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Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Determine the Effectiveness and Safety of Vedolizumab in Prevention of Recurrence of Crohn's Disease of the mucosa in Patients with Surgical Removel of the area between the small and the large bowel.

Phase 1
Conditions
Crohn's disease
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
Registration Number
EUCTR2015-000555-24-ES
Lead Sponsor
Academic Medical Center Amsterdam
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
80
Inclusion Criteria

- In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
- The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. Consent must be documented.
- Established Crohn’s disease as the indication for ileocolonic resection
- Age > 18
- Ileocolonic resection with ileocolonic anastomosis and removal of all tissue macroscopically affected by CD according to the surgeon
- Presence of at least 1 risk factor for recurrence:
o Active smoking > 10 cigarettes/day
o 2nd, 3rd or later resection
o Surgery for perforating complication (abscess, fistula)
o Previous exposure to anti-TNF antibodies
- 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]).
- Anti-TNF discontinued for at least 6 weeks before screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

- Patients that need to continue postoperative medication for their CD as per investigator's discretion, eg for fistulizing perianal CD.
- Previous treatment with VDZ
- Clinically significant CD elsewhere in the gastrointestinal tract not removed with surgery
- Patients with clinically documented short bowel syndrome.
- 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.
- Patients with the following laboratory abnormalities:
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
- Active participation in another trial.
- Evidence of Clostridium difficile infection in the previous 4 weeks.
- Patients with abdominal abscess, active or latent tuberculosis or cancer.
- A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures.
- Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures.
- Patients unable to attend all study visits.
- Patients with a history of non-compliance with clinical study protocols.
- Contraindication for endoscopy.
- History of colonic dysplasia/cancer
- Received other biologics within the last 6 weeks of screening
- Known HIV, chronic hepatitis B or C infection
- Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: The primary objective of this prospective placebo-controlled study is to assess the ability of vedolizumab to prevent postoperative endoscopic recurrence of Crohn’s disease in the neoterminal ileum.;Secondary Objective: Prevention of clinical recurrence of Crohn’s disease;Primary end point(s): Proportion of patients with severe endoscopic postoperative recurrence of CD (Rutgeerts i2b, i3 or i4) after approximately 6 months (Week 26).;Timepoint(s) of evaluation of this end point: week 26
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): 1. The proportion of patients with any endoscopic recurrence of CD (Modified Rutgeerts Grade > i0) after 6 months. <br>2. Changes in the CDAI (Crohn’s disease activity index) between week 0 and 26. This measure will give an indication for clinical recurrence. Although most patients will remain asymptomatic, we will collect global scores as well as individual components.<br>3. Adverse events and serious adverse events<br>4. Quality of life measure with a disease-specific instrument (IBDQ) and a generic QoL instrument (SF-36).<br>5. Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion;Timepoint(s) of evaluation of this end point: secondary endlpoint 1,2 and 4 at week 26<br>Secondary endpoint 3 and 5 at all time points
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