Primary ObjectiveThe primary objective of this prospective open label study is to assess the ability of vedolizumab to promote clinical, endoscopic and histological remission in patients with active Crohn's disease in an 'early' and a…
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Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the proportion of patients with clinical and endoscopic
remission at Week 26 and 52-54, defined as CDAI of 150 or lower and SES-CD < 4.
Secondary outcome
Secondary endpoints for this study are:
Proportion of patients with absence of ulcers at Weeks 26 and 52-54
- Proportion of patients with endoscopic response (SES-CD reduction by >= 50 %)
at Weeks 26 and 52
- Proportion of patients with 25% and 75% reduction of SES-CD at Weeks 26 and 52
- Proportion of patients with clinical response (CDAI decrease of >= 70 points
from baseline) at all time points
- Proportion of patients with clinical remission (CDAI <=150) at all time other
points
- Proportion of patients with corticosteroid- free clinical remission (CDAI
<=150) at all other time points
- Proportion of patients with normalized serum CRP at all time points
- Proportion of patients with no granulocytes in the biopsies at Weeks 26 and
52.
- Proportion of patients with 25%, 50% and 75% reduction in the Geboes
histology score at Weeks 26 and 52.
- Proportion of patients with sustained clinical response (response at all time
points after week 10)
- Proportion of patients with sustained clinical remission (remission at all
time points after week 10)
- Proportion of patients with draining fistulas
- Proportion of patients that need to be hospitalized
- Quality of life measured by IBDQ and Euroquol
- Work productivity Index
- WHO Disability Index
- Serum concentrations of vedolizumab and antibodies to vedolizumab before
every infusion
Background summary
Crohn's disease (CD) is a chronic inflammatory disease of the small bowel and
colon. Symptoms commonly include bloody diarrhea, abdominal pain, weight loss,
and fever. There is no known cause or cure for CD. The aim of current CD
treatments is to induce and maintain remission, to reduce the need of
corticosteroids and avoid resections and fistulas.
Treatment options include systemic and/or topical corticosteroids, purine
analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery.
In 2013, results from the GEMINI II, phase 3, randomized controlled trial
demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining
remission in adult patients with active CD.
VDZ (MLN0002, LDP-2 or MLN02), inhibits the interaction between α4β7 integrin
on memory T and B cells and mucosal addressin cell adhesion molecule-1
expressed on the vascular endothelium of the gut and has been shown to be
effective in both inducing and maintaining clinical remission in UC. The ideal
positioning of vedolizumab in the therapeutic armamentarium for CD remains
unknown. With other (anti-TNF) biologics, outcomes have usually been better if
the treatment was started earlier in the disease course and if the patients had
not been exposed to prior antibody treatments. Therefore, it appears
appropriate and desirable to test the potency of vedolizumab in an earlier
phase of CD.
Indeed, also with vedolizumab patients previously exposed to biologics appear
to have lower success rates with vedolizumab, so a position earlier in the
disease course would most likely lead to better outcomes.
This is an investigator-initiated open label study of VDZ therapy in 2 distinct
populations of CD patients with active disease: 1. patients who have been
diagnosed < 2 years ago and who only been exposed to aminosalicylates,
corticosteroids and thiopurines and 2. patients who have been diagnosed > 2
years and exposed to immunomodulators and/or anti-TNF agents in addition to
steroids and aminosalicylates.
Study objective
Primary Objective
The primary objective of this prospective open label study is to assess the
ability of vedolizumab to promote clinical, endoscopic and histological
remission in patients with active Crohn's disease in an 'early' and a 'late'
disease population after 54 weeks of treatment.
Secondary Objectives
Measures of clinical disease activity (including clinical response and
remission) over the 1 year study period will be described. The mucosal healing
capacity of vedolizumab treatment will be observed by assessing the endoscopic
and histopathologic response to treatment over the 1 year study period.
Study design
Open label, observational and multicenter
Intervention
Entyvio (vedolizumab ) treatment (300 mg intravenous). Patients with a SES-CD
score of less that 50 % at the week 26 endoscopy will receive vedolizumab 4
weekly. An extra vedolizumab dose will be given at week 34, 42 and 50.
Study burden and risks
The endoscopy procedure can cause abdominal discomfort and due to biopsies
there is an extreme small risk of perforation (1 in 10.000) of the bowel.
Blood drawing can cause discomfort , bruising or local pain.
PML :
Progressive mulitfocal leucoencephalopathy (PML) is a rare infection of the
brain caused by the John- Cunningham-virus (JC-virus). Subjects with severely
impaired immune systems are more likely to develop this disease. This disease
was diagnosed in a few patients who were treatment with a medication called
natalizumab (Tysabri®). The overall risk of developing PML is estimated as less
than 1 in 1,000. Up to now, no known cases of PML have been reported by
patients who have been, or are currently treated with vedolizumab . However,
development of PML symptoms in patients who are receiving vedolizumab have to
be assessed. All subject will be assessed for symptoms of PML prior to
infusion.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Moderately to severely active CD (Crohn disease activity index (CDAI)
220-450) with objective evidence of ulcerations visualized on endoscopy., -
Anti-TNF discontinued for at least 4 weeks prior to baseline, -Age 18 to 80, -
GROUP 1 (EARLY CD):, Diagnosis of CD < 24 months prior to enrollment ,
Demonstrated failure to respond to topical or systemic corticosteroids or
intolerance to corticosteroids,
and additionally, but not mandatory, lack of efficacy or intolerance to
thiopurines (azathioprine, 6-mercaptopurine or 6-thioguanine)(any duration).
Patients using thiopurines must have been using the agent for > 3 months (last
4 weeks at stable dose)., GROUP 2 (LATE CD), Demonstrated failure to respond to
at least 3 months of thiopurines or intolerance to thiopurines and: failure to
respond to at least 1 anti-TNF or intolerance to anti-TNF or loss of response
to at least 1 anti-TNF.
Exclusion criteria
- Prior treatment with vedolizumab, alpha4beta7 anti-bodies, beta7 antibodies
and anti MADCAM-1
- History of colonic dysplasia or colonic cancer
- Presence of stoma
- subjects with a pouch
- Received other biologics within the last 4 weeks of baseline
- subjects with ALT or AST 3x the upper limit of normal measured at screening
- Use of 5-ASA or corticosteroid enemas/suppositories within 2 weeks of
enrollment
- Chronic hepatitis B or C infection
- Evidence of or treatment for C. difficile infection or other intestinal
pathogen at screening within 4 weeks prior to enrollment
- Active or latent tuberculosis
- Early CD group: previous exposure to any anti-TNF
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 | EUCTR2014-005376-29-NL |
| ClinicalTrials.gov | NCT02646683 |
| CCMO | NL51800.018.14 |