When some people have their large bowel removed, a surgeon can make a "pouch" from part of the small bowel to connect it to the back passage (anus). Pouchitis is when the pouch becomes inflamed (swollen) or infected. The main aim of this study is to find out if vedolizumab improves pouchitis symptoms and pouch inflammation. Other aims include to find out if vedolizumab is well tolerated and if it causes any medical problems (adverse events or side effects) and to look for any changes in the well-being of participants during their treatment with vedolizumab.
This study consists of two parts: Part 1 includes the induction and maintenance periods, and Part 2 includes the continued maintenance period. Participants will receive up to 12 infusions of vedolizumab. In Part 1 of the study, first 3 infusions are in first 6 weeks (Day 1, Week 2 and Week 6). Participants who are getting benefit may continue with the treatment for up to 7.5 months (30 weeks) in the maintenance period for Part 1. After completing treatment with vedolizumab in Part 1, participants will visit their clinic for a health check at Week 34.
Participants who show clinical response at Week 34 will continue to Part 2, receiving vedolizumab every 8 weeks for an additional 40 weeks, starting at Week 38 and ending with the last dose being at Week 78. Final efficacy assessments, including a pouchoscopy will be performed at Week 82.
The participant weighs >=10 kg at the time of screening and first dose.
>=1 previous episodes of pouchitis within 1 year before the screening visit, with symptoms lasting for at least a total of 4 weeks, treated with >=2 weeks of antibiotic or other prescription therapy (ie, other antibiotics, probiotics, immunomodulators, or anti-tumor necrosis factor [TNFs] within 1 year before screening). Or
Have had an inadequate response with, or lost response to, or be intolerant to antibiotic therapy (ie, requiring maintenance antibiotic therapy taken for >=4 weeks immediately before the baseline endoscopy visit or not able to receive or continue antibiotic treatment due to intolerance or other contraindication).
The participant is aged 2 to 17 years, inclusive, at the time of screening and first dose.
Has symptoms believed to be predominantly due to irritable pouch syndrome.
Has isolated cuffitis.
Is found to have dysplasia at the screening endoscopy.
Has mechanical complications of the pouch (for example [e.g.] pouch stricture or pouch fistula).
Single group
Vedolizumab
DrugVedolizumab intravenous infusion.
Concomitant Antibiotic Therapy
DrugCiprofloxacin, metronidazole, vancomycin, amoxicillin clavulanate or rifaximin.
Percentage of Participants Achieving Clinical Modified Pouchitis Disease Activity Index (mPDAI) Remission at Week 14
Clinical (mPDAI) remission is defined as mPDAI score \<5 and a reduction of mPDAI score by \>=2 points from Baseline. The mPDAI score is calculated as a sum of two subscales based on clinical symptoms (0 to 6) and endoscopic findings (0 to 6): 1) Clinical Symptoms: Stool Frequency (0=usual 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 celsius \[C\]) (0=Absent and 1=Present); 2) Endoscopic Inflammation Findings: Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). The total mPDAI score can range from 0 to 12. A higher mPDAI score is indicative of worse disease.
Percentage of Participants Achieving Clinical (mPDAI) Remission at Week 34
Clinical (mPDAI) remission is defined as mPDAI score \<5 and a reduction of mPDAI score by \>=2 points from Baseline. The mPDAI score is calculated as a sum of two subscales based on clinical symptoms (0 to 6) and endoscopic findings (0 to 6): 1) Clinical Symptoms: Stool Frequency (0=usual 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); 2) Endoscopic Inflammation Findings: Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). The total mPDAI score can range from 0 to 12. A higher mPDAI score is indicative of worse disease.
Percentage of Participants Achieving Pouchitis Disease Activity Index (PDAI) Remission at Week 14
PDAI remission is PDAI score \<7 and reduction of score by \>=3 points from Baseline. PDAI score calculated as sum of 3 subscales based on clinical symptoms (0-6), endoscopic findings (EF) (0-6), and histologic changes (0-6): 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 or abdominal cramps (0=None, 2=Usual),Fever (temperature\>37.8 degree C) (0=Absent,1=Present);2) EF Findings: Edema (0=not present, 1=present);Granularity (0=not present, 1=present); Friability (0=not present,1=present);Loss of vascular pattern (0=not present, 1=present); Mucous exudates (0=not present, 1=present);Ulcerations (0=not present,1=present);3) Acute Histologic Inflammation: Polymorphic nuclear leukocyte infiltration (0=None, 3=Severe+crypt abscess); Ulceration per low power field (mean) (0=0% to 3=\>50%). Total PDAI score ranges 0-18. Higher score means worse disease.
Percentage of Participants Achieving PDAI Remission at Week 34
PDAI remission is PDAI score \<7 and reduction of score by \>=3 points from Baseline. PDAI score calculated as sum of 3 subscales based on clinical symptoms (0-6), EF (0-6), and histologic changes (0-6): 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 or abdominal cramps (0=None, 2=Usual),Fever (temperature\>37.8 degree C) (0=Absent,1=Present);2) EF Findings: Edema (0=not present, 1=present);Granularity (0=not present, 1=present); Friability (0=not present,1=present);Loss of vascular pattern (0=not present, 1=present); Mucous exudates (0=not present, 1=present);Ulcerations (0=not present,1=present);3) Acute Histologic Inflammation: Polymorphic nuclear leukocyte infiltration (0=None, 3=Severe+crypt abscess); Ulceration per low power field (mean) (0=0% to 3=\>50%). Total PDAI score ranges 0-18. Higher score means worse disease.
Percentage of Participants Achieving Clinical (mPDAI) Response at Week 14
Clinical (mPDAI) response is defined as a reduction in mPDAI score by \>=2 points from baseline. The mPDAI score is calculated as a sum of two subscales based on clinical symptoms (0 to 6) and endoscopic findings (0 to 6): 1) Clinical Symptoms: Stool Frequency (0=usual 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); 2) Endoscopic Inflammation Findings: Edema (0=not present to 1=present); Granularity (0=not present to 1=present); Friability (0=not present to 1=present); Loss of vascular pattern (0=not present to 1=present); Mucous exudates (0=not present to 1=present); Ulcerations (0=not present to 1=present). The total mPDAI score can range from 0 to 12. A higher mPDAI score is indicative of worse disease.
