Clinical Trial: Phase 4 Study to Evaluate the Efficacy and Safety of Vedolizumab in the Treatment of Chronic Pouchitis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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)

Brief Summary: 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.

Detailed Summary:

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).

Current Primary Outcome: Percentage of Participants who Achieve Remission at Week 14 [ Time Frame: Week 14 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Time to the Occurrence of Symptomatic Remission [ Time Frame: Baseline up to Week 34 ]
• Change From Screening in PDAI Endoscopic Score at Weeks 14 and 34 [ Time Frame: Screening (Day -28), Weeks 14 and 34 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

Original Secondary Outcome:

• Time to the Occurrence of Symptomatic Remission [ Time Frame: Baseline up to Week 34 ]
• Change From Screening in PDAI Endoscopic Score at Weeks 14 and 34 [ Time Frame: Screening (Day -28), Weeks 14 and 34 ]
  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 ]
  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 ]
  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 at Weeks 14, 22 and 34 [ Time Frame: Day 1, Weeks 14, 22 and 34 ]
  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 Inflammatory Bowel Disease Questionnaire (IBDQ) Subscale Score at Weeks 14, 22 and 34 [ Time Frame: Day 1, Weeks 14, 22 and 34 ]
  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 ]
  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.

Dates:
Date Received: May 26, 2016
Date Started: November 2, 2016
Date Completion: September 30, 2019
Last Updated: May 4, 2017
Last Verified: May 2017