Phase 4 Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis
Phase 4 Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis
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.
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 as compared to
 those receiving a matching placebo. The study will enroll approximately 110 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 treatment and efficacy assessment of 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 (up to Week 48). Participants will also participate in
 a long-term follow-up, by phone after the last dose of study drug up to Week 56.
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. Has a history of ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC)
 completed at least 1 year prior to the Day 1 (Randomization) Visit.

 4. Has pouchitis that is chronic or recurrent, defined by an modified pouchitis disease
 activity index (mPDAI) score ≥5 assessed as average from 3 days immediately prior to
 the Baseline endoscopy and a minimum endoscopic subscore of 2 (outside the staple or
 suture line) with either (a) ≥3 recurrent episodes within 1 year prior to the
 Screening Period treated with ≥ 2 weeks of antibiotic or other prescription therapy,
 or (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks
 immediately prior to the Baseline Endoscopy Visit.

 5. Agrees to take ciprofloxacin (500 mg twice daily) on Day 1 and through Week 4,
 regardless of the previous treatment and to stop any previous antibiotic therapy on
 Day 1 of the study (additional courses of antibiotics will be allowed, as needed, for
 flares after Week 14.)

 6. A male participant who is nonsterilized and sexually active with a female partner of
 childbearing potential agrees to use a barrier method of contraception (e.g., condom
 with spermicide) from signing of informed consent throughout the duration of the study
 and for 18 weeks after last dose. The female partner of a male subject should also be
 advised to use a highly effective method of contraception

 7. A female participant of childbearing potential who is sexually active with a
 nonsterilized male partner agrees to use a highly effective method of 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 isolated or predominant 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.

 6. Has diverting stoma

 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. A diagnostic TB test performed within 30 days of Screening or during the Screening
 Period 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).

 OR

 2. Chest X-ray within 3 months prior to Day 1 that is suspicious for pulmonary TB, and a
 positive or 2 successive indeterminate QuantiFERON test within 30 days prior to
 Screening or during the Screening Period.

 3. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV)
 infection** or a known history of human immunodeficiency virus (HIV) infection (or is
 found to be seropositive at Screening) or subject is immunodeficient (eg, due to organ
 transplantation, history of common variable immunodeficiency, etc).

 * Participants who are positive for hepatitis B virus surface antigen (HBsAg) will be
 excluded. For participants who are negative for HBsAg but are positive for either
 surface antibodies and/or core antibodies, HBV DNA polymerase chain reaction will be
 performed and if any test result meets or exceeds detection sensitivity, the
 participant will be excluded.

 -  If participant is HCV antibody positive, then a viral load test will be
 performed. If the viral load test is positive then the participant will be
 excluded.

 4. Has evidence of active infection with C difficile during Screening (to be
 confirmed by laboratory test)

 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, a history of tendon
 disorders related to quinolone administration and/or glucose-6-phosphate
 dehydrogenase (G6PD) deficiency. Further conditions requiring precautions for use
 of ciprofloxacin have to be considered based on local prescribing information.

 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 prior to Randomization.

 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 had a kidney, heart, or lung transplant.

 11. 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.

 12. Has a history of any major neurological disorders, including stroke, multiple
 sclerosis, brain tumor, demyelinating, or neurodegenerative disease.

 13. Has conditions, which in the opinion of the investigator, may interfere with the
 participant's ability to comply with the study procedures.

 14. 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.

 15. 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.

 16. 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.

 17. 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.

 18. 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.

 19. Has a history of drug abuse (defined as any illicit drug use) or a history of
 alcohol abuse within 1 year prior to Screening.