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.
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 IV All participants will receive an intravenous infusion at Day 1, Weeks 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
102
Vedolizumab placebo-matching IV infusion
Ciprofloxacin tablets
Vedolizumab IV infusion
Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 14
Clinically relevant remission is defined as modified Pouchitis Disease Activity Index (mPDAI) score \<5 and a reduction of mPDAI score by ≥2 points from Baseline. The 12-point mPDAI score is calculated as a sum of from two 6-point subscales, where 0 = best and 12 = worst.: 1) Clinical Symptoms: Stool Frequency (0=usual to postoperative stool frequency to 2=three or more stools/day\>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever \[temperature \>37.8 degrees C\] (0=Absent and 1=Present) for a clinical symptoms subscore of 0 (best) to 6 (worse); 2) Endoscopic Inflammation Findings: Edema, Granularity, Friability, Loss of vascular pattern, Mucous exudates and Ulcerations. Each item is scored on a scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0 (best) to 6 (worst) where higher scores indicate more severe disease.
Time frame: Week 14
Percentage of Participants With Chronic or Recurrent Pouchitis Achieving Clinically Relevant Remission at Week 34
Clinically relevant remission is defined as mPDAI score \<5 and a reduction of mPDAI score by ≥2 points from Baseline. The 12-point mPDAI score is calculated as a sum of from two 6-point subscales, where 0 = best and 12 = worst.: 1) Clinical Symptoms: Stool Frequency (0=usual to postoperative stool frequency to 2=3 or more stools/day\>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever \[temperature \>37.8 degrees C\] (0=Absent and 1=Present) for a clinical symptoms subscore of 0 (best) to 6 (worse); 2) Endoscopic Inflammation Findings: Edema, Granularity, Friability, Loss of vascular pattern, Mucous exudates and Ulcerations. Each item is scored on a scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0 (best) to 6 (worst) where higher scores indicate more severe disease.
Time frame: Week 34
Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Weeks 14 and 34
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University of Chicago Medical Center
Chicago, Illinois, United States
Northshore University HealthSystem
Evanston, Illinois, United States
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
University of North Carolina GI
Chapel Hill, North Carolina, United States
Carolinas HealthCare System Digestive Health
Charlotte, North Carolina, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Texas Digestive Disease Consultants
Southlake, Texas, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, United States
...and 24 more locations
PDAI remission is PDAI score \<7 and a reduction of PDAI score by ≥3 points from Baseline. The 18-point PDAI score is calculated as a sum of three 6-point scales with total possible subscore of 0 (best) to 6 (worse) and possible total score of 0 (best) to 18 (worse):1)Clinical Symptoms:Stool Frequency(0=usual to postoperative stool frequency to 2=3 or more stools/day\>postoperative usual);Rectal bleeding(0=None or rare,1=Present daily);Fecal urgency/abdominal cramps(0=None to 2=Usual),Fever\[temperature\>37.8 degrees C\](0=Absent,1=Present);2)Endoscopic Inflammation:Edema,Granularity,Friability,Loss of vascular pattern,Mucous exudates,Ulcerations. Each item is scored on scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0(best) to 6(worst);3) Acute Histologic Inflammation:Polymorphic nuclear leukocyte infiltration(0=None to 3=Severe plus crypt abscess),Ulceration per low power field\[mean\](0=0% to 3=\>50%) where higher scores indicate more severe disease.
Time frame: Weeks 14 and 34
Time to PDAI Remission
Time to remission-time in days from start of treatment to PDAI Remission(PDAI score \<7 and decrease in PDAI score ≥3 points from Baseline).18-point PDAI score-calculated as sum of 3, 6-point scales with total possible subscore of 0(best) to 6(worse) and possible total score of 0(best)to18(worse):1)Clinical Symptoms:Stool Frequency(0=usual to postoperative stool frequency to 2=3 or more stools/day\>postoperative usual);Rectal bleeding(0=None or rare,1=Present daily);Fecal urgency/abdominal cramps(0=None to 2=Usual),Fever\[temperature\>37.8 degrees C\](0=Absent,1=Present);2)Endoscopic Inflammation:Edema,Granularity,Friability,Loss of vascular pattern,Mucous exudates,Ulcerations.Each item is scored on scale of 0=not present to 1=present summed up to an endoscopic subscore=0(best) to 6(worst);3)Acute Histologic Inflammation:Polymorphic nuclear leukocyte infiltration(0=None to 3=Severe plus crypt abscess),Ulceration per low power field\[mean\](0=0% to 3=\>50%),higher scores=more severe disease.
Time frame: Baseline up to Week 34
Percentage of Participants Achieving a Partial mPDAI Response at Weeks 14 and 34
Partial mPDAI response is defined as a reduction in mPDAI score by ≥2 points from Baseline. The 12-point mPDAI score is calculated as a sum of from two 6-point subscales, where 0 = best and 12 = worst:1) Clinical Symptoms: Stool Frequency (0=usual to postoperative stool frequency to 2=3 or more stools/day\>postoperative usual); Rectal bleeding (0=None or rare to 1=Present daily); Fecal urgency or abdominal cramps (0=None to 2=Usual), Fever \[temperature \>37.8 degrees C\] (0=Absent and 1=Present) for a clinical symptoms subscore of 0 (best) to 6 (worse); 2) Endoscopic Inflammation Findings: Edema, Granularity, Friability, Loss of vascular pattern, Mucous exudates and Ulcerations. Each item is scored on a scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0 (best) to 6 (worst) where higher scores indicate more severe disease. Last observation carried forward (LOCF) method was used for analyses.
Time frame: Weeks 14 and 34
Change From Baseline in PDAI Endoscopic Inflammation Subscore at Weeks 14 and 34
The PDAI Endoscopic Inflammation subscore is a sum of scores from findings for Edema, Granularity, Friability, Loss of vascular pattern, Mucous exudates, and Ulcerations, each scored on 0=not present to 1=present scale summed up to a subscore ranging from 0 (best) to 6 (worse) where higher scores = more severe disease. A negative change from Baseline indicates improvement. LOCF method was used for analyses.
Time frame: Baseline up to Weeks 14 and 34
Change From Baseline in PDAI Acute Histologic Inflammation Subscore at Weeks 14 and 34
The PDAI Acute Histologic Inflammation subscore is a sum score from findings for Polymorphic nuclear leukocyte infiltration (0=None to 3=Severe plus crypt abscess), and Ulceration per low power field \[mean\] (0=0% to 3= \>50%) summed up to a subscore ranging from 0 (best) to 6 (worse) where higher scores = more severe disease. A negative change from Baseline indicates improvement. LOCF method was used for analyses.
Time frame: Baseline up to Weeks 14 and 34
Change From Baseline in Total PDAI Score at Weeks 14 and 34
The 18-point PDAI score is calculated as a sum of three 6-point scales with total possible subscore of 0 (best) to 6 (worse) and possible total score of 0 (best) to 18 (worse):1)Clinical Symptoms:Stool Frequency(0=usual to postoperative stool frequency to 2=3 or more stools/day\>postoperative usual);Rectal bleeding(0=None or rare,1=Present daily);Fecal urgency/abdominal cramps(0=None to 2=Usual),Fever\[temperature\>37.8 degrees C\](0=Absent,1=Present);2)Endoscopic Inflammation:Edema,Granularity,Friability,Loss of vascular pattern,Mucous exudates,Ulcerations. Each item is scored on scale of 0=not present to 1=present summed up to an endoscopic subscore ranging from 0(best) to 6(worst);3)Acute Histologic Inflammation:Polymorphic nuclear leukocyte infiltration(0=None to 3=Severe plus crypt abscess),Ulceration per low power field\[mean\](0=0% to 3=\>50%) where higher scores=more severe disease. A negative change from Baseline indicates improvement. LOCF method was used for analyses.
Time frame: Baseline up to Weeks 14 and 34
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at 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. A negative change from Baseline indicates worsening. LOCF method was used for analyses.
Time frame: Baseline up to Weeks 14, 22, and 34
Change From Baseline in Cleveland Global Quality of Life (CGQL) at 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. The total score ranges from 0 (worst) to 1 (best) where lower scores indicate less quality of life. A negative change from Baseline indicates worsening. LOCF method was used for analyses.
Time frame: Baseline up to Weeks 14, 22, and 34