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

Primary Purpose

Crohn's Disease

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Vedolizumab

Placebo

About this trial

This is an interventional treatment trial for Crohn's Disease focused on measuring Drug therapy, Fistulizing Crohn´s disease, Perianal Fistula

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
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.
Has a diagnosis of CD established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report.
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.
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.
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:

Has a diagnosis of ulcerative colitis or indeterminate colitis.
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.
Has a Crohn's Disease Activity Index (CDAI) score >400.
Has an ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
Has significant anal or rectal stenosis.
Has active or latent tuberculosis (TB), regardless of treatment history.
Has evidence of active Clostridium difficile (C. difficile) infection or is having treatment for C. difficile infection or other intestinal pathogens during Screening.
Has current rectovaginal fistula.
Currently has more than 3 draining perianal fistulae. Note: Other protocol-defined inclusion/exclusion criteria may apply

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group 1: Vedolizumab IV 300 mg + Placebo

Group 2: Vedolizumab 300 mg

Arm Description

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.

Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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

Closed fistulae are no longer draining despite gentle finger compression.

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.

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.

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%.

Full Information

NCT ID

NCT02630966

First Posted

December 11, 2015

Last Updated

November 5, 2019

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT02630966

Brief Title

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

Acronym

ENTERPRISE

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

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

August 10, 2016 (Actual)

Primary Completion Date

September 4, 2018 (Actual)

Study Completion Date

November 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn's Disease

Keywords

Drug therapy, Fistulizing Crohn´s disease, Perianal Fistula

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: Vedolizumab IV 300 mg + Placebo

Arm Type

Experimental

Arm Description

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.

Arm Title

Group 2: Vedolizumab 300 mg

Arm Type

Experimental

Arm Description

Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.

Intervention Type

Drug

Intervention Name(s)

Vedolizumab

Other Intervention Name(s)

Entyvio, MLN0002, Kynteles

Intervention Description

Vedolizumab 300 mg IV infusion

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

0.9% sodium chloride IV infusion

Primary Outcome Measure Information:

Title

Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline)

Description

Closed fistulae are no longer draining despite gentle finger compression.

Time Frame

Baseline, Week 30

Secondary Outcome Measure Information:

Title

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

Description

Closed fistulae are no longer draining despite gentle finger compression.

Time Frame

Weeks 22 and 30

Title

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

Description

Closed fistulae are no longer draining despite gentle finger compression.

Time Frame

Week 30

Title

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

Description

Time Frame

Up to Week 30

Title

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

Description

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 Frame

Up to Week 30

Title

Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline)

Description

Time Frame

Up to Week 30

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 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. Has a diagnosis of CD established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report. 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. 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. 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: Has a diagnosis of ulcerative colitis or indeterminate colitis. 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. Has a Crohn's Disease Activity Index (CDAI) score >400. Has an ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine. Has significant anal or rectal stenosis. Has active or latent tuberculosis (TB), regardless of treatment history. Has evidence of active Clostridium difficile (C. difficile) infection or is having treatment for C. difficile infection or other intestinal pathogens during Screening. Has current rectovaginal fistula. Currently has more than 3 draining perianal fistulae. Note: Other protocol-defined inclusion/exclusion criteria may apply

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director Clinical Science

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37212-1375

Country

United States

Facility Name

Texas Digestive Disease Consultants

City

Southlake

State/Province

Texas

ZIP/Postal Code

76092

Country

United States

Facility Name

Virginia Mason Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98101

Country

United States

Facility Name

University of Calgary

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 4Z6

Country

Canada

Facility Name

GIRI (GI Research Institute)

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6Z 2K5

Country

Canada

Facility Name

CHRU de Lille - Hopital Claude Huriez

City

Lille cedex

ZIP/Postal Code

59037

Country

France

Facility Name

Hopital l'Archet II

City

Nice Cedex 3

ZIP/Postal Code

06202

Country

France

Facility Name

CHU de Rennes - Hopital de Pontchaillou

City

Rennes cedex 9

ZIP/Postal Code

35033

Country

France

Facility Name

Hopital de Brabois

City

Vandoeuvre les Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Azienda Ospedaliera S. Orsola-Malpighi

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

Istituto Clinico Humanitas IRCCS

City

Milan

ZIP/Postal Code

20089

Country

Italy

Facility Name

Academic Medical Center

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Leids Universitair Medisch Centrum

City

Leiden

ZIP/Postal Code

2333 ZA

Country

Netherlands

Facility Name

Erasmus MC

City

Rotterdam

ZIP/Postal Code

3015 CE

Country

Netherlands

Facility Name

Hospital Clinic Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Hospital Universitario y Politecnico La Fe

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

Nottingham University Hospitals NHS Trust

City

Nottingham

ZIP/Postal Code

NG7 2UH

Country

United Kingdom

Facility Name

John Radcliffe Hospital

City

Oxford

ZIP/Postal Code

OX3 9DU

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

34597729

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.

Results Reference

derived

Learn more about this trial

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

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

Crohn's Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial