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Trial record 6 of 49 for:    vedolizumab

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Takeda
Information provided by (Responsible Party):
Takeda Identifier:
First received: December 11, 2015
Last updated: September 8, 2016
Last verified: September 2016
The purpose of this study is to evaluate 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).

Condition Intervention Phase
Crohn Disease
Drug: Vedolizumab
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:

Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Participants with a Reduction of at Least 50% from Day 1 in the Number of Draining Perianal Fistulae at Week 30 [ Time Frame: Day 1, Week 30 ] [ Designated as safety issue: No ]
    Closed fistulae are no longer draining despite gentle finger compression

Secondary Outcome Measures:
  • Percentage of Participants with 100% Perianal Fistulae Closure at Week 30 [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    Closed fistulae are no longer draining despite gentle finger compression

  • Time to First Perianal Fistulae Closure [ Time Frame: Up to Week 30 ] [ Designated as safety issue: No ]
    Closed fistulae are no longer draining despite gentle finger compression

  • Time to Last (100%) Perianal Fistulae Closure [ Time Frame: Up to Week 30 ] [ Designated as safety issue: No ]
    Closed fistulae are no longer draining despite gentle finger compression

  • Duration of Perianal Fistulae Response [ Time Frame: Up to Week 30 ] [ Designated as safety issue: No ]
    Duration of fistula response will be measured by number of days with/without drainage.

Estimated Enrollment: 126
Study Start Date: July 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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, once, at Week 10.
Drug: Vedolizumab
Vedolizumab 300 mg IV
Other Names:
  • Entyvio
  • MLN0002
  • Kynteles
Drug: Placebo
0.9% sodium chloride used as vedolizumab placebo-matching IV
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
Other Names:
  • Entyvio
  • MLN0002
  • Kynteles

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 will enroll approximately 126 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.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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. 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).
  6. Had noncutting perianal seton placement as part of standard care within 1 to 4 weeks prior to randomization.
  7. Is willing and able to undergo MRI per protocol requirements.
  8. Is willing and able to take antibiotic treatment (metronidazole or ciprofloxacin, as per local label) from Day 1 through study Week 6.
  9. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
  10. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
  11. Has a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factors must be up-to-date on colorectal cancer surveillance (may be performed during Screening as standard of care).

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, as evidenced by any of the following:

    1. History of TB.
    2. A diagnostic TB test performed during Screening that is positive, as defined by:

    I. A positive test for tuberculosis (QuantiFERON) or 2 successive indeterminate QuantiFERON tests OR II. A tuberculin skin test reaction greater than or equal to (≥) 10 millimeter (mm) (≥5 mm in participants receiving the equivalent of >15 mg/day prednisone)

  7. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or is found to be seropositive at Screening.
  8. Has evidence of active Clostridium difficile (C. difficile) infection or is having treatment for C. difficile infection or other intestinal pathogens during Screening.
  9. Has evidence of an active infection during Screening (eg, sepsis, cytomegalovirus, or listeriosis), other than related to the fistula(e).
  10. Currently requires or has a planned surgical intervention for CD during the study.
  11. Has a contraindication for MRI.
  12. Has allergies to and/or contraindications for metronidazole and ciprofloxacin (including interacting drugs such as tizanidine).
  13. In the opinion of the investigator, the participant is likely to require greater than 6 weeks of treatment after Day 1 with metronidazole or ciprofloxacin for the treatment of abscess.
  14. Is taking, has taken, or is required to take any excluded medications.
  15. Has received non-biologic investigational therapy within 30 days prior to randomization.
  16. Has received an approved non-biologic therapy (including 5-aminosalicylate [5-ASA], corticosteroid, azathioprine, 6-mercaptopurine [6-MP], etc.) in an investigational protocol within 30 days prior to randomization.
  17. Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives (whichever is longer) of randomization.
  18. Has a history of hypersensitivity or allergies to vedolizumab or its components.
  19. Has any prior exposure to vedolizumab, natalizumab, efalizumab, or rituximab.
  20. Has received any live vaccinations within 30 days prior to randomization.
  21. Has current rectovaginal fistula.
  22. Currently has more than 3 draining perianal fistulae.
  23. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening or Day 1 visit.
  24. Has a history of malignancy, except for the following: adequately-treated nonmetastatic basal cell skin cancer; squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to Screening; or history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to Screening. Participants with a remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received, and must be discussed with the sponsor on a case-by-case basis prior to randomization.
  25. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating or neurodegenerative disease.
  26. Has conditions which, in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures.
  27. Has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety.
  28. Has any of the following laboratory abnormalities during the Screening Period:

    I. Hemoglobin level less than (<) 8 gram per deciliter (g/dL). II. White blood cell (WBC) count <3 * 10^9 per liter (/L). III. Lymphocyte count <0.5 * 10^9/L. IV. Platelet count <100 * 10^9/L or >1200 * 10^9/L. V. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 * the upper limit of normal (ULN). VI. Alkaline phosphatase >3 * ULN. VII. Serum creatinine >1.5 * ULN. Note: Retesting laboratory values during the screening interval maybe considered with consultation from the medical monitor.

  29. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 18 weeks after participating in this study; or intending to donate ova during such time period.
  30. If male, the participant intends to donate sperm during the course of this study or for 18 weeks thereafter.
  31. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
  32. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to Visit 1.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02630966

Contact: Takeda Study Registration Call Center +1-877-825-3327

United States, Illinois
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Chicago, Illinois, United States
United States, Maryland
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Baltimore, Maryland, United States
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Rochester, Minnesota, United States
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Cleveland, Ohio, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Washington
Seattle, Washington, United States
Canada, British Columbia
Vancouver, British Columbia, Canada
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Lille cedex, France
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Nice Cedex 3, France
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Paris Cedex 12, France
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Rennes cedex 9, France
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Vandoeuvre les Nancy, France
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Bologna, Italy
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Milan, Italy
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Amsterdam, Netherlands
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Leiden, Netherlands
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Maastricht, Netherlands
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Rotterdam, Netherlands
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Barcelona, Spain
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Valencia, Spain
United Kingdom
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Birmingham, United Kingdom
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Harrow, United Kingdom
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Nottingham, United Kingdom
Oxford, United Kingdom
Sponsors and Collaborators
Study Director: Medical Director Clinical Science Takeda
  More Information

Responsible Party: Takeda Identifier: NCT02630966     History of Changes
Other Study ID Numbers: Vedolizumab-4003  2015-000852-12  U1111-1174-2252 
Study First Received: December 11, 2015
Last Updated: September 8, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Netherlands: Central Committee for Research Involving Human Subjects
France: National Agency for the Safety of Medicine and Health Products
Italy: Italian Medicines Agency
Spain: Spanish Agency of Medicines and Medical Devices

Keywords provided by Takeda:
Drug therapy

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Gastrointestinal Agents processed this record on December 05, 2016