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

Phase 4
Completed
Conditions
Crohn's Disease
Interventions
Drug: Vedolizumab
Drug: Placebo
Registration Number
NCT02630966
Lead Sponsor
Takeda
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
34
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.

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 1: Vedolizumab IV 300 mg + PlaceboVedolizumabVedolizumab 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.
Group 1: Vedolizumab IV 300 mg + PlaceboPlaceboVedolizumab 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.
Group 2: Vedolizumab 300 mgVedolizumabVedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline)Baseline, Week 30

Closed fistulae are no longer draining despite gentle finger compression.

Secondary Outcome Measures
NameTimeMethod
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 30Weeks 22 and 30

Closed fistulae are no longer draining despite gentle finger compression.

Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline)Week 30

Closed fistulae are no longer draining despite gentle finger compression.

Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)Up to Week 30

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.

Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)Up to Week 30

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.

Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline)Up to Week 30

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%.

Trial Locations

Locations (18)

Hopital de Brabois

🇫🇷

Vandoeuvre les Nancy, France

Hopital l'Archet II

🇫🇷

Nice Cedex 3, France

Academic Medical Center

🇳🇱

Amsterdam, Netherlands

Hospital Universitario y Politecnico La Fe

🇪🇸

Valencia, Spain

Istituto Clinico Humanitas IRCCS

🇮🇹

Milan, Italy

University of Calgary

🇨🇦

Calgary, Alberta, Canada

Erasmus MC

🇳🇱

Rotterdam, Netherlands

CHU de Rennes - Hopital de Pontchaillou

🇫🇷

Rennes cedex 9, France

John Radcliffe Hospital

🇬🇧

Oxford, United Kingdom

Azienda Ospedaliera S. Orsola-Malpighi

🇮🇹

Bologna, Italy

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Texas Digestive Disease Consultants

🇺🇸

Southlake, Texas, United States

Leids Universitair Medisch Centrum

🇳🇱

Leiden, Netherlands

CHRU de Lille - Hopital Claude Huriez

🇫🇷

Lille cedex, France

GIRI (GI Research Institute)

🇨🇦

Vancouver, British Columbia, Canada

Hospital Clinic Barcelona

🇪🇸

Barcelona, Spain

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, United Kingdom

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