of therapy, patients will undergo repeat colonoscopy and
biopsies will be taken from the same areas to assess for endoscopic and
histologic healing. All endoscopic and histologic outcomes will be evaluated by
blinded central reviewers.
Study burden and risks
A colonoscopy with biopsies can cause complications such as bleeding,
peritonitis or a perforation in the bowel wall. These complications are rare,
however the taking of additional biopsies can slightly increase the risk of
these occurring.
100 Dundas Street Suite 200
London N6A 5B6
CA
100 Dundas Street Suite 200
London N6A 5B6
CA
Listed location countries
Age
Inclusion criteria
1. Male or nonpregnant, nonlactating females (18 to 75 years old)
2. Confirmed diagnosis of UC (established by conventional clinical, endoscopic,
and histologic diagnostic criteria)
3. Initiating therapy with infliximab, adalimumab, golimumab, vedolizumab, or
tofacitinib
4. Clinically active disease (defined as a MCS >= 6 with rectal bleeding
subscore (RBS) >= 1)
5. Endoscopically demonstrated pancolitis involving at minimum 4 colonic
segments (transverse colon, descending colon, sigmoid colon and rectum),
(defined by an MCS endoscopic subscore >= 1 in each colonic segment)
6. Provide written informed consent
Exclusion criteria
1. Patients who have failed 2 or more biologic therapies OR who have failed
tofacitinib and 1 or more biologic therapies
2. Patients treated concurrently with rectal corticosteroids or rectal
aminosalicylates (enemas or suppositories)
3. Patients with incomplete colonoscopy not reaching the cecum
4. Patients with inadequate or inappropriately collected biopsy specimens at
baseline
5. Pregnant or lactating women
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 |
|---|---|
| CCMO | NL68564.018.19 |