|- candidate number||27133|
|- NTR Number||NTR6385|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||24-apr-2017|
|- Secondary IDs||METC AMC 2016 002 EudraCT 2015-000555-24|
|- Public Title||A trial to compare if the diseased area beween the colon and the small bowel of patients with Crohn's disease stays free of disease after surgery between a group of patients whom receive no medication versus a group whom receive vedolizumab |
|- Scientific Title||Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Determine the Efficacy and Safety of Vedolizumab in Prevention of Endoscopic Recurrence of Crohn's Disease in Patients with Ileo-colonic Surgical Resection and Ileocolonic Anastamosis
|- hypothesis||Postoperative recurrence of CD (Crohn's disease) is very common in patients having undergone bowel resection, and often leads to further bowel resection. Postoperative recurrence is frustrating to both the physician and patient, and thus an effective strategy to prevent CD recurrence without unwanted side effects is warranted. The reduced incidence of CD recurrence with TNF (tumor neucrosis factor) inhibitor treatment is promising as a therapeutic option, however development of antibodies to anti-TNF biologics and the potential need for dose escalation suggests that an alternative therapeutic option with a different mode of action would be welcome. The efficacy of VDZ (vedolizumab) in the induction and maintenance of remission in CD suggests that VDZ holds potential for preventing CD recurrence following bowel resection. This investigator-initiated study will assess this possibility.|
|- Healt Condition(s) or Problem(s) studied||Crohn's disease|
|- Inclusion criteria||1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. |
2. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Established Crohn’s disease as the indication for ileocolonic resection
4. Age > 18
5. Ileocolonic resection with ileocolonic anastomosis and removal of all tissue macroscopically affected by CD according to the surgeon
6. Presence of at least 1 risk factor for recurrence:
• Active smoking > 10 cigarettes/day
• 2nd, 3rd or later resection
• Surgery for perforating complication (abscess, fistula)
• Previous exposure to anti-TNF antibodies
7. Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).
8. Anti-TNF discontinued for at least 6 weeks before screening.
9. Written informed consent must be obtained and documented
|- Exclusion criteria||1. Patients that need to continue postoperative medication for their CD as per investigator's discretion, eg for fistulizing perianal CD.|
2. Previous treatment with VDZ
3. Clinically significant CD elsewhere in the gastrointestinal tract not removed with surgery
4. Patients with clinically documented short bowel syndrome.
5. Patients with a history of cancer (other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer) with less than 2 disease-free documented years.
6. Patients with the following laboratory abnormalities at screening:
White blood count < 3 x 109/L
Lymphocyte count < 0.5 x 109/L
Hemoglobin < 8 g/dL
Platelet count < 125 x 109/L or > 800 x 109/L
ALT or AST > 3.0 times the upper limit of normal (ULN)
Alkaline Phosphatase > 2.0 times the ULN
Serum Creatinine > 2 times the ULN
Prothrombin time (INR) > 1.5 times normal
7. Active participation in another trial.
8. Patients with abdominal abscess, active or latent tuberculosis or cancer.
9. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures.
10. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures.
11. Patients unable to attend all study visits.
12. Patients with a history of non-compliance with clinical study protocols.
13. Contraindication for endoscopy.
14. History of cancer or colonic dysplasia
15. Received other biologics within the last 6 weeks of screening
16. Known HIV, hepatitis B or C infection
17. Evidence of or treatment for C. difficile infection or other intestinal pathogen within 4 weeks prior to enrollment or at screening
18. Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2017|
|- planned closingdate||1-mei-2018|
|- Target number of participants||40|
|- Interventions||Vedolizumab 300 milligram 8 weekly (4 doses) or placebo 8 wekkly (4 doses)|
|- Primary outcome||The proportion of patients with clinically significant endoscopic recurrence (Rutgeerts i2b, i3 or i4) at week 26. |
|- Secondary outcome||- Proportion of patients without endoscopic recurrence (i0)|
- Symptomatic recurrence (CDAI increase >70 points compared to baseline)
- Proportion of patients with normalized serum CRP at all time points and CRP at all visits
- Proportion of patients with normal fecal calprotectin (<50) at all visits
- Quality of life measured by IBDQ and SF-36
- Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion
|- Timepoints||Primary outcome : week 26-28|
Proportion of patients without endoscopic recurrence (i0) : week 26-28
Symptomatic recurrence (CDAI increase >70 points compared to baseline) : at baseline and every 8 weeks before infusion
Proportion of patients with normalized serum CRP at all time points and CRP at all visits : at baseline and every 8 weeks before infusion
Proportion of patients with normal fecal calprotectin (<50) : at all visits
- Quality of life measured by IBDQ and SF-36 : at baseline and every 8 weeks before infusion
- Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion : at all infusion visits before infusion.
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Prof. dr. G. D'Haens |
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. G. D'Haens |
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam|
(Source(s) of Monetary or Material Support)
|- Brief summary||Study Design: |
This multi-centre randomized placebo-controlled study will look into the effect of vedolizumab
to prevent recurrence of CD after ileocolonic resection. All patients will undergo an
ileocolonoscopy at week 26 following surgery (in line with current recommendations). The
endpoint is the proportion of patients with clinically significant recurrence of CD (Modified
Rutgeerts Grade 2b, 3 or 4) after 6 months after surgery.
In most centers across the world, patients in the postoperative phase are routinely undergoing
ileocolonoscopy 6 months after surgery. To justify a 50% placebo-arm, we will exclude patients
with an unfavorable disease course or severe perianal fistulas.
Proportion of patients with severe endoscopic postoperative recurrence of CD (Rutgeerts i2b, i3
or i4) 6 months after ileocolonic resection with anastomosis (stoma excluded).
It has been established that the endoscopic Rutgeerts’ score is a strong surrogate marker for the
further clinical course of the disease (see appendix for scoring system). All endoscopies will be
video-recorded for later review and central re-reading.
ACCRUAL AND FEASIBILITY
This study will enroll 80 subjects at 13 sites in The Netherlands, Spain, France and Italy.
The feasibility of enrollment in this study is highly plausible given the high rates of resections at
these academic centres and lack of alternative treatments.
TREATMENT, DOSAGE AND ADMINISTRATION
Patients will be consented to participate with 2-3 weeks following ileocolonic resection. The first
study-infusion will also be given within 2-3 weeks if all inclusion and exclusion criteria are met.
Patients will receive intravenous infusions of 300 mg of VDZ or 250 ml or 0,9% sodium chloride
only (placebo) at Week 0, Week 8, Week 16 and 24.
PERMITTED CONCOMITANT MEDICATIONS
Loperamide or cholestyramine for control of bile acid diarrhea
Prednisone will be tapered over 4 weeks postoperatively
All other medications will be discontinued postoperatively.
|- Main changes (audit trail)|
|- RECORD||24-apr-2017 - 29-jun-2017|