Clinical trial NCT02630966: Vedolizumab IV 300 mg in the Treatment of Fistulizing Crohn's Disease
Official title: A Randomized Double-Blind Phase 4 Study to Evaluate the Safety and Proportion of Subjects With Fistula Healing in 2 Dose Regimens of Entyvio (Vedolizumab IV) in the Treatment of Fistulizing Crohn's Disease (ENTERPRISE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Crohn's Disease
Keywords: Drug therapy
Fistulizing Crohn´s disease
Perianal Fistula
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-12-15
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the percentage of participants with perianal fistula healing at Week 30 in 2 different dose regimens of vedolizumab intravenous (IV) 300 milligram (mg) in participants with fistulizing Crohn's disease (CD).

Detailed description: The drug being tested in this study is called vedolizumab IV. Vedolizumab IV is being tested to treat people who have fistulizing CD. This study will look at fistula healing in people who take vedolizumab IV.

The study is planned to enroll approximately 100 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* Group 1: Vedolizumab IV 300 mg dose at Weeks 0, 2, 6, 14 and 22, and a placebo infusion at Week 10 (dummy inactive infusion - this is a solution that looks like the study drug but has no active ingredient).
* Group 2: Vedolizumab IV 300 mg dose at Weeks 0, 2, 6, 10, 14 and 22.

This multi-center trial will be conducted worldwide. The overall time to participate in this study from screening to 18 weeks after the last dose is 44 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative has signed and dated a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Has a diagnosis of CD established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report.
4. Has a diagnosis of a minimum of 1 perianal draining fistula of at least 2 weeks duration as a complication of moderately to severely active CD, as identified on magnetic resonance image (MRI) at Screening. Other types of fistulae (enterocutaneous, abdominal) except rectovaginal fistulae are permitted, but the number of perianal draining fistulae is limited to 3.
5. All countries except France: The participant, historically, had an inadequate response with, lost response to, or was intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNF-α) antagonist for their underlying CD (does not require treatment failure for currently active draining fistula).

   France only: The participant, historically, failed (ie, had an inadequate response with, lost response to, or was intolerant to) infliximab for treatment of their underlying CD or fistulizing CD.
6. If the participant had noncutting perianal seton placement as part of standard care, seton must be removed by Week 14 of the study.

Exclusion Criteria:

1. Has a diagnosis of ulcerative colitis or indeterminate colitis.
2. Has a perianal abscess greater than (\>) 2 centimeter (cm) or an abscess that the investigator feels requires drainage based on either clinical assessment or MRI.
3. Has a Crohn's Disease Activity Index (CDAI) score \>400.
4. Has an ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
5. Has significant anal or rectal stenosis.
6. Has active or latent tuberculosis (TB), regardless of treatment history.
7. Has evidence of active Clostridium difficile (C. difficile) infection or is having treatment for C. difficile infection or other intestinal pathogens during Screening.
8. Has current rectovaginal fistula.
9. Currently has more than 3 draining perianal fistulae. Note: Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline)
timeFrame: Baseline, Week 30
Secondary outcomes:
measure: Percentage of Participants With at Least 50% Reduction of From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline) at Both Weeks 22 and 30
timeFrame: Weeks 22 and 30
measure: Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline)
timeFrame: Week 30
measure: Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)
timeFrame: Up to Week 30
measure: Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)
timeFrame: Up to Week 30
measure: Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline)
timeFrame: Up to Week 30
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: GIRI (GI Research Institute)
state: British Columbia
city: Lille cedex
country: France
facility: CHRU de Lille - Hopital Claude Huriez
city: Nice Cedex 3
country: France
facility: Hopital l'Archet II
city: Rennes cedex 9
country: France
facility: CHU de Rennes - Hopital de Pontchaillou
city: Vandoeuvre les Nancy
country: France
facility: Hopital de Brabois
city: Bologna
country: Italy
facility: Azienda Ospedaliera S. Orsola-Malpighi
city: Milan
country: Italy
facility: Istituto Clinico Humanitas IRCCS
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Schwartz DA, Peyrin-Biroulet L, Lasch K, Adsul S, Danese S. Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn's Disease: ENTERPRISE Study. Clin Gastroenterol Hepatol. 2022 May;20(5):1059-1067.e9. doi: 10.1016/j.cgh.2021.09.028. Epub 2021 Sep 29.