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
MedDRA version: 20.0Level: LLTClassification code 10013099Term: Disease CrohnsSystem Organ Class: 100000004856
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2015-000555-24-IT

Lead Sponsor: AMC MEDICAL RESEARCH B.V.

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. Only patients treated with either conventional therapy or anti-TNF antagonist before surgery and with documented inadequate response, loss of response or intolerance to such treatments can be enrolled
- 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
- Females of childbearing potential will be included if they are either sexually inactive (sexually abstinent for 14 days prior to the first study drug dose continuing through 6 months after the last study drug dose, or, in case of sexually active women, using one of the following highly effective contraceptive methods (i.e.results in < 1 % failure rate when used consistently and correctly) in this trial:
a) intrauterine device(IUD)
b) surgical sterilization of the partner (vasectomy for 6 months minimum)
c) combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
d) progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
e) intrauterine hormone releasing system (IUS)
f) bilateral tubal occlusion
- Females of childbearing potential agree to remain sexually inactive or to keep the same birth control method for at least 6 months following the last dose.
- A female of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first study dose:
a) hysteroscopic sterilization;
b) bilateral tubal ligation or bilateral salpingectomy;
c) hysterectomy;
d) bilateral oophorectomy;
or be postmenopausal with amenorrhea for at least 1-year prior to the first study drug dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status i.e. FSH > 40 IU/L.
- A non-vasectomized male subject agrees to use a condom with spermicide during the study until 180 days beyond the last dose of study medication and the female partner agrees to comply with inclusion 7 or 9. For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male. If male, agrees not to donate sperm from the first study drug dose until 180 days after dosing.
- Anti-TNF discontinued for at least 6 weeks prior to 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.
- 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 and /or colonic cancer
- Received other biologics within the last 6 weeks of screening
- Known HIV, hepatitis B or C infection
- Evidence of or treatment for C. difficile infection or other intestinal pathogen within 4 weeks prior to enrollment or at screening
- Active or latent tuberculosis
- Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.
- Positive PML subjective symptom checklist before enrollment
- Patients exposed to a live vaccine in the previous 4 weeks before screening.
- Patients with a history of hypersensitivity to the active substance or to any of it excipients
-Patients with active or latent severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis and opportunistic infections.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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

Name	Time	Method
Secondary end point(s): The proportion of patients with any endoscopic recurrence of CD (Modified Rutgeerts Grade > i0) after 6 months; Changes in the CDAI (Crohn's disease activity index) and HBI (Harvey Bradshaw index) between week 0 and 26. ; Quality of life measure with a disease-specific instrument (IBDQ) and a generic QoL instrument (SF-36). ; Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion;Timepoint(s) of evaluation of this end point: At week 26; at week 26 ; at week 26 ; at every visit

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