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Trial record 6 of 46 for:    vedolizumab

Phase 4 Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis (EARNEST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Takeda
Information provided by (Responsible Party):
Takeda Identifier:
First received: May 26, 2016
Last updated: September 8, 2016
Last verified: September 2016
The purpose of this study is to assess the efficacy and safety of vedolizumab intravenous (IV) in participants with a proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis (UC) who have developed chronic or recurrent pouchitis, or require continuous antibiotic treatment.

Condition Intervention Phase
Colitis, Ulcerative
Drug: Vedolizumab
Drug: Ciprofloxacin
Drug: Vedolizumab 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, Placebo-Controlled Phase 4 Study to Evaluate the Efficacy and Safety of Entyvio (Vedolizumab IV) in the Treatment of Chronic Pouchitis (EARNEST)

Resource links provided by NLM:

Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Participants who Achieve Remission at Week 14 [ Time Frame: Week 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to the Occurrence of Symptomatic Remission [ Time Frame: Baseline up to Week 34 ] [ Designated as safety issue: No ]
  • Change From Screening in PDAI Endoscopic Score at Weeks 14 and 34 [ Time Frame: Screening (Day -28), Weeks 14 and 34 ] [ Designated as safety issue: No ]
    PDAI endoscopic scale includes edema, granularity, friability, loss of vascular pattern, mucous exudates and ulcerations. Each item is scored on a scale of 0 (no symptoms of pouchitis) to 1 (pouchitis). A total PDAI endoscopic score is calculated by summing the scores from each symptoms. Total score ranges from 0 to 6. Maximum score indicates worsening of the disease.

  • Change From Screening in PDAI Histologic Findings Score at Weeks 14 and 34 [ Time Frame: Screening (Day -28), Weeks 14 and 34 ] [ Designated as safety issue: No ]
    PDAI histologic scale includes polymorphic nuclear leukocyte infiltration (mild=1; moderate + crypt abscess=2 and severe + crypt abscess=3) and ulceration per low power field (mean). A total PDAI histologic scale is calculated by summing the scores from each symptoms. Total score ranges from 0 to 6. Maximum score indicates worsening of the disease.

  • Change From Screening in PDAI Score at Weeks 14 and 34 [ Time Frame: Screening (Day -28), Weeks 14 and 34 ] [ Designated as safety issue: No ]
    PDAI is an objective and quantitative criteria for pouch inflammation after ileal pouch anal anastomosis (IPAA). The 18-point overall score is calculated from 3 separate 6-point scales based on clinical symptoms (0 to 6), endoscopic findings (0 to 6) and histologic changes (0 to 6). The PDAI incorporates histologic features of acute inflammation, along with symptom and inflammation on endoscopy, and establishes a cut-off of 7 for differentiation between 'pouchitis' (≥7 points) and 'no pouchitis' (<7 points).

  • Change From Day 1 in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Subscale Score at Weeks 14, 22 and 34 [ Time Frame: Day 1, Weeks 14, 22 and 34 ] [ Designated as safety issue: No ]
    The IBDQ is an instrument used to assess quality of life in adult participants with inflammatory bowel disease (IBD). It includes 32 questions on 4 domains of Health-Related Quality-of-Life (HRQOL): Bowel Systems (10 items), Emotional Function (12 items), Social Function (5 items), and Systemic Function (5 items). Participants are asked to recall symptoms and quality of life from the last 2 weeks and rate each item on a 7-point Likert scale (1=worst to 7=best). A total IBDQ score is calculated by summing the scores from each domain; the total IBDQ score ranges from 32 to 224, with lower scores reflecting worse HRQOL.

  • Change From Day 1 in 3-Item Cleveland Global Quality of Life (CGQL) at Weeks 14, 22 and 34 [ Time Frame: Day 1, Weeks 14, 22 and 34 ] [ Designated as safety issue: No ]
    The CGQL (Fazio score) is a quality-of-life indicator specifically for participants with ileal pouch-anal anastomosis. Participants rate 3 items (current quality of life, current quality of health, and current energy level), each on a scale of 0 to 10 (0=worst; 10=best). The scores are added, and the final CGQL utility score is obtained by dividing this result by 30.

Estimated Enrollment: 200
Study Start Date: April 2016
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vedolizumab 300 mg
Vedolizumab 300 mg, intravenous (IV) infusion, once at Weeks 0, 2, 6, 14, 22, and 30 along with ciprofloxacin 500 mg, tablet, orally twice daily up to Week 4.
Drug: Vedolizumab
Vedolizumab IV infusion
Other Names:
  • Entyvio
  • MLN0002 IV
  • Kynteles
Drug: Ciprofloxacin
Ciprofloxacin Tablets
Placebo Comparator: Placebo
Vedolizumab placebo-matching IV infusion, once at Weeks 0, 2, 6, 14, 22, and 30 along with ciprofloxacin 500 mg, tablet, orally twice daily up to Week 4.
Drug: Ciprofloxacin
Ciprofloxacin Tablets
Drug: Vedolizumab Placebo
Vedolizumab placebo-matching IV infusion

Detailed Description:

Vedolizumab is being tested to treat people who have chronic pouchitis. This study will look at the healing of inflammation of ileal pouch in people who take vedolizumab The study will enroll approximately 200 patients. Participants will be randomly assigned 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):

  • Vedolizumab 300 mg IV
  • Placebo

All participants will receive an intravenous infusion at Weeks 0, 2, 6, 14, 22, and 30 along with concomitant antibiotic treatment with ciprofloxacin 500 mg twice daily through Week 4.

This multicenter trial will be conducted in North America and Europe. The overall time to participate in this study is 34 weeks. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after the last dose of study drug for a safety follow-up assessment. Participants will also participate in a long-term safety follow-up, by phone, at 6 months after the last dose of study drug (Week 56).


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 signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
  3. Is male or female and aged 18 to 80 years, inclusive.
  4. Has a history of ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) completed at least 1 year prior to the Screening Visit.
  5. Has pouchitis that is chronic or recurrent, defined by an modified Pouchitis Disease Activity Index (mPDAI) ≥5 and >2 episodes within 1 year of the Screening Visit or requiring long-term continuous low-dose antibiotic therapy taken daily on an ongoing basis (eg, ciprofloxacin 250-500 mg/day or metronidazole 500 mg/day taken for several weeks or months at a time) or frequent pulse antibiotic therapy.
  6. Agrees to stop antibiotic therapy on Day 1 of the study and switch to ciprofloxacin through Week 4 of study. (Additional courses of ciprofloxacin will be allowed, as needed, for flares after Week 14.)
  7. 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.
  8. 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.

Exclusion Criteria:

Gastrointestinal Exclusion Criteria

  1. Has Crohn's disease (CD), or CD of the pouch.
  2. Has irritable pouch syndrome (IPS).
  3. Has cuffitis.
  4. Has mechanical complications of the pouch (eg, pouch stricture or pouch fistula).
  5. Currently requires or has a planned surgical intervention for UC during the study.

    Infectious Disease Exclusion Criteria

1. Has evidence of an active infection (eg, sepsis, cytomegalovirus, or listeriosis) during Screening.

2. 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:

    1. A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests OR
    2. A tuberculin skin test reaction ≥10 mm (≥5 mm in participants receiving the equivalent of >15 mg/day prednisone).

      Note if the participant has a negative diagnostic TB test documented in the previous 3 months, screening testing does not need to be repeated provided participant has no risk factors for exposure.

    3. Has a positive test result for hepatitis B surface antigen (HBsAg), antibody to hepatitis C virus (anti-HCV), at Screening or a known history of human immunodeficiency virus infection (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).

    General Exclusion Criteria

    1. Has any prior exposure to vedolizumab, natalizumab, efalizumab, rituximab, etrolizumab, or anti- mucosal addressin cell adhesion molecule-1 (MAdCAM-1) therapy.
    2. Has a history of hypersensitivity or allergies to vedolizumab or its components.
    3. Has allergies to and/or contraindications for ciprofloxacin (including interacting drugs such as tizanidine).
    4. Is taking, has taken, or is required to take any excluded medications.
    5. Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of randomization (whichever is longer).
    6. Has received an investigational nonbiologic therapy within 30 days prior to randomization.
    7. Has received an approved nonbiologic therapy (including 5-aminosalicylate [5-ASA], corticosteroid, azathioprine, 6-mercaptopurine [6-MP], etc.) in an investigational protocol within 30 days prior to randomization.
    8. Has received any live vaccinations within 30 days prior to randomization.
    9. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening.
    10. Has a history of tendon rupture.
    11. Has had a kidney, heart, or lung transplant.
    12. Has myasthenia gravis, peripheral neuropathy, QT prolongation, or a history of seizure.
    13. Has a history of malignancy, except for the following: adequately-treated non-metastatic 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 the Screening visit; and 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 enrollment.
    14. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurodegenerative disease.
    15. Has conditions, which in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures.
    16. 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.
    17. Has any of the following laboratory abnormalities during the Screening Period:
    1. Hemoglobin level <8 g/dL.
    2. White blood cell (WBC) count <3 × 10^9/L.
    3. Lymphocyte count <0.5 × 10^9/L.
    4. Platelet count <100 × 10^9/L or >1200 × 10^9/L.
    5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN).
    6. Alkaline phosphatase >3 × ULN.
    7. Serum creatinine >2 × ULN.

    18. If female, the participant is pregnant or lactating or intending to become pregnant or nurse before, during, or within 18 weeks after the last dose of study medication; or intending to donate ova during such time period.

    19. If male, the participant intends to donate sperm or father a child during the course of this study or for 18 weeks after the last dose of study medication.

    20. 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.

    21. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the 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: NCT02790138

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

  Show 29 Study Locations
Sponsors and Collaborators
Study Director: Medical Director Clinical Science Takeda
  More Information

Responsible Party: Takeda Identifier: NCT02790138     History of Changes
Other Study ID Numbers: Vedolizumab-4004  U1111-1171-0918  2015-003472-78 
Study First Received: May 26, 2016
Last Updated: September 8, 2016
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Colitis, Ulcerative
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Ileal Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Gastrointestinal Agents processed this record on September 30, 2016