Vedolizumab IV 300 mg in the Treatment of Fistulizing Crohn's Disease (ENTERPRISE)

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)

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).

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Vedolizumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GIRI (GI Research Institute)
• France
  • Lille cedex, France, 59037
    • CHRU de Lille - Hopital Claude Huriez
  • Nice Cedex 3, France, 06202
    • Hopital L'Archet II
  • Rennes cedex 9, France, 35033
    • CHU de Rennes - Hopital de Pontchaillou
  • Vandoeuvre les Nancy, France, 54511
    • Hôpital de Brabois
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliera S. Orsola-Malpighi
  • Milan, Italy, 20089
    • Istituto Clinico Humanitas IRCCS
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
• United Kingdom
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals NHS Trust
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212-1375
      • Vanderbilt University Medical Center
  • Texas
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Vedolizumab IV 300 mg + Placebo; Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Drug: Vedolizumab; Vedolizumab 300 mg IV infusion; Other Names: Entyvio; MLN0002; Kynteles; Drug: Placebo; 0.9% sodium chloride IV infusion
Experimental: Group 2: Vedolizumab 300 mg; Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.	Drug: Vedolizumab; Vedolizumab 300 mg IV infusion; Other Names: Entyvio; MLN0002; Kynteles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline)	Closed fistulae are no longer draining despite gentle finger compression.	Baseline, Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Closed fistulae are no longer draining despite gentle finger compression.	Weeks 22 and 30
Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline)	Closed fistulae are no longer draining despite gentle finger compression.	Week 30
Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)	Closed fistulae are no longer draining despite gentle finger compression.The time to first fistula closure was analyzed descriptively using Kaplan-Meier product limit methods, with participants for which no fistula closure is reported being censored at the time of their last fistulae assessment or date of last record (Week 30 or early discontinuation). Estimated median time to fistula closure (and 95%CI) are reported.	Up to Week 30
Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)	Closed fistulae are no longer draining despite gentle finger compression. The time to first fistula closure was analyzed descriptively using Kaplan-Meier product limit methods, with participants for which no fistula closure is reported being censored at the time of their last fistulae assessment or date of last record (Week 30 or early discontinuation). Estimated median time to fistula closure (and 95%CI) are reported.	Up to Week 30
Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline)	Duration of fistula response was measured by number of days with/without drainage. Duration of perianal fistula response (days) was derived as the sum of days with perianal fistula response between Day 1 and the end of the study (Week 30 or early discontinuation). Perianal fistula response is defined as reduction in the number of draining perianal fistulae (of those draining at Baseline) draining of at least 50%.	Up to Week 30

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2016
• Primary Completion (Actual): September 4, 2018
• Study Completion (Actual): November 14, 2018

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 11, 2015
• First Posted (Estimate): December 15, 2015

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Drug therapy; Fistulizing Crohn´s disease; Perianal Fistula
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Gastrointestinal Agents; Vedolizumab
• Other Study ID Numbers: Vedolizumab-4003; 2015-000852-12 (EudraCT Number); U1111-1174-2252 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.