A Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis
Condition: Pouchitis
MeSH terms: Pouchitis
Intervention: Vedolizumab Placebo; Ciprofloxacin; Vedolizumab
Intervention description: Vedolizumab placebo-matching IV infusion; Ciprofloxacin tablets; Vedolizumab IV infusion
Intervention MeSH terms: Ciprofloxacin; Vedolizumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to compare the efficacy of vedolizumab intravenous (IV) and
      placebo in terms of the percentage of participants with chronic or recurrent pouchitis
      achieving clinically relevant remission.
    

Eligibility criteria:

        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 participant 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 (e.g., 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 (e.g., 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 participant is immunodeficient (e.g., 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 Deoxyribonucleic acid (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 Clostridium (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 (e.g., >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
             (e.g., 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.