Vedolizumab-4004

Principal Investigator: John  Valentine
Keywords: vedolizumab , 4004 , vedolizumab-4004 , earnest Department: Gastroenterology
IRB Number: 00093305 Co Investigator:  
Specialty: Gastroenterology, Gastroenterology
Sub Specialties: Inflammatory Bowel Disease/Crohn's/Ulcerative Colitis
Recruitment Status: Recruiting

Contact Information

Julie Will
julie.will@hsc.utah.edu
801-587-9060

Brief Summary

Primary Objective
To compare the efficacy of vedolizumab IV and placebo in terms of the percentage of subjects with chronic or
recurrent pouchitis achieving clinically relevant remission.
 
Secondary Objectives
To assess the efficacy of vedolizumab IV by:
 Percentage of subjects achieving mPDAI <5 and a reduction of overall score by ≥2 points from Baseline.
 Percentage of subjects achieving PDAI <7 and a reduction of overall score by ≥3 points from Baseline.
 Time to remission (defined as a PDAI score <7 and a decrease in PDAI score of ≥3 points from Baseline).
 Percentage of subjects achieving a partial response (defined as reduction of mPDAI score by ≥2 points from
Baseline).
 Change in PDAI endoscopic subscore.
 Change in PDAI histologic subscore.
 Change in total PDAI.
 Change in Inflammatory Bowel Disease Questionnaire (IBDQ), and Cleveland Global Quality of Life (CGQL,
Fazio Score, 3 items).
 
Exploratory Objective
 To assess the change in Robarts Histopathology Index (RHI).
 To assess change in biomarkers (fecal calprotectin and C-reactive protein [CRP]).
 Time to relapse of pouchitis symptoms and number of relapses.
 
Safety Objective
The safety objective is to assess the safety of vedolizumab IV in chronic or recurrent pouchitis.

Inclusion Criteria

1. In the opinion of the investigator, the subject is capable of understanding and complying with
    protocol requirements.
2. The subject or, when applicable, the subject’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. The subject is male or female and aged 18 to 80 years, inclusive.
4. The subject has a history of IPAA for UC completed at least 1 year prior to the Day 1
    (Randomization) Visit.
5. The subject has pouchitis that is chronic or recurrent, defined by an mPDAI score ≥5                    assessed as the 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
6. The subject 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.)
7. A male subject who is nonsterilized* and sexually active with a female partner of childbearing
    potential* agrees to use a barrier method of contraception (eg, 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*.
8. A female subject 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

The exclusion criteria are divided into 3 categories: GI exclusion criteria, infectious disease
exclusion criteria, and general exclusion criteria. Subjects meeting any of the following criteria
will not qualify for entry into the study:
Gastrointestinal Exclusion Criteria
1. The subject has CD or CD of the pouch. Subjects will be excluded if the investigator suspects,
    on the basis of the screening endoscopy, that the pattern of inflammation may be due to CD.
2. The subject has irritable pouch syndrome (IPS).
3. The subject has isolated or predominant cuffitis.
4. The subject has mechanical complications of the pouch (eg, pouch stricture or pouch fistula).
5. The subject currently requires or has a planned surgical intervention for UC during the study.
6. The subject has diverting stoma.
.
Infectious Disease Exclusion Criteria
1. The subject has evidence of an active infection (eg, sepsis, cytomegalovirus, or listeriosis)
     during Screening.
2. The subject has active or latent tuberculosis (TB), regardless of treatment history, as
    evidenced by any of the following:
         a) A diagnostic TB test performed within 30 days of Screening or during the Screening Period
             that is positive, as defined by:
               i. A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests OR
               ii. A tuberculin skin test reaction ≥10 mm (≥5 mm in subjects receiving the equivalent of
                   >15 mg/day prednisone) OR
         b) 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.
                  Note: if the subject has a negative diagnostic TB test documented in the previous 3 months,
                  screening testing does not need to be repeated provided subject has no risk factors for exposure.
3. The subject 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).
     * Subjects who are positive for hepatitis B virus surface antigen (HBsAg) will be excluded.
     For subjects 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 subject will be excluded.
     ** If subject is HCV antibody positive, then a viral load test will be performed. If the viral
     load test is positive then the subject will be excluded.
4. The subject has evidence of active infection with C difficile during Screening (to be confirmed
     by laboratory test).
 
General Exclusion Criteria
1. The subject has any prior exposure to vedolizumab, natalizumab, efalizumab, rituximab,
    etrolizumab, or anti-MAdCAM-1 therapy.
2. The subject has a history of hypersensitivity or allergies to vedolizumab or its components.
3. The subject 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. The subject is taking, has taken, or is required to take any excluded medications (as listed in
    Section 22).
5. The subject has received any investigational or approved biologic or biosimilar agent within
    60 days prior to Randomization
6. The subject has received an investigational nonbiologic therapy within 30 days prior to
    Randomization.
7. The subject 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. The subject has received any live vaccinations within 30 days prior to randomization.
9. The subject has a positive PML subjective symptom checklist at Screening.
10. [Previous criterion #10 incorporated into criterion #3 in amendment number 3].
11. The subject has had a kidney, heart, or lung transplant.
12. [Previous criterion #12 deleted in amendment number 3].
13. The subject 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 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. Subjects 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. The subject has a history of any major neurological disorders, including stroke, multiple
      sclerosis, brain tumor, demyelinating, or neurodegenerative disease.
15. The subject has conditions which, in the opinion of the investigator, may interfere with the
      subject’s ability to comply with the study procedures.
16. The subject has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, 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 subject safety.
17. The subject has any of the following laboratory abnormalities during the Screening Period:
          i. Hemoglobin level <8 g/dL.
          ii. White blood cell (WBC) count <3 × 109/L.
          iii. Lymphocyte count <0.5 × 109/L.
          iv. Platelet count <100 × 109/L or >1200 × 109/L.
          v. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3
             × the upper limit of normal (ULN).
          vi. Alkaline phosphatase >3 × ULN.
          vii. Serum creatinine >2 × ULN.
18. If female, the subject is pregnant or lactating or intending to become pregnant or nurse before,
      during, or within 18 weeks after the last dose of study drug; or intending to donate ova during
      such time period.
19. If male, the subject intends to donate sperm or father a child during the course of this study or
      for 18 weeks after the last dose of study drug.
20. The subject 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. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
      abuse within 1 year prior to Screening.
22. [Previous criterion #22 incorporated into criterion #3 in amendment number 3].