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.

• Register: EUCTR
• Last refreshed on: 22 October 2018
• Main ID: EUCTR2015-000555-24-FR
• Date of registration: 03/01/2017
• Prospective Registration: No
• Primary sponsor: Academic Medical Center Amsterdam
• Public title: 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.
• 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 : REPREVIO (recurrence prevention with Entyvio) - REPREVIO
• Date of first enrolment: 28/12/2016
• Target sample size: 80
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000555-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

France, Netherlands, Spain

Contacts

• Name: IBD trialcenter
• Affiliation: Academic Medical Center

• Name: IBD trialcenter
• Affiliation: Academic Medical Center

Key inclusion & exclusion criteria

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.
- 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:
• Active smoking > 10 cigarettes/day
• 2nd, 3rd or later resection
• Surgery for perforating complication (abscess, fistula)
• 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 NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (eg, defined as at least 1 year since last regular menses with an FSH >40 IU/L or at least 5 years since last regular menses, confirmed before any study medication is implemented).
- Anti-TNF discontinued for at least 6 weeks before screening
- Written informed consent must be obtained and documented
- Enrollment of the patient within 14-21 days after surgery

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
- Patients with active infections such as sepsis, CMV infection and listeriosis
- Patients treated with natalizumab for at least 12 weeks
- Patients with hypernatremia or hyperchloremia.
- Patients requiring oral live vaccinations (typhoid, ROTAvirus and cholera) during the course of the trial.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Crohn's disease

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: Entyvio
Product Name: Vedolizumab IV
Product Code: MLN0002
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: vedolizumab
CAS Number: 943609-66-3
Current Sponsor code: MLN0002
Other descriptive name: VEDOLIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Concentrate and solvent for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 26

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).

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 Outcome(s)

Secondary end point(s): 1. The proportion of patients with any endoscopic recurrence of CD (Modified Rutgeerts Grade > i0) after 6 months.
2. Changes in the CDAI (Crohn’s disease activity index) and HBI (Harvey Bradshaw 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.
3. Adverse events and serious adverse events
4. Quality of life measure with a disease-specific instrument (IBDQ) and a generic QoL instrument (SF-36).
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
Secondary endpoint 3 and 5 at all time points

Secondary ID(s)

2014-100752

2015-000555-24-NL

Source(s) of Monetary Support

Takeda